Post-surgery severe hypocalcemia in primary hyperparathyroidism preoperatively treated with zoledronic acid

Abstract

Zoledronic acid is a newly FDA-approved bisphosphonate for the treatment of hypercalcemia of malignancy. Although the safety and efficacy of this drug in treating hypercalcemia associated with hyperparathyroidism have not yet been established in clinically controlled trials, its off-label use is not uncommon. We describe a patient with primary hyperparathyroidism treated with zoledronic acid who developed severe postoperative hypocalcemia. A 64-yr-old woman was admitted with severe hypercalcemia. She was treated with rehydration, calcitonin, methylprednisolone, furosemide as well as 4 mg/day of zoledronic acid for two consecutive days. Primary hyperparathyroidism caused by a right inferior parathyroid lesion was diagnosed. While awaiting surgery, she continued furosemide, methylprednisolone and hydration: after one week, serum calcium had fallen to such a low level that a short-term calcium carbonate supplementation was required. Three weeks after admission, the patient underwent selective right inferior parathyroidectomy, followed by reduction of PTH. During the postoperative period the patient presented severe hypocalcemia resistant to the usual treatment. Serum calcium levels returned to normal three months after surgery. The severity of hypocalcemia and the resistance to conventional treatments suggest that the effect of hungry bone syndrome could be worse in patients treated with bisphosphonates in the preoperative phase.

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

“…Data from case reports and small case series on the beneficial effect of preoperative treatment with bisphosphonates on the HBS in patients with hyperparathyroid bone disease (7,35,37,51) or with longstanding severe PHPT (49) are conflicting (23,27,35,36,37). Some cases thus report failure of preoperative bisphosphonates to prevent HBS, although this was believed to be due to short duration of treatment or low dosage used, as serum alkaline phosphatase levels had not normalised before surgery (23,38,42,43,44).…”

“…The reported amount of calcium supplementation required to treat the severe hypocalcaemia varies between 6 and 12 g/day (17,21,23,29,40,43,44). Initially, calcium is supplemented intravenously, but treatment with oral preparations should be initiated as early as possible, with concomitant use of adequate doses of active metabolites of vitamin D (calcitriol) or alfacalcidol (2-4 mg/day) (17, 21, 22, 23, 38, 42, 43, 44), or very occasionally higher doses (unpublished personal observations), and with replenishment of magnesium stores as required.…”

“…The amount of magnesium required to correct hypomagnesaemia has not always been reported, and supplementation has been variably given intravenously as magnesium chloride or sulphate or orally as magnesium sulphate (15,17,19,22,26,38,43). In 11 of 18 cases, serum magnesium level was not mentioned, and in one of 18 cases serum magnesium level was within the normal range (16,18,21,23,24,25,27,29,40,41,42,44).…”

Macroadenoma cervical palpable: Una presentación muy inusual de hiperparatiroidismo primario

“…Sin embargo, no existe acuerdo en relación al uso de bisfosfonatos inyectables. Algunos estudios retrospectivos y series de casos sostienen que el uso de bisfosfonatos en el preoperatorio puede mejorar la hipercalcemia y disminuir el riesgo de hueso hambriento en el post operatorio 12,13 , pero existen casos reportados que muestran un efecto contrario 14 . En nuestro paciente, dado la grave hipercalcemia y la alta probabilidad de desarrollo de hueso hambriento después de la cirugía, decidimos pre tratar con bisfosfonatos.…”

Medical Management of Primary Hyperparathyroidism

“…Intravenous infusions of pamidronate (45-90 mg over 2-8 hours) 124,125 and zoledronic acid (4 mg over 15 min) 126 have been effective in lowering the serum calcium in patients with PHPT and parathyroid crisis. Pyrexia and a "flu-like syndrome" may occur at the first infusion and can be managed by administration of acetaminophen.…”