AKT · Endocrine/Paraneoplastic & neuroendocrine

Hypercalcaemia of malignancy (PTHrP)

Paraneoplastic PTH-related peptide / bony metastases / myeloma

Overview

The commonest cause of hypercalcaemia in inpatients/cancer patients — via PTH-related peptide (humoral, e.g. squamous lung, renal, breast cancer), osteolytic bony metastases, or myeloma (cytokine-driven), and rarely tumour 1,25-vitamin D. PTH is SUPPRESSED. Often rapid and symptomatic; treated with IV fluids then bisphosphonate/denosumab and the cancer.

Recognise

Hypercalcaemia in a patient with (often known) malignancy: confusion, dehydration, constipation, polyuria, bone pain
Frequently rapid and symptomatic (vs the milder chronic picture of hyperparathyroidism)
Biochemistry: high calcium with SUPPRESSED PTH; raised PTHrP (humoral) or evidence of bony mets/myeloma

Red flags

Severe (>3.5) / symptomatic hypercalcaemia → emergency IV fluids + bisphosphonate
Hypercalcaemia as the first presentation of an occult cancer/myeloma → investigate

Differentials & how to tell them apart

Primary hyperparathyroidismPTH RAISED/normal, milder/chronic, well outpatient — the key contrast

Myelomabone pain, anaemia, renal impairment, paraprotein, lytic lesions

Vitamin D toxicity / sarcoid / FHHPTH suppressed but specific context; FHH has low urine calcium

Investigations

Corrected calcium (high) with SUPPRESSED PTH; PTHrP; myeloma screen (paraprotein/light chains), imaging for bony mets; renal function.

Management

IV fluids first, then IV bisphosphonate/denosumab; treat the cancer

1Confirm high calcium with SUPPRESSED PTH; identify the mechanism (PTHrP, bony mets, myeloma). Rehydrate with IV saline, then give an IV bisphosphonate (or denosumab).Gate: SUPPRESSED PTH distinguishes malignant hypercalcaemia from primary hyperparathyroidism (raised PTH); rehydrate FIRST because bisphosphonates take a few days; consider denosumab if bisphosphonate-refractory/renal impairment
2Treat the underlying cancer/myeloma (steroids for myeloma/lymphoma); repeat bisphosphonate/denosumab as needed; palliative considerations.

IV 0.9% saline (rehydration) — first-line — restores volume, promotes calcium excretion

IV bisphosphonate (zoledronate) or denosumab — reduces osteoclastic resorption (effect over days)

Treat the malignancy — the definitive control; steroids for myeloma/lymphoma

Key points

Unwell cancer patient + high calcium + SUPPRESSED PTH = hypercalcaemia of malignancy → fluids then bisphosphonate. PTH is the fork from primary hyperparathyroidism. It can be the first sign of an occult cancer or myeloma.

Monitor & prognosis

Calcium, renal function; cancer treatment.

Marker of advanced malignancy.

Source: CKS Hypercalcaemia (known malignancy)