Patient Rounds at NIH: Jim Minor, a pharmacist with the U.S. Public Health Service, provides direct care to patients who are taking investigational drugs.

Abstract

Hypoparathyroidism has heterogeneous genetic and acquired etiologies with a broad spectrum of severity. Herein we describe the clinical outcomes of the largest cohort of hypoparathyroid patients reported to date, who were followed over 27-years.Pooled analysis of current and past studies describing the differential responses to PTH 1–34 injections vs conventional therapy among the varied hypoPT etiologies.192 participants (ages 2–74 years) with hypoparathyroidism who received either calcitriol and calcium or PTH 1–34 by subcutaneous injection.Among the 4 main etiologic categories of hypoparathyroidism (autoimmune polyglandular failure type 1, activating mutation of the calcium receptor, surgical, and idiopathic hypoparathyroidism), we reveal significant differences in PTH 1–34 dose requirements, prevalence of nephrocalcinosis, biomarkers of mineral homeostasis, and pharmacodynamic profiles. Serum 1,25-dihydroxyvitamin D3 increased significantly (P < 0.001) and 25-hydroxyvitamin D levels decreased during PTH 1–34 injections compared to calcitriol therapy (P < 0.01). Post-surgical patients achieved consistently lower urine calcium excretion over long-term PTH 1–34 therapy compared to conventional therapy (p < 0.001), but this was not achieved in the other etiologies. At study entry, patients had a high prevalence of renal insufficiency and nephrocalcinosis which were directly related to the duration of hypoparathyroidism (P < 0.03). Renal function remained stable during participation in our studies for both PTH 1–34 and conventional therapies.We conclude that the effects and dose-response of PTH 1–34 treatment differ according to the etiology of hypoparathyroidism. Postsurgical hypoPT maintained mean serum calcium levels in the mid- to low-normal range while concurrently maintaining normal mean urine calcium during long-term twice-daily PTH 1–34 therapy.