A 69 year old man presented to hospital with acute hypercalcaemia and renal failure. History included nephrectomy for a benign renal tumour and thyroidectomy for thyroid carcinoma. Presentation adjusted calcium was 2.70 mmol/L with an incompletely suppressed parathyroid hormone level of 0.6 pmol/L. The hypercalcaemia was resistant to both intravenous fluids and bisphosphonates, rising to 3.20 mmol/L. Given his previous cancer, hypercalcaemia of malignancy was strongly suspected. Result of PTH-rp level returned as <1.0 pmol/L over 6 weeks later. CT scan demonstrated splenomegaly and small volume lymphadenopathy. Axillary lymph node biopsy done from metabolically active lymph node on PET scan demonstrated CD20 negative angioimmunoblastic lymphoma, which was treated successfully with chemotherapy.
Incompletely suppressed parathyroid level in the context of hypercalcaemia is difficult to interpret. The leading cause of hypercalcaemia in the inpatient setting is malignancy. Malignancies are typically associated with an elevated PTH-rp. Importantly lymphoma can present with hypercalcaemia and either a normal or elevated PTH-rp.
This case demonstrates that whilst PTH-rp level has a role in investigating hypercalcaemia with incompletely suppressed PTH, its use may be limited. The complex preparation of PTH-rp samples is critical for accurate analysis, requiring strict temperature control and decanted containers. PTH-rp sampling often incorporates significant delays through rejected samples and complex laboratory processing. In the context of malignancy, such delays can prove harmful in promptly managing mitotic disease. Furthermore, lymphoma can drive hypercalcaemia through PTH-rp independent mechanisms, both through direct bone effects or 1,25-dihydroxyvitamin D production. We argue increased emphasis should be placed on the measurement of 1,25-dihydroxyvitamin D to help reduce delays in diagnosing the aetiology of hypercalcaemia when clinical and radiological picture do not elicit the diagnosis readily.
In summary, this case highlights the importance of efficient hypercalcaemia investigation when malignancy is suspected, it explores optimal PTH-rp sample preparation and the role of 1,25-dihydroxyvitamin D.