Primary hyperparathyroidism in India

Abstract

Abstract Background Primary hyperparathyroidism (PHPT) in Indians has some unique clinical features, such as early age of onset, extreme osteopenia, crippling bone involvement, large parathyroid tumours, higher proportion of malignancy and severe, prolonged postparathyroidectomy hungry bone syndrome. The current study aimed to study (1) whether these features of PHPT in Indians are due to a variant form of PHPT and (2) pathogenetic factors of such variant disease. Methods Clinical, investigative and pathological features of 29 consecutive patients with PHPT (24 females, five males) who underwent parathyroidectomy at 13–60 (mean 38) years of age were reviewed. Spearman's correlation coefficient was calculated between serum calcidiol levels and biochemical variables, bone mineral density (BMD) before surgery and parathyroid tumour weight. Results Median duration of symptoms was 2·5 (range 1–26) years. Mean total serum calcium, iPTH and ALP levels were 12·4 mg dl−1 (normal 8·5–10·8 mg dl−1), 955 pg ml−1 (normal 9–55 pg ml−1) and 850 units l−1 (normal 35–125 units l−1) respectively, while mean(s.d.) serum calcidiol and calcitriol concentrations were 14(6) ng ml−1 and 52(29) pg ml−1 (versus 9(9) and 30(14) pg ml−1 in matched controls). All patients had symptomatic osteitis fibrosa cystica and eight were bedridden. Single or multiple spontaneous fractures occurred in 14 patients, brown tumours in 20, and long bones were barely visible on plain films in four. BMD z-scores at distal radius and lumbar spine (mean) were −4·2 and −3·8. Palpable parathyroid tumours occurred in 14 patients and nine had renal damage, mainly nephrocalcinosis. Parathyroidectomy invariably resulted in long-standing severe hypocalcaemia, necessitating intravenous calcium infusion for 6 days on average, and long-term oral calcium and vitamin D supplementation. The mean parathyroid gland weight was 8·6 (range 2–36·6) g and signs of carcinoma were found in four. There was a negative correlation (P < 0·05) between serum calcidiol and serum iPTH, and serum ALP and parathyroid gland weight. Conclusion PHPT in Indians manifests as severe, symptomatic musculoskeletal and renal disease. In spite of the severe hyperparathyroidism, the serum calcium levels are only moderately raised. These patients have signs of rapid parathyroid tumour growth resulting in large adenomas and a high proportion of parathyroid carcinomas. The signs of rapid cell proliferation, excessive calcium insensitivity of PTH release and peripheral PTH resistance may clarify roles of widely prevalent vitamin D deficiency in pathogenesis of this variant of PHPT.