Overview
This lecture reviews the definition, evaluation, causes, and management of hypercalcemia, with emphasis on distinguishing parathyroid hormone (PTH)–mediated from non–PTH-mediated cases.
Definition and Diagnosis of Hypercalcemia
- Hypercalcemia is defined as albumin-corrected serum calcium above the upper normal limit for the local laboratory.
- Ionized calcium measurement is usually unnecessary in outpatients unless there are albumin or acid-base disturbances.
- Mild fluctuations near the upper normal limit should be monitored over time rather than treated immediately.
Clinical Significance and Symptoms
- Hypercalcemia may signal underlying disease (e.g., vitamin D toxicity, malignancy) and should prompt diagnostic evaluation.
- Severe or rapidly rising hypercalcemia (typically ≥14 mg/dL) may cause symptoms like polydipsia, polyuria, GI symptoms, mental status changes, or cardiac arrhythmias, and requires urgent treatment.
- Chronic, mild hypercalcemia may be asymptomatic and does not always require treatment.
Initial Evaluation
- Evaluate the history, review old labs, and assess medication and supplement use.
- Perform a physical exam, looking for signs of malignancy or other causes.
- Measure PTH and serum calcium simultaneously to determine if hypercalcemia is PTH-mediated.
PTH-Mediated Hypercalcemia
- Most commonly caused by primary hyperparathyroidism (PHPT).
- Assess for familial causes in young patients or those with a family history.
- Next steps: determine if the patient meets surgical criteria—symptoms, serum calcium >1 mg/dL above normal, creatinine clearance <60 mL/min, 24-hr urine calcium >250 mg (women) or >300 mg (men), kidney stones/nephrocalcinosis, osteoporosis/fractures, or age <50.
- Surgery is preferred, especially in younger/healthier patients; select experienced parathyroid surgeons.
- Medical therapy (e.g., cinacalcet) is reserved for those unfit for surgery, with limited use due to side effects.
Non–PTH-Mediated Hypercalcemia
- Causes include malignancy, vitamin D toxicity, thyrotoxicosis, and milk-alkali syndrome.
- Malignancy-associated hypercalcemia is most common in severe or acute cases; collaborate with oncology for management.
Management of Severe Hypercalcemia
- Immediate treatment: aggressive IV hydration with saline, avoid loop diuretics unless necessary after rehydration.
- Short-term: salmon calcitonin can rapidly lower calcium for a few days.
- Longer-term: IV bisphosphonates (e.g., zoledronic acid) are standard; denosumab is used in refractory cases or renal impairment.
- Monitor for hypocalcemia with denosumab.
Follow-up and Monitoring
- Patients with PHPT not undergoing surgery should have annual calcium, kidney function assessments, periodic bone density tests, spinal imaging, and, if needed, 24-hour urine calcium.
Key Terms & Definitions
- Hypercalcemia — Elevated albumin-corrected serum calcium above the upper laboratory reference limit.
- Ionized Calcium — The biologically active form of calcium in blood.
- PTH (Parathyroid Hormone) — Hormone regulating calcium and phosphorus levels.
- Primary Hyperparathyroidism (PHPT) — Overproduction of PTH, leading to hypercalcemia.
- Bisphosphonates — Drugs inhibiting bone resorption, used for hypercalcemia.
- Denosumab — Monoclonal antibody for hypercalcemia refractory to bisphosphonates or with kidney dysfunction.
Action Items / Next Steps
- Review local laboratory reference ranges for calcium.
- Practice calculating albumin-corrected calcium.
- Read up on diagnostic algorithms for hypercalcemia.
- Review criteria for parathyroidectomy in PHPT.
- Prepare for discussion of management options for hypercalcemia in malignancy.