EpistemisSymptomatic hypercalcemia
Specialty: Endocrine and metabolic.
Why it occurs
- Primary hyperparathyroidism (single adenoma or diffuse hyperplasia of the parathyroid glands with autonomous and deregulated secretion of parathyroid hormone)
- Malignant tumor hypercalcemia (systemic secretion of parathyroid hormone-related peptide (PTHrP) from squamous cell carcinomas of the lung or head and neck, or osteolytic bone destruction from multiple myeloma or breast cancer metastasis)
- Vitamin D or vitamin A poisoning (massive exogenous intake with exaggerated increase in intestinal absorption and bone resorption of calcium)
- Sarcoidosis or active tuberculosis (autonomous extrarenal production of active 1,25-dihydroxyvitamin D by activated alveolar macrophages in granulomas)
- Chronic consumption of thiazide diuretics or lithium carbonate (they decrease urinary calcium excretion or increase the detection threshold of the calcium sensor in the parathyroid)
Initial workup
Total serum calcium corrected by albumin or preferably serum ionized calcium; plasma phosphorus and magnesium; intact parathyroid hormone (iPTH) to immediately differentiate parathyroid-dependent or parathyroid-independent causes; serum PTHrP levels if iPTH is suppressed; quantification of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D; plasma creatinine and urea nitrogen; and 12-lead electrocardiogram to monitor cardiac repolarization.
red flags
Acute and progressive alteration of mental status (lethargy, mental confusion, psychosis, stupor or coma), significant shortening of the QT interval with complex ventricular arrhythmias, severe dehydration with inability to oral fluid replacement due to repetitive nausea and vomiting, exquisite abdominal pain suggestive of acute pancreatitis, or oliguria/anuria due to acute obstructive renal failure due to bilateral nephrolithiasis.
Standard management
- 0.9% physiological saline solution — vigorous intravenous infusion of 2-4 liters daily in the first 24-48 hours to force osmotic diuresis and promote passive renal elimination of calcium
- Furosemide — loop diuretic, administered intravenously at doses of 20-40 mg only *after* intravascular fluid volume has been completely restored, to safely prevent tubular calcium reabsorption
- Zoledronic acid — 4 mg intravenous bisphosphonate infused over 15 minutes, to inhibit osteoclast bone resorption, with maximum effect 2-4 days after administration
- Denosumab — monoclonal antibody directed against the RANK ligand, indicated in cases of malignant hypercalcemia refractory to bisphosphonates or in the presence of severe renal failure
- Salmon calcitonin — administered subcutaneously or intramuscularly at doses of 4-8 IU/kg every 12 hours, with rapid action to reduce serum calcium in the first 24 hours by inhibiting osteoclastic clearance
Educational guidance for study. It is NOT a prescription recommendation. The actual choice depends on the cause, the patient, and current guidelines.
- Area
- Endocrine and metabolic
- Listed causes
- 5
- Treatment options
- 5