Hypercalcaemia
Causes
Common Causes:
Primary Hyperparathyroidism: Most common cause, often due to parathyroid adenoma.
Malignancy-Related Hypercalcaemia: Lung and breast cancer (via secretion of parathyroid hormone-related protein), bony metastases.
Multiple Myeloma: Causes bone resorption, leading to increased serum calcium.
Less Common Causes:
Endocrine Disorders: Adrenal insufficiency
Medications: Thiazide diuretics, lithium
Granulomatous Diseases: Sarcoidosis (can produce active vitamin D), tuberculosis
Familial Hypocalciuric Hypercalcemia: Genetic condition
Vitamin D Intoxication: Excessive intake leading to increased calcium absorption
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Symptoms
"Bones, stones, groans, and moans"
Bones: Painful bones, fractures, osteoporosis
Stones: Kidney stones, nephrocalcinosis
Groans: Abdominal pain, nausea, vomiting, constipation, pancreatitis, peptic ulcer disease (PUD)
Moans: Confusion, lethargy, memory loss, depression
Other specific symptoms:
Polyuria, polydipsia due to nephrogenic diabetes insipidus
Muscular weakness and fatigue
Cardiovascular: Hypertension, short QT interval, bradycardia
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Investigations
Basic Workup:
Calcium Profile: Corrected calcium (adjust for albumin), ionised calcium.
PTH: To differentiate PTH-related causes.
Vitamin D: Both 25-hydroxy and 1,25-dihydroxy vitamin D levels.
Further Investigations Based on Suspected Etiology:
Malignancy Screen: FBE, UEC, ESR, SPEP, SFLC (free light chain).
Urinary Calcium/Creatinine Ratio: High in primary hyperparathyroidism, low in familial hypocalciuric hypercalcemia.
ECG: For QT interval changes.
Imaging:
Parathyroid Imaging: Sestamibi scan, ultrasound, or 4D CT for surgical candidates.
Bone Density and X-rays: For osteoporosis, fractures.
CXR and ACE levels: If sarcoidosis suspected.
Special Tests:
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Management
General Measures:
Hydration: IV normal saline to promote renal excretion of calcium.
Bisphosphonates: For malignancy-related hypercalcaemia or persistent elevated calcium.
Loop Diuretics: Only if volume overloaded, to promote calcium excretion.
Specific Treatments Based on Underlying Cause:
Primary Hyperparathyroidism: Surgical removal of the parathyroid gland.
Malignancy-Related Hypercalcaemia: Treat the underlying malignancy; bisphosphonates or denosumab.
Calcitonin: Subcutaneous injection for short-term calcium lowering.
Steroids: For granulomatous diseases or vitamin D intoxication.
Monitoring and Supportive Care:
Close monitoring of renal function and electrolyte levels.
Avoid medications that may worsen hypercalcaemia (e.g., thiazide diuretics, lithium).
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Notes
If PTH is elevated: Suggests primary hyperparathyroidism. Consider bone density scan for bone damage and renal ultrasound for kidney stones.
If PTH is low or undetectable: Likely due to malignancy or other non-parathyroid causes.
Severe Hypercalcaemia (Ca >3.5 mmol/L): Requires urgent treatment, especially if symptomatic or with altered mental status.
Vitamin D Inhibition: Elevated PTH can lead to reduced conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D.
High Urinary Calcium (>400 mg/day): Increases the likelihood of renal complications; may indicate primary hyperparathyroidism rather than familial hypocalciuric hypercalcemia.
