Endocrine Abstracts

A 65-year-old gentleman was referred by his GP because of acute kidney injury and hypercalcaemia, which was associated with low levels of parathyroid hormone. He had been fit and well and was on no regular medications. Whilst his hypercalcaemia was partly correctible with saline rehydration, cautious use of bisphosphonates and cinacalcet were not effective in preventing rebound, and his nephropathy persisted. Curiously, he had longstanding low plasma alkaline phosphatase, but had normal dentition and no pathological fractures. Physical examination was normal. The cause of his hypercalcaemia was not clear despite usual first line investigations.

His routine biochemistry was as follows: serum calcium 3.41 mmol/l; phosphate 1.13 mmol/l; ALP 19 IU/L, PTH 0.8 pmol/l. eGFR 20 ml/min/1.73m2. Total 25-OH vitamin D nmol/L. 24-hour urine calcium excretion was raised at 16.6mmol. CRP was 2. Myeloma screen, including skeletal survey was negative. PSA, PTH-related-peptide and other tumour markers were normal. CT scan of whole body showed no evidence for carcinomatosis or significant lymphadenopathy. Serum ACE level was 74U/L (range 20-70). Renal biopsy showed chronic changes associated with hypertension. We asked our metabolic bone unit for significance of the low ALP, to consider adult-onset hypophosphatasia as cause, but this was felt to be unlikely given normal bone turnover markers (P1NP and CTx) and urinary phosphoethanolamine.

Instead, our tertiary-centre colleague recommended pragmatic trial of corticosteroids and focus investigations on possible granulomatous disease. Prednisolone, at dose of 30mg, restored normocalcaemia and renal function, after 4 weeks. Subsequently returned tests showed raised 1,25 dihydroxyvitamin D (318 pmol, reference range 43-144) and serum ACE, four months from presentation, had risen to 117U/L. Repeat CT scan at this time showed interim development of small volume mediastinal and hilar lymphadenopathy, which was biopsied to yield histological evidence of non-caseating granuloma, indicative of sarcoidosis.

This case illustrates the value of corticosteroids in managing patients with refractory hypercalcaemia, where neoplastic and PTH-driven causes have been excluded. Of note is that sarcoidosis can cause significant hypercalcaemia despite presenting with apparent low disease activity.

Acknowledgments: Prof Neil Gittoes QEHB ; Dr Anna Sanders Clinical Biochemistry