OR07-03 Continuous Subcutaneous Delivery of RhPTH(1-84) by Pump in Adults with Hypoparathyroidism

摘要

More than 80,000 people in the United States have hypoparathyroidism, a disease of low or absent parathyroid hormone (PTH) leading to hypocalcemia and hyperphosphatemia. Conventional treatment with oral calcium and active vitamin D increases serum calcium concentrations but does not replace the physiologic functions of PTH. Once-daily subcutaneous injections of recombinant human (rh) PTH(1-84) were recently approved for the treatment of hypoparathyroidism, but are not consistent in correcting biochemical abnormalities and alleviating symptoms for all patients. In cases in which single or multiple daily injections of rhPTH(1-84) are insufficient for controlling symptoms, continuous subcutaneous infusion via insulin pump is used as a therapeutic alternative. Pump therapy with PTH(1-34) has some support in the literature as an effective form of treatment for hypoparathyroidism.1However, the effects of pump therapy with rhPTH(1-84) in patients with hypoparathyroidism have not been reported. Five women with chronic postsurgical hypoparathyroidism who received treatment at three different endocrine outpatient clinics in the United States were transitioned from multiple daily injections of rhPTH(1-84) to continuous delivery of rhPTH(1-84) using the Omnipod insulin pump. The patients’ ages ranged from 27 to 60 years old and all had had hypoparathyroidism for at least 5 years. All of the patients were transitioned from conventional therapy with oral calcium and calcitriol to subcutaneous injections of rhPTH(1-84), and then switched to continuous subcutaneous administration using an insulin pump. In all five patients, increased serum calcium concentrations and decreased serum phosphate concentrations were observed with increased frequency of PTH administration. Serum calcium concentrations were within the normal to high-normal range and serum phosphate concentrations were in the normal range on pump therapy. Urinary calcium was well-controlled (<250 mg/day) in four of the five patients. All of the women reported a decrease in symptoms while receiving pump-administered rhPTH(1-84), including a lower incidence of fatigue, brain fog, tingling, and muscle cramps compared to standard therapy and daily injections. This is the first report of patients with hypoparathyroidism on long-term therapy with continuously infused subcutaneous rhPTH(1-84) using a pump. Pump therapy improved key parameters of mineral metabolism; normalizing serum calcium in all patients and urinary calcium in four out of five patients. Clinical trials with larger cohorts are needed to confirm the efficacy of this promising mode of administration of rhPTH(1-84). Reference: 1. Winer KK. Advances in the treatment of hypoparathyroidism with PTH 1-34. Bone. 2019;120:535-541.