Endocrinology — Thyroid Emergency

111. Myxedema Coma

decompensated severe hypothyroidism · hypothermia + AMS + hypoventilation · IV thyroid hormone + HYDROCORTISONE FIRST · ICU · high mortality · Super Compact

Sx: hypothermia (often profound), altered mental status (lethargy → stupor → coma), hypoventilation with CO₂ retention, bradycardia, hypotension, hyponatremia, hypoglycemia; non-pitting edema (myxedema), dry skin, hyporeflexia/delayed relaxation, ileus; usually an elderly patient with known/undiagnosed hypothyroidism + a precipitant · (this is decompensated hypothyroidism with depressed mentation, temperature, and respiration — a clinical diagnosis treated empirically in the ICU; mortality is high, so don't wait for confirmatory labs, and give hydrocortisone before or with the thyroid hormone)

Neg: denies giving thyroid hormone WITHOUT first giving hydrocortisone (coexisting adrenal insufficiency is common; thyroid hormone alone can precipitate adrenal crisis — steroid first/concurrent) · denies waiting for labs to treat (clinical diagnosis — delay kills) · denies aggressive active rewarming (can cause vasodilation/hypotension — use passive) · denies missed precipitant (infection, cold exposure, sedatives/opioids, MI, stroke, levothyroxine nonadherence) · denies over-rapid sodium correction

SHx: known hypothyroidism + levothyroxine adherence (nonadherence a key trigger), prior thyroidectomy/radioiodine, recent infection/cold exposure, sedative/opioid/anesthetic use, recent illness/MI, elderly, winter season, missed diagnosis, prior thyroid disease

Etiology: severe long-standing hypothyroidism that decompensates under a precipitant → failure of thermogenesis, respiratory drive, cardiac output, and mentation · precipitants: infection (most common — esp pneumonia/UTI/sepsis), cold exposure, sedatives/opioids/anesthetics (depress respiration), MI/stroke/heart failure, GI bleed, levothyroxine discontinuation, trauma/surgery · often unrecognized hypothyroidism in an elderly patient

RF: untreated/undertreated hypothyroidism · levothyroxine nonadherence · elderly · infection · cold exposure · sedatives/opioids · recent illness/surgery · female

Data: clinical diagnosis — treat empirically, do NOT delay for labs · TSH (high in primary; low/normal in central), free T4 (low) confirm; cortisol/ACTH BEFORE steroid if possible (coexisting adrenal insufficiency) · severity/precipitant workup: temperature, ABG (CO₂ retention/hypoxia), sodium (hyponatremia), glucose (hypoglycemia), CBC + cultures (infection), ECG (bradycardia/low voltage), CK, BMP, lactate

DDx: myxedema coma · severe uncomplicated hypothyroidism · sepsis/septic shock (may coexist/precipitate) · hypothermia other cause · CNS depression (sedative/opioid, stroke, metabolic) · adrenal crisis · hypoglycemia · hyponatremic encephalopathy · CO₂ narcosis other cause

Home Meds: reconcile (levothyroxine nonadherence often the trigger); avoid sedatives/opioids (worsen hypoventilation — dose-reduce/avoid); review thyroid-affecting drugs (amiodarone, lithium); IV thyroid hormone acutely; resume oral levothyroxine + secure adherence at discharge

Plan

CONSULT: ICU (mandatory — airway/ventilation, hemodynamics, monitoring) · Endocrinology (urgent — hormone dosing, management) · ID/source-specific (precipitant infection) · Cardiology (if cardiac precipitant) · Pulmonary/critical care (ventilation)

– ICU + EMPIRIC TREATMENT (don't wait for labs):
  • HYDROCORTISONE FIRST / concurrently — stress-dose hydrocortisone (e.g. 100 mg IV, then 50 mg q6–8h or 100 mg q8h) BEFORE or with thyroid hormone (coexisting adrenal insufficiency is common; thyroid hormone increases cortisol demand/metabolism → can precipitate adrenal crisis) — draw cortisol first if it won't delay
  • IV THYROID HORMONE — levothyroxine (T4) IV loading dose then daily IV/PO (e.g. loading ~200–400 mcg IV then ~50–100 mcg/day, lower in elderly/cardiac); ± liothyronine (T3) may be added in severe cases per endocrine (controversial — cardiac risk); endocrine-directed dosing
– SUPPORTIVE / treat the physiology:
  • Airway + ventilation (hypoventilation/CO₂ retention often needs intubation/mechanical ventilation)
  • PASSIVE rewarming (blankets) — avoid aggressive active rewarming (vasodilation → hypotension)
  • Careful IV fluids + treat hyponatremia (avoid over-rapid correction) + dextrose for hypoglycemia + cautious vasopressors (may be refractory until thyroid hormone acts)
  • Hold/avoid sedatives + opioids (worsen respiratory depression)
– IDENTIFY + TREAT THE PRECIPITANT: infection (cultures + empiric antibiotics — often the trigger and signs are blunted), MI, etc.
– Myxedema coma is the hypothyroid mirror of thyroid storm: an elderly patient, usually with a precipitant like infection or a sedative, who decompensates into hypothermia, a depressed mental status, and hypoventilation. You treat it empirically in the ICU before the labs confirm it, because the mortality is high. The single most important sequencing rule — the same logic as central hypothyroidism — is to give hydrocortisone before or together with the thyroid hormone, because coexisting adrenal insufficiency is common and replacing thyroid hormone alone raises cortisol demand enough to precipitate an adrenal crisis. Then support the physiology: ventilate the CO₂ retention, rewarm passively (not aggressively, which drops the blood pressure), correct the sodium and glucose carefully, and avoid the sedatives and opioids that deepened the coma. And always find and treat the precipitant — usually an infection whose signs are blunted by the hypothyroidism itself.
– PT/OT: later — critical-illness recovery, deconditioning
– Trend: temperature, mental status, respiratory status/ABG, heart rate/BP, sodium, glucose, thyroid function, cortisol, precipitant resolution, ventilator needs
– Escalation triggers: already ICU — respiratory failure → intubation/ventilation; refractory hypotension → vasopressors + ensure steroid + thyroid hormone given; malignant arrhythmia/cardiac → cardiology; superimposed sepsis → sepsis pathway; failure to improve → reassess dosing/precipitant with endocrine
– Discharge checklist (after ICU recovery): recovered + on oral levothyroxine + precipitant treated + adrenal axis clarified; levothyroxine with administration + strict adherence counseling (nonadherence is a classic trigger) + access secured; steroid plan clarified (taper vs continue if adrenal insufficiency confirmed); TSH recheck (~6 wk) + titration; endocrine + PCP follow-up; sedative/opioid caution; education on sick-day awareness + never stopping levothyroxine; return precautions (lethargy/confusion, cold/low temperature, breathing difficulty, recurrence)

111. Myxedema Coma

complete reference · decompensated hypothyroidism emergency · IV thyroid hormone with hydrocortisone first, passive rewarming, ventilatory support, treat precipitant, high mortality · Full Card

Symptoms / Associated Sx

• Hypothermia (often profound), altered mental status (lethargy progressing to stupor and coma), and hypoventilation with CO₂ retention

• Bradycardia, hypotension, hyponatremia, and hypoglycemia

• Non-pitting edema (myxedema), dry skin, hyporeflexia or delayed relaxation, and ileus

• Usually an elderly patient with known or undiagnosed hypothyroidism and a precipitant

• This is decompensated hypothyroidism with depressed mentation, temperature, and respiration — a clinical diagnosis treated empirically in the ICU; mortality is high, so don't wait for confirmatory labs, and give hydrocortisone before or with the thyroid hormone

Neg

• Pt denies giving thyroid hormone without first giving hydrocortisone (coexisting adrenal insufficiency is common; thyroid hormone alone can precipitate adrenal crisis — steroid first or concurrent)

• Pt denies waiting for labs to treat (a clinical diagnosis — delay kills) and aggressive active rewarming (which can cause vasodilation and hypotension — use passive rewarming)

• Pt denies a missed precipitant (infection, cold exposure, sedatives or opioids, MI, stroke, levothyroxine nonadherence) and over-rapid sodium correction

Social History (SHx)

• Known hypothyroidism and levothyroxine adherence (nonadherence is a key trigger), and prior thyroidectomy or radioiodine

• Recent infection or cold exposure, and sedative, opioid, or anesthetic use

• Recent illness or MI, elderly status, winter season, a missed diagnosis, and prior thyroid disease

Main Etiology

• Severe long-standing hypothyroidism that decompensates under a precipitant, causing failure of thermogenesis, respiratory drive, cardiac output, and mentation

• Precipitants: infection (the most common — especially pneumonia, UTI, sepsis), cold exposure, sedatives, opioids, or anesthetics (which depress respiration), MI, stroke, or heart failure, GI bleeding, levothyroxine discontinuation, and trauma or surgery

• Often unrecognized hypothyroidism in an elderly patient

RF

• Modifiable: levothyroxine nonadherence, sedatives or opioids, and cold exposure

• Non-modifiable: untreated or undertreated hypothyroidism, elderly status, infection, recent illness or surgery, and female sex

Data

• A clinical diagnosis — treat empirically, do not delay for labs

• TSH (high in primary disease; low or normal in central disease) and free T4 (low) confirm it

• Cortisol and ACTH before steroid if possible (coexisting adrenal insufficiency)

• Severity and precipitant workup: temperature, an ABG (CO₂ retention, hypoxia), sodium (hyponatremia), glucose (hypoglycemia), CBC and cultures (infection), an ECG (bradycardia, low voltage), and CK, a BMP, and lactate

DDx

Myxedema coma · severe uncomplicated hypothyroidism · sepsis or septic shock (may coexist or precipitate) · hypothermia of another cause · CNS depression (sedative or opioid, stroke, metabolic) · adrenal crisis · hypoglycemia · hyponatremic encephalopathy · CO₂ narcosis of another cause

Home Meds

• Reconcile (levothyroxine nonadherence is often the trigger)

• Avoid sedatives and opioids (they worsen hypoventilation — dose-reduce or avoid); review thyroid-affecting drugs (amiodarone, lithium)

• Give IV thyroid hormone acutely; resume oral levothyroxine and secure adherence at discharge

Plan

CONSULT: ICU (mandatory — airway and ventilation, hemodynamics, monitoring) · Endocrinology (urgent — hormone dosing, management) · ID or source-specific (a precipitant infection) · Cardiology (if there is a cardiac precipitant) · Pulmonary/critical care (ventilation)

• ICU plus empiric treatment (don't wait for labs):

• • Hydrocortisone first or concurrently — stress-dose hydrocortisone (e.g. 100 mg IV, then 50 mg every 6–8 hours or 100 mg every 8 hours) before or with thyroid hormone (coexisting adrenal insufficiency is common; thyroid hormone increases cortisol demand and metabolism, which can precipitate adrenal crisis) — draw cortisol first if it won't delay

• • IV thyroid hormone — levothyroxine (T4) IV loading dose then daily IV/PO (e.g. a loading dose of ~200–400 mcg IV then ~50–100 mcg/day, lower in elderly or cardiac patients); with liothyronine (T3) possibly added in severe cases per endocrine (controversial — cardiac risk); endocrine-directed dosing

• Supportive care / treat the physiology:

• • Airway and ventilation (hypoventilation and CO₂ retention often need intubation and mechanical ventilation)

• • Passive rewarming (blankets) — avoid aggressive active rewarming (vasodilation → hypotension)

• • Careful IV fluids, treatment of hyponatremia (avoiding over-rapid correction), dextrose for hypoglycemia, and cautious vasopressors (which may be refractory until thyroid hormone acts)

• • Hold or avoid sedatives and opioids (they worsen respiratory depression)

• Identify and treat the precipitant: infection (cultures and empiric antibiotics — often the trigger and the signs are blunted), MI, and others

• PT/OT: later — critical-illness recovery and deconditioning

• Trend: temperature, mental status, respiratory status and ABG, heart rate and BP, sodium, glucose, thyroid function, cortisol, precipitant resolution, and ventilator needs

• Escalation triggers: already in the ICU — respiratory failure → intubation and ventilation; refractory hypotension → vasopressors and ensure the steroid and thyroid hormone are given; malignant arrhythmia or cardiac compromise → cardiology; superimposed sepsis → the sepsis pathway; failure to improve → reassess dosing and the precipitant with endocrine

• Discharge checklist (after ICU recovery): recovered, on oral levothyroxine, with the precipitant treated and the adrenal axis clarified; levothyroxine with administration and strict adherence counseling (nonadherence is a classic trigger) and access secured; a steroid plan clarified (taper versus continue if adrenal insufficiency is confirmed); a TSH recheck (~6 weeks) and titration; endocrine and PCP follow-up; sedative and opioid caution; education on sick-day awareness and never stopping levothyroxine; return precautions for lethargy or confusion, cold or a low temperature, breathing difficulty, or recurrence

Red Flags

• Thyroid hormone given without hydrocortisone → can precipitate adrenal crisis; steroid first or concurrent

• Hypoventilation with CO₂ retention → respiratory failure; anticipate intubation and ventilation

• Aggressive active rewarming → vasodilation and hypotension; use passive rewarming

• A missed precipitant (infection most common, signs blunted) → the coma won't resolve while it's untreated

• Over-rapid sodium correction → osmotic demyelination; correct hyponatremia carefully

Senior IM Resident Pearls

• It's the hypothyroid mirror of thyroid storm. An elderly patient with a precipitant decompensates into hypothermia, depressed mentation, and hypoventilation — treat empirically in the ICU.

• Hydrocortisone before or with the thyroid hormone. Coexisting adrenal insufficiency is common, and thyroid hormone alone can precipitate an adrenal crisis.

• Ventilate the CO₂ retention. Hypoventilation is a leading cause of death — many patients need intubation.

• Rewarm passively. Aggressive active rewarming vasodilates and drops the blood pressure in an already hypotensive patient.

• Avoid sedatives and opioids. They deepened the coma and will worsen the respiratory depression.

• Find the precipitant despite blunted signs. Infection is the usual trigger, and the hypothyroidism masks the fever and inflammatory response.

• Common mistake: giving thyroid hormone first and skipping the steroid — it can unmask and precipitate an adrenal crisis in a coexisting adrenal insufficiency.

Endocrinology — Adrenal

112. Adrenal Insufficiency

primary (Addison) · secondary (pituitary / steroid withdrawal) · fatigue + hypotension + hyponatremia · AM cortisol + ACTH + cosyntropin stim · hydrocortisone ± fludrocortisone · Super Compact

Sx: chronic fatigue, weakness, weight loss, anorexia, nausea, orthostatic hypotension, salt craving, abdominal pain, dizziness; primary (Addison) adds hyperpigmentation (high ACTH) + hyperkalemia (aldosterone deficient); often hyponatremia in both; vague/insidious → frequently missed until crisis · (the distinction that drives management: primary disease loses BOTH cortisol and aldosterone — so hyperkalemia and hyperpigmentation appear — while secondary disease loses only cortisol with aldosterone intact, so no hyperkalemia or hyperpigmentation; both need glucocorticoid, only primary needs mineralocorticoid)

Neg: denies missed adrenal crisis (hypotension/shock, severe hyponatremia — the emergency; see crisis card) · denies abruptly stopping chronic steroids (causes secondary AI — the most common cause overall) · denies missing the diagnosis in vague presentations until decompensation · denies missed concurrent autoimmune disease (polyglandular — thyroid, T1DM) · denies giving levothyroxine before steroid in panhypopituitarism (precipitates crisis)

SHx: chronic glucocorticoid use/recent taper or stop (key cause of secondary), autoimmune disease (Addison, polyglandular), known pituitary disease/surgery/radiation, TB/HIV/fungal (adrenal), anticoagulation/adrenal hemorrhage, checkpoint-inhibitor immunotherapy (hypophysitis/adrenalitis), opioids (suppress axis), family history, recent infection/stress

Etiology: primary (adrenal gland failure): autoimmune adrenalitis (Addison — most common in developed world), infection (TB, HIV, fungal), hemorrhage/infarction, infiltration, metastases, drugs, adrenoleukodystrophy → both cortisol + aldosterone deficient · secondary/tertiary (pituitary-hypothalamic — ACTH deficiency): exogenous steroid withdrawal (most common overall), pituitary tumor/surgery/radiation, hypophysitis (immunotherapy), Sheehan — cortisol deficient, aldosterone preserved (renin-angiotensin intact)

RF: chronic steroid use · autoimmune disease · pituitary disease · immunotherapy · TB/HIV/fungal · anticoagulation (hemorrhage) · opioids

Data: morning (8 AM) cortisol (low) + ACTH (HIGH in primary, LOW/normal in secondary — distinguishes) + cosyntropin (ACTH) stimulation test (inadequate cortisol rise confirms) · BMP (hyponatremia both; hyperkalemia in primary), glucose (hypoglycemia), renin/aldosterone (primary: high renin/low aldosterone) · adrenal antibodies, adrenal imaging if primary non-autoimmune; pituitary MRI if secondary; don't delay treatment in crisis for testing

DDx: primary adrenal insufficiency (Addison) · secondary AI (pituitary/steroid withdrawal) · adrenal crisis (decompensated — emergency) · sepsis · other shock/hypotension · hypothyroidism · depression/chronic fatigue · malignancy · hypercalcemia · SIADH (for hyponatremia)

Home Meds: never abruptly stop chronic steroids (taper); reconcile; glucocorticoid replacement (hydrocortisone) + fludrocortisone if primary; review opioids/axis-suppressing drugs; stress-dosing education; if panhypopituitarism — steroid before levothyroxine

Plan

CONSULT: Endocrinology (diagnosis confirmation, replacement, stress-dosing, complex/pituitary, immunotherapy-related) · ICU if crisis · Oncology (if immunotherapy-related or malignancy) · source-specific (infection, pituitary — neurosurgery)

– IF CRISIS (hypotension/shock, severe hyponatremia/hyperkalemia) → treat immediately: hydrocortisone 100 mg IV + IV saline/dextrose — don't wait for testing (see adrenal crisis card); this card = non-crisis diagnosis + chronic management
– CONFIRM THE DIAGNOSIS + LOCALIZE: AM cortisol + ACTH + cosyntropin stimulation test; ACTH high → primary; ACTH low/normal → secondary (then pituitary workup); draw before steroids if stable (or use dexamethasone, which doesn't interfere with cortisol assay, if must treat before testing)
– GLUCOCORTICOID REPLACEMENT (both types): hydrocortisone (e.g. ~15–25 mg/day divided, larger AM dose to mimic diurnal rhythm) or prednisone; titrate to clinical response (avoid over-replacement)
– MINERALOCORTICOID REPLACEMENT (PRIMARY ONLY): fludrocortisone (e.g. ~0.05–0.2 mg daily) — secondary AI does NOT need it (aldosterone/renin-angiotensin intact); monitor BP, potassium, sodium, edema
– STRESS-DOSE GLUCOCORTICOID EDUCATION (critical): increase dose for illness/fever/surgery/stress (e.g. double or triple for moderate illness; IV hydrocortisone for severe/vomiting/surgery); medical alert bracelet + emergency injectable hydrocortisone kit + sick-day rules — prevents future crises
– TREAT UNDERLYING CAUSE: autoimmune (replacement + screen polyglandular — thyroid/T1DM), infection (TB/fungal treatment), pituitary disease (manage other axes — cortisol before thyroid), immunotherapy (continue replacement, oncology co-manage); taper/manage offending steroids
– The whole card turns on one distinction: primary versus secondary, told by the ACTH. Primary adrenal failure knocks out both cortisol and aldosterone, so you see hyperkalemia and the hyperpigmentation of a high ACTH driving the skin — and you must replace both a glucocorticoid AND a mineralocorticoid (fludrocortisone). Secondary disease, by far most often from someone abruptly stopping chronic steroids, loses only cortisol; the aldosterone axis is intact, so there's no hyperkalemia, no hyperpigmentation, and no need for fludrocortisone. Two safety points: if the patient is in crisis you give hydrocortisone before you finish testing, and the single most important outpatient intervention is stress-dose education with an emergency injection kit, because the patients who die are the ones who didn't up their steroids when they got sick. And in panhypopituitarism, steroid goes in before levothyroxine.
– PT/OT: usually not needed; functional recovery if deconditioned
– Trend: BP/orthostatics, electrolytes (sodium, potassium — esp on fludrocortisone), glucose, symptoms/energy/weight, signs of over- or under-replacement, cause-specific workup
– Escalation triggers: decompensation to crisis (hypotension/shock) → adrenal crisis pathway + ICU; intercurrent illness → stress-dose escalation; immunotherapy-related → oncology + endocrine; pituitary mass/apoplexy → neurosurgery; refractory → endocrine reassessment
– Discharge checklist: on glucocorticoid (+ fludrocortisone if primary) + stable + cause identified; replacement regimen with doses; STRESS-DOSING education + emergency hydrocortisone injection kit + medical alert bracelet + sick-day rules (prevents crisis); never-stop-abruptly counseling; endocrine follow-up; polyglandular/cause-specific screening; if secondary — manage other pituitary axes; return precautions (dizziness/fainting, vomiting/can't keep meds down, severe weakness, signs of crisis — get emergency care + stress dose)

112. Adrenal Insufficiency

complete reference · primary (Addison) vs secondary · ACTH distinguishes, hydrocortisone for both + fludrocortisone for primary, stress-dose education prevents crisis · Full Card

Symptoms / Associated Sx

• Chronic fatigue, weakness, weight loss, anorexia, nausea, orthostatic hypotension, salt craving, abdominal pain, and dizziness

• Primary (Addison) disease adds hyperpigmentation (high ACTH) and hyperkalemia (aldosterone deficient); both forms often have hyponatremia

• The presentation is vague and insidious, so it is frequently missed until crisis

• The distinction that drives management: primary disease loses both cortisol and aldosterone — so hyperkalemia and hyperpigmentation appear — while secondary disease loses only cortisol with aldosterone intact, so there is no hyperkalemia or hyperpigmentation; both need a glucocorticoid, but only primary needs a mineralocorticoid

Neg

• Pt denies a missed adrenal crisis (hypotension or shock, severe hyponatremia — the emergency; see the crisis card)

• Pt denies abruptly stopping chronic steroids (causing secondary AI — the most common cause overall) and missing the diagnosis in vague presentations until decompensation

• Pt denies a missed concurrent autoimmune disease (polyglandular — thyroid, T1DM) and giving levothyroxine before steroid in panhypopituitarism (which precipitates crisis)

Social History (SHx)

• Chronic glucocorticoid use or a recent taper or stop (a key cause of secondary disease), and autoimmune disease (Addison, polyglandular)

• Known pituitary disease, surgery, or radiation, TB, HIV, or fungal disease (adrenal), and anticoagulation or adrenal hemorrhage

• Checkpoint-inhibitor immunotherapy (hypophysitis, adrenalitis), opioids (suppress the axis), family history, and recent infection or stress

Main Etiology

• Primary (adrenal gland failure): autoimmune adrenalitis (Addison — the most common in the developed world), infection (TB, HIV, fungal), hemorrhage or infarction, infiltration, metastases, drugs, and adrenoleukodystrophy → both cortisol and aldosterone deficient

• Secondary or tertiary (pituitary-hypothalamic — ACTH deficiency): exogenous steroid withdrawal (the most common overall), a pituitary tumor, surgery, or radiation, hypophysitis (immunotherapy), and Sheehan syndrome — cortisol deficient with aldosterone preserved (renin-angiotensin intact)

RF

• Modifiable: chronic steroid use, immunotherapy, and opioids

• Non-modifiable: autoimmune disease, pituitary disease, TB/HIV/fungal disease, and anticoagulation (hemorrhage)

Data

• A morning (8 AM) cortisol (low) with ACTH (high in primary, low or normal in secondary — distinguishing them) and a cosyntropin (ACTH) stimulation test (an inadequate cortisol rise confirms it)

• A BMP (hyponatremia in both; hyperkalemia in primary) and glucose (hypoglycemia), with renin and aldosterone (primary: high renin, low aldosterone)

• Adrenal antibodies and adrenal imaging if primary and non-autoimmune; a pituitary MRI if secondary

• Don't delay treatment in crisis for testing

DDx

Primary adrenal insufficiency (Addison) · secondary AI (pituitary, steroid withdrawal) · adrenal crisis (decompensated — an emergency) · sepsis · other shock or hypotension · hypothyroidism · depression or chronic fatigue · malignancy · hypercalcemia · SIADH (for the hyponatremia)

Home Meds

• Never abruptly stop chronic steroids (taper); reconcile medications

• Replace with a glucocorticoid (hydrocortisone) plus fludrocortisone if primary; review opioids and axis-suppressing drugs

• Provide stress-dosing education; if there is panhypopituitarism, give the steroid before levothyroxine

Plan

CONSULT: Endocrinology (diagnosis confirmation, replacement, stress-dosing, complex or pituitary disease, immunotherapy-related disease) · ICU if crisis · Oncology (if immunotherapy-related or malignancy) · source-specific (infection, pituitary — neurosurgery)

• If crisis (hypotension or shock, severe hyponatremia or hyperkalemia) → treat immediately: hydrocortisone 100 mg IV plus IV saline and dextrose — don't wait for testing (see the adrenal crisis card); this card is the non-crisis diagnosis and chronic management

• Confirm the diagnosis and localize: an AM cortisol with ACTH and a cosyntropin stimulation test; ACTH high → primary; ACTH low or normal → secondary (then a pituitary workup); draw before steroids if stable (or use dexamethasone, which doesn't interfere with the cortisol assay, if you must treat before testing)

• Glucocorticoid replacement (both types): hydrocortisone (e.g. ~15–25 mg/day divided, with a larger morning dose to mimic the diurnal rhythm) or prednisone; titrated to clinical response (avoiding over-replacement)

• Mineralocorticoid replacement (primary only): fludrocortisone (e.g. ~0.05–0.2 mg daily) — secondary AI does not need it (the aldosterone and renin-angiotensin axis is intact); monitor BP, potassium, sodium, and edema

• Stress-dose glucocorticoid education (critical): increase the dose for illness, fever, surgery, or stress (e.g. double or triple for moderate illness; IV hydrocortisone for severe illness, vomiting, or surgery); a medical alert bracelet, an emergency injectable hydrocortisone kit, and sick-day rules — preventing future crises

• Treat the underlying cause: autoimmune disease (replacement and screen for polyglandular disease — thyroid, T1DM), infection (TB or fungal treatment), pituitary disease (manage other axes — cortisol before thyroid), immunotherapy (continue replacement, co-manage with oncology); and taper or manage offending steroids

• PT/OT: usually not needed; functional recovery if deconditioned

• Trend: BP and orthostatics, electrolytes (sodium, potassium — especially on fludrocortisone), glucose, symptoms, energy, and weight, signs of over- or under-replacement, and the cause-specific workup

• Escalation triggers: decompensation to crisis (hypotension or shock) → the adrenal crisis pathway and ICU; intercurrent illness → stress-dose escalation; immunotherapy-related disease → oncology and endocrine; a pituitary mass or apoplexy → neurosurgery; refractory disease → endocrine reassessment

• Discharge checklist: on a glucocorticoid (plus fludrocortisone if primary), stable, with the cause identified; a replacement regimen with doses; stress-dosing education with an emergency hydrocortisone injection kit, a medical alert bracelet, and sick-day rules (preventing crisis); never-stop-abruptly counseling; endocrine follow-up; polyglandular and cause-specific screening; if secondary, manage the other pituitary axes; return precautions for dizziness or fainting, vomiting or inability to keep medications down, severe weakness, or signs of crisis (get emergency care and a stress dose)

Red Flags

• Hypotension or shock with severe hyponatremia or hyperkalemia → adrenal crisis; treat with hydrocortisone before testing

• Abruptly stopping chronic steroids → secondary AI; the most common cause overall

• Primary disease → needs both glucocorticoid and mineralocorticoid (fludrocortisone)

• Panhypopituitarism → give the steroid before levothyroxine to avoid precipitating crisis

• Intercurrent illness without stress-dosing → the classic path to a fatal crisis

Senior IM Resident Pearls

• The ACTH tells you primary versus secondary. High ACTH is primary (both hormones lost); low or normal ACTH is secondary (cortisol only).

• Only primary needs fludrocortisone. Secondary disease has an intact aldosterone axis, so there's no hyperkalemia and no mineralocorticoid requirement.

• The most common cause is stopping steroids. Abrupt withdrawal of chronic glucocorticoids suppresses the axis and produces secondary AI.

• Treat crisis before you finish testing. Hydrocortisone and saline come first; dexamethasone won't interfere with a later cortisol assay if you must cover before drawing.

• Stress-dose education saves lives. The patients who die are the ones who didn't increase their steroids when they got sick — give them a kit and a bracelet.

• Screen for polyglandular disease. Autoimmune Addison travels with autoimmune thyroid disease and T1DM.

• Common mistake: diagnosing hyponatremia as SIADH and missing adrenal insufficiency — check a cortisol, because the treatment is entirely different.

Endocrinology — Adrenal Emergency

113. Adrenal Crisis

life-threatening · shock + hyponatremia + hyperkalemia + hypoglycemia · HYDROCORTISONE 100 mg IV immediately — don't wait for labs · aggressive saline · ICU · Super Compact

Sx: hypotension/shock refractory to fluids and pressors, profound weakness, nausea/vomiting, severe abdominal pain (can mimic acute abdomen), fever, confusion/AMS; labs: hyponatremia, hyperkalemia (primary), hypoglycemia; in a known or undiagnosed adrenal-insufficient patient with a stressor · (adrenal crisis is treat-first: give hydrocortisone the moment you suspect it — before any confirmatory testing — because waiting for a cortisol level to come back can cost the patient their life; the classic clue is shock that doesn't respond to fluids and pressors)

Neg: denies delaying hydrocortisone for diagnostic testing (draw cortisol/ACTH if quick, but TREAT FIRST — this is the cardinal error to avoid) · denies missed precipitant (infection, missed steroid doses, surgery/trauma, vomiting, MI) · denies missed adrenal hemorrhage (anticoagulation, sepsis — Waterhouse-Friderichsen) · denies attributing refractory shock solely to sepsis without considering adrenal crisis · denies stopping steroids that caused it

SHx: known adrenal insufficiency/Addison/pituitary disease, chronic steroid use + missed doses or failure to stress-dose, recent illness/infection/surgery/vomiting (can't absorb oral steroid), anticoagulation (hemorrhage), immunotherapy, prior crisis, no medical alert/emergency kit

Etiology: acute severe cortisol deficiency (± aldosterone in primary) overwhelmed by a stressor → loss of vascular tone/pressor responsiveness, sodium/water dysregulation, hypoglycemia → distributive/refractory shock · precipitants: infection/sepsis (most common), failure to stress-dose or missed steroid doses, surgery/trauma, vomiting/GI illness (can't take oral steroid), MI, adrenal hemorrhage/infarction, abrupt steroid cessation, new severe illness in undiagnosed AI

RF: known adrenal insufficiency · chronic steroid use · acute illness/infection/surgery without stress dose · anticoagulation (hemorrhage) · vomiting · undiagnosed AI

Data: DO NOT delay treatment — draw cortisol + ACTH BEFORE steroid only if it won't delay (or use dexamethasone, which doesn't interfere with cortisol assay) · BMP (hyponatremia, hyperkalemia in primary), glucose (hypoglycemia), CBC + cultures/UA/CXR (precipitant infection), lactate; cosyntropin stimulation test later for confirmation; adrenal/pituitary imaging if hemorrhage/mass suspected

DDx: adrenal crisis · septic shock (may coexist/precipitate — consider crisis in refractory septic shock) · other distributive/hypovolemic/cardiogenic shock · acute abdomen · hyperkalemia/hyponatremia other cause · hypoglycemia · myxedema coma · anaphylaxis

Home Meds: give IV (not oral) hydrocortisone — vomiting/shock impair absorption; reconcile chronic steroids (continue/escalate); hold drugs worsening hyperkalemia/hypotension; after recovery establish maintenance + stress-dose plan + emergency kit

Plan

CONSULT: ICU (mandatory — shock, monitoring, refractory hypotension) · Endocrinology (urgent — confirm, taper, chronic plan) · ID/source-specific (precipitant infection) · others per precipitant (surgery, cardiology)

– TREAT IMMEDIATELY ON SUSPICION — don't wait for labs/confirmation:
  • 1) HYDROCORTISONE 100 mg IV immediately, then 50 mg IV q6h (or 100 mg q8h, or continuous infusion ~200 mg/24h) — the life-saving step (provides both glucocorticoid + at stress doses some mineralocorticoid effect)
  (if AI not yet diagnosed + you want to preserve diagnostic testing: dexamethasone 4 mg IV instead — doesn't interfere with the cortisol assay — then do cosyntropin stim, then switch to hydrocortisone)
  • 2) AGGRESSIVE IV FLUIDS — isotonic saline (0.9% NaCl) rapidly (corrects hypovolemia + hyponatremia) + dextrose (D5) for hypoglycemia; large volumes often needed
– MANAGE ELECTROLYTES: hyponatremia + hyperkalemia usually correct with hydrocortisone + saline; treat severe/symptomatic hyperkalemia per protocol; avoid over-rapid sodium correction once improving
– IDENTIFY + TREAT THE PRECIPITANT: infection (cultures + empiric antibiotics — the most common trigger), surgery, MI, adrenal hemorrhage; crisis won't resolve without addressing it
– SUPPORTIVE / ICU: hemodynamic monitoring, vasopressors if needed (often regain responsiveness once steroid given — the diagnostic clue is pressor-refractory shock improving after hydrocortisone), treat hypoglycemia
– AFTER STABILIZATION: taper hydrocortisone to maintenance, add fludrocortisone for primary AI (when hydrocortisone dose < ~50 mg/day — at higher doses hydrocortisone provides mineralocorticoid effect), confirm diagnosis, establish chronic plan + prevention
– There is exactly one thing you must not get wrong in adrenal crisis: give the hydrocortisone immediately, before any test result, because the patient in pressor-refractory shock will die waiting for a cortisol level. If they're not yet diagnosed and you want to keep the diagnostic door open, use dexamethasone instead — it treats the crisis but doesn't cloud the cortisol assay — then do the stimulation test and switch back to hydrocortisone. Everything else is supportive: pour in saline with dextrose, and watch the shock that wouldn't respond to fluids and pressors suddenly improve once the steroid is on board, which is itself almost diagnostic. Always hunt the precipitant — infection most often — and the mineralocorticoid (fludrocortisone) only matters later, for primary disease, once the stress-dose hydrocortisone comes down.
– PT/OT: later — recovery from critical illness
– Trend: BP/perfusion/pressor needs (improvement after steroid), electrolytes (sodium, potassium), glucose, mental status, precipitant resolution, response to hydrocortisone, volume status
– Escalation triggers: already ICU — refractory shock despite hydrocortisone + fluids → reassess (adequate steroid dosing? ongoing precipitant? alternative dx — sepsis/cardiogenic) + pressors; adrenal hemorrhage → imaging + manage anticoagulation; superimposed sepsis → sepsis pathway; recurrent crises → endocrine + adherence/education review
– Discharge checklist (after recovery): crisis resolved + on maintenance steroid (+ fludrocortisone if primary) + precipitant treated; maintenance regimen with doses + STRESS-DOSING education + emergency injectable hydrocortisone kit + medical alert bracelet + sick-day rules (the crisis-prevention bundle); never-stop-abruptly counseling; endocrine follow-up + diagnosis confirmation; caregiver injection training; return precautions (vomiting/can't keep meds down — use injection + seek care, dizziness/fainting, severe weakness, recurrence)

113. Adrenal Crisis

complete reference · shock + hyponatremia + hyperkalemia · immediate hydrocortisone before testing, aggressive saline + dextrose, treat precipitant, crisis-prevention bundle · Full Card

Symptoms / Associated Sx

• Hypotension or shock refractory to fluids and pressors, profound weakness, nausea, vomiting, and severe abdominal pain (which can mimic an acute abdomen)

• Fever and confusion or altered mental status

• Labs: hyponatremia, hyperkalemia (in primary disease), and hypoglycemia

• Occurs in a known or undiagnosed adrenal-insufficient patient with a stressor

• Adrenal crisis is treat-first: give hydrocortisone the moment you suspect it — before any confirmatory testing — because waiting for a cortisol level can cost the patient their life; the classic clue is shock that doesn't respond to fluids and pressors

Neg

• Pt denies delaying hydrocortisone for diagnostic testing (draw cortisol and ACTH if quick, but treat first — this is the cardinal error to avoid)

• Pt denies a missed precipitant (infection, missed steroid doses, surgery or trauma, vomiting, MI) and a missed adrenal hemorrhage (anticoagulation, sepsis — Waterhouse-Friderichsen)

• Pt denies attributing refractory shock solely to sepsis without considering adrenal crisis and stopping the steroids that caused it

Social History (SHx)

• Known adrenal insufficiency, Addison disease, or pituitary disease, and chronic steroid use with missed doses or a failure to stress-dose

• Recent illness, infection, surgery, or vomiting (can't absorb oral steroid), and anticoagulation (hemorrhage)

• Immunotherapy, prior crisis, and no medical alert or emergency kit

Main Etiology

• Acute severe cortisol deficiency (with aldosterone deficiency in primary disease) overwhelmed by a stressor causes loss of vascular tone and pressor responsiveness, sodium and water dysregulation, and hypoglycemia, producing a distributive or refractory shock

• Precipitants: infection or sepsis (the most common), a failure to stress-dose or missed steroid doses, surgery or trauma, vomiting or GI illness (can't take oral steroid), MI, adrenal hemorrhage or infarction, abrupt steroid cessation, and a new severe illness in undiagnosed AI

RF

• Modifiable: chronic steroid use, acute illness, infection, or surgery without a stress dose, and missed doses

• Non-modifiable: known adrenal insufficiency, anticoagulation (hemorrhage), and undiagnosed AI

Data

• Do not delay treatment — draw cortisol and ACTH before steroid only if it won't delay (or use dexamethasone, which doesn't interfere with the cortisol assay)

• A BMP (hyponatremia, hyperkalemia in primary disease) and glucose (hypoglycemia), CBC with cultures/urinalysis/CXR (a precipitant infection), and lactate

• A cosyntropin stimulation test later for confirmation; adrenal or pituitary imaging if hemorrhage or a mass is suspected

DDx

Adrenal crisis · septic shock (may coexist or precipitate — consider crisis in refractory septic shock) · other distributive, hypovolemic, or cardiogenic shock · an acute abdomen · hyperkalemia or hyponatremia of another cause · hypoglycemia · myxedema coma · anaphylaxis

Home Meds

• Give IV (not oral) hydrocortisone — vomiting and shock impair absorption

• Reconcile chronic steroids (continue and escalate); hold drugs worsening hyperkalemia or hypotension

• After recovery, establish a maintenance and stress-dose plan with an emergency kit

Plan

CONSULT: ICU (mandatory — shock, monitoring, refractory hypotension) · Endocrinology (urgent — confirmation, taper, chronic plan) · ID or source-specific (a precipitant infection) · others per precipitant (surgery, cardiology)

• Treat immediately on suspicion — don't wait for labs or confirmation:

• • 1) Hydrocortisone 100 mg IV immediately, then 50 mg IV every 6 hours (or 100 mg every 8 hours, or a continuous infusion of ~200 mg/24 hours) — the life-saving step (providing both glucocorticoid and, at stress doses, some mineralocorticoid effect)

• • If AI is not yet diagnosed and you want to preserve diagnostic testing: dexamethasone 4 mg IV instead (it doesn't interfere with the cortisol assay) — then do the cosyntropin stimulation test, then switch to hydrocortisone

• • 2) Aggressive IV fluids — isotonic saline (0.9% NaCl) rapidly (correcting hypovolemia and hyponatremia) plus dextrose (D5) for hypoglycemia; large volumes are often needed

• Manage electrolytes: hyponatremia and hyperkalemia usually correct with hydrocortisone and saline; treat severe or symptomatic hyperkalemia per protocol; avoid over-rapid sodium correction once improving

• Identify and treat the precipitant: infection (cultures and empiric antibiotics — the most common trigger), surgery, MI, and adrenal hemorrhage; the crisis won't resolve without addressing it

• Supportive care / ICU: hemodynamic monitoring and vasopressors if needed (responsiveness is often regained once the steroid is given — the diagnostic clue is pressor-refractory shock improving after hydrocortisone) and treatment of hypoglycemia

• After stabilization: taper hydrocortisone to maintenance, add fludrocortisone for primary AI (when the hydrocortisone dose is below ~50 mg/day — at higher doses hydrocortisone provides a mineralocorticoid effect), confirm the diagnosis, and establish a chronic plan and prevention

• PT/OT: later — recovery from critical illness

• Trend: BP, perfusion, and pressor needs (improvement after the steroid), electrolytes (sodium, potassium), glucose, mental status, precipitant resolution, the response to hydrocortisone, and volume status

• Escalation triggers: already in the ICU — refractory shock despite hydrocortisone and fluids → reassess (adequate steroid dosing? an ongoing precipitant? an alternative diagnosis — sepsis or cardiogenic shock) and use pressors; adrenal hemorrhage → imaging and management of anticoagulation; superimposed sepsis → the sepsis pathway; recurrent crises → endocrine and an adherence and education review

• Discharge checklist (after recovery): the crisis resolved, on a maintenance steroid (plus fludrocortisone if primary), with the precipitant treated; a maintenance regimen with doses plus stress-dosing education, an emergency injectable hydrocortisone kit, a medical alert bracelet, and sick-day rules (the crisis-prevention bundle); never-stop-abruptly counseling; endocrine follow-up and diagnosis confirmation; caregiver injection training; return precautions for vomiting or inability to keep medications down (use the injection and seek care), dizziness or fainting, severe weakness, or recurrence

Red Flags

• Delaying hydrocortisone for testing → the cardinal error; treat on suspicion before any result

• Pressor-refractory shock → consider adrenal crisis; it often improves only after the steroid

• Vomiting or shock → give IV, not oral, hydrocortisone (absorption is impaired)

• A missed precipitant (infection most common) → the crisis won't resolve while it's untreated

• Adrenal hemorrhage on anticoagulation or in sepsis → Waterhouse-Friderichsen; image and manage

Senior IM Resident Pearls

• Give the hydrocortisone immediately. The patient in pressor-refractory shock will die waiting for a cortisol level — treat on suspicion.

• Use dexamethasone to preserve testing. If the patient isn't yet diagnosed, dexamethasone treats the crisis without clouding the cortisol assay; then do the stimulation test.

• The response is almost diagnostic. Shock that wouldn't respond to fluids and pressors improving after hydrocortisone strongly supports the diagnosis.

• Give it IV, not oral. Vomiting and shock impair absorption — the oral dose won't get there.

• Hunt the precipitant. Infection is the usual trigger; the crisis won't break until it's treated.

• Fludrocortisone is a later concern. Stress-dose hydrocortisone covers the mineralocorticoid need acutely; add fludrocortisone for primary disease as the dose comes down.

• Common mistake: calling it refractory septic shock and never considering adrenal crisis — always think of it when shock doesn't respond as expected.

Endocrinology — Pituitary

114. Pituitary Disorders

pituitary mass · hypopituitarism · pituitary apoplexy (emergency) · mass effect + hormone hyper/hypo-secretion · MRI + full hormonal axis · cortisol replacement FIRST · Super Compact

Sx: mass effect: headache, bitemporal hemianopsia (optic chiasm compression), cranial nerve palsies (cavernous sinus — diplopia); hormone EXCESS: prolactinoma (galactorrhea, amenorrhea, low libido), acromegaly (acral/facial growth — GH), Cushing (ACTH); hormone DEFICIENCY (hypopituitarism): fatigue, hypotension, hypogonadism, hypothyroidism, adrenal insufficiency; APOPLEXY: sudden severe headache + visual loss + ophthalmoplegia + AMS · (across all pituitary problems the cardinal rule is to assess + replace the cortisol axis FIRST — ACTH/adrenal deficiency is the immediately life-threatening one, and giving thyroid hormone before cortisol can precipitate adrenal crisis)

Neg: denies missed pituitary apoplexy (hemorrhage/infarction of pituitary — sudden headache + visual/ocular signs — neurosurgical/endocrine emergency needing stress steroids) · denies giving levothyroxine before cortisol in hypopituitarism (precipitates adrenal crisis — cortisol FIRST) · denies missed secondary adrenal insufficiency · denies missed visual-field/chiasm compromise needing urgent decompression · denies missed prolactinoma (medically treated, not first surgical)

SHx: known pituitary tumor/adenoma, prior pituitary surgery/radiation, head trauma, postpartum hemorrhage (Sheehan), anticoagulation (apoplexy), visual symptoms, symptoms of hormone excess/deficiency, immunotherapy (hypophysitis), family history (MEN1), prior endocrine workup

Etiology: pituitary adenoma (most common — functioning [prolactin/GH/ACTH] or non-functioning), craniopharyngioma, other masses; hypopituitarism from tumor/surgery/radiation/Sheehan/hypophysitis/trauma/infiltration; apoplexy = acute hemorrhage or infarction into a pituitary tumor (often previously unknown), precipitated by anticoagulation, surgery, pregnancy, dynamic testing · prolactinoma is the most common functioning adenoma

RF: known pituitary adenoma · prior pituitary surgery/radiation · anticoagulation (apoplexy) · postpartum hemorrhage (Sheehan) · head trauma · immunotherapy · MEN1

Data: pituitary MRI (with/without contrast — defines mass, apoplexy, chiasm compression) · FULL anterior pituitary panel: prolactin, IGF-1/GH, ACTH + cortisol (8 AM), TSH + free T4, LH/FSH + testosterone/estradiol; posterior (consider DI — Na/urine if polyuria); formal visual field testing (chiasm); cosyntropin stim (adrenal axis); pregnancy test; in apoplexy, urgent MRI + electrolytes + cortisol

DDx: non-functioning pituitary adenoma · prolactinoma · acromegaly (GH) · Cushing disease (ACTH) · hypopituitarism · pituitary apoplexy (emergency) · craniopharyngioma/other sellar mass · Sheehan syndrome · lymphocytic/immunotherapy hypophysitis · empty sella

Home Meds: reconcile; hormone replacement in deficiency order — glucocorticoid (hydrocortisone) FIRST, then levothyroxine, then sex steroids; dopamine agonist (cabergoline) for prolactinoma; hold anticoagulation in apoplexy; stress-dose steroids peri-operatively/in apoplexy

Plan

CONSULT: Endocrinology (hormonal evaluation + replacement — essential) · Neurosurgery (mass with compression, apoplexy — transsphenoidal surgery) · Ophthalmology/Neuro-ophthalmology (visual fields, chiasm) · Radiation oncology (selected) · Oncology (if immunotherapy hypophysitis)

– PITUITARY APOPLEXY (EMERGENCY) — recognize + treat fast: sudden severe headache + visual loss/ophthalmoplegia + AMS → immediate STRESS-DOSE glucocorticoid (hydrocortisone 100 mg IV then 50 mg q6h) (presumed acute secondary adrenal insufficiency — life-saving), urgent pituitary MRI, urgent neurosurgery consult (decompression for visual/neuro compromise), fluid/electrolyte support, ICU if unstable
– ASSESS + REPLACE HORMONES IN THE RIGHT ORDER:
  • CORTISOL FIRST: assess ACTH-cortisol axis; if deficient/unclear → glucocorticoid replacement (hydrocortisone) BEFORE any thyroid hormone (replacing thyroid first accelerates cortisol metabolism → adrenal crisis)
  • THEN thyroid: levothyroxine for central hypothyroidism (after cortisol covered)
  • THEN sex steroids / GH / desmopressin (DI) per axes and endocrine
– MASS WITH COMPRESSION (visual-field/chiasm): neurosurgery — transsphenoidal resection for non-prolactinoma mass with visual compromise; urgent if rapidly progressive/apoplexy
– PROLACTINOMA (special — medical first): dopamine agonist (cabergoline preferred, or bromocriptine) shrinks tumor + normalizes prolactin — first-line even for large prolactinomas (surgery reserved for failure/intolerance) — distinguish from non-functioning adenoma (which is surgical) by prolactin level
– OTHER FUNCTIONING TUMORS: acromegaly (surgery ± somatostatin analog/pegvisomant), Cushing disease (transsphenoidal surgery) — endocrine/neurosurgery directed
– Pituitary disease comes in three flavors — a mass pressing on things (classically the chiasm, giving bitemporal hemianopsia), too much of one hormone (prolactin, GH, or ACTH), or too little of several (hypopituitarism) — but one rule cuts across all of them: deal with cortisol first. If you're replacing hormones, the glucocorticoid goes in before the levothyroxine, because thyroid hormone speeds cortisol clearance and can tip an unrecognized secondary adrenal insufficiency into crisis. The emergency to never miss is apoplexy — a sudden hemorrhage into a pituitary tumor presenting as thunderclap headache with visual and eye-movement findings — where you give stress-dose hydrocortisone immediately, get an urgent MRI, and call neurosurgery. And remember the one tumor you treat with a pill rather than a scalpel: the prolactinoma responds to a dopamine agonist like cabergoline, even when it's large.
– PT/OT: usually not needed acutely; rehab after surgery/visual impairment
– Trend: visual fields/acuity, neuro status, hormone levels/replacement adequacy, electrolytes/sodium (DI/SIADH post-op), cortisol coverage, tumor size on imaging, post-op recovery
– Escalation triggers: apoplexy/acute visual loss → emergent neurosurgery + stress steroids + ICU; secondary adrenal insufficiency/crisis → hydrocortisone (see adrenal crisis card); progressive chiasm compression → urgent surgery; post-op DI/SIADH → sodium management; immunotherapy hypophysitis → oncology + endocrine
– Discharge checklist: hormones assessed + replaced in correct order + mass managed/plan + visual status documented; replacement regimen (cortisol first, with stress-dose education if ACTH-deficient + emergency hydrocortisone kit); dopamine agonist if prolactinoma; surgery/radiation plan; endocrine + neurosurgery + ophthalmology follow-up; tumor surveillance imaging; DI/desmopressin plan if applicable; return precautions (worsening headache, vision changes, signs of adrenal insufficiency, polyuria/excessive thirst, recurrence)

114. Pituitary Disorders

complete reference · mass + hypopituitarism + apoplexy · MRI + full axis, cortisol replacement first, stress steroids for apoplexy, dopamine agonist for prolactinoma · Full Card

Symptoms / Associated Sx

• Mass effect: headache, bitemporal hemianopsia (optic chiasm compression), and cranial nerve palsies (cavernous sinus — diplopia)

• Hormone excess: prolactinoma (galactorrhea, amenorrhea, low libido), acromegaly (acral and facial growth — GH), and Cushing disease (ACTH)

• Hormone deficiency (hypopituitarism): fatigue, hypotension, hypogonadism, hypothyroidism, and adrenal insufficiency

• Apoplexy: sudden severe headache with visual loss, ophthalmoplegia, and altered mental status

• Across all pituitary problems the cardinal rule is to assess and replace the cortisol axis first — ACTH or adrenal deficiency is the immediately life-threatening one, and giving thyroid hormone before cortisol can precipitate adrenal crisis

Neg

• Pt denies a missed pituitary apoplexy (hemorrhage or infarction of the pituitary — sudden headache with visual or ocular signs — a neurosurgical and endocrine emergency needing stress steroids)

• Pt denies giving levothyroxine before cortisol in hypopituitarism (which precipitates adrenal crisis — cortisol first) and a missed secondary adrenal insufficiency

• Pt denies a missed visual-field or chiasm compromise needing urgent decompression and a missed prolactinoma (medically treated, not first surgical)

Social History (SHx)

• A known pituitary tumor or adenoma, prior pituitary surgery or radiation, and head trauma

• Postpartum hemorrhage (Sheehan), anticoagulation (apoplexy), and visual symptoms or symptoms of hormone excess or deficiency

• Immunotherapy (hypophysitis), family history (MEN1), and a prior endocrine workup

Main Etiology

• Pituitary adenoma (the most common — functioning [prolactin, GH, ACTH] or non-functioning), craniopharyngioma, and other masses

• Hypopituitarism from a tumor, surgery, radiation, Sheehan syndrome, hypophysitis, trauma, or infiltration

• Apoplexy = acute hemorrhage or infarction into a pituitary tumor (often previously unknown), precipitated by anticoagulation, surgery, pregnancy, or dynamic testing

• Prolactinoma is the most common functioning adenoma

RF

• Modifiable: anticoagulation (apoplexy) and immunotherapy

• Non-modifiable: a known pituitary adenoma, prior pituitary surgery or radiation, postpartum hemorrhage (Sheehan), head trauma, and MEN1

Data

• A pituitary MRI (with and without contrast — defining the mass, apoplexy, and chiasm compression)

• A full anterior pituitary panel: prolactin, IGF-1/GH, ACTH and cortisol (8 AM), TSH and free T4, and LH/FSH with testosterone or estradiol

• The posterior axis (consider DI — sodium and urine if polyuria); formal visual field testing (chiasm)

• A cosyntropin stimulation test (adrenal axis); a pregnancy test; in apoplexy, an urgent MRI with electrolytes and cortisol

DDx

Non-functioning pituitary adenoma · prolactinoma · acromegaly (GH) · Cushing disease (ACTH) · hypopituitarism · pituitary apoplexy (an emergency) · craniopharyngioma or another sellar mass · Sheehan syndrome · lymphocytic or immunotherapy hypophysitis · empty sella syndrome

Home Meds

• Reconcile medications

• Replace hormones in deficiency order — glucocorticoid (hydrocortisone) first, then levothyroxine, then sex steroids

• Use a dopamine agonist (cabergoline) for prolactinoma; hold anticoagulation in apoplexy; stress-dose steroids peri-operatively and in apoplexy

Plan

CONSULT: Endocrinology (hormonal evaluation and replacement — essential) · Neurosurgery (a mass with compression, or apoplexy — transsphenoidal surgery) · Ophthalmology/Neuro-ophthalmology (visual fields, chiasm) · Radiation oncology (selected cases) · Oncology (if immunotherapy hypophysitis)

• Pituitary apoplexy (emergency) — recognize and treat fast: sudden severe headache with visual loss or ophthalmoplegia and altered mental status → immediate stress-dose glucocorticoid (hydrocortisone 100 mg IV then 50 mg every 6 hours) (presumed acute secondary adrenal insufficiency — life-saving), an urgent pituitary MRI, an urgent neurosurgery consult (decompression for visual or neuro compromise), fluid and electrolyte support, and ICU if unstable

• Assess and replace hormones in the right order:

• • Cortisol first: assess the ACTH-cortisol axis; if deficient or unclear → glucocorticoid replacement (hydrocortisone) before any thyroid hormone (replacing thyroid first accelerates cortisol metabolism → adrenal crisis)

• • Then thyroid: levothyroxine for central hypothyroidism (after cortisol is covered)

• • Then sex steroids, GH, or desmopressin (DI) per the axes and endocrine

• Mass with compression (visual-field or chiasm): neurosurgery — transsphenoidal resection for a non-prolactinoma mass with visual compromise; urgent if rapidly progressive or apoplexy

• Prolactinoma (special — medical first): a dopamine agonist (cabergoline preferred, or bromocriptine) shrinks the tumor and normalizes prolactin — first-line even for large prolactinomas (surgery reserved for failure or intolerance) — distinguish it from a non-functioning adenoma (which is surgical) by the prolactin level

• Other functioning tumors: acromegaly (surgery with a somatostatin analog or pegvisomant) and Cushing disease (transsphenoidal surgery) — endocrine- and neurosurgery-directed

• PT/OT: usually not needed acutely; rehabilitation after surgery or visual impairment

• Trend: visual fields and acuity, neuro status, hormone levels and replacement adequacy, electrolytes and sodium (DI or SIADH post-op), cortisol coverage, tumor size on imaging, and post-operative recovery

• Escalation triggers: apoplexy or acute visual loss → emergent neurosurgery with stress steroids and ICU; secondary adrenal insufficiency or crisis → hydrocortisone (see the adrenal crisis card); progressive chiasm compression → urgent surgery; post-operative DI or SIADH → sodium management; immunotherapy hypophysitis → oncology and endocrine

• Discharge checklist: hormones assessed and replaced in the correct order, the mass managed or planned, and visual status documented; a replacement regimen (cortisol first, with stress-dose education if ACTH-deficient and an emergency hydrocortisone kit); a dopamine agonist if prolactinoma; a surgery or radiation plan; endocrine, neurosurgery, and ophthalmology follow-up; tumor surveillance imaging; a DI and desmopressin plan if applicable; return precautions for worsening headache, vision changes, signs of adrenal insufficiency, polyuria or excessive thirst, or recurrence

Red Flags

• Sudden severe headache with visual loss and ophthalmoplegia → pituitary apoplexy; stress steroids, urgent MRI, and neurosurgery

• Levothyroxine before cortisol in hypopituitarism → can precipitate adrenal crisis; cortisol first

• Bitemporal hemianopsia or progressive visual-field loss → chiasm compression needing urgent decompression

• A markedly elevated prolactin → prolactinoma; treat medically, don't operate first

• Post-operative polyuria or hyponatremia → diabetes insipidus or SIADH; manage the sodium

Senior IM Resident Pearls

• Three flavors: mass, excess, deficiency. A mass pressing on the chiasm, too much of one hormone, or too little of several — but one rule cuts across all.

• Cortisol first, always. When replacing hormones, the glucocorticoid goes in before the levothyroxine to avoid precipitating adrenal crisis.

• Never miss apoplexy. Thunderclap headache with visual and eye-movement findings means stress-dose hydrocortisone, urgent MRI, and neurosurgery.

• The prolactinoma is the pill, not the scalpel. A dopamine agonist like cabergoline shrinks even large prolactinomas; surgery is for the rest.

• Check the prolactin to sort the mass. A high prolactin points to a prolactinoma (medical); a normal one with a mass points to a non-functioning adenoma (surgical).

• Watch the sodium after surgery. Transsphenoidal surgery can cause diabetes insipidus or a delayed SIADH.

• Common mistake: starting levothyroxine for the central hypothyroidism before checking and covering cortisol — it can unmask a secondary adrenal insufficiency.

Endocrinology — Sodium/Water

115. SIADH

syndrome of inappropriate ADH · euvolemic hyponatremia · low serum osm + inappropriately concentrated urine + high urine Na · fluid restriction first · correct ≤6–8 mEq/L/24h · Super Compact

Sx: often asymptomatic (chronic/mild) or nonspecific (nausea, headache, malaise, difficulty concentrating); moderate-severe/acute: confusion, lethargy, gait instability, falls; severe (rapid/<120): seizures, obtundation, coma, respiratory arrest (cerebral edema); clinically EUVOLEMIC (no edema, no orthostasis) · (SIADH is a diagnosis of exclusion in a euvolemic, hypo-osmolar patient with inappropriately concentrated urine — but the dominant management principle is the RATE of correction: too fast risks osmotic demyelination, so cap it, especially in chronic hyponatremia)

Neg: denies over-rapid sodium correction (>6–8 mEq/L/24h risks osmotic demyelination syndrome/central pontine myelinolysis — esp chronic, alcoholic, malnourished, hypokalemic, liver disease) · denies missed hypovolemia or hypervolemia (SIADH requires euvolemia — must exclude volume depletion, heart failure, cirrhosis) · denies missed adrenal insufficiency + hypothyroidism (both mimic SIADH — check cortisol + TSH) · denies giving fluids that worsen it (isotonic in SIADH can paradoxically lower sodium)

SHx: CNS disease (stroke, hemorrhage, tumor, infection, trauma), pulmonary disease (pneumonia, TB, small-cell lung cancer — ectopic ADH), malignancy (SCLC esp), medications (SSRIs, carbamazepine, antipsychotics, chemotherapy, desmopressin, NSAIDs), pain/nausea/post-op (ADH stimuli), recent surgery, MDMA/ecstasy, HIV

Etiology: inappropriate (non-osmotic, non-volume) ADH secretion → free water retention → dilutional hyponatremia with euvolemia (natriuresis maintains near-euvolemia) · causes (4 buckets): CNS disorders, pulmonary disease, malignancy (ectopic ADH — SCLC classic), drugs; also pain/nausea/post-operative state, idiopathic (elderly)

RF: CNS/pulmonary disease · malignancy (SCLC) · SSRIs/carbamazepine/antipsychotics · post-op/pain/nausea · elderly · HIV

Data: classic SIADH labs: low serum sodium + low serum osmolality, INAPPROPRIATELY high urine osmolality (>100, usually >300), elevated urine sodium (>30–40), euvolemia, normal renal/cardiac/hepatic/thyroid/adrenal function · EXCLUDE mimics: TSH (hypothyroidism), AM cortisol (adrenal insufficiency); assess volume status carefully; uric acid (low in SIADH); glucose (exclude pseudohyponatremia); search for underlying cause (CXR/CT chest/CNS imaging)

DDx: SIADH · hypovolemic hyponatremia (diuretics, GI/renal losses) · hypervolemic hyponatremia (heart failure, cirrhosis, nephrotic) · adrenal insufficiency · hypothyroidism · psychogenic polydipsia/low solute (tea-and-toast) · pseudohyponatremia · cerebral salt wasting (hypovolemic — opposite fluid management) · reset osmostat

Home Meds: review + stop offending drugs (SSRIs, carbamazepine, antipsychotics, desmopressin, etc.); reconcile; avoid free water; manage underlying cause; if cancer-related, oncology co-manage; restart appropriate meds with monitoring

Plan

CONSULT: Nephrology (hyponatremia management, correction-rate concerns, refractory) · Endocrinology (if endocrine cause/overlap) · Oncology (malignancy — SCLC) · Neurology (CNS cause); ICU if severe symptomatic (seizures/coma)

– FIRST exclude mimics + assess volume: confirm euvolemia + classic labs; rule out hypothyroidism (TSH) + adrenal insufficiency (cortisol) — both present like SIADH but need hormone replacement, not fluid restriction
– SEVERITY-BASED TREATMENT:
  • SEVERE SYMPTOMATIC (seizures, coma, severe AMS): HYPERTONIC 3% saline — e.g. 100–150 mL IV bolus(es) to acutely raise sodium ~4–6 mEq/L to stop symptoms (ICU/close monitoring); do NOT exceed total correction limits
  • ASYMPTOMATIC / MILD-MODERATE: FLUID RESTRICTION first-line (e.g. <800–1000 mL/day); treat the underlying cause
  • Adjuncts if restriction insufficient: oral salt tablets ± loop diuretic, urea, or vaptan (tolvaptan — selected, monitor closely, avoid in liver disease)
– RATE OF CORRECTION (the cardinal safety rule): limit to ≤6–8 mEq/L per 24 hours (more conservative ~6 in high-risk: chronic, alcoholic, malnourished, hypokalemic, liver disease) to prevent osmotic demyelination syndrome; frequent sodium checks (q2–4h while actively correcting)
  • If OVER-corrected → re-lower sodium (D5W ± desmopressin) to bring back within limits — overcorrection is a real risk in SIADH once the ADH stimulus resolves (autocorrection/aquaresis)
– TREAT THE UNDERLYING CAUSE: stop offending drugs, treat infection/pneumonia, manage malignancy (oncology — durable fix for ectopic ADH), CNS disease
– Two ideas run SIADH. The diagnostic one: it's euvolemic hyponatremia with inappropriately concentrated urine and high urine sodium, and it's a diagnosis of exclusion — so before you commit, rule out the two great mimics, hypothyroidism and adrenal insufficiency, which look identical but are fixed with hormones, not water restriction. The management one, which matters more for safety, is the rate of correction: cap the rise at six to eight milliequivalents in twenty-four hours, because going faster risks osmotic demyelination, a devastating and often irreversible brain injury — and the highest-risk patients (chronic, malnourished, alcoholic) need the most caution. Reserve hypertonic saline for the patient actively seizing or comatose, use fluid restriction for everyone else, and watch for the patient who suddenly autocorrects too fast once their pneumonia clears and the ADH stimulus disappears — you may have to deliberately re-lower the sodium.
– PT/OT: usually not needed; fall risk with hyponatremia/gait instability
– Trend: sodium frequently (q2–4h while correcting, the key parameter), urine output (watch for aquaresis/autocorrection), mental status/symptoms, volume status, response to restriction, underlying-cause workup
– Escalation triggers: seizures/coma → hypertonic saline + ICU; over-rapid correction → re-lower (D5W/desmopressin) + nephrology; refractory to restriction → adjuncts/vaptan + nephrology; malignancy → oncology; unclear cause → broaden workup
– Discharge checklist: sodium safely corrected + cause identified/treated + offending drugs addressed; fluid-restriction + dietary instructions; medication changes (avoid culprit drugs); cause-specific plan (oncology if SCLC); sodium monitoring + follow-up labs; nephrology/cause-specialty + PCP follow-up; counseling on free-water avoidance + symptom recognition; return precautions (confusion, severe headache, seizures, increasing lethargy, falls)

115. SIADH

complete reference · euvolemic hyponatremia · exclude hypothyroid/adrenal mimics, fluid restriction first, hypertonic saline for severe, cap correction at 6–8 mEq/L/24h · Full Card

Symptoms / Associated Sx

• Often asymptomatic (chronic or mild) or nonspecific (nausea, headache, malaise, difficulty concentrating)

• Moderate-to-severe or acute disease: confusion, lethargy, gait instability, and falls

• Severe disease (rapid onset or sodium below 120): seizures, obtundation, coma, and respiratory arrest (cerebral edema)

• Clinically euvolemic (no edema, no orthostasis)

• SIADH is a diagnosis of exclusion in a euvolemic, hypo-osmolar patient with inappropriately concentrated urine — but the dominant management principle is the rate of correction: too fast risks osmotic demyelination, so cap it, especially in chronic hyponatremia

Neg

• Pt denies over-rapid sodium correction (more than 6–8 mEq/L per 24 hours risks osmotic demyelination syndrome or central pontine myelinolysis — especially in chronic, alcoholic, malnourished, hypokalemic, or liver disease patients)

• Pt denies a missed hypovolemia or hypervolemia (SIADH requires euvolemia — must exclude volume depletion, heart failure, cirrhosis) and a missed adrenal insufficiency or hypothyroidism (both mimic SIADH — check cortisol and TSH)

• Pt denies giving fluids that worsen it (isotonic saline in SIADH can paradoxically lower sodium)

Social History (SHx)

• CNS disease (stroke, hemorrhage, tumor, infection, trauma) and pulmonary disease (pneumonia, TB, small-cell lung cancer — ectopic ADH)

• Malignancy (SCLC especially) and medications (SSRIs, carbamazepine, antipsychotics, chemotherapy, desmopressin, NSAIDs)

• Pain, nausea, or the post-operative state (ADH stimuli), recent surgery, MDMA/ecstasy, and HIV

Main Etiology

• Inappropriate (non-osmotic, non-volume) ADH secretion causes free water retention and a dilutional hyponatremia with euvolemia (natriuresis maintains near-euvolemia)

• Causes (four buckets): CNS disorders, pulmonary disease, malignancy (ectopic ADH — SCLC classic), and drugs; also the pain, nausea, or post-operative state, and idiopathic disease (in the elderly)

RF

• Modifiable: SSRIs, carbamazepine, or antipsychotics, and the post-operative, pain, or nausea state

• Non-modifiable: CNS or pulmonary disease, malignancy (SCLC), elderly status, and HIV

Data

• Classic SIADH labs: a low serum sodium with low serum osmolality, an inappropriately high urine osmolality (above 100, usually above 300), an elevated urine sodium (above 30–40), euvolemia, and normal renal, cardiac, hepatic, thyroid, and adrenal function

• Exclude mimics: TSH (hypothyroidism) and an AM cortisol (adrenal insufficiency)

• Assess volume status carefully; uric acid (low in SIADH); glucose (exclude pseudohyponatremia); and search for an underlying cause (CXR, CT chest, CNS imaging)

DDx

SIADH · hypovolemic hyponatremia (diuretics, GI or renal losses) · hypervolemic hyponatremia (heart failure, cirrhosis, nephrotic syndrome) · adrenal insufficiency · hypothyroidism · psychogenic polydipsia or low-solute intake (tea-and-toast) · pseudohyponatremia · cerebral salt wasting (hypovolemic — the opposite fluid management) · reset osmostat

Home Meds

• Review and stop offending drugs (SSRIs, carbamazepine, antipsychotics, desmopressin, and others)

• Reconcile medications; avoid free water; manage the underlying cause

• If cancer-related, co-manage with oncology; restart appropriate medications with monitoring

Plan

CONSULT: Nephrology (hyponatremia management, correction-rate concerns, refractory disease) · Endocrinology (if there is an endocrine cause or overlap) · Oncology (malignancy — SCLC) · Neurology (a CNS cause); ICU if severe symptomatic (seizures, coma)

• First exclude mimics and assess volume: confirm euvolemia and the classic labs; rule out hypothyroidism (TSH) and adrenal insufficiency (cortisol) — both present like SIADH but need hormone replacement, not fluid restriction

• Severity-based treatment:

• • Severe symptomatic (seizures, coma, severe altered mental status): hypertonic 3% saline — e.g. 100–150 mL IV bolus(es) to acutely raise sodium by ~4–6 mEq/L to stop symptoms (ICU and close monitoring); do not exceed total correction limits

• • Asymptomatic or mild-to-moderate: fluid restriction first-line (e.g. below 800–1000 mL/day); treat the underlying cause

• • Adjuncts if restriction is insufficient: oral salt tablets with a loop diuretic, urea, or a vaptan (tolvaptan — selected, monitor closely, avoid in liver disease)

• Rate of correction (the cardinal safety rule): limit to ≤6–8 mEq/L per 24 hours (more conservative, ~6, in high-risk patients: chronic, alcoholic, malnourished, hypokalemic, liver disease) to prevent osmotic demyelination syndrome; check sodium frequently (every 2–4 hours while actively correcting)

• • If over-corrected → re-lower the sodium (D5W with desmopressin) to bring it back within limits — overcorrection is a real risk in SIADH once the ADH stimulus resolves (autocorrection or aquaresis)

• Treat the underlying cause: stop offending drugs, treat infection or pneumonia, manage malignancy (oncology — the durable fix for ectopic ADH), and manage CNS disease

• PT/OT: usually not needed; fall risk with hyponatremia and gait instability

• Trend: sodium frequently (every 2–4 hours while correcting, the key parameter), urine output (watch for aquaresis or autocorrection), mental status and symptoms, volume status, the response to restriction, and the underlying-cause workup

• Escalation triggers: seizures or coma → hypertonic saline and ICU; over-rapid correction → re-lower (D5W or desmopressin) with nephrology; refractory to restriction → adjuncts or a vaptan with nephrology; malignancy → oncology; an unclear cause → broaden the workup

• Discharge checklist: sodium safely corrected, the cause identified and treated, and offending drugs addressed; fluid-restriction and dietary instructions; medication changes (avoiding culprit drugs); a cause-specific plan (oncology if SCLC); sodium monitoring and follow-up labs; nephrology or cause-specialty and PCP follow-up; counseling on free-water avoidance and symptom recognition; return precautions for confusion, severe headache, seizures, increasing lethargy, or falls

Red Flags

• Over-rapid correction (more than 6–8 mEq/L/24h) → osmotic demyelination; cap the rate and check sodium often

• Seizures or coma → severe symptomatic hyponatremia; hypertonic 3% saline in the ICU

• A low cortisol or abnormal TSH → adrenal insufficiency or hypothyroidism mimicking SIADH; replace the hormone

• Sudden autocorrection once the cause resolves → overcorrection risk; be ready to re-lower with D5W or desmopressin

• A small-cell lung cancer → the durable cause of ectopic ADH; involve oncology

Senior IM Resident Pearls

• It's euvolemic hyponatremia, diagnosed by exclusion. Inappropriately concentrated urine with a high urine sodium in a euvolemic patient — after ruling out the mimics.

• Rule out the two great mimics. Hypothyroidism and adrenal insufficiency look identical but are fixed with hormones, not water restriction.

• The rate is everything. Cap the rise at 6–8 mEq/L in 24 hours, because faster risks the devastating, often irreversible osmotic demyelination.

• Hypertonic saline is for the actively seizing or comatose. Everyone else starts with fluid restriction.

• Watch for autocorrection. When the pneumonia clears and the ADH stimulus disappears, the patient can correct too fast on their own.

• Isotonic saline can backfire. In SIADH with very concentrated urine, normal saline can paradoxically lower the sodium.

• Common mistake: treating presumed SIADH with fluids without checking cortisol and TSH — a missed adrenal insufficiency or hypothyroidism won't respond and may worsen.

Endocrinology — Sodium/Water

116. Diabetes Insipidus

polyuria + polydipsia + dilute urine · central (ADH deficiency) vs nephrogenic (ADH resistance) · hypernatremia if water access impaired · desmopressin vs treat-cause · Super Compact

Sx: polyuria (large-volume dilute urine), polydipsia, nocturia, excessive thirst; if water access intact + thirst intact → sodium stays near-normal; if access impaired (unconscious, elderly, post-op, no thirst) → HYPERNATREMIA + dehydration, AMS, weakness · (DI is a problem of making/responding to ADH — dilute urine despite a rising sodium — and the key split is central [no ADH, responds to desmopressin] vs nephrogenic [kidney resists ADH, doesn't respond]; the danger is hypernatremia when the patient can't drink to keep up)

Neg: denies over-rapid correction of chronic hypernatremia (cerebral edema risk — lower sodium slowly, ~10 mEq/L/24h max) · denies missing it post-pituitary-surgery/TBI (central DI common — watch urine output + sodium) · denies missed nephrogenic cause (lithium, hypercalcemia, hypokalemia — reversible) · denies confusing with primary polydipsia (water deprivation test) · denies restricting access to water in a thirsty DI patient

SHx: pituitary/hypothalamic disease or surgery (central), head trauma/TBI, CNS tumor/infiltration, lithium use (nephrogenic — common), hypercalcemia/hypokalemia (nephrogenic), CKD/obstructive uropathy, pregnancy (gestational DI), family history (hereditary nephrogenic), recent neurosurgery, medications

Etiology: central DI: ADH (vasopressin) deficiency — pituitary/hypothalamic surgery, trauma, tumor, infiltrative (sarcoid/histiocytosis), autoimmune, idiopathic · nephrogenic DI: renal resistance to ADH — lithium (most common acquired), hypercalcemia, hypokalemia, CKD, obstruction, hereditary · gestational (placental vasopressinase) · → inability to concentrate urine → free-water loss → hypernatremia if not replaced

RF: pituitary surgery/TBI (central) · lithium · hypercalcemia/hypokalemia · CNS tumor/infiltration · CKD/obstruction · pregnancy · family history

Data: serum sodium + osmolality (high/high-normal), urine osmolality (inappropriately LOW/dilute) + urine specific gravity, 24h urine volume · water deprivation test then desmopressin challenge: central responds (urine concentrates) vs nephrogenic doesn't · serum/urine osm response; copeptin (surrogate for ADH); glucose (exclude osmotic diuresis), calcium, potassium, lithium level; pituitary MRI if central

DDx: central DI · nephrogenic DI · primary (psychogenic) polydipsia (low sodium, suppressed ADH appropriately) · osmotic diuresis (hyperglycemia, mannitol) · diuretic use · resolving AKI/post-obstructive diuresis · hypercalcemia/hypokalemia-related · gestational DI

Home Meds: review nephrogenic-causing drugs (lithium — coordinate with psychiatry before changing); reconcile; central → desmopressin (DDAVP); correct hypercalcemia/hypokalemia; ensure water access; manage thiazide for nephrogenic; resume with monitoring

Plan

CONSULT: Endocrinology (diagnosis, central DI/desmopressin management) · Nephrology (nephrogenic DI, electrolytes, refractory) · Neurosurgery (post-op/pituitary central DI) · Psychiatry (if lithium-related — don't stop unilaterally)

– CORRECT WATER BALANCE / HYPERNATREMIA SAFELY: ensure access to water/oral intake if able + replace the free-water deficit (oral water or IV D5W/hypotonic fluids); correct CHRONIC hypernatremia SLOWLY (~≤10 mEq/L per 24 h) to avoid cerebral edema; match ongoing urine losses; frequent sodium checks
– CENTRAL DI — replace ADH: desmopressin (DDAVP) (intranasal, oral, or parenteral — dose-titrated to control polyuria + normalize sodium); monitor for over-treatment (hyponatremia — don't over-restrict free water while on DDAVP)
– NEPHROGENIC DI — treat the cause + reduce urine output: remove offending drug (lithium — with psychiatry), correct hypercalcemia/hypokalemia (often reversible); thiazide diuretic + low-sodium/low-solute diet (± amiloride for lithium-induced, ± NSAID) to reduce urine volume (desmopressin generally ineffective — kidney resists ADH)
– POST-NEUROSURGICAL/TBI central DI: watch urine output + sodium closely (can be transient, permanent, or triphasic DI→SIADH→DI); careful fluid management + desmopressin as needed with endocrine/neurosurgery
– DISTINGUISH from primary polydipsia (water deprivation test — primary polydipsia concentrates urine with deprivation; DI does not) to avoid mistreating
– DI is the inability to concentrate urine: the patient pours out large volumes of dilute urine even as the serum sodium climbs. The fork is central versus nephrogenic, and the desmopressin challenge settles it — central DI lacks ADH and responds beautifully to desmopressin, while nephrogenic DI is a kidney that won't listen to ADH, so you treat the cause (very often lithium, or a high calcium or low potassium) and use a thiazide rather than more hormone. The thing that actually hurts patients is the sodium: as long as a person is awake and thirsty with water at the bedside, they keep up, but the post-op, sedated, or elderly patient who can't drink develops dangerous hypernatremia — and when you correct a chronic hypernatremia, go slow, because dropping it too fast swells the brain. Post-pituitary-surgery, watch the urine output and sodium like a hawk; DI there can be transient or follow a triphasic course.
– PT/OT: usually not needed; safety if AMS from hypernatremia
– Trend: sodium + osmolality, urine output/volume + concentration, fluid balance, response to desmopressin/thiazide, mental status, lithium level/calcium/potassium, post-op trajectory
– Escalation triggers: severe symptomatic hypernatremia/AMS → careful correction + ICU; massive urine output with rising sodium (post-op central DI) → desmopressin + endocrine/neurosurgery; refractory nephrogenic → nephrology; over-correction (cerebral edema) → slow/adjust; triphasic post-op course → close monitoring
– Discharge checklist: sodium stabilized + type identified + cause addressed; central → desmopressin with dosing + over-treatment (hyponatremia) counseling; nephrogenic → offending-drug/electrolyte management + thiazide + diet; ensure water access + thirst counseling; sodium monitoring + follow-up; endocrine/nephrology + cause-specialty follow-up; return precautions (excessive thirst/urination, confusion, signs of dehydration, weakness, low sodium if on desmopressin)

116. Diabetes Insipidus

complete reference · central vs nephrogenic · desmopressin challenge distinguishes, desmopressin for central, treat cause + thiazide for nephrogenic, correct hypernatremia slowly · Full Card

Symptoms / Associated Sx

• Polyuria (large-volume dilute urine), polydipsia, nocturia, and excessive thirst

• If water access and thirst are intact, the sodium stays near-normal

• If access is impaired (unconscious, elderly, post-operative, no thirst), there is hypernatremia with dehydration, altered mental status, and weakness

• DI is a problem of making or responding to ADH — dilute urine despite a rising sodium — and the key split is central (no ADH, responds to desmopressin) versus nephrogenic (the kidney resists ADH, doesn't respond); the danger is hypernatremia when the patient can't drink to keep up

Neg

• Pt denies over-rapid correction of chronic hypernatremia (cerebral edema risk — lower sodium slowly, ~10 mEq/L per 24 hours maximum)

• Pt denies missing it after pituitary surgery or TBI (central DI is common — watch urine output and sodium) and a missed nephrogenic cause (lithium, hypercalcemia, hypokalemia — reversible)

• Pt denies confusing it with primary polydipsia (a water deprivation test) and restricting access to water in a thirsty DI patient

Social History (SHx)

• Pituitary or hypothalamic disease or surgery (central), head trauma or TBI, and CNS tumor or infiltration

• Lithium use (nephrogenic — common), hypercalcemia or hypokalemia (nephrogenic), and CKD or obstructive uropathy

• Pregnancy (gestational DI), family history (hereditary nephrogenic disease), recent neurosurgery, and medications

Main Etiology

• Central DI: ADH (vasopressin) deficiency — pituitary or hypothalamic surgery, trauma, tumor, infiltrative disease (sarcoidosis, histiocytosis), autoimmune disease, or idiopathic

• Nephrogenic DI: renal resistance to ADH — lithium (the most common acquired cause), hypercalcemia, hypokalemia, CKD, obstruction, or hereditary disease

• Gestational DI (placental vasopressinase)

• The inability to concentrate urine causes free-water loss and hypernatremia if not replaced

RF

• Modifiable: lithium, hypercalcemia or hypokalemia, and obstruction

• Non-modifiable: pituitary surgery or TBI (central), CNS tumor or infiltration, CKD, pregnancy, and family history

Data

• Serum sodium and osmolality (high or high-normal), urine osmolality (inappropriately low or dilute) with urine specific gravity, and the 24-hour urine volume

• A water deprivation test then a desmopressin challenge: central DI responds (urine concentrates) versus nephrogenic DI which doesn't

• The serum and urine osmolality response; copeptin (a surrogate for ADH)

• Glucose (exclude osmotic diuresis), calcium, potassium, and a lithium level; a pituitary MRI if central

DDx

Central DI · nephrogenic DI · primary (psychogenic) polydipsia (low sodium, ADH appropriately suppressed) · osmotic diuresis (hyperglycemia, mannitol) · diuretic use · resolving AKI or post-obstructive diuresis · hypercalcemia or hypokalemia-related disease · gestational DI

Home Meds

• Review nephrogenic-causing drugs (lithium — coordinate with psychiatry before changing); reconcile medications

• Central: desmopressin (DDAVP); correct hypercalcemia and hypokalemia

• Ensure water access; manage a thiazide for nephrogenic disease; resume with monitoring

Plan

CONSULT: Endocrinology (diagnosis, central DI and desmopressin management) · Nephrology (nephrogenic DI, electrolytes, refractory disease) · Neurosurgery (post-operative or pituitary central DI) · Psychiatry (if lithium-related — don't stop unilaterally)

• Correct water balance and hypernatremia safely: ensure access to water or oral intake if able and replace the free-water deficit (oral water or IV D5W/hypotonic fluids); correct chronic hypernatremia slowly (~≤10 mEq/L per 24 hours) to avoid cerebral edema; match ongoing urine losses; check sodium frequently

• Central DI — replace ADH: desmopressin (DDAVP) (intranasal, oral, or parenteral — dose-titrated to control polyuria and normalize sodium); monitor for over-treatment (hyponatremia — don't over-restrict free water while on DDAVP)

• Nephrogenic DI — treat the cause and reduce urine output: remove the offending drug (lithium — with psychiatry), correct hypercalcemia or hypokalemia (often reversible); a thiazide diuretic with a low-sodium, low-solute diet (with amiloride for lithium-induced disease, and an NSAID) to reduce urine volume (desmopressin is generally ineffective — the kidney resists ADH)

• Post-neurosurgical or TBI central DI: watch urine output and sodium closely (it can be transient, permanent, or a triphasic DI → SIADH → DI course); careful fluid management and desmopressin as needed with endocrine and neurosurgery

• Distinguish from primary polydipsia (a water deprivation test — primary polydipsia concentrates urine with deprivation; DI does not) to avoid mistreating

• PT/OT: usually not needed; safety if there is altered mental status from hypernatremia

• Trend: sodium and osmolality, urine output, volume, and concentration, fluid balance, the response to desmopressin or a thiazide, mental status, the lithium level, calcium, and potassium, and the post-operative trajectory

• Escalation triggers: severe symptomatic hypernatremia or altered mental status → careful correction with ICU; massive urine output with a rising sodium (post-operative central DI) → desmopressin with endocrine and neurosurgery; refractory nephrogenic disease → nephrology; over-correction (cerebral edema) → slow or adjust; a triphasic post-operative course → close monitoring

• Discharge checklist: sodium stabilized, the type identified, and the cause addressed; central → desmopressin with dosing and over-treatment (hyponatremia) counseling; nephrogenic → offending-drug and electrolyte management with a thiazide and diet; ensure water access and thirst counseling; sodium monitoring and follow-up; endocrine, nephrology, and cause-specialty follow-up; return precautions for excessive thirst or urination, confusion, signs of dehydration, weakness, or a low sodium if on desmopressin

Red Flags

• Over-rapid correction of chronic hypernatremia → cerebral edema; lower sodium slowly

• Impaired water access (post-op, sedated, elderly) → dangerous hypernatremia; the patient can't keep up

• Massive dilute urine output after pituitary surgery → central DI; watch sodium and give desmopressin

• Lithium, hypercalcemia, or hypokalemia → reversible nephrogenic causes; treat them

• Hyponatremia while on desmopressin → over-treatment; don't over-restrict free water on DDAVP

Senior IM Resident Pearls

• It's the inability to concentrate urine. Large volumes of dilute urine even as the serum sodium climbs is the signature.

• The desmopressin challenge settles central versus nephrogenic. Central DI responds beautifully; nephrogenic DI doesn't, because the kidney won't listen to ADH.

• Nephrogenic DI is usually a treatable cause. Lithium, a high calcium, or a low potassium — fix those and use a thiazide rather than more hormone.

• The sodium is what hurts patients. An awake, thirsty patient with water keeps up; the sedated or elderly one who can't drink develops dangerous hypernatremia.

• Correct chronic hypernatremia slowly. Dropping it too fast swells the brain — aim for no more than ~10 mEq/L per 24 hours.

• Watch the post-op pituitary patient closely. Central DI there can be transient, permanent, or follow a triphasic DI → SIADH → DI course.

• Common mistake: stopping lithium unilaterally for nephrogenic DI — coordinate with psychiatry, since the psychiatric stakes of stopping it can be high.

Endocrinology — Adrenal

117. Pheochromocytoma

catecholamine-secreting tumor · paroxysmal headache + palpitations + sweating + hypertension · plasma/urine metanephrines · ALPHA-blockade BEFORE beta · surgical cure · Super Compact

Sx: classic triad: episodic/paroxysmal headache + palpitations + diaphoresis, with hypertension (sustained or paroxysmal, often severe/labile); also anxiety/sense of doom, pallor, tremor, weight loss, hyperglycemia; hypertensive crisis precipitated by anesthesia, surgery, contrast, certain drugs, tumor manipulation · (the single most important treatment principle: ALPHA-blockade must come BEFORE any beta-blockade — giving a beta-blocker first leaves alpha-mediated vasoconstriction unopposed and can trigger a severe hypertensive crisis)

Neg: denies giving a beta-blocker before adequate alpha-blockade (unopposed alpha vasoconstriction → hypertensive crisis — the cardinal error) · denies taking to surgery without adequate preoperative blockade + volume expansion · denies missed hereditary syndrome (MEN2, VHL, NF1, SDH mutations) · denies missed hypertensive emergency needing acute IV control · denies provoking a crisis (unblocked contrast/glucagon/manipulation)

SHx: family history/known syndrome (MEN2, von Hippel-Lindau, NF1, paraganglioma/SDH), prior episodes of spells, resistant/paroxysmal hypertension, young hypertension, incidental adrenal mass (incidentaloma), prior crisis with anesthesia/contrast, medications

Etiology: catecholamine-secreting tumor of adrenal medulla chromaffin cells (pheochromocytoma) or extra-adrenal sympathetic ganglia (paraganglioma) → episodic/sustained excess epinephrine/norepinephrine → hypertension + adrenergic symptoms · ~30–40% hereditary (MEN2, VHL, NF1, SDHx); "rule of 10s" (historically — bilateral, extra-adrenal, malignant, familial) · can be lethal if unrecognized at surgery/stress

RF: hereditary syndromes (MEN2/VHL/NF1/SDH) · family history of pheo/paraganglioma · adrenal incidentaloma · young/resistant/paroxysmal hypertension

Data: biochemical confirmation FIRST: plasma free metanephrines (high sensitivity) and/or 24-hour urine fractionated metanephrines + catecholamines · THEN localize: CT or MRI of adrenals/abdomen; functional imaging (MIBG scintigraphy, or DOTATATE/FDG-PET) for extra-adrenal/metastatic/multifocal · genetic testing/counseling; glucose (hyperglycemia); avoid provocative testing

DDx: pheochromocytoma/paraganglioma · essential/resistant hypertension · hypertensive emergency other cause · panic/anxiety disorder · hyperthyroidism · carcinoid · drug effect (sympathomimetics, MAOI interactions, withdrawal) · renovascular hypertension · primary aldosteronism · thyroid storm

Home Meds: start alpha-blocker (phenoxybenzamine or doxazosin) — never beta-first; avoid drugs that provoke release (certain anesthetics, unopposed beta-blockers, metoclopramide, glucagon); reconcile antihypertensives; manage hyperglycemia; perioperative blockade plan with surgery/anesthesia

Plan

CONSULT: Endocrinology (diagnosis, preoperative blockade, management) · Endocrine/Adrenal Surgery (definitive resection) · Anesthesiology (high-risk perioperative — hemodynamic swings) · Genetics (hereditary syndrome screening) · Cardiology/ICU (crisis, cardiomyopathy)

– ACUTE HYPERTENSIVE CRISIS (if presenting in crisis): IV phentolamine (alpha-blocker) or IV nitroprusside/nicardipine for rapid control in a monitored setting (ICU); do NOT give an unopposed beta-blocker; treat arrhythmias cautiously after alpha control
– CARDINAL SEQUENCE — ALPHA-BLOCKADE FIRST (then beta if needed):
  • 1) ALPHA-BLOCKADE: phenoxybenzamine (non-selective, irreversible) or selective alpha-1 (doxazosin/prazosin/terazosin) — start + titrate up over ~10–14 days preoperatively to control BP + allow vascular bed to relax
  • 2) VOLUME EXPANSION + liberal salt after alpha-blockade started (chronic catecholamine excess contracts intravascular volume; expansion prevents post-resection hypotension)
  • 3) BETA-BLOCKADE ONLY AFTER adequate alpha-blockade — added for tachycardia/arrhythmia (e.g. propranolol/metoprolol); NEVER before alpha (unopposed alpha → crisis)
  • ± calcium channel blocker / metyrosine (catecholamine synthesis inhibition) as adjuncts per endocrine
– DEFINITIVE TREATMENT — SURGICAL RESECTION (often laparoscopic adrenalectomy): curative, but ONLY after adequate preoperative alpha-blockade + volume expansion (operating unprepared risks fatal intraoperative crisis); anticipate post-resection hypotension (volume + pressor ready)
– GENETIC EVALUATION: screen for hereditary syndromes (MEN2 → also medullary thyroid cancer/hyperparathyroidism; VHL; NF1; SDH paraganglioma) — counsel + screen family; affects surveillance
– MALIGNANT/METASTATIC disease: oncology/endocrine co-management (surgery, MIBG therapy, systemic therapy) — defined by metastases, not histology
– There is one rule about pheochromocytoma that you must never get wrong: alpha-blockade comes before beta-blockade, always. The tumor floods the body with catecholamines hitting both alpha (vasoconstriction) and beta (heart rate) receptors; if you block beta first, you strip away the vasodilatory beta-2 tone and the heart-rate escape while leaving alpha-mediated vasoconstriction completely unopposed, and the blood pressure rockets into a crisis. So you start an alpha-blocker like phenoxybenzamine or doxazosin, titrate it over a week or two, expand the volume (these patients are chronically volume-contracted and will crash hypotensive after the tumor comes out), and only then add a beta-blocker if the heart rate needs it. The cure is surgical, but only after that preparation — taking an unblocked pheo to the OR can kill the patient on the table. And because a third are hereditary, send genetics and think MEN2, VHL, and NF1.
– PT/OT: usually not needed; postoperative recovery
– Trend: blood pressure + heart rate (paroxysms), symptoms/spells, volume status, glucose, adequacy of blockade (preop), perioperative hemodynamics, post-resection BP (hypotension), biochemical cure (post-op metanephrines)
– Escalation triggers: hypertensive crisis → IV phentolamine/nitroprusside + ICU (never unopposed beta-blocker); catecholamine cardiomyopathy/arrhythmia → cardiology/ICU; intraoperative instability → anesthesia/surgery; metastatic disease → oncology; post-resection refractory hypotension → volume + pressors + ICU
– Discharge checklist: diagnosis confirmed + on adequate alpha-blockade + surgical plan (or post-resection recovered); alpha-blocker with the never-beta-first principle clearly documented; perioperative blockade + volume plan; genetic counseling/testing arranged; BP/symptom monitoring; endocrine + surgery follow-up; post-resection biochemical surveillance (recurrence) + lifelong follow-up if hereditary; family screening; return precautions (severe headache/palpitations/sweating spells, very high BP, chest pain, fainting)

117. Pheochromocytoma

complete reference · catecholamine-secreting tumor, hypertensive crises · metanephrines confirm, alpha-blockade before beta, volume expansion, surgical cure after preparation, genetic screening · Full Card

Symptoms / Associated Sx

• The classic triad: episodic or paroxysmal headache, palpitations, and diaphoresis, with hypertension (sustained or paroxysmal, often severe and labile)

• Also anxiety or a sense of doom, pallor, tremor, weight loss, and hyperglycemia

• Hypertensive crisis precipitated by anesthesia, surgery, contrast, certain drugs, or tumor manipulation

• The single most important treatment principle: alpha-blockade must come before any beta-blockade — giving a beta-blocker first leaves alpha-mediated vasoconstriction unopposed and can trigger a severe hypertensive crisis

Neg

• Pt denies giving a beta-blocker before adequate alpha-blockade (unopposed alpha vasoconstriction → hypertensive crisis — the cardinal error)

• Pt denies going to surgery without adequate preoperative blockade and volume expansion and a missed hereditary syndrome (MEN2, VHL, NF1, SDH mutations)

• Pt denies a missed hypertensive emergency needing acute IV control and provoking a crisis (unblocked contrast, glucagon, or manipulation)

Social History (SHx)

• Family history or a known syndrome (MEN2, von Hippel-Lindau, NF1, paraganglioma/SDH), prior episodes of spells, and resistant or paroxysmal hypertension

• Young hypertension and an incidental adrenal mass (incidentaloma)

• Prior crisis with anesthesia or contrast, and medications

Main Etiology

• A catecholamine-secreting tumor of adrenal medulla chromaffin cells (pheochromocytoma) or extra-adrenal sympathetic ganglia (paraganglioma) causes episodic or sustained excess epinephrine and norepinephrine, producing hypertension and adrenergic symptoms

• About 30–40% are hereditary (MEN2, VHL, NF1, SDHx); the historical "rule of 10s" (bilateral, extra-adrenal, malignant, familial)

• Can be lethal if unrecognized at surgery or stress

RF

• Modifiable: avoidance of provocative drugs and unprepared procedures

• Non-modifiable: hereditary syndromes (MEN2, VHL, NF1, SDH), family history of pheochromocytoma or paraganglioma, an adrenal incidentaloma, and young, resistant, or paroxysmal hypertension

Data

• Biochemical confirmation first: plasma free metanephrines (high sensitivity) and/or 24-hour urine fractionated metanephrines and catecholamines

• Then localize: CT or MRI of the adrenals and abdomen; functional imaging (MIBG scintigraphy, or DOTATATE/FDG-PET) for extra-adrenal, metastatic, or multifocal disease

• Genetic testing and counseling; glucose (hyperglycemia); avoid provocative testing

DDx

Pheochromocytoma or paraganglioma · essential or resistant hypertension · hypertensive emergency of another cause · panic or anxiety disorder · hyperthyroidism · carcinoid · drug effect (sympathomimetics, MAOI interactions, withdrawal) · renovascular hypertension · primary aldosteronism · thyroid storm

Home Meds

• Start an alpha-blocker (phenoxybenzamine or doxazosin) — never beta-first

• Avoid drugs that provoke release (certain anesthetics, unopposed beta-blockers, metoclopramide, glucagon); reconcile antihypertensives; manage hyperglycemia

• Plan perioperative blockade with surgery and anesthesia

Plan

CONSULT: Endocrinology (diagnosis, preoperative blockade, management) · Endocrine/Adrenal Surgery (definitive resection) · Anesthesiology (high-risk perioperative care — hemodynamic swings) · Genetics (hereditary syndrome screening) · Cardiology/ICU (crisis, cardiomyopathy)

• Acute hypertensive crisis (if presenting in crisis): IV phentolamine (an alpha-blocker) or IV nitroprusside or nicardipine for rapid control in a monitored setting (ICU); do not give an unopposed beta-blocker; treat arrhythmias cautiously after alpha control

• Cardinal sequence — alpha-blockade first (then beta if needed):

• • 1) Alpha-blockade: phenoxybenzamine (non-selective, irreversible) or a selective alpha-1 agent (doxazosin, prazosin, terazosin) — start and titrate up over ~10–14 days preoperatively to control BP and allow the vascular bed to relax

• • 2) Volume expansion and liberal salt after alpha-blockade is started (chronic catecholamine excess contracts the intravascular volume; expansion prevents post-resection hypotension)

• • 3) Beta-blockade only after adequate alpha-blockade — added for tachycardia or arrhythmia (e.g. propranolol, metoprolol); never before alpha (unopposed alpha → crisis)

• • A calcium channel blocker or metyrosine (catecholamine synthesis inhibition) as adjuncts per endocrine

• Definitive treatment — surgical resection (often laparoscopic adrenalectomy): curative, but only after adequate preoperative alpha-blockade and volume expansion (operating unprepared risks a fatal intraoperative crisis); anticipate post-resection hypotension (have volume and a pressor ready)

• Genetic evaluation: screen for hereditary syndromes (MEN2 → also medullary thyroid cancer and hyperparathyroidism; VHL; NF1; SDH paraganglioma) — counsel and screen family; this affects surveillance

• Malignant or metastatic disease: oncology and endocrine co-management (surgery, MIBG therapy, systemic therapy) — defined by metastases, not histology

• PT/OT: usually not needed; postoperative recovery

• Trend: blood pressure and heart rate (paroxysms), symptoms and spells, volume status, glucose, the adequacy of blockade (preoperatively), perioperative hemodynamics, post-resection BP (hypotension), and biochemical cure (post-operative metanephrines)

• Escalation triggers: hypertensive crisis → IV phentolamine or nitroprusside with ICU (never an unopposed beta-blocker); catecholamine cardiomyopathy or arrhythmia → cardiology/ICU; intraoperative instability → anesthesia and surgery; metastatic disease → oncology; post-resection refractory hypotension → volume, pressors, and ICU

• Discharge checklist: the diagnosis confirmed, on adequate alpha-blockade, with a surgical plan (or post-resection recovered); the alpha-blocker with the never-beta-first principle clearly documented; a perioperative blockade and volume plan; genetic counseling and testing arranged; BP and symptom monitoring; endocrine and surgery follow-up; post-resection biochemical surveillance (recurrence) and lifelong follow-up if hereditary; family screening; return precautions for severe headache, palpitations, or sweating spells, very high BP, chest pain, or fainting

Red Flags

• A beta-blocker before adequate alpha-blockade → unopposed alpha vasoconstriction and a hypertensive crisis; the cardinal error

• Surgery without preoperative blockade and volume expansion → a potentially fatal intraoperative crisis

• Hypertensive crisis → IV phentolamine or nitroprusside in the ICU, never an unopposed beta-blocker

• Post-resection refractory hypotension → the chronically contracted volume now unopposed; have fluids and pressors ready

• A hereditary syndrome (MEN2, VHL, NF1, SDH) → screen genetically and screen the family

Senior IM Resident Pearls

• Alpha before beta, always. Block beta first and you leave alpha-mediated vasoconstriction unopposed, rocketing the blood pressure into a crisis.

• Expand the volume. These patients are chronically volume-contracted from catecholamine excess and will crash hypotensive once the tumor is out.

• The cure is surgical — but only after preparation. Taking an unblocked pheochromocytoma to the OR can kill the patient on the table.

• Confirm biochemically before imaging. Plasma or urine metanephrines establish the diagnosis; imaging then localizes.

• Think hereditary. A third are familial — MEN2, VHL, and NF1 — so send genetics and screen the family.

• Anticipate the post-resection crash. Have volume and a pressor ready as the catecholamine drive disappears.

• Common mistake: reaching for a beta-blocker to control the tachycardia before alpha-blockade is established — it precipitates the very crisis you're trying to prevent.

Endocrinology — Calcium/Mineral

118. Hyperparathyroidism

primary (adenoma) · symptomatic hypercalcemia · high/inappropriately normal PTH with high calcium · exclude FHH · parathyroidectomy is definitive · Super Compact

Sx: often asymptomatic (found on routine calcium); symptomatic = hypercalcemia: "stones (nephrolithiasis/nephrocalcinosis), bones (pain, osteoporosis, fractures), groans (constipation, nausea, PUD, pancreatitis), psychiatric overtones (fatigue, depression, cognitive change)"; polyuria/polydipsia, weakness · (the diagnosis is the combination of high calcium with a PTH that is high or inappropriately normal — PTH should be suppressed when calcium is high, so a "normal" PTH in the face of hypercalcemia is actually abnormal; the one critical thing to exclude before surgery is familial hypocalciuric hypercalcemia, which looks identical but must NOT be operated on)

Neg: denies missed familial hypocalciuric hypercalcemia (FHH) (low urine calcium — mimics primary HPT but parathyroidectomy is wrong/ineffective; check 24h urine calcium/calcium-creatinine clearance ratio) · denies missed severe symptomatic hypercalcemia needing acute treatment · denies missed secondary/tertiary HPT (CKD context) · denies missed MEN syndrome (MEN1/MEN2A) · denies missed end-organ damage (renal stones, osteoporosis)

SHx: kidney stones/fractures/osteoporosis history, family history (MEN1/MEN2A, FHH), CKD (secondary/tertiary), neck irradiation, lithium use, vitamin D status, prior calcium abnormalities, menopausal status (bone), prior parathyroid/thyroid surgery

Etiology: primary hyperparathyroidism: autonomous PTH oversecretion — single parathyroid adenoma (~80–85%, most common), multigland hyperplasia, rarely parathyroid carcinoma → high calcium, low phosphate · secondary: appropriate PTH rise to hypocalcemia (CKD, vitamin D deficiency) · tertiary: autonomous PTH after long-standing secondary (CKD) · associated MEN1/MEN2A

RF: female/postmenopausal · age · neck irradiation · lithium · MEN1/MEN2A/family history · CKD (secondary/tertiary)

Data: confirm: elevated calcium (ionized/corrected) + PTH (high or inappropriately normal) + low/low-normal phosphate · EXCLUDE FHH: 24-hour urine calcium (LOW in FHH, normal/high in primary HPT) + calcium-creatinine clearance ratio · 25-vitamin D, renal function, DEXA (bone density — distal radius), renal imaging (stones); parathyroid localization for surgery: sestamibi scan + neck ultrasound (± 4D-CT); ECG (short QT if severe)

DDx: primary hyperparathyroidism (adenoma/hyperplasia/carcinoma) · familial hypocalciuric hypercalcemia (low urine calcium — don't operate) · malignancy hypercalcemia (suppressed PTH — see hypercalcemia card) · secondary/tertiary HPT (CKD) · lithium-induced · tertiary HPT · other PTH-independent hypercalcemia

Home Meds: hold thiazides/lithium/calcium+vitamin D supplements (can worsen); ensure adequate hydration; reconcile; cinacalcet if non-surgical candidate; treat vitamin D deficiency cautiously; bisphosphonate/denosumab for bone per endocrine

Plan

CONSULT: Endocrinology (diagnosis, surgical criteria, medical management) · Endocrine/Parathyroid Surgery (parathyroidectomy — definitive) · Nephrology (CKD secondary/tertiary, stones) · Genetics (if MEN suspected)

– IF ACUTE SEVERE SYMPTOMATIC HYPERCALCEMIA (e.g. Ca very high/symptomatic) — treat first (self-contained):
  • 1) IV isotonic saline (0.9% NaCl) ~200–300 mL/h (rehydrate + promote calciuresis)
  • 2) Calcitonin 4 units/kg SC/IM q12h (rapid, transient ~48h)
  • 3) Bisphosphonate (zoledronic acid 4 mg IV) (durable, onset ~24–48h)
  then proceed to definitive evaluation/treatment of the HPT
– CONFIRM DIAGNOSIS + EXCLUDE FHH: high calcium + non-suppressed PTH = primary HPT; ALWAYS check 24-hour urine calcium to exclude FHH (low urine calcium) before considering surgery — operating on FHH is futile/harmful
– DEFINITIVE TREATMENT — PARATHYROIDECTOMY (curative): indicated for symptomatic disease or, in asymptomatic patients, when surgical criteria are met:
  • symptomatic (stones, fractures, overt symptoms)
  • calcium >1 mg/dL above upper normal
  • osteoporosis (T-score ≤ −2.5) or fragility fracture or vertebral fracture
  • renal: eGFR <60, nephrolithiasis/nephrocalcinosis, or hypercalciuria
  • age <50
  requires preop localization (sestamibi + ultrasound); watch for postoperative hypocalcemia/hungry bone
– MEDICAL MANAGEMENT (non-surgical candidates / declines): cinacalcet (calcimimetic) lowers calcium + PTH; bisphosphonate/denosumab for bone density; hydration; monitor calcium/renal/bone; avoid aggravating drugs
– SECONDARY/TERTIARY (CKD): nephrology-directed — phosphate control, active vitamin D, calcimimetics; tertiary may need parathyroidectomy
– Primary hyperparathyroidism is the mirror image of malignancy hypercalcemia: here the PTH is high or inappropriately normal — and remember that a "normal" PTH with a high calcium is actually inappropriate, because the gland should have shut off. The one thing you cannot skip before sending someone to surgery is a 24-hour urine calcium to rule out familial hypocalciuric hypercalcemia, a benign genetic mimic with a low urine calcium where a parathyroidectomy is useless and harmful. The definitive treatment is removing the overactive gland, and there's a clean list of criteria — symptoms, a calcium more than a point above normal, osteoporosis or fracture, renal involvement, or age under fifty — that tells you when even an asymptomatic patient should have surgery. If they can't or won't have surgery, cinacalcet lowers the calcium and a bisphosphonate protects the bones. And acutely, severe symptomatic hypercalcemia gets the same saline-then-calcitonin-then-bisphosphonate sequence regardless of cause.
– PT/OT: usually not needed; fall/fracture prevention if bone disease
– Trend: calcium (corrected/ionized), PTH, phosphate, renal function, symptoms, post-op calcium (hypocalcemia/hungry bone), bone density over time
– Escalation triggers: severe symptomatic hypercalcemia/crisis → acute treatment + ICU if needed (see hypercalcemia card); parathyroid carcinoma (very high calcium/PTH, palpable mass) → urgent surgery/oncology; post-parathyroidectomy severe hypocalcemia/hungry bone → aggressive calcium/calcitriol; CKD tertiary → nephrology
– Discharge checklist: diagnosis confirmed (FHH excluded) + surgical vs medical plan + calcium controlled; if post-parathyroidectomy: calcium + vitamin D with hungry-bone monitoring; if medical: cinacalcet ± bone agent + monitoring; hydration + avoid thiazides/lithium/excess calcium-vitamin D; endocrine/surgery/nephrology follow-up; DEXA + renal surveillance; MEN/genetic evaluation if indicated; return precautions (confusion, severe constipation/nausea, polyuria/dehydration, kidney stone symptoms, post-op paresthesias/tetany — hypocalcemia)

118. Hyperparathyroidism

complete reference · primary (adenoma) + symptomatic hypercalcemia · non-suppressed PTH with high calcium, exclude FHH, parathyroidectomy by criteria, cinacalcet if non-surgical · Full Card

Symptoms / Associated Sx

• Often asymptomatic (found on a routine calcium)

• Symptomatic disease = hypercalcemia: "stones (nephrolithiasis, nephrocalcinosis), bones (pain, osteoporosis, fractures), groans (constipation, nausea, peptic ulcer disease, pancreatitis), and psychiatric overtones (fatigue, depression, cognitive change)"

• Polyuria, polydipsia, and weakness

• The diagnosis is the combination of high calcium with a PTH that is high or inappropriately normal — PTH should be suppressed when calcium is high, so a "normal" PTH in the face of hypercalcemia is actually abnormal; the one critical thing to exclude before surgery is familial hypocalciuric hypercalcemia, which looks identical but must not be operated on

Neg

• Pt denies a missed familial hypocalciuric hypercalcemia (FHH) (low urine calcium — it mimics primary HPT but parathyroidectomy is wrong and ineffective; check a 24-hour urine calcium and the calcium-creatinine clearance ratio)

• Pt denies a missed severe symptomatic hypercalcemia needing acute treatment and a missed secondary or tertiary HPT (CKD context)

• Pt denies a missed MEN syndrome (MEN1, MEN2A) and missed end-organ damage (renal stones, osteoporosis)

Social History (SHx)

• Kidney stones, fractures, or osteoporosis history, and family history (MEN1, MEN2A, FHH)

• CKD (secondary or tertiary disease), neck irradiation, and lithium use

• Vitamin D status, prior calcium abnormalities, menopausal status (bone), and prior parathyroid or thyroid surgery

Main Etiology

• Primary hyperparathyroidism: autonomous PTH oversecretion — a single parathyroid adenoma (~80–85%, the most common), multigland hyperplasia, or rarely parathyroid carcinoma → high calcium, low phosphate

• Secondary: an appropriate PTH rise to hypocalcemia (CKD, vitamin D deficiency)

• Tertiary: autonomous PTH after long-standing secondary disease (CKD)

• Associated with MEN1 and MEN2A

RF

• Modifiable: lithium and neck irradiation

• Non-modifiable: female or postmenopausal status, age, MEN1, MEN2A, or family history, and CKD (secondary or tertiary disease)

Data

• Confirm: elevated calcium (ionized or corrected) with PTH (high or inappropriately normal) and a low or low-normal phosphate

• Exclude FHH: a 24-hour urine calcium (low in FHH, normal or high in primary HPT) and the calcium-creatinine clearance ratio

• 25-vitamin D, renal function, a DEXA (bone density — distal radius), and renal imaging (stones)

• Parathyroid localization for surgery: a sestamibi scan and neck ultrasound (with 4D-CT); an ECG (short QT if severe)

DDx

Primary hyperparathyroidism (adenoma, hyperplasia, carcinoma) · familial hypocalciuric hypercalcemia (low urine calcium — don't operate) · malignancy hypercalcemia (suppressed PTH — see the hypercalcemia card) · secondary or tertiary HPT (CKD) · lithium-induced disease · tertiary HPT · other PTH-independent hypercalcemia

Home Meds

• Hold thiazides, lithium, and calcium and vitamin D supplements (can worsen it); ensure adequate hydration; reconcile medications

• Use cinacalcet if a non-surgical candidate; treat vitamin D deficiency cautiously

• Consider a bisphosphonate or denosumab for bone per endocrine

Plan

CONSULT: Endocrinology (diagnosis, surgical criteria, medical management) · Endocrine/Parathyroid Surgery (parathyroidectomy — definitive) · Nephrology (CKD secondary or tertiary disease, stones) · Genetics (if MEN is suspected)

• If acute severe symptomatic hypercalcemia (e.g. very high or symptomatic calcium) — treat first (self-contained):

• • 1) IV isotonic saline (0.9% NaCl) ~200–300 mL/h (rehydrate and promote calciuresis)

• • 2) Calcitonin 4 units/kg SC/IM every 12 hours (rapid, transient ~48 hours)

• • 3) Bisphosphonate (zoledronic acid 4 mg IV) (durable, onset ~24–48 hours)

• then proceed to definitive evaluation and treatment of the hyperparathyroidism

• Confirm the diagnosis and exclude FHH: high calcium with a non-suppressed PTH = primary HPT; always check a 24-hour urine calcium to exclude FHH (low urine calcium) before considering surgery — operating on FHH is futile and harmful

• Definitive treatment — parathyroidectomy (curative): indicated for symptomatic disease or, in asymptomatic patients, when surgical criteria are met:

• • symptomatic (stones, fractures, overt symptoms)

• • calcium more than 1 mg/dL above the upper normal

• • osteoporosis (T-score ≤ −2.5), a fragility fracture, or a vertebral fracture

• • renal: eGFR below 60, nephrolithiasis or nephrocalcinosis, or hypercalciuria

• • age below 50

• requires preoperative localization (sestamibi and ultrasound); watch for postoperative hypocalcemia and hungry bone

• Medical management (non-surgical candidates or those who decline): cinacalcet (a calcimimetic) lowers calcium and PTH; a bisphosphonate or denosumab for bone density; hydration; monitor calcium, renal function, and bone; avoid aggravating drugs

• Secondary or tertiary disease (CKD): nephrology-directed — phosphate control, active vitamin D, calcimimetics; tertiary disease may need parathyroidectomy

• PT/OT: usually not needed; fall and fracture prevention if there is bone disease

• Trend: calcium (corrected or ionized), PTH, phosphate, renal function, symptoms, post-operative calcium (hypocalcemia, hungry bone), and bone density over time

• Escalation triggers: severe symptomatic hypercalcemia or crisis → acute treatment with ICU if needed (see the hypercalcemia card); parathyroid carcinoma (very high calcium and PTH, a palpable mass) → urgent surgery and oncology; post-parathyroidectomy severe hypocalcemia or hungry bone → aggressive calcium and calcitriol; CKD tertiary disease → nephrology

• Discharge checklist: the diagnosis confirmed (FHH excluded), a surgical versus medical plan, and calcium controlled; if post-parathyroidectomy: calcium and vitamin D with hungry-bone monitoring; if medical: cinacalcet with a bone agent and monitoring; hydration and avoid thiazides, lithium, and excess calcium or vitamin D; endocrine, surgery, and nephrology follow-up; DEXA and renal surveillance; MEN or genetic evaluation if indicated; return precautions for confusion, severe constipation or nausea, polyuria or dehydration, kidney stone symptoms, or post-operative paresthesias or tetany (hypocalcemia)

Red Flags

• Low urine calcium → familial hypocalciuric hypercalcemia; don't operate, as parathyroidectomy is useless and harmful

• Severe symptomatic hypercalcemia → treat acutely with saline, calcitonin, and a bisphosphonate before definitive care

• Very high calcium and PTH with a palpable neck mass → parathyroid carcinoma; urgent surgery

• Post-parathyroidectomy paresthesias or tetany → hypocalcemia or hungry bone; aggressive calcium and calcitriol

• A "normal" PTH with hypercalcemia → inappropriate and abnormal; the gland should have shut off

Senior IM Resident Pearls

• It's the mirror of malignancy hypercalcemia. Here the PTH is high or inappropriately normal, whereas malignancy suppresses it.

• A "normal" PTH with a high calcium is abnormal. The gland should have shut off — its failure to do so is the diagnosis.

• Always exclude FHH before surgery. A 24-hour urine calcium catches this benign mimic where a parathyroidectomy is useless and harmful.

• Know the surgical criteria. Symptoms, calcium more than a point above normal, osteoporosis or fracture, renal involvement, or age under fifty — even when asymptomatic.

• Cinacalcet for the non-surgical patient. It lowers calcium and PTH; a bisphosphonate protects the bones.

• Watch for hungry bone after surgery. Severe post-operative hypocalcemia can follow removal of a long-overactive gland.

• Common mistake: sending a patient with FHH to parathyroidectomy — the low urine calcium would have spared them a futile operation.

Endocrinology — Calcium/Mineral

119. Hypoparathyroidism

low PTH → severe hypocalcemia · most often POST-SURGICAL (thyroid/parathyroid) · tetany + QT prolongation · IV calcium for symptomatic + ACTIVE vitamin D (calcitriol) · Super Compact

Sx: hypocalcemia symptoms: perioral/distal paresthesias, muscle cramps, carpopedal spasm, tetany, Chvostek + Trousseau signs; severe → laryngospasm, seizures, prolonged QT → arrhythmia, bronchospasm, AMS; chronic → cataracts, basal ganglia calcification, dental/skin changes · (hypoparathyroidism is too little PTH causing hypocalcemia — and in the hospital the overwhelmingly common scenario is the post-thyroidectomy or post-parathyroidectomy patient whose calcium drops in the days after surgery; the unique treatment wrinkle is that with no PTH to activate vitamin D, you must give the ACTIVE form, calcitriol)

Neg: denies missed POST-SURGICAL hypoparathyroidism (after thyroid/parathyroid/neck surgery — including hungry bone — the dominant inpatient cause; monitor calcium post-op) · denies missed hypomagnesemia (causes + perpetuates refractory hypocalcemia — must replace Mg) · denies giving plain vitamin D instead of active calcitriol (no PTH to activate it) · denies missed severe symptomatic case needing IV calcium · denies missed prolonged QT/arrhythmia · denies over-treating into hypercalciuria/stones

SHx: recent thyroid/parathyroid/neck surgery or radiation (key cause), autoimmune disease (isolated or polyglandular — APS-1), prior hypocalcemia, family history (genetic — DiGeorge/22q11, calcium-sensing receptor mutations), magnesium status (alcohol, PPI, diuretics), infiltrative disease, prior neck irradiation

Etiology: deficient PTH → ↓ bone resorption + ↓ renal calcium reabsorption + ↓ activation of vitamin D (low calcitriol → ↓ gut calcium absorption) + ↑ phosphate → hypocalcemia + hyperphosphatemia · causes: POST-SURGICAL (most common — thyroidectomy/parathyroidectomy/neck dissection, transient or permanent; hungry bone), autoimmune, genetic (DiGeorge, CaSR-activating mutations), infiltrative, radiation, severe hypomagnesemia (functional)

RF: thyroid/parathyroid/neck surgery (key) · autoimmune disease (APS-1) · genetic syndromes (DiGeorge) · neck irradiation · hypomagnesemia · infiltrative disease

Data: confirm: low calcium (ionized/corrected) + LOW or inappropriately normal PTH + HIGH phosphate (the combination — low PTH with low calcium and high phosphate) · MAGNESIUM (always — replace if low), 25-vitamin D, renal function · ECG (prolonged QT); surgical history review; genetic/autoimmune workup if non-surgical; 24h urine calcium for chronic management

DDx: post-surgical hypoparathyroidism (incl hungry bone after parathyroidectomy) · autoimmune hypoparathyroidism · genetic (DiGeorge/CaSR) · hypomagnesemia-induced (functional) · vitamin D deficiency (but PTH HIGH — distinguishes) · CKD-related · pseudohypoparathyroidism (PTH resistance — high PTH) · acute (transfusion/pancreatitis)

Home Meds: calcium + ACTIVE vitamin D (calcitriol) — core therapy; replace magnesium; reconcile; thiazide may reduce hypercalciuria in chronic management; avoid loop diuretics (calciuric); recombinant PTH for difficult cases; monitor to avoid over-replacement

Plan

CONSULT: Endocrinology (diagnosis, chronic management, refractory, recombinant PTH) · Surgery (if post-operative — coordinate; hungry bone) · ICU (severe symptomatic — laryngospasm, seizures, arrhythmia) · Genetics (if syndromic/non-surgical)

– SEVERITY-BASED TREATMENT:
  • SYMPTOMATIC/SEVERE (tetany, laryngospasm, seizures, prolonged QT/arrhythmia, very low calcium): IV CALCIUM — calcium gluconate 1–2 g in 50–100 mL D5W over ~10–20 min for acute symptoms, then a calcium gluconate infusion for ongoing/severe (titrate to calcium + symptoms); continuous ECG monitoring (calcium chloride only via central line)
  • ASYMPTOMATIC/MILD–MODERATE: oral calcium + active vitamin D
– CHECK + REPLACE MAGNESIUM (critical): hypomagnesemia causes + perpetuates refractory hypocalcemia — calcium won't correct until magnesium is replaced
– CORE CHRONIC THERAPY — CALCIUM + ACTIVE VITAMIN D (CALCITRIOL): because there is no PTH to convert vitamin D to its active form, give calcitriol (active vitamin D), not just plain ergocalciferol/cholecalciferol, plus oral calcium supplements; titrate to a low-normal calcium that relieves symptoms while avoiding hypercalciuria (PTH deficiency removes the renal calcium-sparing effect → stone/nephrocalcinosis risk)
– POST-SURGICAL course: may be transient (recovers over days–weeks) or permanent; hungry bone syndrome (post-parathyroidectomy): aggressive calcium + calcitriol + magnesium, can be profound + prolonged; monitor calcium closely post-op
– REFRACTORY/DIFFICULT-TO-CONTROL: recombinant human PTH (e.g. PTH 1-84 / teriparatide) per endocrine for those needing high calcium/calcitriol doses or with complications; thiazide diuretic + low-sodium diet to reduce urinary calcium losses
– MONITOR for over-treatment: avoid hypercalcemia/hypercalciuria (stones, renal impairment); follow calcium, phosphate, 24h urine calcium, renal function
– Two things make hypoparathyroidism distinctive. First, the cause: by far the most common inpatient version is iatrogenic — the calcium that drifts down in the days after a thyroidectomy or parathyroidectomy — so anyone who's had neck surgery gets their calcium watched. Second, the treatment twist: PTH normally activates vitamin D, so without it, plain vitamin D sits there useless, and you must give the active form, calcitriol, alongside calcium. The acute management mirrors any severe hypocalcemia — IV calcium gluconate under cardiac monitoring for tetany, laryngospasm, seizures, or a long QT, and never forget to check and replace the magnesium, which will keep the calcium refractory until it's fixed. The long-term art is keeping the calcium just into the low-normal range to relieve symptoms without spilling calcium into the urine and causing stones, since the missing PTH also removes the kidney's calcium-sparing action.
– PT/OT: usually not needed; safety if tetany/weakness
– Trend: calcium (ionized/corrected — frequent if severe/on infusion), magnesium, phosphate, ECG/QT, symptoms (Chvostek/Trousseau), 24h urine calcium (chronic), renal function, post-op trajectory
– Escalation triggers: tetany/laryngospasm/seizures/arrhythmia → IV calcium + ICU + continuous monitoring; refractory despite calcium → replace magnesium + reassess; post-parathyroidectomy hungry bone → aggressive repletion + endocrine; difficult chronic control → recombinant PTH + endocrine
– Discharge checklist: calcium corrected/stabilized + magnesium replete + on calcium + calcitriol; calcium + ACTIVE vitamin D (calcitriol) with doses + monitoring; avoid-hypercalciuria plan (target low-normal calcium); recombinant PTH plan if refractory; endocrine/surgery follow-up; calcium/phosphate/urine-calcium/renal monitoring; education on adherence + symptom recognition; return precautions (paresthesias, cramps/spasms, twitching, seizures, breathing difficulty — laryngospasm, kidney stone symptoms)

119. Hypoparathyroidism

complete reference · low PTH severe hypocalcemia · most often post-surgical, check magnesium, IV calcium for symptomatic, calcium + active vitamin D (calcitriol), avoid hypercalciuria · Full Card

Symptoms / Associated Sx

• Hypocalcemia symptoms: perioral and distal paresthesias, muscle cramps, carpopedal spasm, tetany, and Chvostek and Trousseau signs

• Severe disease: laryngospasm, seizures, a prolonged QT with arrhythmia, bronchospasm, and altered mental status

• Chronic disease: cataracts, basal ganglia calcification, and dental and skin changes

• Hypoparathyroidism is too little PTH causing hypocalcemia — and in the hospital the overwhelmingly common scenario is the post-thyroidectomy or post-parathyroidectomy patient whose calcium drops in the days after surgery; the unique treatment wrinkle is that with no PTH to activate vitamin D, you must give the active form, calcitriol

Neg

• Pt denies a missed post-surgical hypoparathyroidism (after thyroid, parathyroid, or neck surgery — including hungry bone — the dominant inpatient cause; monitor calcium post-operatively)

• Pt denies a missed hypomagnesemia (which causes and perpetuates refractory hypocalcemia — must replace magnesium) and giving plain vitamin D instead of active calcitriol (no PTH to activate it)

• Pt denies a missed severe symptomatic case needing IV calcium, a missed prolonged QT or arrhythmia, and over-treating into hypercalciuria or stones

Social History (SHx)

• Recent thyroid, parathyroid, or neck surgery or radiation (a key cause), and autoimmune disease (isolated or polyglandular — APS-1)

• Prior hypocalcemia and family history (genetic — DiGeorge/22q11, calcium-sensing receptor mutations)

• Magnesium status (alcohol, PPIs, diuretics), infiltrative disease, and prior neck irradiation

Main Etiology

• Deficient PTH causes reduced bone resorption, reduced renal calcium reabsorption, reduced activation of vitamin D (low calcitriol → reduced gut calcium absorption), and increased phosphate → hypocalcemia and hyperphosphatemia

• Causes: post-surgical (the most common — thyroidectomy, parathyroidectomy, neck dissection, transient or permanent; hungry bone), autoimmune disease, genetic disease (DiGeorge, CaSR-activating mutations), infiltrative disease, radiation, and severe hypomagnesemia (functional)

RF

• Modifiable: hypomagnesemia

• Non-modifiable: thyroid, parathyroid, or neck surgery (the key cause), autoimmune disease (APS-1), genetic syndromes (DiGeorge), neck irradiation, and infiltrative disease

Data

• Confirm: a low calcium (ionized or corrected) with a low or inappropriately normal PTH and a high phosphate (the combination — low PTH with low calcium and high phosphate)

• Magnesium (always — replace if low), 25-vitamin D, and renal function

• An ECG (prolonged QT)

• A surgical history review; a genetic or autoimmune workup if non-surgical; a 24-hour urine calcium for chronic management

DDx

Post-surgical hypoparathyroidism (including hungry bone after parathyroidectomy) · autoimmune hypoparathyroidism · genetic disease (DiGeorge, CaSR) · hypomagnesemia-induced (functional) disease · vitamin D deficiency (but PTH is high — distinguishing it) · CKD-related disease · pseudohypoparathyroidism (PTH resistance — high PTH) · acute disease (transfusion, pancreatitis)

Home Meds

• Give calcium with active vitamin D (calcitriol) — the core therapy; replace magnesium; reconcile medications

• Consider a thiazide to reduce hypercalciuria in chronic management; avoid loop diuretics (calciuric)

• Use recombinant PTH for difficult cases; monitor to avoid over-replacement

Plan

CONSULT: Endocrinology (diagnosis, chronic management, refractory disease, recombinant PTH) · Surgery (if post-operative — coordinate; hungry bone) · ICU (severe symptomatic disease — laryngospasm, seizures, arrhythmia) · Genetics (if syndromic or non-surgical)

• Severity-based treatment:

• • Symptomatic or severe (tetany, laryngospasm, seizures, prolonged QT or arrhythmia, very low calcium): IV calcium — calcium gluconate 1–2 g in 50–100 mL of D5W over ~10–20 minutes for acute symptoms, then a calcium gluconate infusion for ongoing or severe disease (titrated to calcium and symptoms); continuous ECG monitoring (calcium chloride only via a central line)

• • Asymptomatic or mild-to-moderate: oral calcium with active vitamin D

• Check and replace magnesium (critical): hypomagnesemia causes and perpetuates refractory hypocalcemia — calcium won't correct until magnesium is replaced

• Core chronic therapy — calcium with active vitamin D (calcitriol): because there is no PTH to convert vitamin D to its active form, give calcitriol (active vitamin D), not just plain ergocalciferol or cholecalciferol, plus oral calcium supplements; titrate to a low-normal calcium that relieves symptoms while avoiding hypercalciuria (PTH deficiency removes the renal calcium-sparing effect → stone and nephrocalcinosis risk)

• Post-surgical course: may be transient (recovering over days to weeks) or permanent; hungry bone syndrome (post-parathyroidectomy): aggressive calcium with calcitriol and magnesium, which can be profound and prolonged; monitor calcium closely post-operatively

• Refractory or difficult-to-control disease: recombinant human PTH (e.g. PTH 1-84 / teriparatide) per endocrine for those needing high calcium or calcitriol doses or with complications; a thiazide diuretic with a low-sodium diet to reduce urinary calcium losses

• Monitor for over-treatment: avoid hypercalcemia and hypercalciuria (stones, renal impairment); follow calcium, phosphate, a 24-hour urine calcium, and renal function

• PT/OT: usually not needed; safety if there is tetany or weakness

• Trend: calcium (ionized or corrected — frequent if severe or on an infusion), magnesium, phosphate, the ECG and QT, symptoms (Chvostek and Trousseau signs), a 24-hour urine calcium (chronic), renal function, and the post-operative trajectory

• Escalation triggers: tetany, laryngospasm, seizures, or arrhythmia → IV calcium with ICU and continuous monitoring; refractory disease despite calcium → replace magnesium and reassess; post-parathyroidectomy hungry bone → aggressive repletion with endocrine; difficult chronic control → recombinant PTH with endocrine

• Discharge checklist: calcium corrected or stabilized, magnesium replete, and on calcium and calcitriol; calcium and active vitamin D (calcitriol) with doses and monitoring; an avoid-hypercalciuria plan (targeting a low-normal calcium); a recombinant PTH plan if refractory; endocrine and surgery follow-up; calcium, phosphate, urine-calcium, and renal monitoring; education on adherence and symptom recognition; return precautions for paresthesias, cramps or spasms, twitching, seizures, breathing difficulty (laryngospasm), or kidney stone symptoms

Red Flags

• Tetany, laryngospasm, seizures, or a prolonged QT → IV calcium with continuous monitoring and ICU

• Refractory hypocalcemia despite calcium → unreplaced hypomagnesemia; fix the magnesium

• Plain vitamin D given instead of calcitriol → ineffective; there's no PTH to activate it

• Post-parathyroidectomy → hungry bone syndrome; profound, prolonged calcium requirement

• Over-replacement → hypercalciuria, stones, and renal impairment; target a low-normal calcium

Senior IM Resident Pearls

• The common cause is iatrogenic. The calcium that drifts down in the days after a thyroidectomy or parathyroidectomy is post-surgical hypoparathyroidism.

• Give the active vitamin D. Without PTH to activate it, plain vitamin D is useless — calcitriol is the form that works.

• Check and replace magnesium. A low magnesium keeps the calcium refractory no matter how much you give.

• Acute management mirrors any severe hypocalcemia. IV calcium gluconate under cardiac monitoring for tetany, laryngospasm, seizures, or a long QT.

• Target a low-normal calcium. The missing PTH removes the kidney's calcium-sparing action, so aiming higher spills calcium into the urine and causes stones.

• Recombinant PTH for the difficult cases. It's the replacement option when calcium and calcitriol can't control the disease.

• Common mistake: prescribing plain cholecalciferol for hypoparathyroidism — without PTH it never gets activated, and the calcium stays low.

Endocrinology — Onco-Endocrine

120. Endocrine Complications of Cancer Therapy

immune checkpoint inhibitor endocrinopathies · hypophysitis · thyroiditis · adrenal insufficiency · checkpoint-inhibitor T1DM/DKA · recognize, replace hormones, usually continue immunotherapy · Super Compact

Sx: often nonspecific + attributed to cancer/chemo — fatigue, weakness, nausea, headache; syndrome-specific: hypophysitis (headache, visual changes, secondary adrenal insufficiency + central hypothyroidism — esp anti-CTLA-4/ipilimumab), thyroiditis (transient thyrotoxicosis → hypothyroidism — esp anti-PD-1/PD-L1), primary adrenal insufficiency, checkpoint-inhibitor diabetes (acute, can present as DKA) · (immune checkpoint inhibitors unleash autoimmunity against endocrine glands; the endocrine immune-related adverse events are common, can be permanent, and — unlike most other irAEs — are usually managed by replacing the missing hormone and CONTINUING immunotherapy rather than stopping it)

Neg: denies missed adrenal insufficiency/crisis (hypophysitis or primary — life-threatening, give stress steroids; don't attribute fatigue/hypotension to cancer) · denies giving levothyroxine before cortisol if hypophysitis/central (precipitates adrenal crisis — cortisol first) · denies missed checkpoint-inhibitor DKA (new acute insulin-dependent diabetes — check glucose/ketones) · denies missing screening labs (TSH/cortisol/glucose monitoring on therapy) · denies stopping immunotherapy unnecessarily (most endocrinopathies → replace + continue)

SHx: cancer type + therapy (immune checkpoint inhibitors — anti-PD-1 [nivolumab/pembrolizumab], anti-PD-L1, anti-CTLA-4 [ipilimumab], combinations [highest risk]; also tyrosine kinase inhibitors → thyroid dysfunction), timing relative to therapy cycles, prior autoimmune/endocrine disease, other irAEs (colitis, pneumonitis, hepatitis), baseline endocrine labs

Etiology: immune checkpoint inhibitors remove T-cell tolerance → autoimmune endocrine gland inflammation → endocrine irAEs: hypophysitis (→ secondary adrenal insufficiency + central hypothyroidism ± other axes), thyroiditis (thyrotoxic then hypothyroid), primary adrenal insufficiency, checkpoint-inhibitor T1DM (autoimmune islet destruction — abrupt), rarely hypoparathyroidism · also: TKIs cause hypothyroidism, mitotane/other agents affect adrenal; many are permanent

RF: checkpoint inhibitor therapy (combination anti-CTLA-4 + anti-PD-1 highest) · prior autoimmune disease · prior/other irAEs · certain tumor types

Data: screen + diagnose by axis: TSH + free T4 (thyroid), AM cortisol + ACTH (adrenal — primary vs central), glucose + ketones/C-peptide (CPI-diabetes), in hypophysitis full pituitary panel + pituitary MRI · routine monitoring on therapy (TSH, cortisol, glucose each cycle); distinguish thyroiditis phase (thyrotoxic vs hypothyroid); electrolytes (Na/K — adrenal); oncology co-interpretation

DDx: checkpoint-inhibitor hypophysitis · CPI thyroiditis (thyrotoxic/hypothyroid phase) · CPI primary adrenal insufficiency · CPI-induced diabetes/DKA · TKI-induced hypothyroidism · non-thyroidal illness (sick euthyroid) · cancer-related fatigue/cachexia · other irAEs · sepsis (for adrenal crisis presentation)

Home Meds: hormone replacement (often permanent): hydrocortisone (adrenal — FIRST), levothyroxine (after cortisol), insulin (CPI-diabetes); coordinate with oncology re: continuing/holding immunotherapy; stress-dose steroid education; reconcile

Plan

CONSULT: Endocrinology (diagnosis, hormone replacement, monitoring — essential) · Oncology (immunotherapy decisions, irAE management — co-manage) · ICU if crisis (adrenal crisis, DKA, severe) · others per axis (ophthalmology if visual hypophysitis)

– RECOGNIZE + SCREEN: maintain high suspicion in any checkpoint-inhibitor patient with fatigue/nausea/headache/hypotension; routine monitoring TSH/cortisol/glucose on therapy catches these early
– ADRENAL INSUFFICIENCY (hypophysitis-related secondary OR primary) — the priority:
  • If adrenal crisis (hypotension/shock): hydrocortisone 100 mg IV immediately + IV saline — don't wait (see adrenal crisis card)
  • Maintenance: hydrocortisone replacement + stress-dose education + emergency kit + bracelet; often permanent
  • CORTISOL BEFORE LEVOTHYROXINE if both central hypothyroidism + adrenal insufficiency (hypophysitis) — thyroid first precipitates crisis
– HYPOPHYSITIS: hormone replacement of deficient axes (cortisol first, then levothyroxine, then sex steroids); high-dose steroids only for mass effect/severe headache/visual compromise (not routinely needed just to replace hormones); pituitary MRI; usually permanent hormone deficits
– THYROID DYSFUNCTION: thyroiditis often biphasic — thyrotoxic phase (transient): beta-blocker for symptoms (no thionamide — it's destructive release, not synthesis); hypothyroid phase: levothyroxine (often permanent — but ensure adrenal axis covered first if any hypophysitis concern)
– CHECKPOINT-INHIBITOR DIABETES: can be abrupt + present as DKA → treat DKA (fluids/insulin/electrolytes per DKA pathway) + insulin (insulin-dependent, usually permanent); check glucose/ketones; endocrine + diabetes education
– IMMUNOTHERAPY CONTINUATION: unlike most irAEs, endocrine irAEs usually do NOT require permanent immunotherapy discontinuation — replace the hormone + continue therapy (oncology decision); high-dose immunosuppression usually NOT needed for the endocrinopathy itself (reserved for severe/mass effect)
– Checkpoint inhibitors work by taking the brakes off the immune system, and sometimes it turns on the endocrine glands — so the pattern to recognize is a cancer patient on immunotherapy with vague fatigue, nausea, or headache that's actually a new hormone deficiency. The dangerous one is adrenal insufficiency, whether from hypophysitis (secondary) or direct adrenal attack (primary): don't write off the fatigue and low blood pressure as "the cancer," and if they're in crisis, hydrocortisone goes in immediately. The thyroid typically does a biphasic dance — a transient thyrotoxic phase you treat with just a beta-blocker (no thionamide, because it's destructive release), settling into a usually permanent hypothyroidism needing levothyroxine — but cover cortisol first if there's any hypophysitis. And watch for the abrupt checkpoint-inhibitor diabetes that can crash in as DKA. The reassuring counterpoint to all the other immune toxicities: these endocrinopathies are usually managed by replacing the hormone and continuing the immunotherapy, not stopping it.
– PT/OT: usually not needed; per overall cancer care
– Trend: relevant hormone axes (TSH/free T4, cortisol/ACTH, glucose), electrolytes, symptoms, adequacy of replacement, thyroiditis phase transitions, other emerging irAEs, response
– Escalation triggers: adrenal crisis → hydrocortisone + ICU; DKA → DKA pathway ± ICU; hypophysitis with visual compromise/mass effect → high-dose steroids + endocrine/ophthalmology/neurosurgery; severe/multiple irAEs → oncology + immunosuppression decisions; thyroid storm (rare) → storm pathway
– Discharge checklist: deficiencies identified + hormones replaced (correct order) + immunotherapy plan with oncology; replacement regimen (hydrocortisone with stress-dose education + emergency kit + bracelet if adrenal; levothyroxine; insulin if CPI-diabetes — often LIFELONG); ongoing endocrine monitoring on therapy; endocrine + oncology follow-up; education on permanence + stress-dosing + DKA/crisis warning signs; return precautions (severe fatigue/dizziness/hypotension — adrenal, high glucose/vomiting — DKA, headache/visual changes — hypophysitis, palpitations — thyroid)

120. Endocrine Complications of Cancer Therapy

complete reference · checkpoint-inhibitor endocrinopathies · hypophysitis, thyroiditis, adrenal insufficiency, CPI-diabetes/DKA · recognize, replace (cortisol first), usually continue immunotherapy · Full Card

Symptoms / Associated Sx

• Often nonspecific and attributed to cancer or chemotherapy — fatigue, weakness, nausea, and headache

• Syndrome-specific: hypophysitis (headache, visual changes, secondary adrenal insufficiency and central hypothyroidism — especially with anti-CTLA-4/ipilimumab), thyroiditis (transient thyrotoxicosis then hypothyroidism — especially with anti-PD-1/PD-L1), primary adrenal insufficiency, and checkpoint-inhibitor diabetes (acute, can present as DKA)

• Immune checkpoint inhibitors unleash autoimmunity against endocrine glands; the endocrine immune-related adverse events are common, can be permanent, and — unlike most other irAEs — are usually managed by replacing the missing hormone and continuing immunotherapy rather than stopping it

Neg

• Pt denies a missed adrenal insufficiency or crisis (hypophysitis-related or primary — life-threatening, give stress steroids; don't attribute fatigue or hypotension to cancer)

• Pt denies giving levothyroxine before cortisol if hypophysitis or central disease (which precipitates adrenal crisis — cortisol first) and a missed checkpoint-inhibitor DKA (new acute insulin-dependent diabetes — check glucose and ketones)

• Pt denies missing screening labs (TSH, cortisol, glucose monitoring on therapy) and stopping immunotherapy unnecessarily (most endocrinopathies → replace and continue)

Social History (SHx)

• Cancer type and therapy (immune checkpoint inhibitors — anti-PD-1 [nivolumab, pembrolizumab], anti-PD-L1, anti-CTLA-4 [ipilimumab], combinations [highest risk]; also tyrosine kinase inhibitors → thyroid dysfunction)

• Timing relative to therapy cycles and prior autoimmune or endocrine disease

• Other irAEs (colitis, pneumonitis, hepatitis) and baseline endocrine labs

Main Etiology

• Immune checkpoint inhibitors remove T-cell tolerance, causing autoimmune endocrine gland inflammation → endocrine irAEs: hypophysitis (→ secondary adrenal insufficiency and central hypothyroidism with other axes), thyroiditis (thyrotoxic then hypothyroid), primary adrenal insufficiency, checkpoint-inhibitor T1DM (autoimmune islet destruction — abrupt), and rarely hypoparathyroidism

• Also: TKIs cause hypothyroidism, and mitotane and other agents affect the adrenal; many of these are permanent

RF

• Modifiable: the specific checkpoint inhibitor regimen (combination anti-CTLA-4 plus anti-PD-1 is the highest risk)

• Non-modifiable: prior autoimmune disease, prior or other irAEs, and certain tumor types

Data

• Screen and diagnose by axis: TSH and free T4 (thyroid), an AM cortisol and ACTH (adrenal — primary versus central), glucose with ketones and C-peptide (CPI-diabetes), and in hypophysitis a full pituitary panel and a pituitary MRI

• Routine monitoring on therapy (TSH, cortisol, glucose each cycle)

• Distinguish the thyroiditis phase (thyrotoxic versus hypothyroid); electrolytes (sodium, potassium — adrenal); oncology co-interpretation

DDx

Checkpoint-inhibitor hypophysitis · CPI thyroiditis (thyrotoxic or hypothyroid phase) · CPI primary adrenal insufficiency · CPI-induced diabetes or DKA · TKI-induced hypothyroidism · non-thyroidal illness (sick euthyroid syndrome) · cancer-related fatigue or cachexia · other irAEs · sepsis (for an adrenal crisis presentation)

Home Meds

• Replace hormones (often permanent): hydrocortisone (adrenal — first), levothyroxine (after cortisol), and insulin (CPI-diabetes)

• Coordinate with oncology regarding continuing or holding immunotherapy; provide stress-dose steroid education

• Reconcile medications

Plan

CONSULT: Endocrinology (diagnosis, hormone replacement, monitoring — essential) · Oncology (immunotherapy decisions, irAE management — co-manage) · ICU if crisis (adrenal crisis, DKA, severe disease) · others per axis (ophthalmology if visual hypophysitis)

• Recognize and screen: maintain high suspicion in any checkpoint-inhibitor patient with fatigue, nausea, headache, or hypotension; routine monitoring of TSH, cortisol, and glucose on therapy catches these early

• Adrenal insufficiency (hypophysitis-related secondary or primary) — the priority:

• • If adrenal crisis (hypotension or shock): hydrocortisone 100 mg IV immediately plus IV saline — don't wait (see the adrenal crisis card)

• • Maintenance: hydrocortisone replacement with stress-dose education, an emergency kit, and a bracelet; often permanent

• • Cortisol before levothyroxine if there is both central hypothyroidism and adrenal insufficiency (hypophysitis) — thyroid first precipitates crisis

• Hypophysitis: hormone replacement of deficient axes (cortisol first, then levothyroxine, then sex steroids); high-dose steroids only for mass effect, severe headache, or visual compromise (not routinely needed just to replace hormones); a pituitary MRI; usually permanent hormone deficits

• Thyroid dysfunction: thyroiditis is often biphasic — the thyrotoxic phase (transient): a beta-blocker for symptoms (no thionamide — it's destructive release, not synthesis); the hypothyroid phase: levothyroxine (often permanent — but ensure the adrenal axis is covered first if there is any hypophysitis concern)

• Checkpoint-inhibitor diabetes: can be abrupt and present as DKA → treat the DKA (fluids, insulin, electrolytes per the DKA pathway) plus insulin (insulin-dependent, usually permanent); check glucose and ketones; endocrine and diabetes education

• Immunotherapy continuation: unlike most irAEs, endocrine irAEs usually do not require permanent immunotherapy discontinuation — replace the hormone and continue therapy (an oncology decision); high-dose immunosuppression is usually not needed for the endocrinopathy itself (reserved for severe disease or mass effect)

• PT/OT: usually not needed; per overall cancer care

• Trend: the relevant hormone axes (TSH and free T4, cortisol and ACTH, glucose), electrolytes, symptoms, the adequacy of replacement, thyroiditis phase transitions, other emerging irAEs, and the response

• Escalation triggers: adrenal crisis → hydrocortisone and ICU; DKA → the DKA pathway with possible ICU; hypophysitis with visual compromise or mass effect → high-dose steroids with endocrine, ophthalmology, and neurosurgery; severe or multiple irAEs → oncology and immunosuppression decisions; thyroid storm (rare) → the storm pathway

• Discharge checklist: deficiencies identified, hormones replaced (in the correct order), and an immunotherapy plan with oncology; a replacement regimen (hydrocortisone with stress-dose education, an emergency kit, and a bracelet if adrenal; levothyroxine; insulin if CPI-diabetes — often lifelong); ongoing endocrine monitoring on therapy; endocrine and oncology follow-up; education on permanence, stress-dosing, and DKA or crisis warning signs; return precautions for severe fatigue, dizziness, or hypotension (adrenal), high glucose or vomiting (DKA), headache or visual changes (hypophysitis), or palpitations (thyroid)

Red Flags

• Fatigue and hypotension in a checkpoint-inhibitor patient → adrenal insufficiency; don't write it off as cancer, and give hydrocortisone in crisis

• Levothyroxine before cortisol in hypophysitis → can precipitate adrenal crisis; cortisol first

• New high glucose with ketones → checkpoint-inhibitor diabetes presenting as DKA

• Hypophysitis with visual compromise or mass effect → high-dose steroids and urgent specialty input

• Stopping immunotherapy reflexively → usually unnecessary for endocrinopathies; replace the hormone and continue

Senior IM Resident Pearls

• Recognize the pattern. A cancer patient on immunotherapy with vague fatigue, nausea, or headache may have a new hormone deficiency, not just cancer.

• Adrenal insufficiency is the dangerous one. Whether from hypophysitis or direct adrenal attack, don't dismiss the fatigue and low blood pressure — give hydrocortisone in crisis.

• The thyroid does a biphasic dance. A transient thyrotoxic phase (beta-blocker only, no thionamide) settles into a usually permanent hypothyroidism needing levothyroxine.

• Cover cortisol first. If there's any hypophysitis, the glucocorticoid goes in before the levothyroxine.

• Watch for abrupt CPI diabetes. It can crash in as DKA — check glucose and ketones in the symptomatic patient.

• Usually continue the immunotherapy. Unlike other immune toxicities, endocrinopathies are managed by replacing the hormone, not stopping the drug.

• Common mistake: giving high-dose immunosuppression for the endocrinopathy itself — replacement is the treatment; steroids beyond physiologic replacement are reserved for mass effect or visual compromise.