P03.009 Hypercalcaemia of malignancy

Hypercalcemia of malignancy (HCM) is a metabolic complication affecting up to 30% of patients with advanced cancer. It arises due to various mechanisms employed by tumors to disrupt calcium homeostasis and can significantly worsen patient outcomes. Understanding HCM is crucial for PLAB (Professional Licence Assessment Board) candidates, as it necessitates prompt diagnosis, management, and knowledge of potential pitfalls.

Pathophysiology:

HCM can occur through several mechanisms, each involving a different culprit:

• Parathyroid Hormone-related Peptide (PTHrP): The most common cause, PTHrP is produced by some tumors and mimics the actions of parathyroid hormone (PTH). It increases bone resorption, leading to calcium release into the bloodstream.
• Local Osteolytic Activity: Cancers like multiple myeloma or bone metastases directly break down bone, releasing calcium.
• Excess 1,25-dihydroxyvitamin D (calcitriol): Certain lymphomas can produce excess calcitriol, which enhances intestinal calcium absorption.

Clinical Presentation:

HCM can be a subtle or dramatic presentation, depending on the severity and underlying malignancy. Here’s a breakdown of signs and symptoms to consider:

• Musculoskeletal: Bone pain, weakness, fractures (increased risk)
• Neurological: Confusion, lethargy, fatigue, coma (severe cases)
• Gastrointestinal: Nausea, vomiting, constipation
• Renal: Polyuria, dehydration, nephrolithiasis (kidney stones)
• Psychological: Anxiety, depression

Diagnosis:

• Serum calcium level: Elevated total and ionized calcium levels are the cornerstone of diagnosis.
• Corrected calcium: Adjusts for serum albumin levels, as low albumin can falsely lower total calcium.
• Serum PTH level: Usually suppressed in PTHrP-mediated HCM and elevated in primary hyperparathyroidism (differential diagnosis).
• Imaging studies: X-rays, CT scans, or bone scans might be used to identify bone lesions or metastases.

Points to Remember for PLAB:

• HCM is a potential complication in various malignancies.
• A high index of suspicion is necessary, especially in patients with advanced cancer and suggestive symptoms.
• Prompt diagnosis is crucial to prevent complications like renal failure and altered mental status.
• Management involves treating the underlying malignancy, correcting electrolyte imbalances, and potentially using medications like bisphosphonates (inhibits bone resorption) or calcitonin (inhibits calcium reabsorption).
• Collaboration with oncologists and endocrinologists is often necessary for optimal management.

Differential Diagnoses:

• Primary hyperparathyroidism
• Vitamin D intoxication
• Granulomatous diseases (sarcoidosis)
• Paget’s disease of bone
• Milk-alkali syndrome

PLAB Pitfalls to Avoid:

• Delaying diagnosis due to non-specific symptoms.
• Misattributing symptoms to the underlying malignancy without considering HCM.
• Failing to differentiate HCM from other causes of hypercalcemia.
• Inappropriate use of calcium supplements can worsen the condition.