HHM PTHrP — RACP Adult Medicine MCQ

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ModerateEndocrinologyHHM PTHrPRACP Adult Medicine

A 65-year-old man with lung squamous cell carcinoma presents with confusion, polyuria, and dehydration. Corrected calcium is 3.8 mmol/L. PTH is suppressed (<0.5 pmol/L). PTHrP is markedly elevated. Phosphate is low. He has no bone metastases on PET-CT. What is the most likely mechanism?

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Correct answer: B — Malignancy-associated hypercalcaemia

Severe hypercalcaemia with suppressed PTH and elevated PTHrP without bone metastases = humoral hypercalcaemia of malignancy (HHM). PTHrP mimics PTH action (renal calcium reabsorption, osteoclast activation) but is from tumour secretion. Common in SCC lung, RCC, breast cancer. Treatment: aggressive IV saline (4-6 L/day) + IV zoledronic acid (4 mg over 15 min). Denosumab for bisphosphonate-refractory cases. Definitive treatment = treat underlying malignancy.

Reference: eTG Endocrine – 2024 – Hypercalcaemia; NCCN 2025