Endocrine Abstracts

Background : Adrenocortical cancer (ACC) is a very rare but aggressive tumour with annual incidence of 2 cases per million populations. Hypercalcaemia is a commonly encountered paraneoplastic manifestation of certain cancers such as lung, breast, kidney, gynaecological and neuroendocrine tumours but very rare in ACC. So far, there are only two cases of ACC and PTHrP-related hypercalcaemia reported in the literature.

Case report: 32-year-old man presented with one-week history of constant vomiting, constipation, 1-stone weight loss and lethargy. He was found to have severe hypercalcaemia with corrected calcium (CCa) of 3.55mmol/l, low phosphate level of 0.54mmol/lwith normal renal function on routine biochemical workup. His parathyroid hormone (PTH) was suppressed at 0.4 pmol/land his vitamin D was 32.5nmol/l. His myeloma screening was negative, ACE, thyroid function and LDH were normal. PTHrP was elevated at 15.8pg/ml (reference <13.9). The abdominal ultrasound showed suspected right adrenal mass. CT scan confirmed a 9.4x7 cm heterogeneous right adrenal mass with no evidence of lymphadenopathy or metastases. His baseline endocrine work up showed failed overnight dexamethasone suppression test failed (cortisol 128nmol/l), normal DHEAS but slightly elevated androstenedione (6.9nmol/l), testosterone level 19.4nmol/lwith normal LH , and normal plasma metanephrines. The 24 hour urinary steroid metabolomics profile was consistent with an androgen-and glucocorticoid-producing ACC He required admissions for intravenous fluids and pamidronate treatment twice before he underwent open right adrenalectomy and histology confirmed adrenocortical carcinoma with Weiss score of 6 and Ki67 index 40%. PTH staining was negative. His calcium normalised after adrenalectomy (CCa 2.4 mmol/l). He was started on adjuvant mitotane treatment due to high proliferation index and is being followed up in our adrenal clinic for disease monitoring.

Conclusion: PTHrP-related hypercalcaemia is not commonly associated with ACC and carries a poor prognosis. In this case, staining for PTH was negative but this does not exclude that the tumour was excreting it if it was released quickly. The normalisation of calcium post-ACC resection confirmed the source of PTHrP.

References: 1. Marthe Rizk-Rabin, et tal., Differential expression of Parathyroid Hormone-related Protein in Adrenocortical tumours: Autocrine/ Paracrine effects on the growth and signalling pathways in H295R cells, Cancer Epidemiology Biomarkers 2008. 2. Sven Gruber, et tal., Paraneoplastic hypercalcaemia in a PTH Producing Adrenocortical Carcinoma – a Rare and Deadly Condition, Journal of the endocrine Society. 3. S M Orland, et tal., Detection of the hypercalcaemic hormone of malignancy in an adrenal cortical carcinoma, Journal of Urology, 1986 Nov