THERAPY OF ENDOCRINE DISEASE: Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature

Abstract

Hungry bone syndrome (HBS) refers to the rapid, profound, and prolonged hypocalcaemia associated with hypophosphataemia and hypomagnesaemia, and is exacerbated by suppressed parathyroid hormone (PTH) levels, which follows parathyroidectomy in patients with severe primary hyperparathyroidism (PHPT) and preoperative high bone turnover. It is a relatively uncommon, but serious adverse effect of parathyroidectomy. We conducted a literature search of all available studies reporting a 'hungry bone syndrome' in patients who had a parathyroidectomy for PHPT, to identify patients at risk and address the pitfalls in their management. The severe hypocalcaemia is believed to be due to increased influx of calcium into bone, due to the sudden removal of the effect of high circulating levels of PTH on osteoclastic resorption, leading to a decrease in the activation frequency of new remodelling sites and to a decrease in remodelling space, although there is no good documentation for this. Various risk factors have been suggested for the development of HBS, including older age, weight/volume of the resected parathyroid glands, radiological evidence of bone disease and vitamin D deficiency. The syndrome is reported in 25-90% of patients with radiological evidence of hyperparathyroid bone disease vs only 0-6% of patients without skeletal involvement. There is insufficient data-based evidence on the best means to treat, minimise or prevent this severe complication of parathyroidectomy. Treatment is aimed at replenishing the severe calcium deficit by using high doses of calcium supplemented by high doses of active metabolites of vitamin D. Adequate correction of magnesium deficiency and normalisation of bone turnover are required for resolution of the hypocalcaemia which may last for a number of months after successful surgery. Preoperative treatment with bisphosphonates has been suggested to reduce post-operative hypocalcaemia, but there are to date no prospective studies addressing this issue. European Journal of Endocrinology 168 R45-R53

Transient Increased Calcium and Calcitriol Requirements After Discontinuation of Human Synthetic Parathyroid Hormone 1-34 (hPTH 1-34) Replacement Therapy in Hypoparathyroidism

“…Although the mechanism is not wellunderstood, hungry bone syndrome after parathyroidectomy is thought to be due to the abrupt cessation of PTH-mediated bone resorption despite continued increased bone formation; calcium is shunted into the skeleton resulting in postoperative hypocalcemia, increased calcium and vitamin D requirements, and consequent gains in bone mass. (29) The risk of postoperative hungry bone syndrome appears to associated with older age, large parathyroid adenomas, (30) and preexisting radiologic evidence of hyperparathyroid bone disease. (31,32) Several studies, but not all, have reported an increased risk correlating with higher preoperative levels of PTH, calcium, and alkaline phosphatase.…”

Her Aching Bones: Atypical Parathyroid Adenoma

“…During the perioperative period, her parathyroid hormone level was closely monitored, and calcium was administered to prevent hungry bone syndrome, where sudden severe hypocalcemia may ensue due to an acute drop in parathyroid hormone. 11 After an uneventful postoperative period, she was discharged home with a normal parathyroid hormone level. She was instructed to continue taking oral calcium and vitamin D.…”

Mediastinal Parathyroid Adenoma Mimicking Cancer Metastatic to Bone

“…Risk factors for this condition include larger volume adenomas, older age, associated bone disease, and vitamin D deficiency (23). Fortunately, the patient did not develop this complication with the lowest postoperative ionized calcium level occurring on postoperative day 6 at 1.17 mmol/L (normal, 1.19 to 1.31 mmol/L).…”