HYPERCALCEMIA

"Bones, Stones, Groans, and Psychic Moans" — serum Ca >10.5 mg/dL; acute/severe causes AMS, arrhythmias, and renal failure

SYMPTOMS / ASSOCIATED SX

• "Bones, Stones, Groans, and Psychic Moans" — classic mnemonic

• Bones: bone pain, osteitis fibrosa cystica (primary hyperparathyroidism)

• Stones: nephrolithiasis (calcium oxalate/phosphate), nephrocalcinosis, polyuria, polydipsia

• Groans: nausea, vomiting, constipation, anorexia, pancreatitis

• Psychic Moans: depression, confusion, fatigue, AMS, coma (Ca >14 mg/dL)

• ECG: shortened QT interval; bradyarrhythmia, AV block at high levels

DENIES

• Bone pain (primary hyperparathyroidism, metastatic disease, multiple myeloma)

• Symptoms of malignancy: weight loss, B symptoms, lymphadenopathy

• Vitamin D or calcium supplement use

• Lithium use (stimulates PTH secretion); thiazide diuretics (reduce urinary Ca excretion)

SOCIAL HISTORY

• Lithium use; thiazide diuretics; excessive vitamin D/A supplements

• Immobilization (increases osteoclastic activity)

MAIN ETIOLOGY

• Primary hyperparathyroidism (most common outpatient — 90% adenoma, 10% hyperplasia); elevated PTH

• Malignancy (most common inpatient): PTHrP-mediated (squamous cell, RCC, breast, bladder), lytic bone mets (breast, myeloma), 1,25-OH D production (lymphoma)

• Granulomatous: sarcoidosis, TB, histoplasmosis — extrarenal 1-alpha hydroxylase

• Medications: thiazides, lithium, vitamin D/A toxicity, milk-alkali syndrome

• Familial hypocalciuric hypercalcemia (FHH): benign; CASR mutation; Ca:Cr clearance ratio <0.01

MOST COMMON DDX

• Primary hyperparathyroidism (PTH elevated; outpatient, usually mild, often asymptomatic)

• Malignancy-associated (PTH suppressed; acute/severe; PTHrP elevated or lytic lesions)

• Sarcoidosis (PTH low, 1,25-OH D elevated; bilateral hilar adenopathy; ACE elevated)

• FHH (benign; 24h urine Ca low; Ca:Cr clearance <0.01; CASR mutation — do NOT operate)

• Vitamin D toxicity (25-OH D elevated; supplement history)

• Milk-alkali syndrome (CaCO3 excess + alkalosis + AKI)

DATA

• Serum Ca (total and ionized); albumin — correct Ca: add 0.8 per 1 g/dL albumin below 4

• Intact PTH — low/suppressed (malignancy/granulomatous/vitamin D) vs. elevated (PHPT/FHH/lithium)

• PTHrP; 25-OH vitamin D; 1,25-OH vitamin D (elevated in granulomatous)

• BMP (Cr — AKI; Phos — low in PHPT, high in vitamin D toxicity)

• ACE, ESR/CRP (sarcoidosis); SPEP, UPEP (myeloma)

• CXR (hilar adenopathy — sarcoidosis; pulmonary mass — malignancy)

• ECG (shortened QT, bradyarrhythmia)

• 24h urine Ca + Cr (FHH: Ca:Cr clearance <0.01)

HOME MEDS

• Thiazides — hold (reduce urinary Ca, worsen hypercalcemia)

• Calcium supplements, vitamin D — hold

• Lithium — reassess with endocrinology

• Digoxin — hold; hypercalcemia potentiates toxicity

PLAN

• Acute/symptomatic hypercalcemia (Ca >12 or symptomatic):

  • IV hydration: NS 0.9% 200–500 mL/h; goal urine output 100–150 mL/h; 3–6 L over 24h typically

  • Furosemide 20–40 mg IV ONLY AFTER adequate hydration — NOT before (risk worsening dehydration)

  • Zoledronic acid 4 mg IV over 15 min (preferred; requires Cr <3.5; do not use if CrCl <35)

  • Pamidronate 60–90 mg IV over 2–4h (alternative if moderate CKD)

  • Bisphosphonate onset 2–4 days; peak effect 4–7 days; duration 3–4 weeks

  • Calcitonin 4 IU/kg SC/IM q12h — rapid onset 4–6h; lowers Ca 1–2 mg/dL; tachyphylaxis in 48–72h (bridge to bisphosphonate)

  • Denosumab 120 mg SC q4 weeks (if bisphosphonate-refractory or CKD)

• Specific causes:

  • Primary hyperparathyroidism: parathyroidectomy if symptomatic; cinacalcet 30 mg PO BID if not surgical candidate

  • Granulomatous (sarcoidosis): prednisone 20–40 mg PO daily (reduces 1-alpha hydroxylase)

  • Vitamin D toxicity: stop supplement; glucocorticoids if severe; fluids

• Dialysis: emergent if severe + oliguric AKI or refractory (calcium-free dialysate)

• DISCHARGE:

  • Primary hyperparathyroidism: outpatient endocrine/surgery; monitor Ca, Cr, DEXA annually

  • Malignancy-associated: oncology; bisphosphonate maintenance; palliative care if appropriate

  • Low-calcium diet (<1000 mg/day) if primary hyperparathyroidism or granulomatous

RED FLAGS

• Ca >14 mg/dL or symptomatic at any level (AMS, seizure, arrhythmia) → hypercalcemic crisis; aggressive IVF + immediate bisphosphonate + calcitonin; ICU

• Shortened QT + bradyarrhythmia → ECG monitoring; Ca >15 → emergent dialysis

• Digoxin + hypercalcemia → markedly increased toxicity; hold digoxin

• Hypercalcemia + AMS → always rule out malignancy (PTHrP) and granulomatous disease

• Bisphosphonates in CKD: zoledronic acid contraindicated if CrCl <35; use pamidronate or denosumab

SENIOR IM RESIDENT PEARLS

• "Bones, Stones, Groans, Psychic Moans" — commit to memory

• Primary hyperparathyroidism is most common outpatient; malignancy is most common inpatient

• PTH is the single most important test — interpret before ordering all others

• Calcitonin: fastest-acting (4–6h) but tachyphylaxis develops in 48–72h — use as bridge to bisphosphonate

• Common mistake: giving furosemide BEFORE adequate hydration — causes dangerous dehydration in volume-depleted patient

• FHH: Ca:Cr clearance ratio <0.01 on 24h urine; benign CASR mutation; no treatment needed — do NOT operate

• Common mistake: diagnosing primary hyperparathyroidism without ruling out FHH — unnecessary parathyroidectomy is ineffective and harmful