Endocrine Abstracts

Case history: A 49-year-old male was readmitted with asymptomatic hypercalcaemia and renal impairment following a recent admission where he was diagnosed and commenced on treatment for miliary tuberculosis. He was on month 6 of standard anti-tuberculous therapy (ATT) and one month off glucocorticoids commenced for CNS-involvement. High dose cholecalciferol was started on initial admission when he was found to be normocalcaemic but vitamin-D deficient, and continued. The clinical concern was of hypervitaminosis-D.

Investigations: Calcium on initial admission was 2.29mmol/l (2.2-2.6mmol/l) and serum phosphate 1.31mmol/l (0.8-1.5mmol/l) with serum 25(OH)D3 21nmol/l (>50nmol/l). Creatinine was 30-40umol/l.

Results and treatment: Cholecalciferol was commenced at 4000 units/day on initial admission. Synacthen stimulated cortisol at 60 minutes was 526nmol/l after 16 weeks exposure to glucocorticoids, and weaning prednisolone stopped. Improved radiology and weight-gain (BMI17.18 kg/m2 from 13.19 kg/m2) suggested reduced disease-burden. The patient was discharged following 16 weeks’ inpatient stay to respiratory follow-up. Calcium 2.76mmol/l, phosphate 1.4mmol/l and creatinine 70umol/l were detected on outpatient bloods after 4 months 4000units/day vitamin-d3, and one month off glucocorticoids. Vitamin-D3 was stopped, and increased oral fluids advised. Two weeks later, a serum calcium 3.67mmol/l and creatinine 123umol/l prompted readmission. Serum-ACE was 73u/l (20-70), PTH suppressed (2.2 pmol/l) and repeat serum 25(OH)D3 95nmol/l. Calcium 3.64mmol/l on day 3 despite 2-3 litres/24hrs 0.9%sodium-chloride prompted starting 30 mg prednisolone. Zolendronate was administered on day 7 due to ongoing hypercalcaemia (3.53mmol/l) and rising creatinine (158umol/l). Normocalcaemia (calcium 2.57mmol/l) and downtrending creatinine 98umol/l was seen on day 12, and the patient discharged on 15 mg prednisolone. On 15 mg prednisolone, normocalcaemia (2.34mmol/l) with improved creatinine 61umol/l was seen at 2 months. Serum 1,25-dihydroxyvitamin-D3 from the second admission returned at 149 pmol/l (55–139 pmol/l).

Discussion: Hypervitaminosis-D with hypercalcemia occurs secondary to excess vitamin-D consumption or extrarenal 1-alpha-hydroxylase activity and is a rare but well-cited complication of tuberculosis. With the toxic effects of vitamin-D supplementation thought not to occur until 25(OH)D3 levels exceed 150 ng/mL(374nmol/l), elevated 1,25(OH)2-D3 and improved hypercalcaemia following glucocorticoids favour granulomatous hypercalcaemia in our patient. Efficacy data on the use of adjunctive vitamin-D3 supplementation to standard ATT on improved tuberculosis outcomes is conflicting. Vitamin-D deficiency is common in patients with tuberculosis however, and replacement in those deficient is reasonable. Close monitoring of serum calcium and using more conservative vitamin-D3 doses could ameliorate the dangers of hypercalcaemia seen to occur in these patients more often following supplementation.