Endocrinology — Diabetes

101. Diabetes Mellitus with Uncontrolled Hyperglycemia

severe hyperglycemia without DKA/HHS · medication noncompliance · newly diagnosed diabetes · rule out the emergencies first, then control glucose + find the driver · Super Compact

Sx: polyuria, polydipsia, blurry vision, fatigue, weight loss (esp new T1DM), recurrent infections; often asymptomatic and found on labs · screen for emergency features: Kussmaul breathing/fruity breath (DKA), profound dehydration/AMS (HHS), abdominal pain/vomiting · (the first job with any high glucose is to exclude DKA and HHS — check a gas, ketones, and osmolality before you relax; "just hyperglycemia" is a diagnosis of exclusion)

Neg: denies missed DKA (anion-gap acidosis + ketones — check even in T2DM) · denies missed HHS (glucose often >600, high osmolality, AMS) · denies missed precipitant (infection, MI, missed insulin, steroids, new drug) · denies missed new T1DM presenting as "T2DM" (antibody-positive, ketosis-prone) · denies missed pancreatic/secondary diabetes

SHx: diabetes type/duration, current regimen + adherence (cost, access, technique), prior A1c/control, hypoglycemia history, recent steroid/medication changes, diet, infections, prior DKA/HHS, family history, alcohol; barriers to care (insulin affordability is a common cause of noncompliance)

Etiology: insulin deficiency (absolute — T1DM/late T2DM) or resistance (T2DM) → hyperglycemia · common drivers of acute worsening: medication nonadherence (esp insulin — cost/access), infection/illness (stress hyperglycemia), corticosteroids/other hyperglycemic drugs, dietary indiscretion, new-onset diabetes, pancreatic disease, undertreated regimen

RF: nonadherence/insulin access barriers · infection/acute illness · steroids · obesity/insulin resistance · new diagnosis · poor baseline control

Data: glucose, basic metabolic panel (anion gap), venous blood gas + serum/urine ketones (RULE OUT DKA), calculated osmolality (rule out HHS) · A1c (chronicity + baseline control) · CBC + infection workup if precipitant suspected (UA, CXR, cultures per signs) · C-peptide + diabetes autoantibodies (GAD-65) if new/uncertain type; lipid panel, renal function, urine albumin; ECG/troponin if cardiac risk

DDx: uncomplicated uncontrolled hyperglycemia · DKA (gap acidosis + ketones) · HHS (very high glucose/osm, AMS) · stress hyperglycemia · steroid-induced hyperglycemia · new-onset T1DM vs T2DM · pancreatogenic/secondary diabetes · MODY

Home Meds: reconcile diabetes regimen + identify nonadherence cause; hold metformin if AKI/contrast/unstable; hold SGLT2 inhibitor if acutely ill/poor intake (euglycemic DKA risk); review steroids + other hyperglycemic agents; resume/adjust home regimen at discharge with education

Plan

CONSULT: Endocrinology / inpatient glycemic-management or diabetes team (regimen design, new diagnosis, insulin initiation/education) · Diabetes educator (technique, survival skills, esp new T1DM) · Social work/pharmacy (insulin affordability/access — addresses the root cause) · source-specific if precipitant (ID, cardiology)

– FIRST exclude DKA + HHS (gas, ketones, osmolality) — if present, treat per those pathways (see DKA and HHS cards); this card = significant hyperglycemia WITHOUT those emergencies
– GLUCOSE CONTROL (inpatient — insulin is the mainstay; avoid sliding-scale-only):
  • Basal-bolus (preferred) for most: weight-based total daily dose (e.g. ~0.4–0.5 units/kg/day, lower if insulin-naïve/elderly/CKD) split ~50% basal (glargine/detemir/degludec once daily) + ~50% rapid-acting (lispro/aspart) divided with meals, + correction-scale rapid-acting for highs
  • Adjust daily based on glucose trends; avoid sliding-scale insulin alone (reactive, poor control)
  • Targets (non-critical inpatient): generally ~140–180 mg/dL; avoid hypoglycemia (individualize, looser if frail/elderly)
  • NPO/enteral feeds: basal continued, nutritional insulin matched to intake
– TREAT THE PRECIPITANT: infection (cultures + antibiotics per source), steroids (adjust insulin upward, anticipate hyperglycemia), MI/illness; address the trigger or glucose won't stay controlled
– NEW-ONSET DIABETES workup + classification: C-peptide + autoantibodies if type unclear; if T1DM/ketosis-prone → insulin + diabetes-survival-skills education (never sulfonylurea/metformin alone); T2DM → individualized regimen
– ADDRESS NONADHERENCE at the root: identify why (cost, access, fear, technique, depression) → social work + pharmacy for insulin affordability, simplify regimen, education, follow-up — discharge without this just bounces back
– Two reflexes prevent the classic misses here. First, never accept "just hyperglycemia" until a gas, ketones, and an osmolality have ruled out DKA and HHS — both can hide behind an unremarkable-looking high glucose, and euglycemic DKA on an SGLT2 inhibitor is the sneakiest of all. Second, when noncompliance is the story, the real treatment isn't a better insulin regimen — it's finding out why, and an enormous fraction of "noncompliance" is simply that the patient can't afford insulin. Get pharmacy and social work involved or you'll see them again next week. And give every uncontrolled diabetic basal-bolus insulin, not sliding-scale alone, which only chases highs after they happen.
– PT/OT: usually not needed; diabetes self-management education central
– Trend: point-of-care glucose (before meals + bedtime), resolution of any gap/ketones, response to regimen, precipitant resolution, A1c for baseline
– Escalation triggers: evolving DKA/HHS (rising gap, ketones, AMS, rising osm) → switch to emergency pathway ± ICU; persistent severe hyperglycemia despite escalation → endocrine + reassess precipitant; severe infection/sepsis → source pathway + ICU
– Discharge checklist: glucose improving + precipitant addressed + a clear home regimen; insulin/oral regimen with doses + titration plan; affordability/access SECURED (the key to preventing readmission); glucometer/CGM + supplies + technique taught; diabetes education (survival skills if new); hypoglycemia counseling; A1c-based plan; PCP/endocrine follow-up; sick-day rules; return precautions (vomiting, abdominal pain, very high/low glucose, confusion, signs of infection)

101. Diabetes Mellitus with Uncontrolled Hyperglycemia

complete reference · severe hyperglycemia + noncompliance + newly diagnosed · exclude DKA/HHS, basal-bolus insulin, treat the driver, fix access barriers · Full Card

Symptoms / Associated Sx

• Polyuria, polydipsia, blurry vision, fatigue, weight loss (especially in new T1DM), and recurrent infections; often asymptomatic and found on labs

• Screen for emergency features: Kussmaul breathing or fruity breath (DKA), profound dehydration or altered mental status (HHS), and abdominal pain or vomiting

• The first job with any high glucose is to exclude DKA and HHS — check a gas, ketones, and osmolality before relaxing; "just hyperglycemia" is a diagnosis of exclusion

Neg

• Pt denies a missed DKA (anion-gap acidosis with ketones — check even in T2DM)

• Pt denies a missed HHS (glucose often above 600, high osmolality, altered mental status) and a missed precipitant (infection, MI, missed insulin, steroids, a new drug)

• Pt denies a missed new T1DM presenting as "T2DM" (antibody-positive, ketosis-prone) and a missed pancreatic or secondary diabetes

Social History (SHx)

• Diabetes type and duration, the current regimen and adherence (cost, access, technique), and prior A1c and control

• Hypoglycemia history, recent steroid or medication changes, diet, and infections

• Prior DKA or HHS, family history, and alcohol; barriers to care (insulin affordability is a common cause of noncompliance)

Main Etiology

• Insulin deficiency (absolute — T1DM or late T2DM) or resistance (T2DM) produces hyperglycemia

• Common drivers of acute worsening: medication nonadherence (especially insulin — cost and access), infection or illness (stress hyperglycemia), corticosteroids and other hyperglycemic drugs, dietary indiscretion, new-onset diabetes, pancreatic disease, and an undertreated regimen

RF

• Modifiable: nonadherence and insulin access barriers, steroids, and obesity or insulin resistance

• Non-modifiable: a new diagnosis, intercurrent infection or illness, and poor baseline control

Data

• Glucose, a basic metabolic panel (anion gap), a venous blood gas with serum/urine ketones (to rule out DKA), and a calculated osmolality (to rule out HHS)

• A1c (chronicity and baseline control)

• CBC and an infection workup if a precipitant is suspected (urinalysis, CXR, cultures per signs)

• C-peptide and diabetes autoantibodies (GAD-65) if the type is new or uncertain; a lipid panel, renal function, and urine albumin; an ECG and troponin if there is cardiac risk

DDx

Uncomplicated uncontrolled hyperglycemia · DKA (gap acidosis with ketones) · HHS (very high glucose and osmolality, altered mental status) · stress hyperglycemia · steroid-induced hyperglycemia · new-onset T1DM versus T2DM · pancreatogenic or secondary diabetes · MODY

Home Meds

• Reconcile the diabetes regimen and identify the cause of nonadherence

• Hold metformin if there is AKI, contrast, or instability, and the SGLT2 inhibitor if acutely ill or with poor intake (euglycemic DKA risk); review steroids and other hyperglycemic agents

• Resume and adjust the home regimen at discharge with education

Plan

CONSULT: Endocrinology or the inpatient glycemic-management/diabetes team (regimen design, new diagnosis, insulin initiation and education) · Diabetes educator (technique, survival skills, especially new T1DM) · Social work/pharmacy (insulin affordability and access — addressing the root cause) · source-specific consults if there is a precipitant (ID, cardiology)

• First exclude DKA and HHS (gas, ketones, osmolality) — if present, treat per those pathways (see the DKA and HHS cards); this card is significant hyperglycemia without those emergencies

• Glucose control (inpatient — insulin is the mainstay; avoid sliding-scale-only therapy):

• • Basal-bolus (preferred) for most: a weight-based total daily dose (e.g. ~0.4–0.5 units/kg/day, lower if insulin-naïve, elderly, or with CKD) split into ~50% basal (glargine, detemir, or degludec once daily) and ~50% rapid-acting (lispro, aspart) divided with meals, plus a correction scale of rapid-acting insulin for highs

• • Adjust daily based on glucose trends; avoid sliding-scale insulin alone (reactive, poor control)

• • Targets (non-critical inpatient): generally about 140–180 mg/dL; avoid hypoglycemia (individualize, looser if frail or elderly)

• • NPO or enteral feeds: continue basal, matching nutritional insulin to intake

• Treat the precipitant: infection (cultures and antibiotics per source), steroids (adjust insulin upward, anticipating hyperglycemia), and MI or illness; address the trigger or glucose won't stay controlled

• New-onset diabetes workup and classification: C-peptide and autoantibodies if the type is unclear; if T1DM or ketosis-prone → insulin with diabetes-survival-skills education (never a sulfonylurea or metformin alone); T2DM → an individualized regimen

• Address nonadherence at the root: identify why (cost, access, fear, technique, depression) → social work and pharmacy for insulin affordability, regimen simplification, education, and follow-up — discharge without this just bounces back

• PT/OT: usually not needed; diabetes self-management education is central

• Trend: point-of-care glucose (before meals and at bedtime), resolution of any gap or ketones, the response to the regimen, precipitant resolution, and A1c for baseline

• Escalation triggers: evolving DKA or HHS (a rising gap, ketones, altered mental status, rising osmolality) → switch to the emergency pathway with possible ICU; persistent severe hyperglycemia despite escalation → endocrine and reassess the precipitant; severe infection or sepsis → the source pathway and ICU

• Discharge checklist: glucose improving, the precipitant addressed, and a clear home regimen; an insulin or oral regimen with doses and a titration plan, with affordability and access secured (the key to preventing readmission); a glucometer or CGM with supplies and technique taught; diabetes education (survival skills if new); hypoglycemia counseling; an A1c-based plan; PCP and endocrine follow-up; sick-day rules; return precautions for vomiting, abdominal pain, very high or low glucose, confusion, or signs of infection

Red Flags

• An anion-gap acidosis with ketones → DKA; switch to the DKA pathway (and check even in T2DM)

• Very high glucose and osmolality with altered mental status → HHS

• Euglycemic DKA on an SGLT2 inhibitor → a normal-ish glucose hides a gap acidosis

• A new ketosis-prone presentation → likely T1DM; insulin, not oral agents

• Insulin nonadherence from cost → the readmission driver; engage pharmacy and social work

Senior IM Resident Pearls

• "Just hyperglycemia" is a diagnosis of exclusion. A gas, ketones, and an osmolality rule out DKA and HHS, both of which can hide behind an unremarkable high glucose.

• Euglycemic DKA is the sneakiest miss. On an SGLT2 inhibitor, a near-normal glucose can mask a full anion-gap ketoacidosis — check the gas.

• Noncompliance usually means unaffordable. A huge share of "nonadherence" is cost — get pharmacy and social work involved or the patient returns next week.

• Basal-bolus beats sliding-scale-only. Sliding scale alone reactively chases highs after they happen; scheduled basal and nutritional insulin actually controls glucose.

• Classify new diabetes before choosing therapy. A ketosis-prone, antibody-positive patient has T1DM and needs insulin, not a sulfonylurea.

• Steroids drive predictable hyperglycemia. Anticipate it and uptitrate insulin proactively rather than reacting to the spikes.

• Common mistake: discharging on a fancier regimen without fixing the access barrier — the technical fix fails if the patient still can't get or afford the insulin.

Endocrinology — Hyperglycemic Emergency

102. Diabetic Ketoacidosis (DKA)

T1DM · ketosis-prone T2DM · infection-triggered · the triad: hyperglycemia + anion-gap acidosis + ketosis · fluids → potassium → insulin · close the gap, don't just lower glucose · Super Compact

Sx: polyuria/polydipsia, nausea/vomiting, abdominal pain, Kussmaul (deep) respirations, fruity/acetone breath, dehydration, weakness, AMS (severity-dependent); often a precipitant (infection, missed insulin, new T1DM, MI) · (DKA is defined by the acidosis + ketosis, not the glucose number — the treatment endpoint is closing the anion gap, NOT just normalizing glucose, and euglycemic DKA exists, especially on SGLT2 inhibitors)

Neg: denies stopping insulin when glucose normalizes but gap still open (must continue insulin + add dextrose — stopping early relapses the ketosis) · denies missed hypokalemia before insulin (insulin drives K⁺ into cells — giving insulin with low K⁺ can cause fatal arrhythmia) · denies missed precipitant (the "I"s: infection, infarction, insulin omission, etc.) · denies missed euglycemic DKA · denies missed cerebral edema (esp children)

SHx: diabetes type (esp T1DM), insulin regimen + adherence/access, prior DKA episodes, recent illness/infection/symptoms, SGLT2-inhibitor use (euglycemic DKA), alcohol, pregnancy, new-onset presentation, pump malfunction

Etiology: absolute/relative insulin deficiency + counterregulatory hormone excess (glucagon, catecholamines, cortisol) → unrestrained lipolysis → ketone-body (beta-hydroxybutyrate) overproduction → high-anion-gap metabolic acidosis + osmotic diuresis (volume + electrolyte depletion) · precipitants: infection (most common), insulin omission/nonadherence, new-onset T1DM, MI/stroke, pancreatitis, drugs (steroids, SGLT2i — euglycemic), pump failure

RF: T1DM · insulin nonadherence/access barriers · infection/acute illness · new diagnosis · SGLT2 inhibitor · pump use · prior DKA

Data: glucose, BMP (anion gap, K⁺, bicarbonate), venous blood gas (pH), serum beta-hydroxybutyrate (preferred ketone) or urine ketones, serum osmolality · diagnostic triad: glucose >250 (or euglycemic), pH/bicarb low with elevated anion gap, ketonemia · precipitant workup: CBC, cultures/UA/CXR (infection), ECG + troponin (MI), lipase, pregnancy test; phosphate, magnesium; monitor: glucose q1h, BMP/gas/K⁺ q2–4h

DDx: DKA · HHS (higher glucose/osm, minimal ketosis/acidosis — overlap exists) · starvation/alcoholic ketoacidosis (less hyperglycemia) · lactic acidosis · toxic alcohol ingestion (high osm gap) · other high-anion-gap acidosis (uremia, salicylates) · sepsis

Home Meds: hold home oral agents/non-insulin during acute DKA; hold SGLT2 inhibitor (causative/euglycemic DKA); transition to subcutaneous insulin only after gap closed; reconcile + restart home insulin with overlap; hold nephrotoxins; address access barriers at discharge

Plan

CONSULT: ICU/step-down (severe DKA — pH <7.0, hemodynamic instability, AMS, refractory) · Endocrinology (management, transition, recurrent DKA, new T1DM) · ID/source-specific (precipitant infection) · Cardiology (MI trigger) · Social work/pharmacy (insulin access — prevents recurrent DKA)

– 1) IV FLUIDS first (volume resuscitation): isotonic saline (0.9% NaCl) ~1 L bolus, then ~250–500 mL/h; switch to 0.45% NaCl if corrected sodium normal/high; add dextrose (D5) to fluids once glucose ~200–250 mg/dL (allows continued insulin to clear ketones without hypoglycemia)
– 2) POTASSIUM — check BEFORE and during insulin (critical):
  • K⁺ <3.3 → HOLD insulin, replete potassium first (insulin would worsen life-threatening hypokalemia)
  • K⁺ 3.3–5.0 → give insulin AND add potassium (e.g. 20–30 mEq/L) to maintain 4–5
  • K⁺ >5.0 → insulin, no potassium yet; recheck (total-body K⁺ is depleted despite the number)
– 3) INSULIN (after K⁺ checked): regular insulin IV infusion ~0.1 units/kg/h (± initial bolus per protocol); titrate to lower glucose ~50–75 mg/dL/h + close the anion gap; do NOT stop the insulin infusion when glucose normalizes if gap still open — instead add/increase dextrose and continue insulin until ketoacidosis resolves
– RESOLUTION CRITERIA (the real endpoint): anion gap closed + bicarbonate ≥15–18 + pH >7.3 + ketones clearing + patient eating — glucose alone does not define resolution
– TRANSITION to subcutaneous insulin: once resolution criteria met + tolerating PO → give basal (long-acting) insulin 1–2 h BEFORE stopping the IV infusion (overlap prevents rebound ketosis), then basal-bolus regimen
– TREAT THE PRECIPITANT: infection (cultures + antibiotics), MI, etc. — DKA won't resolve smoothly with an untreated trigger
– Bicarbonate: generally NOT recommended; consider only for severe acidosis (pH <6.9) per protocol · phosphate: replace only if severe (<1.0) or symptomatic · magnesium as needed
– Three rules keep DKA care safe. First, the sequence is fluids, then potassium, then insulin — and you check the potassium before the first unit of insulin, because insulin shifts K⁺ into cells and giving it to a hypokalemic patient can stop the heart. Second, the endpoint is the closed anion gap, not the glucose: when sugar falls to ~200 you add dextrose and keep the insulin running, because stopping it because "the sugar's normal" relapses the ketosis. Third, overlap the basal insulin with the drip before you turn the drip off, or the patient rebounds. And always hunt the precipitant — infection most often — and watch for euglycemic DKA on SGLT2 inhibitors, where the glucose lies but the gas tells the truth.
– PT/OT: usually not needed acutely; diabetes education before discharge
– Trend: glucose q1h, anion gap/bicarbonate/K⁺ q2–4h, pH, ketones (BHB), mental status, volume status/urine output, precipitant resolution
– Escalation triggers: severe acidosis (pH <7.0)/AMS/instability → ICU; refractory acidosis or not closing the gap → reassess (insulin delivery, ongoing precipitant, alternative dx) + endocrine; cerebral edema signs (headache, declining mentation — esp young) → emergent neuro/ICU + mannitol/hypertonic per protocol; cardiac arrhythmia (K⁺) → ICU
– Discharge checklist: gap closed + on stable subcutaneous regimen + precipitant treated; insulin regimen with doses + sick-day rules (never stop insulin when ill) + access/affordability SECURED; glucometer/CGM + supplies + technique; diabetes/ketone-monitoring education; SGLT2 inhibitor reconsideration if it triggered euglycemic DKA; endocrine + PCP follow-up; return precautions (vomiting, can't keep fluids down, high glucose + ketones, rapid breathing, abdominal pain, confusion)

102. Diabetic Ketoacidosis (DKA)

complete reference · T1DM + ketosis-prone T2DM + infection-triggered · fluids → potassium → insulin, close the gap, overlap basal before stopping the drip · Full Card

Symptoms / Associated Sx

• Polyuria and polydipsia, nausea, vomiting, and abdominal pain, Kussmaul (deep) respirations, fruity or acetone breath, dehydration, weakness, and altered mental status (severity-dependent)

• There is often a precipitant (infection, missed insulin, new T1DM, MI)

• DKA is defined by the acidosis and ketosis, not the glucose number — the treatment endpoint is closing the anion gap, not just normalizing glucose, and euglycemic DKA exists, especially on SGLT2 inhibitors

Neg

• Pt denies stopping insulin when glucose normalizes but the gap is still open (must continue insulin and add dextrose — stopping early relapses the ketosis)

• Pt denies a missed hypokalemia before insulin (insulin drives potassium into cells — giving insulin with low potassium can cause a fatal arrhythmia)

• Pt denies a missed precipitant (the "I"s: infection, infarction, insulin omission), a missed euglycemic DKA, and a missed cerebral edema (especially in children)

Social History (SHx)

• Diabetes type (especially T1DM), the insulin regimen and adherence or access, and prior DKA episodes

• Recent illness, infection, or symptoms, and SGLT2-inhibitor use (euglycemic DKA)

• Alcohol, pregnancy, a new-onset presentation, and pump malfunction

Main Etiology

• Absolute or relative insulin deficiency with counterregulatory hormone excess (glucagon, catecholamines, cortisol) drives unrestrained lipolysis, ketone-body (beta-hydroxybutyrate) overproduction, a high-anion-gap metabolic acidosis, and an osmotic diuresis (volume and electrolyte depletion)

• Precipitants: infection (the most common), insulin omission or nonadherence, new-onset T1DM, MI or stroke, pancreatitis, drugs (steroids, SGLT2 inhibitors — euglycemic), and pump failure

RF

• Modifiable: insulin nonadherence or access barriers, SGLT2-inhibitor use, and pump use

• Non-modifiable: T1DM, intercurrent infection or illness, a new diagnosis, and prior DKA

Data

• Glucose, a BMP (anion gap, potassium, bicarbonate), a venous blood gas (pH), serum beta-hydroxybutyrate (the preferred ketone) or urine ketones, and serum osmolality

• The diagnostic triad: glucose above 250 (or euglycemic), a low pH and bicarbonate with an elevated anion gap, and ketonemia

• Precipitant workup: CBC, cultures/urinalysis/CXR (infection), an ECG and troponin (MI), lipase, and a pregnancy test; phosphate and magnesium

• Monitor: glucose hourly, and the BMP, gas, and potassium every 2–4 hours

DDx

DKA · HHS (higher glucose and osmolality, minimal ketosis or acidosis — overlap exists) · starvation or alcoholic ketoacidosis (less hyperglycemia) · lactic acidosis · toxic alcohol ingestion (a high osmolar gap) · another high-anion-gap acidosis (uremia, salicylates) · sepsis

Home Meds

• Hold home oral agents and non-insulin agents during acute DKA, and hold the SGLT2 inhibitor (a cause of euglycemic DKA)

• Transition to subcutaneous insulin only after the gap is closed; reconcile and restart home insulin with overlap

• Hold nephrotoxins and address access barriers at discharge

Plan

CONSULT: ICU or step-down (severe DKA — pH below 7.0, hemodynamic instability, altered mental status, refractory disease) · Endocrinology (management, transition, recurrent DKA, new T1DM) · ID or source-specific (a precipitant infection) · Cardiology (an MI trigger) · Social work/pharmacy (insulin access — prevents recurrent DKA)

• 1) IV fluids first (volume resuscitation): isotonic saline (0.9% NaCl) ~1 L bolus, then ~250–500 mL/h; switch to 0.45% NaCl if the corrected sodium is normal or high; add dextrose (D5) to fluids once glucose reaches ~200–250 mg/dL (allowing continued insulin to clear ketones without causing hypoglycemia)

• 2) Potassium — check before and during insulin (critical):

• • K⁺ below 3.3 → hold insulin and replete potassium first (insulin would worsen life-threatening hypokalemia)

• • K⁺ 3.3–5.0 → give insulin and add potassium (e.g. 20–30 mEq/L) to maintain 4–5

• • K⁺ above 5.0 → give insulin, no potassium yet; recheck (total-body potassium is depleted despite the number)

• 3) Insulin (after potassium is checked): a regular insulin IV infusion at ~0.1 units/kg/h (with an initial bolus per protocol); titrate to lower glucose by ~50–75 mg/dL/h and close the anion gap; do not stop the insulin infusion when glucose normalizes if the gap is still open — instead add or increase dextrose and continue insulin until the ketoacidosis resolves

• Resolution criteria (the real endpoint): the anion gap closed, bicarbonate ≥15–18, pH above 7.3, ketones clearing, and the patient eating — glucose alone does not define resolution

• Transition to subcutaneous insulin: once resolution criteria are met and the patient is tolerating oral intake → give basal (long-acting) insulin 1–2 hours before stopping the IV infusion (the overlap prevents rebound ketosis), then a basal-bolus regimen

• Treat the precipitant: infection (cultures and antibiotics), MI, and others — DKA won't resolve smoothly with an untreated trigger

• Bicarbonate: generally not recommended; consider only for severe acidosis (pH below 6.9) per protocol. Phosphate: replace only if severe (below 1.0) or symptomatic. Magnesium: as needed

• PT/OT: usually not needed acutely; diabetes education before discharge

• Trend: glucose hourly, the anion gap, bicarbonate, and potassium every 2–4 hours, pH, ketones (BHB), mental status, volume status and urine output, and precipitant resolution

• Escalation triggers: severe acidosis (pH below 7.0), altered mental status, or instability → ICU; refractory acidosis or failure to close the gap → reassess (insulin delivery, an ongoing precipitant, an alternative diagnosis) with endocrine; signs of cerebral edema (headache, declining mentation — especially in the young) → emergent neuro/ICU with mannitol or hypertonic saline per protocol; a cardiac arrhythmia (potassium) → ICU

• Discharge checklist: the gap closed, on a stable subcutaneous regimen, with the precipitant treated; an insulin regimen with doses, sick-day rules (never stop insulin when ill), and access and affordability secured; a glucometer or CGM with supplies and technique; diabetes and ketone-monitoring education; reconsideration of the SGLT2 inhibitor if it triggered euglycemic DKA; endocrine and PCP follow-up; return precautions for vomiting, inability to keep fluids down, high glucose with ketones, rapid breathing, abdominal pain, or confusion

Red Flags

• Potassium below 3.3 → hold insulin and replete first; insulin would precipitate a fatal arrhythmia

• Glucose normalized but the gap still open → add dextrose and continue insulin; don't stop the drip

• pH below 7.0, altered mental status, or instability → ICU

• Headache or declining mentation, especially in the young → cerebral edema; emergent treatment

• Euglycemic DKA on an SGLT2 inhibitor → the glucose lies; the gas reveals the acidosis

Senior IM Resident Pearls

• The sequence is fluids, then potassium, then insulin. Check the potassium before the first unit — insulin shifts it into cells and can stop a hypokalemic heart.

• The endpoint is the closed gap, not the glucose. When sugar falls to ~200, add dextrose and keep the insulin running until the ketoacidosis resolves.

• Overlap the basal before stopping the drip. Give long-acting insulin 1–2 hours before turning off the infusion or the patient rebounds into ketosis.

• Always hunt the precipitant. Infection is the most common trigger — DKA won't resolve smoothly while the cause is untreated.

• Beta-hydroxybutyrate is the ketone to follow. Urine ketones lag and can mislead; serum BHB tracks resolution accurately.

• Euglycemic DKA on SGLT2 inhibitors is real. A near-normal glucose can hide a full ketoacidosis — believe the gas.

• Common mistake: bolusing bicarbonate for the acidosis — it isn't needed except at a pH below 6.9, and it can worsen hypokalemia and cerebral edema.

Endocrinology — Hyperglycemic Emergency

103. Hyperosmolar Hyperglycemic State (HHS)

profound hyperglycemia + hyperosmolality + severe dehydration + AMS, minimal ketosis · elderly T2DM · huge fluid deficit · correct osmolality slowly · Super Compact

Sx: profound dehydration, altered mental status (lethargy → coma, correlates with osmolality), focal neuro signs/seizures possible; polyuria/polydipsia over days–weeks, weakness; often elderly T2DM with impaired thirst/access to water · (HHS develops insidiously over days, producing enormous water deficits — the dominant problem is dehydration and hyperosmolality, and the mental status tracks the osmolality, so this is a slow, careful fluid resuscitation, not a glucose race)

Neg: denies missed precipitant (infection most common — pneumonia, UTI, sepsis; also MI, stroke, missed meds, new T2DM) · denies correcting osmolality/sodium too fast (rapid shifts risk cerebral edema) · denies missed concurrent DKA (overlap/mixed picture) · denies missed thromboembolism (hyperviscosity → VTE/stroke risk) · denies attributing AMS solely to HHS without excluding stroke

SHx: T2DM (often), age/frailty, impaired access to water (nursing home, dementia, immobility), recent infection/illness, medication adherence, diuretics/steroids, prior HHS, baseline cognition/functional status, new-onset diabetes

Etiology: relative insulin deficiency (enough to suppress ketogenesis but not hyperglycemia) + a precipitant + impaired water intake → marked hyperglycemia → osmotic diuresis → profound water/electrolyte loss → hyperosmolality + dehydration, often over days · precipitants: infection (most common), MI/stroke, medication nonadherence, new T2DM, drugs (steroids, diuretics), poor water access · minimal ketosis (residual insulin suppresses lipolysis)

RF: elderly/frail · impaired water access (dementia, institutionalized) · infection/acute illness · T2DM · diuretics/steroids · poor adherence

Data: glucose (often >600, can be >1000), serum osmolality (markedly elevated, typically >320 mOsm/kg), BMP (corrected Na⁺, K⁺), VBG/ketones (minimal — distinguishes from DKA) · precipitant workup: CBC, cultures/UA/CXR (infection), ECG + troponin, neuro imaging if focal/stroke suspicion · phosphate, magnesium, lactate; monitor glucose q1h, BMP/osm/K⁺ q2–4h

DDx: HHS · DKA (more acidosis/ketosis, often younger/T1DM) · mixed DKA-HHS · stroke/other neuro cause of AMS (must exclude — can coexist) · sepsis · hypernatremic dehydration · other hyperosmolar states

Home Meds: hold oral hypoglycemics/non-insulin during acute management; hold diuretics (worsen dehydration) + nephrotoxins; hold SGLT2 inhibitor; transition to insulin regimen; reconcile + restart with access plan; VTE prophylaxis (hyperviscosity thrombosis risk)

Plan

CONSULT: ICU/step-down (severe AMS, instability, severe osmolality) · Endocrinology (management, transition) · ID/source-specific (precipitant infection — often the trigger) · Neurology (if focal deficit/seizure/stroke concern) · Cardiology (MI trigger)

– AGGRESSIVE IV FLUID RESUSCITATION is the cornerstone (deficits often ~8–10 L — larger than DKA): isotonic saline (0.9% NaCl) ~1 L bolus(es) for initial volume/perfusion, then transition to 0.45% NaCl guided by corrected sodium + volume status; add dextrose (D5) once glucose ~250–300 mg/dL
– CORRECT OSMOLALITY/SODIUM GRADUALLY: aim to lower osmolality + corrected sodium slowly (avoid rapid shifts → cerebral edema); much of the glucose drop comes from fluids alone before insulin
– POTASSIUM (same principles as DKA): check before/during insulin; K⁺ <3.3 → hold insulin + replete; 3.3–5.0 → insulin + add K⁺ to maintain 4–5; >5.0 → insulin, no K⁺ yet, recheck
– INSULIN (lower-dose, AFTER fluids started + K⁺ checked): regular insulin IV infusion ~0.05–0.1 units/kg/h, titrate to lower glucose gradually (~50–75 mg/dL/h); fluids do much of the work — insulin is secondary in HHS; continue insulin + dextrose until osmolality normalizes + mental status recovers
– RESOLUTION (the endpoint): normal osmolality + recovered mental status + hemodynamic stability + adequate glucose control (target glucose ~250–300 during treatment, not lower, until osm corrected)
– TRANSITION: once osmolality normal + mentating + eating → overlap subcutaneous basal insulin before stopping the infusion → basal-bolus regimen
– TREAT THE PRECIPITANT + VTE PROPHYLAXIS: aggressive source workup/treatment (infection most common); prophylactic anticoagulation (hyperviscosity → high thrombosis/stroke/VTE risk); careful neuro monitoring
– HHS is a dehydration disease with a glucose problem riding along — the patient, usually an older person who couldn't get to water, has lost eight to ten liters, and the mental status tracks the osmolality, not the sugar. So the treatment is fluids, fluids, fluids, given carefully: correct the osmolality and sodium slowly because a fast shift can cause cerebral edema, and let the saline do most of the glucose-lowering before a modest insulin drip finishes the job. Don't aim the glucose too low too fast. Always find the trigger — infection most often — and remember these hyperviscous patients clot, so anticoagulate prophylactically and keep stroke on the differential for the altered mentation.
– PT/OT: often needed (elderly, deconditioned, prolonged AMS); functional + cognitive recovery, fall/delirium prevention
– Trend: glucose q1h, osmolality/corrected sodium/K⁺ q2–4h, mental status (should track osmolality recovery), volume status/urine output, precipitant resolution, neuro exam
– Escalation triggers: persistent/worsening AMS despite osmolality correction → neuro imaging (stroke?) + neuro/ICU; hemodynamic instability/severe osmolality → ICU; cerebral edema signs → emergent management; refractory hyperglycemia/ongoing precipitant → endocrine + reassess; new focal deficit → stroke workup
– Discharge checklist: osmolality + mentation recovered + on stable insulin regimen + precipitant treated; insulin regimen with doses, sick-day rules, hydration counseling + ENSURE WATER ACCESS (the recurrence driver in the frail/institutionalized); glucometer + supplies + education/caregiver involvement; functional/cognitive assessment + placement if needed; endocrine + PCP follow-up; return precautions (confusion, poor fluid intake, very high glucose, weakness, signs of infection)

103. Hyperosmolar Hyperglycemic State (HHS)

complete reference · severe dehydration + AMS + elderly · aggressive but gradual fluids, low-dose insulin, slow osmolality correction, VTE prophylaxis · Full Card

Symptoms / Associated Sx

• Profound dehydration, altered mental status (lethargy progressing to coma, correlating with osmolality), and possible focal neurologic signs or seizures

• Polyuria and polydipsia over days to weeks, and weakness

• Often an elderly patient with T2DM and impaired thirst or access to water

• HHS develops insidiously over days, producing enormous water deficits — the dominant problem is dehydration and hyperosmolality, and the mental status tracks the osmolality, so this is a slow, careful fluid resuscitation, not a glucose race

Neg

• Pt denies a missed precipitant (infection is the most common — pneumonia, UTI, sepsis; also MI, stroke, missed medications, new T2DM)

• Pt denies correcting osmolality or sodium too fast (rapid shifts risk cerebral edema) and a missed concurrent DKA (an overlap or mixed picture)

• Pt denies a missed thromboembolism (hyperviscosity → VTE and stroke risk) and attributing altered mental status solely to HHS without excluding stroke

Social History (SHx)

• T2DM (often), age and frailty, and impaired access to water (nursing home, dementia, immobility)

• Recent infection or illness, medication adherence, and diuretics or steroids

• Prior HHS, baseline cognition and functional status, and new-onset diabetes

Main Etiology

• Relative insulin deficiency (enough to suppress ketogenesis but not hyperglycemia), a precipitant, and impaired water intake drive marked hyperglycemia → osmotic diuresis → profound water and electrolyte loss → hyperosmolality and dehydration, often over days

• Precipitants: infection (the most common), MI or stroke, medication nonadherence, new T2DM, drugs (steroids, diuretics), and poor water access

• Minimal ketosis (residual insulin suppresses lipolysis)

RF

• Modifiable: impaired water access, diuretics or steroids, and poor adherence

• Non-modifiable: elderly or frail status, intercurrent infection or illness, and T2DM

Data

• Glucose (often above 600, sometimes above 1000), serum osmolality (markedly elevated, typically above 320 mOsm/kg), a BMP (corrected sodium, potassium), and a VBG with ketones (minimal — distinguishing from DKA)

• Precipitant workup: CBC, cultures/urinalysis/CXR (infection), an ECG and troponin, and neuro imaging if there is a focal deficit or stroke suspicion

• Phosphate, magnesium, and lactate

• Monitor glucose hourly and the BMP, osmolality, and potassium every 2–4 hours

DDx

HHS · DKA (more acidosis and ketosis, often younger or T1DM) · mixed DKA-HHS · stroke or another neurologic cause of altered mental status (must exclude — can coexist) · sepsis · hypernatremic dehydration · other hyperosmolar states

Home Meds

• Hold oral hypoglycemics and non-insulin agents during acute management, and hold diuretics (which worsen dehydration), nephrotoxins, and the SGLT2 inhibitor

• Transition to an insulin regimen; reconcile and restart with an access plan

• Give VTE prophylaxis (hyperviscosity thrombosis risk)

Plan

CONSULT: ICU or step-down (severe altered mental status, instability, severe osmolality) · Endocrinology (management, transition) · ID or source-specific (a precipitant infection — often the trigger) · Neurology (a focal deficit, seizure, or stroke concern) · Cardiology (an MI trigger)

• Aggressive IV fluid resuscitation is the cornerstone (deficits are often ~8–10 L — larger than DKA): isotonic saline (0.9% NaCl) ~1 L bolus(es) for initial volume and perfusion, then transition to 0.45% NaCl guided by the corrected sodium and volume status; add dextrose (D5) once glucose reaches ~250–300 mg/dL

• Correct osmolality and sodium gradually: aim to lower the osmolality and corrected sodium slowly (avoiding rapid shifts → cerebral edema); much of the glucose drop comes from fluids alone before insulin

• Potassium (the same principles as DKA): check before and during insulin; K⁺ below 3.3 → hold insulin and replete; 3.3–5.0 → insulin with added potassium to maintain 4–5; above 5.0 → insulin, no potassium yet, recheck

• Insulin (lower-dose, after fluids are started and potassium is checked): a regular insulin IV infusion at ~0.05–0.1 units/kg/h, titrated to lower glucose gradually (~50–75 mg/dL/h); fluids do much of the work — insulin is secondary in HHS; continue insulin with dextrose until osmolality normalizes and mental status recovers

• Resolution (the endpoint): normal osmolality, recovered mental status, hemodynamic stability, and adequate glucose control (a glucose target of ~250–300 during treatment, not lower, until osmolality is corrected)

• Transition: once osmolality is normal and the patient is mentating and eating → overlap subcutaneous basal insulin before stopping the infusion → a basal-bolus regimen

• Treat the precipitant and give VTE prophylaxis: an aggressive source workup and treatment (infection most common); prophylactic anticoagulation (hyperviscosity → high thrombosis, stroke, and VTE risk); and careful neuro monitoring

• PT/OT: often needed (elderly, deconditioned, prolonged altered mental status); functional and cognitive recovery, with fall and delirium prevention

• Trend: glucose hourly, osmolality, corrected sodium, and potassium every 2–4 hours, mental status (which should track osmolality recovery), volume status and urine output, precipitant resolution, and the neuro exam

• Escalation triggers: persistent or worsening altered mental status despite osmolality correction → neuro imaging (stroke?) with neuro/ICU; hemodynamic instability or severe osmolality → ICU; signs of cerebral edema → emergent management; refractory hyperglycemia or an ongoing precipitant → endocrine and reassessment; a new focal deficit → a stroke workup

• Discharge checklist: osmolality and mentation recovered, on a stable insulin regimen, with the precipitant treated; an insulin regimen with doses, sick-day rules, and hydration counseling, ensuring water access (the recurrence driver in the frail or institutionalized); a glucometer with supplies and education and caregiver involvement; a functional and cognitive assessment with placement if needed; endocrine and PCP follow-up; return precautions for confusion, poor fluid intake, very high glucose, weakness, or signs of infection

Red Flags

• Rapid correction of osmolality or sodium → cerebral edema; correct slowly

• Persistent altered mental status after osmolality correction → image for stroke (which can coexist)

• Hyperviscosity → high VTE and stroke risk; give prophylactic anticoagulation

• A missed precipitant (infection most common) → HHS won't resolve while the trigger is untreated

• Potassium below 3.3 → hold insulin and replete first (as in DKA)

Senior IM Resident Pearls

• HHS is a dehydration disease with a glucose problem along for the ride. The deficit is eight to ten liters, and the mental status tracks the osmolality, not the sugar.

• Fluids do most of the work. Let saline bring the glucose down before a modest insulin drip finishes the job — insulin is secondary here.

• Correct slowly. Lower osmolality and sodium gradually, because a fast shift risks cerebral edema; don't aim the glucose too low too fast.

• Anticoagulate prophylactically. These hyperviscous patients clot — VTE, stroke, and arterial events are real risks.

• Keep stroke on the differential. If the mentation doesn't recover as the osmolality normalizes, image the head.

• Find the trigger and fix water access. Infection is the usual precipitant, and the frail patient who couldn't reach water will return without an access plan.

• Common mistake: running a DKA-style high-dose insulin drip in HHS — it drops glucose too fast relative to the fluid resuscitation and risks dangerous osmotic shifts.

Endocrinology — Glucose Emergency

104. Hypoglycemia

insulin-related · sulfonylurea-related · poor oral intake · treat first then investigate · sulfonylurea + renal failure = prolonged, admit · octreotide for refractory SU hypoglycemia · Super Compact

Sx: adrenergic (early): tremor, sweating, palpitations, anxiety, hunger; neuroglycopenic (lower glucose): confusion, behavioral change, slurred speech, seizures, focal deficits, coma · Whipple triad: symptoms + low glucose + relief with correction · hypoglycemia unawareness (recurrent lows/autonomic neuropathy/beta-blockers blunt warning symptoms) · (treat the low glucose immediately — don't wait for confirmation in a symptomatic patient — then ask WHY, because a sulfonylurea or a long-acting insulin will keep dropping the glucose for many hours)

Neg: denies discharging sulfonylurea-induced hypoglycemia early (long duration + renal impairment → prolonged/recurrent lows over 24–72h — ADMIT + observe) · denies missed cause (insulin error, renal failure reducing clearance, poor intake/missed meal, sepsis, adrenal insufficiency, alcohol, liver failure) · denies missed factitious/surreptitious cause · denies inadequate ongoing dextrose after initial correction

SHx: diabetes meds (insulin doses/timing, sulfonylureas — esp glyburide/glipizide), renal/hepatic function (reduced drug + insulin clearance), recent reduced intake/NPO/missed meals, alcohol use, recent med changes, prior severe hypoglycemia/unawareness, weight loss; non-diabetic causes (insulinoma, adrenal insufficiency, sepsis)

Etiology: glucose supply < demand/utilization · most common inpatient: medication (insulin or insulin secretagogue) excess relative to intake · amplifiers: renal failure (↓insulin + ↓sulfonylurea clearance → prolonged), poor/absent intake (NPO, missed meals, anorexia), liver failure (↓gluconeogenesis), sepsis, adrenal insufficiency, alcohol (blocks gluconeogenesis) · non-diabetic: insulinoma, post-bariatric, factitious

RF: insulin/sulfonylurea use · renal/hepatic impairment · poor intake/NPO · elderly · alcohol · tight glycemic targets · hypoglycemia unawareness · sepsis/critical illness

Data: point-of-care + confirmatory lab glucose · if cause unclear or non-diabetic: during hypoglycemia draw insulin, C-peptide, proinsulin, beta-hydroxybutyrate, sulfonylurea screen, cortisol (differentiates exogenous insulin vs secretagogue vs insulinoma vs deficiency) · renal/hepatic function, CBC/cultures if sepsis; review med administration record (insulin/SU errors)

DDx: medication (insulin/sulfonylurea) hypoglycemia · poor intake/starvation · renal-failure-prolonged hypoglycemia · adrenal insufficiency · sepsis · alcohol-related · liver failure · insulinoma · post-bariatric/reactive · factitious/surreptitious

Home Meds: hold the offending agent (insulin/sulfonylurea); review + reduce/adjust diabetes regimen; reconcile interacting drugs; renally/hepatically adjust; reassess glycemic targets (looser if elderly/CKD/recurrent lows); restart cautiously with education

Plan

CONSULT: Endocrinology (recurrent/refractory/unclear cause, regimen redesign, suspected insulinoma) · ICU (refractory/severe with instability) · Social work/pharmacy (medication errors, access, education) · source-specific (sepsis, adrenal — if underlying)

– TREAT IMMEDIATELY (don't wait for labs in a symptomatic patient):
  • Conscious + able to swallow: 15–20 g fast oral carbohydrate (juice, glucose tabs), recheck in 15 min, repeat if still low, then give a meal/complex carb
  • Unable to take PO / severe / unconscious: D50 IV (~25 g, 1 amp) via IV access; if no IV access → glucagon 1 mg IM/SC (less effective in glycogen-depleted/alcoholic/liver failure)
  • Then START/CONTINUE a dextrose infusion (D5 or D10) for ongoing/recurrent risk — a single amp wears off fast
– FIND + ADDRESS THE CAUSE: hold the offending agent; correct/treat the amplifier (renal failure, sepsis, adrenal insufficiency, poor intake); send the diagnostic labs (insulin/C-peptide/SU screen) DURING a low if cause unclear
– SULFONYLUREA-INDUCED HYPOGLYCEMIA (special handling): ADMIT for observation 24–72h (effect outlasts a single correction, esp with renal impairment); maintain dextrose infusion + frequent glucose checks; for refractory/recurrent SU hypoglycemia → octreotide (suppresses insulin secretion — the specific antidote, reduces dextrose requirement + recurrence); avoid over-reliance on repeated dextrose boluses alone
– LONG-ACTING INSULIN overdose: prolonged risk → continuous dextrose + extended monitoring until the insulin effect resolves
– PREVENT RECURRENCE: adjust regimen (reduce/hold agent, change to lower-risk agent), liberalize targets in the vulnerable, treat underlying illness, education + glucagon kit (for insulin users) at discharge
– Hypoglycemia is treat-first, investigate-second: give the sugar the moment a patient is symptomatic, then add a dextrose infusion because a single amp of D50 wears off in minutes. The trap that catches people is the sulfonylurea, especially in a patient with renal failure — its effect lasts for many hours, so the glucose you "fixed" drops again, which is exactly why these patients get admitted and observed for a day or more, and why octreotide is the specific antidote for the refractory ones. Always ask why the glucose was low: a missed meal, a renal failure that's now retaining insulin, an unrecognized adrenal insufficiency, or a medication error — and fix that, not just the number.
– PT/OT: usually not needed; fall risk if neuroglycopenia/elderly
– Trend: serial glucose (frequent, esp after sulfonylurea/long-acting insulin), mental status/symptom resolution, dextrose requirement, cause-specific markers, recurrence
– Escalation triggers: refractory/recurrent hypoglycemia despite dextrose → octreotide (if SU) + ICU + endocrine + reassess cause; persistent neuroglycopenia/seizures → ICU; suspected insulinoma/factitious → endocrine workup; underlying sepsis/adrenal crisis → respective pathway
– Discharge checklist: euglycemic off offending agent + cause addressed + NO recurrent lows for an appropriate observation period (longer for SU); revised diabetes regimen with reduced hypoglycemia risk + liberalized targets if vulnerable; glucagon kit + education (patient + caregiver) for insulin users; hypoglycemia-unawareness counseling; access/affordability + meal-pattern plan; endocrine/PCP follow-up; return precautions (recurrent lows, confusion, inability to eat, seizures)

104. Hypoglycemia

complete reference · insulin + sulfonylurea + poor intake · treat first, dextrose infusion, admit + octreotide for sulfonylurea, find and fix the cause · Full Card

Symptoms / Associated Sx

• Adrenergic (early): tremor, sweating, palpitations, anxiety, and hunger

• Neuroglycopenic (with lower glucose): confusion, behavioral change, slurred speech, seizures, focal deficits, and coma

• Whipple triad: symptoms with a low glucose and relief with correction

• Hypoglycemia unawareness (recurrent lows, autonomic neuropathy, or beta-blockers blunt the warning symptoms)

• Treat the low glucose immediately — don't wait for confirmation in a symptomatic patient — then ask why, because a sulfonylurea or a long-acting insulin will keep dropping the glucose for many hours

Neg

• Pt denies discharging sulfonylurea-induced hypoglycemia early (the long duration plus renal impairment causes prolonged or recurrent lows over 24–72 hours — admit and observe)

• Pt denies a missed cause (an insulin error, renal failure reducing clearance, poor intake or a missed meal, sepsis, adrenal insufficiency, alcohol, liver failure)

• Pt denies a missed factitious or surreptitious cause and inadequate ongoing dextrose after the initial correction

Social History (SHx)

• Diabetes medications (insulin doses and timing, sulfonylureas — especially glyburide and glipizide), and renal or hepatic function (reduced drug and insulin clearance)

• Recent reduced intake, NPO status, or missed meals, alcohol use, and recent medication changes

• Prior severe hypoglycemia or unawareness, and weight loss; non-diabetic causes (insulinoma, adrenal insufficiency, sepsis)

Main Etiology

• Glucose supply falls below demand or utilization

• The most common inpatient cause is medication (insulin or an insulin secretagogue) excess relative to intake

• Amplifiers: renal failure (reduced insulin and sulfonylurea clearance → prolonged lows), poor or absent intake (NPO, missed meals, anorexia), liver failure (reduced gluconeogenesis), sepsis, adrenal insufficiency, and alcohol (which blocks gluconeogenesis)

• Non-diabetic causes: insulinoma, post-bariatric, and factitious hypoglycemia

RF

• Modifiable: insulin or sulfonylurea use, tight glycemic targets, and alcohol

• Non-modifiable: renal or hepatic impairment, poor intake or NPO status, elderly status, hypoglycemia unawareness, and sepsis or critical illness

Data

• Point-of-care plus confirmatory laboratory glucose

• If the cause is unclear or non-diabetic: during hypoglycemia, draw insulin, C-peptide, proinsulin, beta-hydroxybutyrate, a sulfonylurea screen, and cortisol (differentiating exogenous insulin from a secretagogue, insulinoma, or deficiency)

• Renal and hepatic function, CBC and cultures if sepsis; review the medication administration record (insulin and sulfonylurea errors)

DDx

Medication (insulin or sulfonylurea) hypoglycemia · poor intake or starvation · renal-failure-prolonged hypoglycemia · adrenal insufficiency · sepsis · alcohol-related hypoglycemia · liver failure · insulinoma · post-bariatric or reactive hypoglycemia · factitious or surreptitious hypoglycemia

Home Meds

• Hold the offending agent (insulin or sulfonylurea)

• Review, reduce, and adjust the diabetes regimen; reconcile interacting drugs; adjust renally and hepatically

• Reassess glycemic targets (looser if elderly, CKD, or recurrent lows) and restart cautiously with education

Plan

CONSULT: Endocrinology (recurrent, refractory, or unclear-cause hypoglycemia, regimen redesign, suspected insulinoma) · ICU (refractory or severe with instability) · Social work/pharmacy (medication errors, access, education) · source-specific (sepsis, adrenal disease — if underlying)

• Treat immediately (don't wait for labs in a symptomatic patient):

• • Conscious and able to swallow: 15–20 g of fast oral carbohydrate (juice, glucose tablets), recheck in 15 minutes, repeat if still low, then give a meal or complex carbohydrate

• • Unable to take oral intake, severe, or unconscious: D50 IV (~25 g, 1 amp) via IV access; if there is no IV access → glucagon 1 mg IM/SC (less effective in glycogen-depleted, alcoholic, or liver-failure patients)

• • Then start or continue a dextrose infusion (D5 or D10) for ongoing or recurrent risk — a single amp wears off fast

• Find and address the cause: hold the offending agent; correct or treat the amplifier (renal failure, sepsis, adrenal insufficiency, poor intake); and send the diagnostic labs (insulin, C-peptide, sulfonylurea screen) during a low if the cause is unclear

• Sulfonylurea-induced hypoglycemia (special handling): admit for observation 24–72 hours (the effect outlasts a single correction, especially with renal impairment); maintain a dextrose infusion with frequent glucose checks; for refractory or recurrent sulfonylurea hypoglycemia → octreotide (which suppresses insulin secretion — the specific antidote, reducing the dextrose requirement and recurrence); avoid over-reliance on repeated dextrose boluses alone

• Long-acting insulin overdose: a prolonged risk → continuous dextrose with extended monitoring until the insulin effect resolves

• Prevent recurrence: adjust the regimen (reduce or hold the agent, change to a lower-risk agent), liberalize targets in the vulnerable, treat the underlying illness, and provide education and a glucagon kit (for insulin users) at discharge

• PT/OT: usually not needed; fall risk if there is neuroglycopenia or elderly status

• Trend: serial glucose (frequent, especially after a sulfonylurea or long-acting insulin), mental status and symptom resolution, the dextrose requirement, cause-specific markers, and recurrence

• Escalation triggers: refractory or recurrent hypoglycemia despite dextrose → octreotide (if sulfonylurea), ICU, endocrine, and reassessment of the cause; persistent neuroglycopenia or seizures → ICU; suspected insulinoma or factitious disease → an endocrine workup; underlying sepsis or adrenal crisis → the respective pathway

• Discharge checklist: euglycemic off the offending agent, the cause addressed, and no recurrent lows for an appropriate observation period (longer for sulfonylureas); a revised diabetes regimen with reduced hypoglycemia risk and liberalized targets if vulnerable; a glucagon kit and education (patient and caregiver) for insulin users; hypoglycemia-unawareness counseling; an access, affordability, and meal-pattern plan; endocrine and PCP follow-up; return precautions for recurrent lows, confusion, inability to eat, or seizures

Red Flags

• Sulfonylurea hypoglycemia, especially with renal impairment → prolonged and recurrent; admit, observe 24–72 hours, and use octreotide if refractory

• A single dextrose bolus without an infusion → wears off in minutes; the glucose drops again

• Long-acting insulin overdose → a prolonged risk needing extended dextrose and monitoring

• Persistent neuroglycopenia or seizures → ICU-level care

• Unexplained hypoglycemia in a non-diabetic → draw insulin, C-peptide, and a sulfonylurea screen during the low

Senior IM Resident Pearls

• Treat first, investigate second. Give the sugar the moment a patient is symptomatic, then add a dextrose infusion because a single amp of D50 wears off in minutes.

• The sulfonylurea is the trap. Its effect lasts hours — longer with renal failure — so these patients get admitted and observed, and octreotide is the specific antidote for the refractory ones.

• Always ask why. A missed meal, a renal failure now retaining insulin, an unrecognized adrenal insufficiency, or a medication error — fix the cause, not just the number.

• Draw the diagnostic labs during the low. Insulin, C-peptide, and a sulfonylurea screen drawn while hypoglycemic distinguish exogenous insulin, a secretagogue, and an insulinoma.

• Glucagon needs glycogen. It's less effective in alcoholic, malnourished, or liver-failure patients who lack the glycogen stores it mobilizes.

• Liberalize targets in the vulnerable. The elderly or CKD patient with recurrent lows is better served by looser glucose goals than by tight control that keeps causing hypoglycemia.

• Common mistake: sending a sulfonylurea patient home after the glucose normalizes once — the drug outlasts the correction, and they return obtunded hours later.

Endocrinology — Diabetes

105. Diabetes-Related Infection

diabetic foot infection · cellulitis · osteomyelitis · the endocrine view: glucose control + the infection feed each other · co-manage with ID + surgery · Super Compact

Sx: local infection signs (foot ulcer + erythema/drainage, cellulitis, deep abscess) often with blunted systemic response (neuropathy + vascular disease mask pain/fever); uncontrolled hyperglycemia as the presenting clue (an unexplained sugar spike often signals an occult infection) · severe/necrotizing/limb-threatening features · (in a diabetic, a sudden loss of glucose control with no other explanation is an infection until proven otherwise — and the infection and the hyperglycemia worsen each other in a vicious cycle, so you must break both)

Neg: denies missed deep infection/osteomyelitis (probe-to-bone, chronic ulcer → image) · denies missed critical limb ischemia (won't heal without revascularization) · denies missed necrotizing infection/emphysematous infection (surgical emergency) · denies treating infection without controlling glucose (impairs immunity/healing) · denies missed DKA/HHS triggered BY the infection · denies under-recognizing severity (blunted signs)

SHx: diabetes control (A1c), neuropathy, peripheral arterial disease, prior foot ulcers/amputations/infections, prior MRSA/resistant organisms, immunosuppression, glycemic-control barriers, smoking, footwear/self-care, recurrent infections (poor control marker)

Etiology: hyperglycemia impairs neutrophil function/immunity + microvascular disease impairs perfusion/healing + neuropathy enables unrecognized injury → increased susceptibility + severity + poor healing · diabetes-associated/severe infections: foot infections (often polymicrobial), osteomyelitis, emphysematous pyelonephritis/cholecystitis, mucormycosis (DKA), necrotizing infections, malignant otitis externa

RF: poor glycemic control · neuropathy/PAD · prior ulcer/amputation · immunosuppression · smoking · prior resistant organisms · recurrent infection

Data: glucose/A1c, BMP + gas/ketones (infection often precipitates DKA/HHS), CBC, ESR/CRP, blood cultures if systemic · infection-specific: deep/bone culture (not swab), X-ray/MRI for osteomyelitis, probe-to-bone, vascular assessment (ABI/perfusion), imaging for abscess/gas · lactate; source-directed workup (UA, CXR, etc.)

DDx: diabetic foot infection/cellulitis/osteomyelitis · necrotizing soft tissue infection · emphysematous pyelonephritis/cholecystitis · mucormycosis (DKA, rhino-orbital — emergency) · malignant otitis externa · Charcot foot (mimics infection) · critical limb ischemia · sepsis from any source

Home Meds: optimize glucose (usually insulin inpatient — basal-bolus); hold metformin if AKI/sepsis/contrast; reconcile + renally dose antibiotics (ID-directed); continue PAD meds (statin/antiplatelet); address smoking; resume tailored regimen at discharge

Plan

CONSULT: Infectious Disease (antibiotic selection/duration — these are frequently co-managed) · Surgery/Podiatry (debridement, drainage, source control, amputation decisions) · Vascular Surgery (ischemia → revascularization) · Endocrinology/glycemic team (glucose control) · Wound care/PT (offloading)

– BREAK THE VICIOUS CYCLE — control glucose AND treat infection together:
  • GLYCEMIC CONTROL (the endocrine job): basal-bolus insulin (target ~140–180 mg/dL inpatient), anticipate higher insulin needs during infection, rule out + treat infection-triggered DKA/HHS (check gas/ketones/osm); good control improves immune function + healing
  • INFECTION TREATMENT (ID + surgery co-managed): source control (debride/drain/revascularize), culture-directed antibiotics — for limb-threatening/polymicrobial foot infection, broad coverage per local formulary (e.g. cefepime + metronidazole + vancomycin); tailor to ID + cultures + the specific infection (see diabetic foot, osteomyelitis, cellulitis references for full regimens/durations)
– SOURCE CONTROL (as important as antibiotics): debride necrotic tissue, drain abscesses, revascularize ischemic limbs, offload pressure — abx + glucose control fail without it
– WATCH FOR THE DIABETES-SPECIFIC SEVERE INFECTIONS: necrotizing infection (emergent surgery), emphysematous pyelonephritis/cholecystitis (gas-forming, urgent intervention), mucormycosis (rhino-orbital in DKA — emergent ENT/surgery + amphotericin), malignant otitis externa — high index of suspicion
– TREAT INFECTION-TRIGGERED HYPERGLYCEMIC EMERGENCY: if DKA/HHS present, run that pathway concurrently (fluids/insulin/electrolytes) while treating the infection
– The endocrine lens on a diabetic infection is the feedback loop: hyperglycemia cripples the immune response and slows healing, while the infection spikes the glucose and can tip the patient into DKA or HHS — so you have to attack both ends at once. A practical corollary: an unexplained surge in insulin requirement or a sugar that suddenly won't come down is often the first sign of an occult infection, so go looking. And don't be lulled by a comfortable-looking patient — neuropathy and vascular disease blunt pain and fever, so a severe, even limb-threatening infection can present quietly. The antibiotics and surgery are co-managed with ID and surgery; your job is to recognize the cycle, control the glucose, and not miss the diabetes-specific emergencies like mucormycosis or an emphysematous infection.
– PT/OT + wound care: offloading (total-contact cast/boot), mobility, wound management, footwear education, amputation rehab if needed
– Trend: glucose/insulin requirement (rising need = worsening infection), gap/ketones/osm, infection markers (WBC/CRP), wound/healing, cultures, perfusion, source-control status
– Escalation triggers: necrotizing/emphysematous/mucormycosis features → emergent surgery/specialty; limb-threatening ischemia → urgent vascular; sepsis/septic shock → ICU + sepsis pathway; infection-triggered DKA/HHS → emergency pathway ± ICU; uncontrollable hyperglycemia → reassess for undrained source
– Discharge checklist: infection controlled + source addressed + glucose optimized + any hyperglycemic emergency resolved; antibiotic regimen + duration (ID-directed, longer if osteomyelitis) + tailored insulin/diabetes regimen with access secured; offloading + wound-care plan; vascular/podiatry/surgery + ID + endocrine follow-up; smoking cessation + foot-care education + recurrence prevention; return precautions (spreading infection, fever, worsening wound, uncontrolled glucose, vomiting/abdominal pain — DKA)

105. Diabetes-Related Infection

complete reference · foot infection + cellulitis + osteomyelitis · break the glucose-infection cycle, source control, ID co-management, watch diabetes-specific severe infections · Full Card

Symptoms / Associated Sx

• Local infection signs (a foot ulcer with erythema or drainage, cellulitis, a deep abscess), often with a blunted systemic response (neuropathy and vascular disease mask pain and fever)

• Uncontrolled hyperglycemia as the presenting clue (an unexplained sugar spike often signals an occult infection)

• Severe, necrotizing, or limb-threatening features

• In a diabetic, a sudden loss of glucose control with no other explanation is an infection until proven otherwise — and the infection and the hyperglycemia worsen each other in a vicious cycle, so you must break both

Neg

• Pt denies a missed deep infection or osteomyelitis (probe-to-bone, a chronic ulcer → image) and a missed critical limb ischemia (won't heal without revascularization)

• Pt denies a missed necrotizing or emphysematous infection (a surgical emergency) and treating the infection without controlling glucose (which impairs immunity and healing)

• Pt denies a missed DKA or HHS triggered by the infection and under-recognizing severity (blunted signs)

Social History (SHx)

• Diabetes control (A1c), neuropathy, and peripheral arterial disease

• Prior foot ulcers, amputations, or infections, and prior MRSA or resistant organisms

• Immunosuppression, glycemic-control barriers, smoking, footwear and self-care, and recurrent infections (a poor-control marker)

Main Etiology

• Hyperglycemia impairs neutrophil function and immunity, microvascular disease impairs perfusion and healing, and neuropathy enables unrecognized injury — producing increased susceptibility, severity, and poor healing

• Diabetes-associated and severe infections: foot infections (often polymicrobial), osteomyelitis, emphysematous pyelonephritis or cholecystitis, mucormycosis (DKA), necrotizing infections, and malignant otitis externa

RF

• Modifiable: poor glycemic control, smoking, and foot self-care

• Non-modifiable: neuropathy or PAD, a prior ulcer or amputation, immunosuppression, prior resistant organisms, and recurrent infection

Data

• Glucose and A1c, a BMP with a gas and ketones (infection often precipitates DKA/HHS), CBC, ESR/CRP, and blood cultures if systemic

• Infection-specific: a deep or bone culture (not a swab), X-ray or MRI for osteomyelitis, the probe-to-bone test, a vascular assessment (ABI, perfusion), and imaging for an abscess or gas

• Lactate; a source-directed workup (urinalysis, CXR, and others)

DDx

Diabetic foot infection, cellulitis, or osteomyelitis · necrotizing soft tissue infection · emphysematous pyelonephritis or cholecystitis · mucormycosis (DKA, rhino-orbital — an emergency) · malignant otitis externa · Charcot foot (mimics infection) · critical limb ischemia · sepsis from any source

Home Meds

• Optimize glucose (usually insulin as an inpatient — basal-bolus)

• Hold metformin if there is AKI, sepsis, or contrast; reconcile and renally dose antibiotics (ID-directed)

• Continue PAD medications (a statin, an antiplatelet); address smoking; resume a tailored regimen at discharge

Plan

CONSULT: Infectious Disease (antibiotic selection and duration — these are frequently co-managed) · Surgery/Podiatry (debridement, drainage, source control, amputation decisions) · Vascular Surgery (ischemia → revascularization) · Endocrinology or the glycemic team (glucose control) · Wound care/PT (offloading)

• Break the vicious cycle — control glucose and treat the infection together:

• • Glycemic control (the endocrine job): basal-bolus insulin (a target of ~140–180 mg/dL inpatient), anticipating higher insulin needs during infection, and rule out and treat infection-triggered DKA or HHS (check the gas, ketones, and osmolality); good control improves immune function and healing

• • Infection treatment (ID and surgery co-managed): source control (debride, drain, revascularize), with culture-directed antibiotics — for a limb-threatening or polymicrobial foot infection, broad coverage per the local formulary (e.g. cefepime plus metronidazole plus vancomycin); tailored to ID, cultures, and the specific infection (see the diabetic foot, osteomyelitis, and cellulitis references for full regimens and durations)

• Source control (as important as antibiotics): debride necrotic tissue, drain abscesses, revascularize ischemic limbs, and offload pressure — antibiotics and glucose control fail without it

• Watch for the diabetes-specific severe infections: necrotizing infection (emergent surgery), emphysematous pyelonephritis or cholecystitis (gas-forming, urgent intervention), mucormycosis (rhino-orbital in DKA — emergent ENT/surgery with amphotericin), and malignant otitis externa — maintain a high index of suspicion

• Treat infection-triggered hyperglycemic emergency: if DKA or HHS is present, run that pathway concurrently (fluids, insulin, electrolytes) while treating the infection

• PT/OT and wound care: offloading (a total-contact cast or boot), mobility, wound management, footwear education, and amputation rehabilitation if needed

• Trend: glucose and insulin requirement (a rising need signals worsening infection), the gap, ketones, and osmolality, infection markers (WBC, CRP), the wound and healing, cultures, perfusion, and source-control status

• Escalation triggers: necrotizing, emphysematous, or mucormycosis features → emergent surgery or specialty; limb-threatening ischemia → urgent vascular care; sepsis or septic shock → ICU and the sepsis pathway; infection-triggered DKA or HHS → the emergency pathway with possible ICU; uncontrollable hyperglycemia → reassess for an undrained source

• Discharge checklist: the infection controlled with the source addressed, glucose optimized, and any hyperglycemic emergency resolved; an antibiotic regimen and duration (ID-directed, longer if osteomyelitis) with a tailored insulin and diabetes regimen and access secured; an offloading and wound-care plan; vascular, podiatry/surgery, ID, and endocrine follow-up; smoking cessation, foot-care education, and recurrence prevention; return precautions for spreading infection, fever, a worsening wound, uncontrolled glucose, or vomiting and abdominal pain (DKA)

Red Flags

• An unexplained surge in insulin requirement → an occult infection; go looking for the source

• Necrotizing, emphysematous, or rhino-orbital (mucormycosis) features → surgical and specialty emergencies

• Critical limb ischemia → the foot won't heal without revascularization

• Blunted pain and fever → neuropathy and vascular disease mask severity; don't be falsely reassured

• Infection-triggered DKA or HHS → run the hyperglycemic-emergency pathway concurrently

Senior IM Resident Pearls

• It's a feedback loop. Hyperglycemia cripples immunity and healing while the infection spikes the glucose — attack both ends at once.

• A sugar that suddenly won't come down means look for infection. An unexplained surge in insulin requirement is often the first sign of an occult source.

• Don't be lulled by a comfortable patient. Neuropathy and vascular disease blunt pain and fever, so a limb-threatening infection can present quietly.

• Source control is co-equal with antibiotics. Debridement, drainage, revascularization, and offloading do what no antibiotic or insulin can.

• Know the diabetes-specific emergencies. Necrotizing infection, emphysematous pyelonephritis, and rhino-orbital mucormycosis in DKA are not to be missed.

• Check a gas in the sick diabetic with infection. The infection may have already tipped them into DKA or HHS that needs concurrent treatment.

• Common mistake: treating the infection while letting the glucose run high — poor control sabotages the immune response and healing the antibiotics depend on.

Endocrinology — Calcium/Mineral

106. Hypercalcemia

malignancy · primary hyperparathyroidism · "stones, bones, groans, psychiatric overtones" · IV fluids first, then calcitonin + bisphosphonate · PTH splits the differential · Super Compact

Sx: "stones (kidney), bones (pain), groans (abdominal — constipation, nausea, PUD, pancreatitis), psychiatric overtones (confusion, lethargy, depression)"; polyuria/polydipsia + dehydration (calcium causes nephrogenic DI), weakness, shortened QT · severity + acuity drive symptoms (chronic mild often asymptomatic; acute severe → AMS, coma) · (confirm with ionized or albumin-corrected calcium, then let the PTH level split the diagnosis — high/normal PTH points to hyperparathyroidism, suppressed PTH points to malignancy or another non-PTH cause)

Neg: denies missed malignancy (the most common inpatient cause — PTHrP, bone mets, myeloma; suppressed PTH) · denies missed primary hyperparathyroidism (most common outpatient cause; high/inappropriately normal PTH) · denies under-resuscitation before other therapy (volume depletion is universal) · denies missed contributing meds (thiazides, lithium, calcium/vitamin D, vitamin A) · denies missed severe-symptomatic crisis needing aggressive treatment

SHx: known/suspected malignancy (breast, lung, renal, myeloma, squamous), prior hyperparathyroidism/parathyroid disease, kidney stones/fractures, medications (thiazides, lithium, supplements, vitamin A/D), family history (MEN/familial), granulomatous disease (sarcoid/TB → vitamin D), immobilization, dietary supplements

Etiology: two dominant causes: (1) primary hyperparathyroidism (autonomous PTH, usually adenoma — most common overall/outpatient) → high/normal PTH; (2) malignancy (PTHrP-mediated humoral, osteolytic bone mets, or myeloma; most common inpatient) → suppressed PTH · others: granulomatous (↑1,25-vitamin D), medications, vitamin D toxicity, milk-alkali, immobilization, thyrotoxicosis, familial hypocalciuric hypercalcemia

RF: malignancy · parathyroid disease/MEN · thiazides/lithium · vitamin D/calcium excess · granulomatous disease · immobilization · CKD (tertiary HPT)

Data: confirm with ionized calcium (or albumin-corrected); then PTH (the key branch point) · if PTH suppressed → PTHrP, 25- + 1,25-vitamin D, SPEP/UPEP/free light chains (myeloma), malignancy workup, imaging · if PTH high/normal → primary hyperparathyroidism workup (24h urine calcium to exclude FHH, parathyroid imaging) · BMP (renal function), phosphate, Mg, ECG (short QT), vitamin D

DDx: primary hyperparathyroidism · malignancy (PTHrP/bone mets/myeloma) · granulomatous (sarcoid/TB) · vitamin D toxicity · medication (thiazide/lithium) · milk-alkali · familial hypocalciuric hypercalcemia (low urine calcium — don't operate) · thyrotoxicosis · immobilization · tertiary hyperparathyroidism (CKD)

Home Meds: HOLD thiazides, lithium, calcium + vitamin D supplements, vitamin A; avoid volume depletion; reconcile; resume/adjust based on cause; review nephrotoxins

Plan

CONSULT: Endocrinology (diagnosis, hyperparathyroidism, refractory) · Oncology/Hematology (malignancy, myeloma — treat the underlying cancer) · Nephrology (severe/renal failure, dialysis for refractory) · Surgery (parathyroidectomy for primary HPT) · ICU (severe symptomatic crisis)

– SEVERITY-BASED TREATMENT (acute symptomatic / Ca usually >14 or symptomatic — treat aggressively):
  • 1) IV FLUIDS first — isotonic saline (0.9% NaCl) ~200–300 mL/h (restore volume + promote calciuresis; all hypercalcemic patients are dehydrated from calcium-induced DI) — the foundational step
  • 2) CALCITONIN (4 units/kg SC/IM q12h) for rapid (but transient, ~48h, tachyphylaxis) calcium lowering in symptomatic/severe cases — bridges until bisphosphonate works
  • 3) BISPHOSPHONATE (zoledronic acid 4 mg IV, or pamidronate) — the durable lowering agent (onset ~24–48h, peak ~2–4 days); preferred for malignancy hypercalcemia; renally dose/caution in renal impairment
  • DENOSUMAB for bisphosphonate-refractory or significant renal impairment (malignancy)
  • Avoid loop diuretics routinely (only if volume overload after rehydration — older teaching of forced diuresis is outdated)
– TREAT THE UNDERLYING CAUSE (definitive): malignancy → oncologic treatment (the durable fix; bisphosphonate/denosumab control calcium meanwhile); primary hyperparathyroidism → parathyroidectomy (definitive; surgical referral by criteria); granulomatous/vitamin D → glucocorticoids; stop offending meds
– GLUCOCORTICOIDS for hypercalcemia of granulomatous disease, vitamin D toxicity, or some lymphomas/myeloma
– DIALYSIS for severe, refractory hypercalcemia with renal failure or life-threatening levels
– The two questions that organize hypercalcemia: how sick is the patient, and what's the PTH? Severity drives the urgency — every hypercalcemic patient is volume-depleted (calcium causes a nephrogenic diabetes insipidus), so saline comes first, always; calcitonin then buys you 48 hours of fast lowering while the bisphosphonate, the durable agent, takes a day or two to work. The PTH splits the diagnosis cleanly: high or inappropriately normal means hyperparathyroidism heading toward a parathyroidectomy, while suppressed means malignancy until proven otherwise, and the cancer is both the cause and the definitive target. Forget the old "loop diuretics for forced diuresis" teaching — fluids do the work, and loops are only for volume overload after you've rehydrated.
– PT/OT: mobilization (immobilization worsens hypercalcemia); fall prevention if AMS
– Trend: calcium (ionized/corrected) — frequent, mental status, renal function/urine output, ECG (QT), volume status, response to each agent, underlying-cause workup
– Escalation triggers: severe symptomatic crisis (AMS, coma, arrhythmia, Ca very high) → ICU + aggressive multimodal therapy; refractory despite fluids+calcitonin+bisphosphonate → denosumab/dialysis + specialty; renal failure → nephrology; underlying malignancy → urgent oncology
– Discharge checklist: calcium improved/controlled + cause identified + underlying treatment plan; offending meds stopped; cause-specific plan (oncology for malignancy, surgery referral for primary HPT, steroids for granulomatous); hydration counseling; medication reconciliation (avoid calcium/vitamin D/thiazides as appropriate); endocrine + cause-specialty follow-up; calcium monitoring plan; return precautions (confusion, severe constipation/nausea, polyuria/dehydration, weakness)

106. Hypercalcemia

complete reference · malignancy + primary hyperparathyroidism · saline first then calcitonin + bisphosphonate, PTH-driven differential, treat the cause · Full Card

Symptoms / Associated Sx

• "Stones (kidney), bones (pain), groans (abdominal — constipation, nausea, peptic ulcer disease, pancreatitis), and psychiatric overtones (confusion, lethargy, depression)"

• Polyuria and polydipsia with dehydration (calcium causes a nephrogenic diabetes insipidus), weakness, and a shortened QT

• Severity and acuity drive symptoms (chronic mild disease is often asymptomatic; acute severe disease causes altered mental status and coma)

• Confirm with an ionized or albumin-corrected calcium, then let the PTH level split the diagnosis — a high or normal PTH points to hyperparathyroidism, while a suppressed PTH points to malignancy or another non-PTH cause

Neg

• Pt denies a missed malignancy (the most common inpatient cause — PTHrP, bone metastases, myeloma; with a suppressed PTH)

• Pt denies a missed primary hyperparathyroidism (the most common outpatient cause; with a high or inappropriately normal PTH) and under-resuscitation before other therapy (volume depletion is universal)

• Pt denies missed contributing medications (thiazides, lithium, calcium or vitamin D, vitamin A) and a missed severe-symptomatic crisis needing aggressive treatment

Social History (SHx)

• Known or suspected malignancy (breast, lung, renal, myeloma, squamous), prior hyperparathyroidism or parathyroid disease, and kidney stones or fractures

• Medications (thiazides, lithium, supplements, vitamin A or D) and family history (MEN, familial disease)

• Granulomatous disease (sarcoidosis, TB → vitamin D), immobilization, and dietary supplements

Main Etiology

• Two dominant causes: primary hyperparathyroidism (autonomous PTH, usually an adenoma — the most common overall and outpatient) → a high or normal PTH; and malignancy (PTHrP-mediated humoral disease, osteolytic bone metastases, or myeloma; the most common inpatient cause) → a suppressed PTH

• Others: granulomatous disease (elevated 1,25-vitamin D), medications, vitamin D toxicity, milk-alkali syndrome, immobilization, thyrotoxicosis, and familial hypocalciuric hypercalcemia

RF

• Modifiable: thiazides or lithium, vitamin D or calcium excess, and immobilization

• Non-modifiable: malignancy, parathyroid disease or MEN, granulomatous disease, and CKD (tertiary hyperparathyroidism)

Data

• Confirm with an ionized calcium (or albumin-corrected); then PTH (the key branch point)

• If PTH is suppressed → PTHrP, 25- and 1,25-vitamin D, SPEP/UPEP and free light chains (myeloma), a malignancy workup, and imaging

• If PTH is high or normal → a primary hyperparathyroidism workup (24-hour urine calcium to exclude FHH, parathyroid imaging)

• A BMP (renal function), phosphate, magnesium, an ECG (short QT), and vitamin D

DDx

Primary hyperparathyroidism · malignancy (PTHrP, bone metastases, myeloma) · granulomatous disease (sarcoidosis, TB) · vitamin D toxicity · medication (thiazide, lithium) · milk-alkali syndrome · familial hypocalciuric hypercalcemia (low urine calcium — don't operate) · thyrotoxicosis · immobilization · tertiary hyperparathyroidism (CKD)

Home Meds

• Hold thiazides, lithium, calcium and vitamin D supplements, and vitamin A

• Avoid volume depletion; reconcile medications

• Resume and adjust based on the cause; review nephrotoxins

Plan

CONSULT: Endocrinology (diagnosis, hyperparathyroidism, refractory disease) · Oncology/Hematology (malignancy, myeloma — treating the underlying cancer) · Nephrology (severe disease or renal failure, dialysis for refractory cases) · Surgery (parathyroidectomy for primary hyperparathyroidism) · ICU (severe symptomatic crisis)

• Severity-based treatment (acute symptomatic disease, or calcium usually above 14 or symptomatic — treat aggressively):

• • 1) IV fluids first — isotonic saline (0.9% NaCl) ~200–300 mL/h (restoring volume and promoting calciuresis; all hypercalcemic patients are dehydrated from calcium-induced diabetes insipidus) — the foundational step

• • 2) Calcitonin (4 units/kg SC/IM every 12 hours) for rapid (but transient, ~48 hours, with tachyphylaxis) calcium lowering in symptomatic or severe cases — bridging until the bisphosphonate works

• • 3) Bisphosphonate (zoledronic acid 4 mg IV, or pamidronate) — the durable lowering agent (onset ~24–48 hours, peak ~2–4 days); preferred for malignancy hypercalcemia; renally dose and use caution in renal impairment

• • Denosumab for bisphosphonate-refractory disease or significant renal impairment (malignancy)

• • Avoid loop diuretics routinely (only if there is volume overload after rehydration — the older teaching of forced diuresis is outdated)

• Treat the underlying cause (definitive): malignancy → oncologic treatment (the durable fix; a bisphosphonate or denosumab controls calcium meanwhile); primary hyperparathyroidism → parathyroidectomy (definitive; surgical referral by criteria); granulomatous disease or vitamin D toxicity → glucocorticoids; stop offending medications

• Glucocorticoids for hypercalcemia of granulomatous disease, vitamin D toxicity, or some lymphomas and myeloma

• Dialysis for severe, refractory hypercalcemia with renal failure or life-threatening levels

• PT/OT: mobilization (immobilization worsens hypercalcemia); fall prevention if altered mental status

• Trend: calcium (ionized or corrected) frequently, mental status, renal function and urine output, the ECG (QT), volume status, the response to each agent, and the underlying-cause workup

• Escalation triggers: a severe symptomatic crisis (altered mental status, coma, arrhythmia, very high calcium) → ICU and aggressive multimodal therapy; refractory disease despite fluids, calcitonin, and a bisphosphonate → denosumab or dialysis with specialty input; renal failure → nephrology; an underlying malignancy → urgent oncology

• Discharge checklist: calcium improved or controlled, the cause identified, and an underlying treatment plan; offending medications stopped; a cause-specific plan (oncology for malignancy, surgical referral for primary hyperparathyroidism, steroids for granulomatous disease); hydration counseling; medication reconciliation (avoiding calcium, vitamin D, and thiazides as appropriate); endocrine and cause-specialty follow-up; a calcium monitoring plan; return precautions for confusion, severe constipation or nausea, polyuria or dehydration, or weakness

Red Flags

• A severe symptomatic crisis (altered mental status, coma, arrhythmia, very high calcium) → ICU and aggressive multimodal therapy

• A suppressed PTH → malignancy until proven otherwise; pursue the cancer workup

• Under-resuscitation → every hypercalcemic patient is volume-depleted; saline comes first

• Refractory disease despite fluids, calcitonin, and a bisphosphonate → denosumab or dialysis

• Familial hypocalciuric hypercalcemia (low urine calcium) → don't operate; it mimics hyperparathyroidism

Senior IM Resident Pearls

• Two questions organize it: how sick, and what's the PTH? Severity drives the urgency, and the PTH splits the diagnosis.

• Saline comes first, always. Every hypercalcemic patient is volume-depleted from a calcium-induced nephrogenic diabetes insipidus.

• Calcitonin buys time; the bisphosphonate is durable. Calcitonin lowers calcium fast for about 48 hours while the bisphosphonate takes a day or two to work.

• A suppressed PTH means malignancy until proven otherwise. The cancer is both the cause and the definitive target.

• Forget forced diuresis. Fluids do the work, and loop diuretics are only for volume overload after rehydration.

• Check the urine calcium before operating. Familial hypocalciuric hypercalcemia mimics hyperparathyroidism but should not go to surgery.

• Common mistake: reaching for a loop diuretic early — it worsens the volume depletion that's central to the problem; rehydrate first.

Endocrinology — Calcium/Mineral

107. Hypocalcemia

CKD · hypoparathyroidism (post-surgical) · vitamin D deficiency · neuromuscular irritability · check magnesium · IV calcium for symptomatic/severe, oral + vitamin D for the rest · Super Compact

Sx: neuromuscular irritability: perioral/distal paresthesias, muscle cramps, carpopedal spasm, tetany; Chvostek sign (facial twitch on tapping) + Trousseau sign (carpal spasm with BP cuff); severe → laryngospasm, seizures, prolonged QT → arrhythmia, AMS · acuity matters (rapid drop more symptomatic than chronic) · (confirm with ionized or albumin-corrected calcium, ALWAYS check magnesium — hypomagnesemia both causes hypocalcemia and makes it refractory — and remember alkalosis/hyperventilation can drop ionized calcium and produce symptoms at a normal total)

Neg: denies missed hypomagnesemia (causes + perpetuates refractory hypocalcemia — replace Mg or calcium won't correct) · denies missed post-surgical/post-thyroidectomy/post-parathyroidectomy hypoparathyroidism (including hungry bone syndrome) · denies missed severe symptomatic case needing IV calcium · denies pseudohypocalcemia (low albumin — correct or use ionized) · denies missed prolonged QT/arrhythmia risk

SHx: recent thyroid/parathyroid/neck surgery (post-surgical hypoparathyroidism — common, key cause), CKD/dialysis, vitamin D deficiency/malabsorption (bariatric, celiac, GI), medications (loop diuretics, bisphosphonates, denosumab, cinacalcet, PPIs → Mg loss), pancreatitis, alcohol (Mg), blood transfusions (citrate), prior neck irradiation, autoimmune (polyglandular)

Etiology: by PTH: low PTH (hypoparathyroidism — most often POST-SURGICAL after thyroid/parathyroid surgery; also autoimmune, infiltrative, hypomagnesemia-induced) vs high PTH (secondary — vitamin D deficiency, CKD with ↓1,25-vitamin D + phosphate retention, malabsorption) · other: hypomagnesemia, acute pancreatitis, citrate (transfusion), tumor lysis, sepsis, drugs, respiratory alkalosis (↓ionized)

RF: neck/thyroid/parathyroid surgery · CKD · vitamin D deficiency/malabsorption · hypomagnesemia (alcohol, PPI, diuretics) · pancreatitis · massive transfusion · sepsis

Data: ionized calcium (or albumin-corrected) to confirm; then PTH, MAGNESIUM, phosphate, 25-vitamin D, renal function · ECG (prolonged QT); PTH branch (low → hypoparathyroidism; high → vitamin D deficiency/CKD/secondary); albumin; amylase/lipase if pancreatitis; surgical history review

DDx: post-surgical hypoparathyroidism (hungry bone after parathyroidectomy) · vitamin D deficiency · CKD-related · hypomagnesemia-induced · pancreatitis · pseudohypocalcemia (low albumin) · respiratory alkalosis (low ionized) · citrate/transfusion · pseudohypoparathyroidism · sepsis/critical illness

Home Meds: review/adjust offending drugs (loops, PPIs, bisphosphonates/denosumab, cinacalcet); supplement calcium + vitamin D (+ active vitamin D/calcitriol if hypoparathyroidism or CKD); replace magnesium; reconcile; CKD-specific phosphate/vitamin D management with nephrology

Plan

CONSULT: Endocrinology (hypoparathyroidism, refractory, management) · Nephrology (CKD-mineral bone disease) · Surgery (if post-operative — coordinate; hungry bone) · ICU (severe symptomatic — tetany, laryngospasm, seizures, arrhythmia)

– SEVERITY-BASED TREATMENT:
  • SYMPTOMATIC or SEVERE (tetany, laryngospasm, seizures, prolonged QT/arrhythmia, or very low calcium): IV CALCIUM — calcium gluconate (1–2 g in 50–100 mL D5W over ~10–20 min) for acute symptoms, followed by a calcium gluconate infusion for ongoing/severe (titrate to calcium + symptoms); continuous ECG monitoring; (calcium chloride only via central line — more irritating)
  • ASYMPTOMATIC / MILD–MODERATE: oral calcium (calcium carbonate/citrate) + vitamin D repletion
– CHECK + REPLACE MAGNESIUM (critical): hypomagnesemia causes + perpetuates refractory hypocalcemia — replace magnesium (IV/PO) or calcium will not correct no matter how much you give
– TREAT BY CAUSE (PTH-directed):
  • Hypoparathyroidism (low PTH — e.g. post-surgical): calcium + ACTIVE vitamin D (calcitriol) (no PTH to activate vitamin D, so give the active form); long-term calcium/calcitriol ± recombinant PTH per endocrine; hungry bone syndrome (post-parathyroidectomy): aggressive calcium ± calcitriol + magnesium
  • Vitamin D deficiency: ergocalciferol/cholecalciferol repletion + calcium
  • CKD: nephrology-directed (active vitamin D, phosphate binders, address secondary hyperparathyroidism)
– CORRECT ACUITY-DEPENDENTLY: chronic hypocalcemia is corrected gently (over-rapid correction unnecessary if asymptomatic); symptomatic gets prompt IV
– Two things you can't skip in hypocalcemia. First, check the magnesium — low magnesium both causes hypocalcemia and makes it stubbornly refractory, so if you pour calcium in without fixing the magnesium, the calcium won't budge. Second, let the PTH and the surgical history guide you: the classic inpatient story is the post-thyroidectomy or post-parathyroidectomy patient with a suddenly low calcium from hypoparathyroidism, and because they have no PTH to activate vitamin D, they need the active form, calcitriol, not just plain vitamin D. Match the urgency to the symptoms — tetany, laryngospasm, seizures, or a long QT get IV calcium now under cardiac monitoring, while the asymptomatic patient gets oral repletion.
– 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, paresthesias), PTH/vitamin D, post-op trajectory (hungry bone)
– Escalation triggers: tetany/laryngospasm/seizures/arrhythmia → IV calcium + ICU + continuous monitoring; refractory despite calcium → check/replace magnesium + reassess; post-parathyroidectomy hungry bone → aggressive repletion + endocrine; severe CKD-MBD → nephrology
– Discharge checklist: calcium corrected/stabilized + magnesium replete + cause identified; oral calcium + vitamin D (active vitamin D/calcitriol if hypoparathyroidism or CKD) with doses + monitoring plan; cause-specific management (post-surgical follow-up, vitamin D repletion, CKD plan); endocrine/nephrology/surgery follow-up; calcium/magnesium monitoring; medication review (offending drugs); return precautions (paresthesias, cramps/spasms, twitching, seizures, difficulty breathing — laryngospasm)

107. Hypocalcemia

complete reference · CKD + hypoparathyroidism + vitamin D deficiency · check magnesium, PTH-directed therapy, calcitriol for hypoparathyroidism, IV calcium for symptomatic · Full Card

Symptoms / Associated Sx

• Neuromuscular irritability: perioral and distal paresthesias, muscle cramps, carpopedal spasm, and tetany

• Chvostek sign (facial twitch on tapping) and Trousseau sign (carpal spasm with a BP cuff)

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

• Acuity matters (a rapid drop is more symptomatic than chronic disease)

• Confirm with an ionized or albumin-corrected calcium, always check magnesium (hypomagnesemia both causes hypocalcemia and makes it refractory), and remember alkalosis or hyperventilation can drop ionized calcium and produce symptoms at a normal total

Neg

• Pt denies a missed hypomagnesemia (which causes and perpetuates refractory hypocalcemia — replace magnesium or calcium won't correct)

• Pt denies a missed post-surgical, post-thyroidectomy, or post-parathyroidectomy hypoparathyroidism (including hungry bone syndrome) and a missed severe symptomatic case needing IV calcium

• Pt denies pseudohypocalcemia (low albumin — correct or use ionized) and a missed prolonged QT or arrhythmia risk

Social History (SHx)

• Recent thyroid, parathyroid, or neck surgery (post-surgical hypoparathyroidism — common, a key cause), CKD or dialysis, and vitamin D deficiency or malabsorption (bariatric surgery, celiac disease, GI disease)

• Medications (loop diuretics, bisphosphonates, denosumab, cinacalcet, PPIs → magnesium loss), pancreatitis, and alcohol (magnesium)

• Blood transfusions (citrate), prior neck irradiation, and autoimmune disease (polyglandular)

Main Etiology

• By PTH: low PTH (hypoparathyroidism — most often post-surgical after thyroid or parathyroid surgery; also autoimmune, infiltrative, or hypomagnesemia-induced) versus high PTH (secondary — vitamin D deficiency, CKD with reduced 1,25-vitamin D and phosphate retention, malabsorption)

• Other: hypomagnesemia, acute pancreatitis, citrate (transfusion), tumor lysis, sepsis, drugs, and respiratory alkalosis (reduced ionized calcium)

RF

• Modifiable: hypomagnesemia (alcohol, PPIs, diuretics) and offending medications

• Non-modifiable: neck, thyroid, or parathyroid surgery, CKD, vitamin D deficiency or malabsorption, pancreatitis, massive transfusion, and sepsis

Data

• An ionized calcium (or albumin-corrected) to confirm; then PTH, magnesium, phosphate, 25-vitamin D, and renal function

• An ECG (prolonged QT)

• The PTH branch (low → hypoparathyroidism; high → vitamin D deficiency, CKD, or secondary disease); albumin; amylase and lipase if pancreatitis; and a review of the surgical history

DDx

Post-surgical hypoparathyroidism (hungry bone after parathyroidectomy) · vitamin D deficiency · CKD-related hypocalcemia · hypomagnesemia-induced hypocalcemia · pancreatitis · pseudohypocalcemia (low albumin) · respiratory alkalosis (low ionized calcium) · citrate or transfusion-related disease · pseudohypoparathyroidism · sepsis or critical illness

Home Meds

• Review and adjust offending drugs (loops, PPIs, bisphosphonates, denosumab, cinacalcet)

• Supplement calcium and vitamin D (with active vitamin D/calcitriol if there is hypoparathyroidism or CKD); replace magnesium

• Reconcile medications; CKD-specific phosphate and vitamin D management with nephrology

Plan

CONSULT: Endocrinology (hypoparathyroidism, refractory disease, management) · Nephrology (CKD-mineral bone disease) · Surgery (if post-operative — coordinate; hungry bone) · ICU (severe symptomatic disease — tetany, laryngospasm, seizures, arrhythmia)

• Severity-based treatment:

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

• • Asymptomatic or mild–moderate: oral calcium (calcium carbonate or citrate) plus vitamin D repletion

• Check and replace magnesium (critical): hypomagnesemia causes and perpetuates refractory hypocalcemia — replace magnesium (IV/PO) or calcium will not correct no matter how much you give

• Treat by cause (PTH-directed):

• • Hypoparathyroidism (low PTH — e.g. post-surgical): calcium plus active vitamin D (calcitriol) (there is no PTH to activate vitamin D, so give the active form); long-term calcium and calcitriol, with recombinant PTH per endocrine; hungry bone syndrome (post-parathyroidectomy): aggressive calcium with calcitriol and magnesium

• • Vitamin D deficiency: ergocalciferol or cholecalciferol repletion plus calcium

• • CKD: nephrology-directed (active vitamin D, phosphate binders, addressing secondary hyperparathyroidism)

• Correct acuity-dependently: chronic hypocalcemia is corrected gently (over-rapid correction is unnecessary if asymptomatic); symptomatic disease gets prompt IV calcium

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

• Trend: calcium (ionized or corrected) frequently if severe or on an infusion, magnesium, phosphate, the ECG and QT, symptoms (Chvostek and Trousseau signs, paresthesias), PTH and vitamin D, and the post-operative trajectory (hungry bone)

• Escalation triggers: tetany, laryngospasm, seizures, or arrhythmia → IV calcium, ICU, and continuous monitoring; refractory disease despite calcium → check and replace magnesium and reassess; post-parathyroidectomy hungry bone → aggressive repletion with endocrine; severe CKD-mineral bone disease → nephrology

• Discharge checklist: calcium corrected or stabilized, magnesium replete, and the cause identified; oral calcium and vitamin D (active vitamin D/calcitriol if hypoparathyroidism or CKD) with doses and a monitoring plan; cause-specific management (post-surgical follow-up, vitamin D repletion, a CKD plan); endocrine, nephrology, and surgery follow-up; calcium and magnesium monitoring; a medication review (offending drugs); return precautions for paresthesias, cramps or spasms, twitching, seizures, or difficulty breathing (laryngospasm)

Red Flags

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

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

• Post-thyroidectomy or post-parathyroidectomy → hypoparathyroidism or hungry bone syndrome; needs active vitamin D

• A low albumin → pseudohypocalcemia; correct or use ionized calcium before treating

• Respiratory alkalosis or hyperventilation → low ionized calcium producing symptoms at a normal total

Senior IM Resident Pearls

• Check the magnesium. Low magnesium both causes hypocalcemia and makes it refractory — calcium won't budge until you fix it.

• The classic inpatient story is post-surgical. A suddenly low calcium after thyroidectomy or parathyroidectomy is hypoparathyroidism until proven otherwise.

• Hypoparathyroidism needs the active vitamin D. With no PTH to activate vitamin D, give calcitriol, not just plain ergocalciferol or cholecalciferol.

• Match urgency to symptoms. Tetany, laryngospasm, seizures, or a long QT get IV calcium now; the asymptomatic patient gets oral repletion.

• Watch for hungry bone after parathyroidectomy. The newly active bone soaks up calcium aggressively, requiring large repletion plus magnesium.

• Correct the albumin or use ionized. A low albumin produces a falsely low total calcium that doesn't need treatment.

• Common mistake: chasing a refractory calcium with more and more calcium while ignoring the magnesium — replace the magnesium and the calcium follows.

Endocrinology — Thyroid

108. Thyrotoxicosis / Severe Hyperthyroidism

Graves disease · toxic multinodular goiter · toxic adenoma · beta-blocker + thionamide · screen every patient for thyroid storm features · Super Compact

Sx: heat intolerance, weight loss with increased appetite, palpitations/tachycardia (esp atrial fibrillation), tremor, anxiety/irritability, hyperdefecation, sweating, insomnia, proximal muscle weakness; Graves-specific: ophthalmopathy (proptosis), pretibial myxedema, diffuse goiter · elderly: "apathetic" (weight loss + AF + depression, few classic signs) · (once you confirm thyrotoxicosis, the immediate safety question is whether this is thyroid storm — fever, marked tachycardia, AMS, GI/hepatic dysfunction — because storm is treated far more aggressively; screen every severe hyperthyroid patient)

Neg: denies missed thyroid storm (decompensated — fever, severe tachycardia/arrhythmia, AMS, heart failure; use Burch-Wartofsky — see storm card) · denies missed atrial fibrillation/cardiac complications · denies missed precipitant (infection, iodine/contrast, amiodarone, recent radioiodine, pregnancy, surgery) · denies giving iodine before a thionamide (worsens it) · denies missed agranulocytosis from thionamide

SHx: prior thyroid disease/Graves, family/autoimmune history, medications (amiodarone — thyroid-toxic, iodine/contrast exposure, levothyroxine excess/factitious), recent pregnancy, neck surgery/radioiodine, supplements, smoking (worsens Graves eye disease), goiter/nodule history

Etiology: excess thyroid hormone action · causes: Graves disease (autoimmune TSH-receptor antibodies — most common, with eye/skin signs + diffuse goiter), toxic multinodular goiter + toxic adenoma (autonomous nodules, esp older/iodine exposure), thyroiditis (transient — subacute/painful, postpartum, silent), exogenous/factitious, amiodarone-induced, iodine-induced (Jod-Basedow), rare TSH-secreting tumor/struma ovarii

RF: autoimmune/family history · female · iodine/amiodarone/contrast exposure · existing nodular goiter · postpartum · smoking (Graves eye)

Data: TSH (suppressed) + free T4 (and free T3 — T3-toxicosis) confirm; then determine cause: TSH-receptor antibodies (TRAb — Graves), radioactive iodine uptake/thyroid scan (diffuse Graves vs nodular vs low-uptake thyroiditis) · thyroid ultrasound (nodules); ECG (AF/tachyarrhythmia); CBC (baseline before thionamide — agranulocytosis), LFTs (baseline + hepatotoxicity); precipitant workup if severe

DDx: Graves disease · toxic multinodular goiter/adenoma · thyroiditis (transient, low uptake — don't give thionamide) · exogenous/factitious thyrotoxicosis · amiodarone-induced · iodine-induced · TSH-secreting adenoma · thyroid storm (decompensated — see card) · other causes of AF/weight loss/anxiety

Home Meds: beta-blocker for symptom control; start thionamide (cause-dependent); avoid iodine/contrast (can worsen); reconcile amiodarone with cardiology (thyroid effects); baseline CBC/LFTs before thionamide; manage AF (rate control + anticoagulation assessment)

Plan

CONSULT: Endocrinology (diagnosis, definitive therapy planning, thionamide management) · Cardiology (atrial fibrillation, heart failure, anticoagulation) · Ophthalmology (Graves ophthalmopathy) · Surgery (thyroidectomy candidates) · ICU if storm features

– FIRST screen for thyroid storm (Burch-Wartofsky: fever, severe tachycardia, AMS, GI/hepatic dysfunction, CHF) — if present, treat per storm pathway + ICU (see thyroid storm card); this card = thyrotoxicosis without decompensation
– SYMPTOM CONTROL — BETA-BLOCKER (first-line for symptoms): propranolol (also blocks peripheral T4→T3 conversion at high dose) or atenolol/metoprolol; controls tachycardia, tremor, anxiety, palpitations — start promptly for symptomatic patients/AF (rate control)
– THIONAMIDE — reduce hormone synthesis (cause-dependent): methimazole (preferred first-line for most — once daily, fewer side effects) OR propylthiouracil/PTU (preferred in 1st-trimester pregnancy + thyroid storm); NOT for thyroiditis (no synthesis to block — it's hormone release, self-limited)
  • Counsel + monitor for agranulocytosis (fever/sore throat → stop + CBC) and hepatotoxicity (LFTs); baseline CBC/LFTs
– IODINE (only when indicated, AFTER thionamide, esp pre-op/storm): potassium iodide/Lugol's blocks release — give ≥1 h AFTER thionamide (iodine before a thionamide can fuel synthesis); not for routine outpatient thyrotoxicosis
– DEFINITIVE THERAPY (for Graves/toxic nodular — planned, not acute): radioactive iodine ablation, antithyroid drugs (Graves may remit), or thyroidectomy — endocrine-directed by cause/patient factors (eye disease, pregnancy, size, preference)
– MANAGE CARDIAC COMPLICATIONS: atrial fibrillation (rate control with beta-blocker, assess anticoagulation), heart failure; treat precipitants (infection)
– THYROIDITIS (low-uptake, transient): supportive — beta-blocker + NSAIDs (subacute painful) ± steroids; no thionamide; self-limited (may pass through hypothyroid phase)
– The workup has two steps: confirm the thyrotoxicosis (suppressed TSH, high free T4/T3), then find the mechanism, because it changes the treatment — a radioiodine uptake scan separates the high-uptake causes you treat with a thionamide (Graves, toxic nodules) from the low-uptake thyroiditis you must NOT, since thyroiditis is leaking pre-formed hormone with nothing to block. The two acute drugs are a beta-blocker for the symptoms and a thionamide for synthesis. Two safety reflexes: screen everyone for thyroid storm before you relax, and if you ever give iodine, give it after the thionamide, never before, or you'll feed the gland the substrate it needs. And warn every patient on a thionamide that a fever and sore throat means stop the drug and check a count — agranulocytosis is the dangerous idiosyncratic reaction.
– PT/OT: usually not needed; cardiac rehab if HF
– Trend: heart rate/rhythm, symptoms, thyroid function (free T4/T3 — TSH lags), CBC (agranulocytosis), LFTs (hepatotoxicity), cardiac status, response
– Escalation triggers: thyroid storm features (fever, AMS, severe tachycardia/CHF) → storm pathway + ICU; agranulocytosis (fever/sore throat + low ANC) → stop thionamide + ID/heme; severe cardiac decompensation → cardiology/ICU; thionamide hepatotoxicity → stop + endocrine
– Discharge checklist: symptoms controlled + on beta-blocker + thionamide (if indicated) + definitive-therapy plan; thionamide with agranulocytosis/hepatotoxicity counseling (STOP + seek care for fever/sore throat); AF/anticoagulation plan; endocrine follow-up (titrate, definitive therapy), cardiology, ophthalmology if eye disease; thyroid-function monitoring; avoid iodine/contrast; smoking cessation (eye disease); return precautions (fever/sore throat — agranulocytosis, jaundice, palpitations/chest pain, worsening — storm features, eye changes)

108. Thyrotoxicosis / Severe Hyperthyroidism

complete reference · Graves + toxic multinodular goiter · beta-blocker + thionamide, uptake scan distinguishes thyroiditis, screen for storm, definitive therapy planned · Full Card

Symptoms / Associated Sx

• Heat intolerance, weight loss with increased appetite, palpitations and tachycardia (especially atrial fibrillation), tremor, anxiety and irritability, hyperdefecation, sweating, insomnia, and proximal muscle weakness

• Graves-specific: ophthalmopathy (proptosis), pretibial myxedema, and a diffuse goiter

• The elderly may have "apathetic" hyperthyroidism (weight loss, AF, and depression with few classic signs)

• Once thyrotoxicosis is confirmed, the immediate safety question is whether this is thyroid storm (fever, marked tachycardia, altered mental status, GI/hepatic dysfunction) — because storm is treated far more aggressively; screen every severe hyperthyroid patient

Neg

• Pt denies a missed thyroid storm (decompensated — fever, severe tachycardia or arrhythmia, altered mental status, heart failure; use Burch-Wartofsky — see the storm card)

• Pt denies a missed atrial fibrillation or cardiac complication and a missed precipitant (infection, iodine or contrast, amiodarone, recent radioiodine, pregnancy, surgery)

• Pt denies giving iodine before a thionamide (which worsens it) and a missed agranulocytosis from a thionamide

Social History (SHx)

• Prior thyroid disease or Graves, family or autoimmune history, and medications (amiodarone — thyroid-toxic, iodine or contrast exposure, levothyroxine excess or factitious use)

• Recent pregnancy, neck surgery, or radioiodine, and supplements

• Smoking (worsens Graves eye disease) and goiter or nodule history

Main Etiology

• Excess thyroid hormone action

• Causes: Graves disease (autoimmune TSH-receptor antibodies — the most common, with eye and skin signs and a diffuse goiter), toxic multinodular goiter and toxic adenoma (autonomous nodules, especially in older patients or with iodine exposure), thyroiditis (transient — subacute/painful, postpartum, silent), exogenous or factitious thyrotoxicosis, amiodarone-induced and iodine-induced (Jod-Basedow) disease, and rare TSH-secreting tumor or struma ovarii

RF

• Modifiable: iodine, amiodarone, or contrast exposure, and smoking (Graves eye disease)

• Non-modifiable: autoimmune or family history, female sex, an existing nodular goiter, and the postpartum state

Data

• TSH (suppressed) and free T4 (and free T3 — T3-toxicosis) to confirm

• Then determine the cause: TSH-receptor antibodies (TRAb — Graves) and a radioactive iodine uptake or thyroid scan (diffuse Graves versus nodular disease versus low-uptake thyroiditis)

• Thyroid ultrasound (nodules); an ECG (AF, tachyarrhythmia)

• CBC (baseline before a thionamide — agranulocytosis) and LFTs (baseline and hepatotoxicity); a precipitant workup if severe

DDx

Graves disease · toxic multinodular goiter or adenoma · thyroiditis (transient, low uptake — don't give a thionamide) · exogenous or factitious thyrotoxicosis · amiodarone-induced disease · iodine-induced disease · a TSH-secreting adenoma · thyroid storm (decompensated — see card) · other causes of AF, weight loss, or anxiety

Home Meds

• Start a beta-blocker for symptom control and a thionamide (cause-dependent)

• Avoid iodine and contrast (can worsen it); reconcile amiodarone with cardiology (thyroid effects)

• Obtain baseline CBC and LFTs before a thionamide; manage AF (rate control and anticoagulation assessment)

Plan

CONSULT: Endocrinology (diagnosis, definitive therapy planning, thionamide management) · Cardiology (atrial fibrillation, heart failure, anticoagulation) · Ophthalmology (Graves ophthalmopathy) · Surgery (thyroidectomy candidates) · ICU if there are storm features

• First screen for thyroid storm (Burch-Wartofsky: fever, severe tachycardia, altered mental status, GI/hepatic dysfunction, CHF) — if present, treat per the storm pathway with ICU (see the thyroid storm card); this card is thyrotoxicosis without decompensation

• Symptom control — beta-blocker (first-line for symptoms): propranolol (which also blocks peripheral T4-to-T3 conversion at high dose) or atenolol/metoprolol; this controls tachycardia, tremor, anxiety, and palpitations — start promptly for symptomatic patients and AF (rate control)

• Thionamide — reduce hormone synthesis (cause-dependent): methimazole (preferred first-line for most — once daily, with fewer side effects) or propylthiouracil/PTU (preferred in first-trimester pregnancy and thyroid storm); not for thyroiditis (there is no synthesis to block — it is hormone release, and self-limited)

• • Counsel and monitor for agranulocytosis (fever or sore throat → stop and check a CBC) and hepatotoxicity (LFTs); obtain baseline CBC and LFTs

• Iodine (only when indicated, after a thionamide, especially pre-operatively or for storm): potassium iodide or Lugol's solution blocks release — give it at least 1 hour after the thionamide (iodine before a thionamide can fuel synthesis); not for routine outpatient thyrotoxicosis

• Definitive therapy (for Graves or toxic nodular disease — planned, not acute): radioactive iodine ablation, antithyroid drugs (Graves may remit), or thyroidectomy — endocrine-directed by cause and patient factors (eye disease, pregnancy, size, preference)

• Manage cardiac complications: atrial fibrillation (rate control with a beta-blocker, assess anticoagulation) and heart failure; treat precipitants (infection)

• Thyroiditis (low-uptake, transient): supportive care — a beta-blocker and NSAIDs (subacute painful disease) with steroids; no thionamide; self-limited (may pass through a hypothyroid phase)

• PT/OT: usually not needed; cardiac rehabilitation if there is heart failure

• Trend: heart rate and rhythm, symptoms, thyroid function (free T4/T3 — TSH lags), CBC (agranulocytosis), LFTs (hepatotoxicity), cardiac status, and the response

• Escalation triggers: thyroid storm features (fever, altered mental status, severe tachycardia or CHF) → the storm pathway and ICU; agranulocytosis (fever or sore throat with a low ANC) → stop the thionamide and involve ID/heme; severe cardiac decompensation → cardiology/ICU; thionamide hepatotoxicity → stop and involve endocrine

• Discharge checklist: symptoms controlled, on a beta-blocker and a thionamide (if indicated), with a definitive-therapy plan; the thionamide with agranulocytosis and hepatotoxicity counseling (stop and seek care for fever or sore throat); an AF and anticoagulation plan; endocrine follow-up (titration, definitive therapy), cardiology, and ophthalmology if there is eye disease; thyroid-function monitoring; avoid iodine and contrast; smoking cessation (eye disease); return precautions for fever or sore throat (agranulocytosis), jaundice, palpitations or chest pain, worsening (storm features), or eye changes

Red Flags

• Fever, marked tachycardia, altered mental status, or CHF → thyroid storm; the storm pathway and ICU

• Fever and sore throat on a thionamide → agranulocytosis; stop the drug and check an ANC

• Iodine given before a thionamide → can fuel hormone synthesis; always thionamide first

• Low-uptake thyroiditis → don't give a thionamide; it's leaking pre-formed hormone

• Atrial fibrillation → rate control and an anticoagulation assessment

Senior IM Resident Pearls

• Confirm, then find the mechanism. A suppressed TSH with high free T4/T3 confirms thyrotoxicosis; the uptake scan tells you the cause and therefore the treatment.

• The uptake scan separates thyroiditis from the rest. Low-uptake thyroiditis leaks pre-formed hormone with nothing to block — a thionamide does nothing.

• Beta-blocker for symptoms, thionamide for synthesis. These are the two acute drugs; propranolol also blunts peripheral T4-to-T3 conversion.

• Screen everyone for storm. Decompensation changes the urgency and the regimen entirely — don't relax until you've ruled it out.

• Iodine after the thionamide, never before. Given first, iodine feeds the gland the substrate it needs to make more hormone.

• Warn about agranulocytosis. A fever and sore throat on a thionamide means stop the drug and check a count — it's the dangerous idiosyncratic reaction.

• Common mistake: starting a thionamide for thyroiditis — the transient hormone leak is self-limited and managed with a beta-blocker and NSAIDs, not synthesis blockade.

Endocrinology — Thyroid Emergency

109. Thyroid Storm

decompensated thyrotoxicosis · life-threatening · Burch-Wartofsky score · the bundle in order: beta-blocker → PTU → iodine (≥1h after) → steroid · ICU · Super Compact

Sx: decompensated thyrotoxicosis — high fever (hyperpyrexia), severe tachycardia/atrial fibrillation, high-output heart failure, agitation/delirium/psychosis → seizures/coma, GI-hepatic dysfunction (nausea/vomiting/diarrhea, jaundice), profuse sweating, dehydration · usually a known/undiagnosed hyperthyroid patient with a precipitant · (thyroid storm is a clinical diagnosis — don't wait for labs, which look like ordinary hyperthyroidism; the Burch-Wartofsky score grades likelihood across fever, CNS, GI-hepatic, cardiac, and AF, and a high score means treat NOW in the ICU)

Neg: denies giving iodine before the thionamide (iodine first fuels hormone synthesis — always thionamide first, iodine ≥1h later) · denies waiting for labs to treat (clinical diagnosis — delay kills) · denies missed precipitant (infection, surgery, iodine/contrast, DKA, MI, trauma, childbirth, radioiodine, abrupt thionamide discontinuation) · denies using aspirin to cool (displaces T4 from binding — worsens; use acetaminophen) · denies under-recognizing high-output heart failure

SHx: known/prior hyperthyroidism or Graves, thionamide nonadherence/recent discontinuation, recent iodine/contrast/amiodarone, recent surgery/radioiodine, infection, pregnancy/childbirth, missed diagnosis, family/autoimmune history

Etiology: severe decompensated thyrotoxicosis (Graves, toxic nodular, thyroiditis) tipped over by a precipitant → exaggerated hormone effect + adrenergic surge → multi-organ dysfunction (cardiac, CNS, thermoregulatory, GI-hepatic) · precipitants: infection (most common), surgery/thyroid manipulation, iodinated contrast/iodine, radioiodine therapy, DKA, MI/stroke, trauma, parturition, abrupt antithyroid-drug cessation

RF: untreated/undertreated hyperthyroidism · thionamide nonadherence · iodine/contrast/amiodarone · recent surgery/radioiodine · infection · pregnancy

Data: clinical diagnosis (Burch-Wartofsky score) — DO NOT delay treatment for labs · TSH (suppressed) + free T4/T3 (high) confirm thyrotoxicosis but don't distinguish storm from uncomplicated; precipitant workup: CBC, cultures/UA/CXR (infection), ECG (AF/ischemia), troponin, glucose (DKA), LFTs (hepatic dysfunction), BMP, lactate; baseline CBC/LFTs before thionamide

DDx: thyroid storm · severe uncomplicated thyrotoxicosis · sepsis/septic shock (may coexist/precipitate) · heat stroke · malignant hyperthermia/neuroleptic malignant syndrome · pheochromocytoma crisis · sympathomimetic toxicity · delirium/agitation other cause · acute heart failure other cause

Home Meds: reconcile (often thionamide nonadherence is the trigger); avoid iodinated contrast; hold amiodarone discussion with cardiology; manage AF/anticoagulation; resume/intensify antithyroid therapy + plan definitive treatment

Plan

CONSULT: ICU (mandatory — multi-organ support, monitoring) · Endocrinology (urgent — bundle guidance, definitive therapy) · Cardiology (AF, high-output heart failure) · ID/source-specific (precipitant infection) · Surgery (if surgical precipitant/definitive plan)

– ICU + TREAT EMPIRICALLY on clinical suspicion — the BUNDLE IN ORDER:
  • 1) BETA-BLOCKER — propranolol (IV/PO; controls adrenergic storm + tachycardia AND blocks peripheral T4→T3 conversion at high dose); esmolol infusion if cardiac instability/need titratability; cautious in high-output failure (cardiology)
  • 2) THIONAMIDE — PTU (propylthiouracil) preferred in storm (blocks new synthesis AND peripheral T4→T3 conversion — the advantage over methimazole here); high-dose loading then scheduled
  • 3) IODINE — potassium iodide/SSKI or Lugol's solution — give ≥1 HOUR AFTER the thionamide (Wolff-Chaikoff effect blocks hormone release; giving it before/without a thionamide would supply substrate for synthesis)
  • 4) GLUCOCORTICOID — hydrocortisone (e.g. 100 mg IV q8h) or dexamethasone (blocks peripheral T4→T3 conversion + treats possible relative adrenal insufficiency + may help autoimmune component)
– SUPPORTIVE / treat the storm physiology: cooling + acetaminophen for fever (NOT aspirin — displaces T4, worsens), IV fluids + dextrose + electrolytes (high metabolic demand), treat heart failure/arrhythmia, treat agitation; VTE prophylaxis
– IDENTIFY + TREAT THE PRECIPITANT: infection (cultures + antibiotics), DKA, MI, etc. — storm won't resolve without it
– REFRACTORY/ADJUNCT: bile acid sequestrant (cholestyramine) interrupts enterohepatic hormone recirculation; plasmapheresis/therapeutic plasma exchange for refractory/critical cases; emergent thyroidectomy rarely
– AFTER stabilization: plan definitive therapy (radioiodine or thyroidectomy) for the underlying hyperthyroidism with endocrine
– Thyroid storm is a clinical diagnosis you treat before the labs come back, because the thyroid panel looks just like ordinary hyperthyroidism — the difference is the decompensation, which the Burch-Wartofsky score helps you quantify. Learn the bundle as an ordered sequence: beta-blocker to break the adrenergic storm, PTU (preferred over methimazole here because it also blocks peripheral conversion), then iodine but only at least an hour AFTER the thionamide — give iodine first and you've just handed the gland the raw material to make more hormone — and a glucocorticoid, which blocks conversion and covers a possible relative adrenal insufficiency. Two bedside details that catch people: cool with acetaminophen, never aspirin, which displaces T4 and makes things worse; and always find the precipitant, usually infection, because the storm won't break until it's treated. Mortality is high — this is an ICU diagnosis.
– PT/OT: later — recovery from critical illness, deconditioning
– Trend: temperature, heart rate/rhythm, mental status, cardiac/volume status, thyroid function (trend), LFTs, precipitant resolution, Burch-Wartofsky improvement, organ function
– Escalation triggers: already ICU — refractory storm despite the bundle → plasmapheresis + emergent endocrine/surgery; cardiovascular collapse/malignant arrhythmia → advanced cardiac support; multi-organ failure → organ support; superimposed sepsis → sepsis pathway
– Discharge checklist (after ICU recovery): storm resolved + on antithyroid regimen + precipitant treated + definitive-therapy plan; thionamide + beta-blocker with strict adherence + agranulocytosis counseling; arranged radioiodine/thyroidectomy; endocrine + cardiology follow-up; AF/anticoagulation plan; avoid iodine/contrast; education on adherence (nonadherence is a classic trigger) + storm warning signs; return precautions (fever, palpitations, agitation/confusion, vomiting, recurrence of storm symptoms)

109. Thyroid Storm

complete reference · decompensated thyrotoxicosis emergency · Burch-Wartofsky, the ordered bundle (beta-blocker → PTU → iodine after → steroid), acetaminophen not aspirin, treat precipitant · Full Card

Symptoms / Associated Sx

• Decompensated thyrotoxicosis — high fever (hyperpyrexia), severe tachycardia or atrial fibrillation, and high-output heart failure

• Agitation, delirium, or psychosis progressing to seizures or coma, GI-hepatic dysfunction (nausea, vomiting, diarrhea, jaundice), profuse sweating, and dehydration

• Usually a known or undiagnosed hyperthyroid patient with a precipitant

• Thyroid storm is a clinical diagnosis — don't wait for labs, which look like ordinary hyperthyroidism; the Burch-Wartofsky score grades likelihood across fever, CNS, GI-hepatic, cardiac, and AF features, and a high score means treat now in the ICU

Neg

• Pt denies giving iodine before the thionamide (iodine first fuels hormone synthesis — always thionamide first, iodine at least 1 hour later)

• Pt denies waiting for labs to treat (a clinical diagnosis — delay kills) and a missed precipitant (infection, surgery, iodine or contrast, DKA, MI, trauma, childbirth, radioiodine, abrupt thionamide discontinuation)

• Pt denies using aspirin to cool (it displaces T4 from binding — worsening it; use acetaminophen) and under-recognizing high-output heart failure

Social History (SHx)

• Known or prior hyperthyroidism or Graves, thionamide nonadherence or recent discontinuation, and recent iodine, contrast, or amiodarone

• Recent surgery or radioiodine, infection, and pregnancy or childbirth

• A missed diagnosis and family or autoimmune history

Main Etiology

• Severe decompensated thyrotoxicosis (Graves, toxic nodular disease, thyroiditis) tipped over by a precipitant produces an exaggerated hormone effect and adrenergic surge, causing multi-organ dysfunction (cardiac, CNS, thermoregulatory, GI-hepatic)

• Precipitants: infection (the most common), surgery or thyroid manipulation, iodinated contrast or iodine, radioiodine therapy, DKA, MI or stroke, trauma, parturition, and abrupt antithyroid-drug cessation

RF

• Modifiable: thionamide nonadherence, iodine, contrast, or amiodarone exposure, and undertreated hyperthyroidism

• Non-modifiable: untreated hyperthyroidism, recent surgery or radioiodine, infection, and pregnancy

Data

• A clinical diagnosis (the Burch-Wartofsky score) — do not delay treatment for labs

• TSH (suppressed) and free T4/T3 (high) confirm thyrotoxicosis but don't distinguish storm from uncomplicated disease

• Precipitant workup: CBC, cultures/urinalysis/CXR (infection), an ECG (AF, ischemia), troponin, glucose (DKA), and LFTs (hepatic dysfunction), a BMP, and lactate

• Baseline CBC and LFTs before a thionamide

DDx

Thyroid storm · severe uncomplicated thyrotoxicosis · sepsis or septic shock (may coexist or precipitate) · heat stroke · malignant hyperthermia or neuroleptic malignant syndrome · pheochromocytoma crisis · sympathomimetic toxicity · delirium or agitation of another cause · acute heart failure of another cause

Home Meds

• Reconcile (thionamide nonadherence is often the trigger)

• Avoid iodinated contrast; discuss amiodarone with cardiology; manage AF and anticoagulation

• Resume and intensify antithyroid therapy and plan definitive treatment

Plan

CONSULT: ICU (mandatory — multi-organ support, monitoring) · Endocrinology (urgent — bundle guidance, definitive therapy) · Cardiology (AF, high-output heart failure) · ID or source-specific (a precipitant infection) · Surgery (if there is a surgical precipitant or definitive plan)

• ICU plus treat empirically on clinical suspicion — the bundle in order:

• • 1) Beta-blocker — propranolol (IV/PO; controls the adrenergic storm and tachycardia and blocks peripheral T4-to-T3 conversion at high dose); an esmolol infusion if there is cardiac instability or a need for titratability; cautious in high-output failure (cardiology)

• • 2) Thionamide — PTU (propylthiouracil) preferred in storm (it blocks new synthesis and peripheral T4-to-T3 conversion — the advantage over methimazole here); high-dose loading then scheduled dosing

• • 3) Iodine — potassium iodide/SSKI or Lugol's solution — give it at least 1 hour after the thionamide (the Wolff-Chaikoff effect blocks hormone release; giving it before or without a thionamide would supply substrate for synthesis)

• • 4) Glucocorticoid — hydrocortisone (e.g. 100 mg IV every 8 hours) or dexamethasone (blocks peripheral T4-to-T3 conversion, treats a possible relative adrenal insufficiency, and may help the autoimmune component)

• Supportive care / treat the storm physiology: cooling with acetaminophen for fever (not aspirin — it displaces T4 and worsens the storm), IV fluids with dextrose and electrolytes (high metabolic demand), treatment of heart failure and arrhythmia, treatment of agitation, and VTE prophylaxis

• Identify and treat the precipitant: infection (cultures and antibiotics), DKA, MI, and others — the storm won't resolve without it

• Refractory or adjunct measures: a bile acid sequestrant (cholestyramine) interrupts enterohepatic hormone recirculation; plasmapheresis or therapeutic plasma exchange for refractory or critical cases; and rarely emergent thyroidectomy

• After stabilization: plan definitive therapy (radioiodine or thyroidectomy) for the underlying hyperthyroidism with endocrine

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

• Trend: temperature, heart rate and rhythm, mental status, cardiac and volume status, thyroid function (trend), LFTs, precipitant resolution, Burch-Wartofsky improvement, and organ function

• Escalation triggers: already in the ICU — refractory storm despite the bundle → plasmapheresis with emergent endocrine and surgery; cardiovascular collapse or malignant arrhythmia → advanced cardiac support; multi-organ failure → organ support; superimposed sepsis → the sepsis pathway

• Discharge checklist (after ICU recovery): the storm resolved, on an antithyroid regimen, with the precipitant treated and a definitive-therapy plan; a thionamide and beta-blocker with strict adherence and agranulocytosis counseling; arranged radioiodine or thyroidectomy; endocrine and cardiology follow-up; an AF and anticoagulation plan; avoid iodine and contrast; education on adherence (nonadherence is a classic trigger) and storm warning signs; return precautions for fever, palpitations, agitation or confusion, vomiting, or recurrence of storm symptoms

Red Flags

• Fever, severe tachycardia, altered mental status, and GI-hepatic dysfunction → thyroid storm; treat empirically and move to the ICU

• Iodine before the thionamide → fuels hormone synthesis; always thionamide first, iodine at least an hour later

• Aspirin for fever → displaces T4 and worsens the storm; use acetaminophen

• A missed precipitant (infection most common) → the storm won't break until it's treated

• Refractory storm despite the bundle → plasmapheresis and emergent endocrine/surgery

Senior IM Resident Pearls

• Treat before the labs return. The thyroid panel looks like ordinary hyperthyroidism — the diagnosis is the decompensation, which Burch-Wartofsky quantifies.

• Learn the bundle as an ordered sequence. Beta-blocker, then PTU, then iodine at least an hour later, then a glucocorticoid.

• PTU is preferred here. Unlike methimazole, it also blocks peripheral T4-to-T3 conversion, which matters in the acute storm.

• Iodine after the thionamide, never before. Given first, iodine supplies the gland the substrate to make more hormone.

• Cool with acetaminophen, not aspirin. Aspirin displaces T4 from binding proteins and worsens the thyrotoxicosis.

• Find the precipitant. Infection is the usual trigger — the storm won't resolve while it's untreated.

• Common mistake: giving iodine and the thionamide together or iodine first — sequence matters, and getting it wrong transiently worsens the storm.

Endocrinology — Thyroid

110. Severe Hypothyroidism

symptomatic hypothyroidism · medication noncompliance · levothyroxine replacement · start low in elderly/cardiac · steroid BEFORE thyroid if central/adrenal concern · Super Compact

Sx: fatigue, cold intolerance, weight gain, constipation, dry skin, hair loss, bradycardia, delayed (slow-relaxing) reflexes, depression/cognitive slowing, menstrual changes, myalgias, hoarseness, periorbital/peripheral edema; severe/chronic → effusions, anemia, hyponatremia · (the most common reason for severe hypothyroidism in a previously diagnosed patient is simply stopping levothyroxine — and the key safety screen is for myxedema coma features, hypothermia + altered mental status + hypoventilation, because that decompensated form is a separate emergency)

Neg: denies missed myxedema coma features (hypothermia, AMS/obtundation, hypoventilation/CO₂ retention, hypotension — that's the emergency; see myxedema card) · denies missed central hypothyroidism / concurrent adrenal insufficiency (must give glucocorticoid BEFORE levothyroxine — replacing thyroid first can precipitate adrenal crisis) · denies starting full-dose levothyroxine in an elderly/cardiac patient (angina/arrhythmia risk) · denies missed reversible cause/precipitant

SHx: known hypothyroidism + levothyroxine adherence (the common driver), prior thyroid surgery/radioiodine/neck radiation, autoimmune disease (Hashimoto), medications (amiodarone, lithium, checkpoint inhibitors), pituitary disease (central), absorption issues (celiac, bariatric, PPI/calcium/iron timing), pregnancy, recent illness

Etiology: primary (thyroid gland failure — high TSH): Hashimoto autoimmune thyroiditis (most common), post-thyroidectomy/radioiodine, iodine deficiency/excess, drugs (amiodarone, lithium, immunotherapy), levothyroxine nonadherence/malabsorption · central (pituitary/hypothalamic — low/inappropriately normal TSH + low free T4): pituitary disease — important because it implies possible concurrent adrenal insufficiency

RF: autoimmune disease/Hashimoto · prior thyroid surgery/RAI/radiation · levothyroxine nonadherence · amiodarone/lithium/immunotherapy · pituitary disease · female · malabsorption

Data: TSH + free T4 — high TSH + low free T4 = primary; low/inappropriately normal TSH + low free T4 = central (check pituitary axis + cortisol) · TPO antibodies (Hashimoto); screen severity: temperature, mental status, sodium (hyponatremia), CBC (anemia), CK, glucose, lipids; cortisol/ACTH if central or adrenal concern (before levothyroxine); ECG (bradycardia, low voltage); precipitant workup if severe

DDx: primary hypothyroidism (Hashimoto/post-ablative) · central hypothyroidism · levothyroxine nonadherence/malabsorption · myxedema coma (decompensated — emergency) · sick euthyroid (non-thyroidal illness) · depression · anemia/other fatigue causes · drug-induced (amiodarone/lithium/immunotherapy)

Home Meds: levothyroxine — reconcile + identify nonadherence cause; review absorption interactions (separate from calcium/iron/PPI; take empty stomach); review thyroid-affecting drugs (amiodarone, lithium); if central/adrenal concern → glucocorticoid first; resume/optimize with education + access plan

Plan

CONSULT: Endocrinology (severe/central/refractory, dosing in cardiac disease, immunotherapy-related) · Cardiology (if cardiac disease — careful repletion) · ICU if myxedema coma features · Social work/pharmacy (levothyroxine access/adherence — prevents recurrence)

– FIRST screen for myxedema coma (hypothermia, AMS, hypoventilation, hypotension, hyponatremia) — if present, that's the emergency: ICU + IV levothyroxine + stress-dose hydrocortisone (see myxedema coma card); this card = severe but compensated hypothyroidism
– RULE OUT / COVER ADRENAL INSUFFICIENCY if central hypothyroidism or panhypopituitarism suspected: give glucocorticoid (hydrocortisone) BEFORE starting levothyroxine — replacing thyroid hormone first accelerates cortisol metabolism and can precipitate adrenal crisis; check cortisol/ACTH
– LEVOTHYROXINE REPLACEMENT (the core treatment):
  • Young/healthy: full replacement ~1.6 mcg/kg/day oral levothyroxine once daily, empty stomach
  • Elderly or known/suspected coronary disease: START LOW + go slow (e.g. ~25–50 mcg/day, titrate gradually) — rapid full replacement can precipitate angina/arrhythmia/MI
  • Malabsorption: address cause, ensure correct administration (separate from calcium/iron/PPI/food)
– ADDRESS THE NONADHERENCE ROOT CAUSE: why stopped (cost, forgot, side effects, didn't feel benefit) → education, simplify, secure access/affordability, follow-up — the readmission driver
– TREAT PRECIPITANTS / CONTRIBUTORS: infection, review offending drugs (amiodarone/lithium/immunotherapy); manage associated findings (hyponatremia, anemia)
– MONITOR + TITRATE: recheck TSH ~6 weeks after dose changes (don't chase daily); symptom + labs guide titration
– Most severe hypothyroidism in a known patient is just a stopped levothyroxine, so the real fix is finding out why they stopped and securing access, not a clever dosing scheme. Two safety reflexes matter more than the dose. First, screen for myxedema coma — hypothermia, altered mentation, hypoventilation — because that's a separate ICU emergency. Second, if there's any suggestion of central hypothyroidism or panhypopituitarism, give the glucocorticoid BEFORE the levothyroxine, because replacing thyroid hormone first speeds cortisol clearance and can tip an unrecognized adrenal insufficiency into crisis. On dosing, young and healthy can take full weight-based replacement, but in the elderly or anyone with coronary disease, start low and go slow — flooding a slow heart with thyroid hormone provokes angina and arrhythmia. And recheck the TSH at six weeks, not every day.
– PT/OT: usually not needed unless severe deconditioning/myopathy
– Trend: symptoms, heart rate, mental status, sodium, free T4 (early)/TSH (delayed — 6 wk), tolerance of repletion (chest pain/palpitations in cardiac patients), precipitant resolution
– Escalation triggers: myxedema coma features (hypothermia, AMS, hypoventilation) → ICU + emergency pathway; cardiac symptoms on repletion (angina/arrhythmia) → slow/hold + cardiology; suspected adrenal insufficiency → steroids first + endocrine; severe hyponatremia/refractory → respective management
– Discharge checklist: on appropriate levothyroxine dose + nonadherence cause addressed + access secured + precipitant treated; levothyroxine with administration counseling (empty stomach, separate from calcium/iron/PPI) + adherence/affordability plan; TSH recheck (~6 wk) + titration plan; endocrine/PCP follow-up; cardiac caution counseling if applicable; education on never abruptly stopping; return precautions (worsening fatigue/cold, confusion/slowed mentation, chest pain/palpitations on therapy, very low temperature)

110. Severe Hypothyroidism

complete reference · symptomatic + noncompliance · levothyroxine repletion, start low in elderly/cardiac, glucocorticoid before thyroid if central, screen for myxedema coma, fix adherence · Full Card

Symptoms / Associated Sx

• Fatigue, cold intolerance, weight gain, constipation, dry skin, hair loss, bradycardia, and delayed (slow-relaxing) reflexes

• Depression or cognitive slowing, menstrual changes, myalgias, hoarseness, and periorbital or peripheral edema

• Severe or chronic disease: effusions, anemia, and hyponatremia

• The most common reason for severe hypothyroidism in a previously diagnosed patient is simply stopping levothyroxine — and the key safety screen is for myxedema coma features (hypothermia, altered mental status, hypoventilation), because that decompensated form is a separate emergency

Neg

• Pt denies a missed myxedema coma (hypothermia, altered mental status or obtundation, hypoventilation or CO₂ retention, hypotension — that's the emergency; see the myxedema card)

• Pt denies a missed central hypothyroidism or concurrent adrenal insufficiency (must give a glucocorticoid before levothyroxine — replacing thyroid first can precipitate adrenal crisis)

• Pt denies starting full-dose levothyroxine in an elderly or cardiac patient (angina or arrhythmia risk) and a missed reversible cause or precipitant

Social History (SHx)

• Known hypothyroidism and levothyroxine adherence (the common driver), and prior thyroid surgery, radioiodine, or neck radiation

• Autoimmune disease (Hashimoto), medications (amiodarone, lithium, checkpoint inhibitors), and pituitary disease (central)

• Absorption issues (celiac disease, bariatric surgery, PPI/calcium/iron timing), pregnancy, and recent illness

Main Etiology

• Primary (thyroid gland failure — high TSH): Hashimoto autoimmune thyroiditis (the most common), post-thyroidectomy or radioiodine disease, iodine deficiency or excess, drugs (amiodarone, lithium, immunotherapy), and levothyroxine nonadherence or malabsorption

• Central (pituitary or hypothalamic — low or inappropriately normal TSH with low free T4): pituitary disease — important because it implies possible concurrent adrenal insufficiency

RF

• Modifiable: levothyroxine nonadherence, amiodarone, lithium, or immunotherapy, and malabsorption

• Non-modifiable: autoimmune disease or Hashimoto, prior thyroid surgery, RAI, or radiation, pituitary disease, and female sex

Data

• TSH and free T4 — a high TSH with low free T4 is primary; a low or inappropriately normal TSH with low free T4 is central (check the pituitary axis and cortisol)

• TPO antibodies (Hashimoto)

• Screen severity: temperature, mental status, sodium (hyponatremia), CBC (anemia), CK, glucose, and lipids

• Cortisol and ACTH if there is a central or adrenal concern (before levothyroxine); an ECG (bradycardia, low voltage); a precipitant workup if severe

DDx

Primary hypothyroidism (Hashimoto, post-ablative) · central hypothyroidism · levothyroxine nonadherence or malabsorption · myxedema coma (decompensated — an emergency) · sick euthyroid syndrome (non-thyroidal illness) · depression · anemia or another cause of fatigue · drug-induced disease (amiodarone, lithium, immunotherapy)

Home Meds

• Reconcile levothyroxine and identify the cause of nonadherence

• Review absorption interactions (separate from calcium, iron, and PPIs; take on an empty stomach) and thyroid-affecting drugs (amiodarone, lithium)

• If there is a central or adrenal concern → a glucocorticoid first; resume and optimize with education and an access plan

Plan

CONSULT: Endocrinology (severe, central, or refractory disease, dosing in cardiac disease, immunotherapy-related disease) · Cardiology (if there is cardiac disease — careful repletion) · ICU if there are myxedema coma features · Social work/pharmacy (levothyroxine access and adherence — prevents recurrence)

• First screen for myxedema coma (hypothermia, altered mental status, hypoventilation, hypotension, hyponatremia) — if present, that's the emergency: ICU, IV levothyroxine, and stress-dose hydrocortisone (see the myxedema coma card); this card is severe but compensated hypothyroidism

• Rule out and cover adrenal insufficiency if central hypothyroidism or panhypopituitarism is suspected: give a glucocorticoid (hydrocortisone) before starting levothyroxine — replacing thyroid hormone first accelerates cortisol metabolism and can precipitate adrenal crisis; check cortisol and ACTH

• Levothyroxine replacement (the core treatment):

• • Young or healthy: full replacement at ~1.6 mcg/kg/day of oral levothyroxine once daily, on an empty stomach

• • Elderly or with known or suspected coronary disease: start low and go slow (e.g. ~25–50 mcg/day, titrated gradually) — rapid full replacement can precipitate angina, arrhythmia, or MI

• • Malabsorption: address the cause and ensure correct administration (separate from calcium, iron, PPIs, and food)

• Address the nonadherence root cause: why it was stopped (cost, forgot, side effects, didn't feel benefit) → education, simplification, secured access and affordability, and follow-up — the readmission driver

• Treat precipitants and contributors: infection, a review of offending drugs (amiodarone, lithium, immunotherapy); and manage associated findings (hyponatremia, anemia)

• Monitor and titrate: recheck TSH at ~6 weeks after dose changes (don't chase it daily); symptoms and labs guide titration

• PT/OT: usually not needed unless there is severe deconditioning or myopathy

• Trend: symptoms, heart rate, mental status, sodium, free T4 (early) and TSH (delayed — 6 weeks), tolerance of repletion (chest pain or palpitations in cardiac patients), and precipitant resolution

• Escalation triggers: myxedema coma features (hypothermia, altered mental status, hypoventilation) → ICU and the emergency pathway; cardiac symptoms on repletion (angina, arrhythmia) → slow or hold and involve cardiology; suspected adrenal insufficiency → steroids first with endocrine; severe hyponatremia or refractory disease → the respective management

• Discharge checklist: on an appropriate levothyroxine dose, the nonadherence cause addressed, access secured, and the precipitant treated; levothyroxine with administration counseling (empty stomach, separate from calcium, iron, and PPIs) and an adherence and affordability plan; a TSH recheck (~6 weeks) and titration plan; endocrine and PCP follow-up; cardiac caution counseling if applicable; education on never abruptly stopping; return precautions for worsening fatigue or cold, confusion or slowed mentation, chest pain or palpitations on therapy, or a very low temperature

Red Flags

• Hypothermia, altered mental status, and hypoventilation → myxedema coma; ICU and the emergency pathway

• Central hypothyroidism or panhypopituitarism → give a glucocorticoid before levothyroxine to avoid precipitating adrenal crisis

• Full-dose levothyroxine in the elderly or a cardiac patient → angina, arrhythmia, or MI; start low and go slow

• Chest pain or palpitations on repletion → slow or hold and reassess with cardiology

• Recurrent severe hypothyroidism → an unaddressed access or adherence barrier

Senior IM Resident Pearls

• Most cases are a stopped levothyroxine. The real fix is finding out why and securing access, not a clever dosing scheme.

• Screen for myxedema coma first. Hypothermia, altered mentation, and hypoventilation make it a separate ICU emergency.

• Steroid before thyroid if central. Replacing thyroid hormone first speeds cortisol clearance and can tip an unrecognized adrenal insufficiency into crisis.

• Start low and go slow in the elderly and cardiac patient. Flooding a slow heart with thyroid hormone provokes angina and arrhythmia.

• Recheck the TSH at six weeks. It lags behind dose changes, so daily or weekly checks just mislead.

• Mind the absorption. Levothyroxine needs an empty stomach and separation from calcium, iron, and PPIs, or "nonadherence" may actually be malabsorption.

• Common mistake: giving levothyroxine to a panhypopituitary patient without first covering with hydrocortisone — it can precipitate an adrenal crisis.