Hypercalcaemia of malignancy
Effect · PTHrP PTH suppressed
The commonest cause of hypercalcaemia in inpatients and the diagnosis to reach for when PTH is suppressed. Three mechanisms: PTHrP acting at the PTH1R, osteolytic metastases, and unregulated 1-alpha-hydroxylation in lymphoma.
Traced from the start
Detail
- Humoral (PTHrP)
- Squamous cell carcinoma of lung, head and neck or oesophagus, renal cell carcinoma and breast carcinoma; PTHrP acts at PTH1R, so phosphate is low as in primary hyperparathyroidism, but PTH is suppressed and calcitriol is low
- Osteolytic
- Myeloma and breast carcinoma metastases, through locally produced cytokines and RANKL
- Calcitriol-mediated
- Hodgkin and non-Hodgkin lymphoma, by the same unregulated macrophage 1-alpha-hydroxylation as granulomatous disease
- Discriminator
- A suppressed PTH points away from primary hyperparathyroidism; measure PTHrP if the cause is not already obvious
- Treatment
- Intravenous 0.9% sodium chloride, then zoledronic acid; denosumab if bisphosphonate-refractory or in renal impairment; corticosteroids for the calcitriol-mediated forms
When it goes wrong
Hypercalcaemia with a suppressed PTH in a smoker with a lung mass
Humoral hypercalcaemia of malignancy from PTHrP; it carries a poor prognosis
Hypercalcaemia with anaemia, renal impairment and back pain
Myeloma: request serum protein electrophoresis, serum free light chains and imaging for lytic lesions
Practise this structure
2 questions in the bank tagged Ionised Calcium.
A 22-year-old woman is brought to the emergency department 30 minutes after an argument at home, breathing rapidly and deeply. She complains of tingling around…
Foundations · middle twist
A 22-year-old woman is brought to the emergency department after 30 minutes of rapid, deep breathing that began during an argument. She reports tingling around…
Foundations · middle twist