Hypoparathyroidism: Less Severe Hypocalcemia With Treatment With Vitamin D2 Compared With Calcitriol

Elizabeth A. Streeten; Yasaman Mohtasebi; Manige Konig; Lisa Davidoff; Kathleen Ryan


J Clin Endocrinol Metab. 2017;102(5):1505-1510. 

In This Article

Abstract and Introduction


Context: Options for chronic treatment of hypoparathyroidism include calcitriol, recombinant human parathyroid hormone, and high-dose vitamin D (D2). D2 is used in a minority of patients because of fear of prolonged hypercalcemia and renal toxicity. There is a paucity of recent data about D2 use in hypoparathyroidism.

Objective: Compare renal function, hypercalcemia, and hypocalcemia in patients with hypoparathyroidism treated chronically with either D2 (D2 group) or calcitriol.

Design, Setting, and Patients: A retrospective study of patients with hypoparathyroidism treated at the University of Maryland Hospital. Participants were identified by a billing record search with diagnosis confirmed by chart review. Thirty patients were identified; 16 were treated chronically with D2, 14 with calcitriol. Data were extracted from medical records.

Main Outcome Measures: Serum creatinine and calcium, hospitalizations, and emergency department (ED) visits for hypercalcemia and hypocalcemia.

Results: D2 and calcitriol groups were similar in age (58.9 ± 16.7 vs 50.9 ± 22.6 years, P = 0.28), sex, and treatment duration (17.8 ± 14.2 vs 8.5 ± 4.4 years, P = 0.076). Hospitalization or ED visits for hypocalcemia occurred in none of the D2 group vs four of 14 in the calcitriol group (P = 0.03); three in the calcitriol group had multiple ED visits. There were no differences between D2 and calcitriol groups in hospitalizations or ED visits for hypercalcemia, serum creatinine or calcium, or kidney stones.

Conclusion: We found less morbidity from hypocalcemia in hypoparathyroid patients treated chronically with D2 compared with calcitriol and found no difference in renal function or morbidity from hypercalcemia. Treatment with D2 should be considered in patients with hypoparathyroidism, particularly in those who experience recurrent hypocalcemia.


Hypoparathyroidism is due to the absence or partial deficiency of parathyroid hormone, which leads to hypocalcemia, hyperphosphatemia, and hypercalciuria.[1] The most feared chronic complication of hypoparathyroidism treatment is renal toxicity, manifesting as kidney stone or nephrocalcinosis, followed by renal insufficiency.[2] Additional risks of treatment of hypoparathyroidism include acute episodes of hypercalcemia and hypocalcemia requiring emergency medical treatment.[3] Treatment of hypoparathyroidism remains a challenge and no one treatment has been shown to be satisfactory for every patient.[4] Currently available treatments for hypoparathyroidism include high-dose vitamin D (ergocalciferol, D2 and cholecalciferol, D3), the active metabolite 1,25-dihydroxvitamin D (calcitriol), recombinant human parathyroid hormone, in addition to calcium supplements.[5] In the United States, only D2 (not D3) is available as a Food and Drug Administration–approved medication, although comparable doses of D3 (50,000 IU tablets) are available over the counter in some pharmacies and from Internet sources. Calcitriol is the drug used most commonly in the United States for chronic hypoparathyroidism now, with only ~6% treated with D2[3] and increasing numbers of patients on human recombinant parathyroid hormone.[6] However, in our clinical experience, D2 is effective and safe, with most hypoparathyroid patients requiring 50,000 IU per day. However, we are aware of no reports comparing treatment outcome with D2 vs calcitriol for hypoparathyroidism.

D2 was the only treatment available for hypoparathyroidism prior to 1933.[7] At that time, the long half-life of D2 and potential for prolonged hypercalcemia and renal insufficiency from vitamin D toxicity was one factor that led to the development of dihydrotachysterol (DHT; 1-α-hydroxycholecalciferol), which had a shorter half-life.[8] In 1939, Albright et al.[8] studied three patients with hypoparathyroidism, comparing DHT with D2 and showed that the ability of the drugs to maintain eucalcemia was similar. They further showed that D2 caused hypercalcemia only when very high doses, 200,000 to 400,000 IU/d, were used, much higher than doses of D2 used today for hypoparathyroidism.

In this retrospective study, our goal was to compare renal function and incidents of hypercalcemia and hypocalcemia requiring medical treatment in patients with hypoparathyroidism treated chronically with D2 (D2 group) vs calcitriol.