Therapy with PTH 1-34 or calcitriol and calcium in diverse etiologies of hypoparathyroidism over 27 years at a single tertiary care center.

Abstract

OBJECTIVE:

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.

DESIGN:

Pooled analysis of current and past studies describing the differential responses to PTH 1-34 injections vs conventional therapy among the varied hypoPT etiologies.

METHODS:

192 participants (ages 2-74 years) with hypoparathyroidism who received either calcitriol and calcium or PTH 1-34 by subcutaneous injection.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Karen K Winer, Shangyuan Ye, Elise M N Ferré, Monica M Schmitt, Bo Zhang, Gordon B Cutler Jr, Michail S Lionakis
• Journal: Bone (Bone) Vol. 149 Pg. 115977 (08 2021) ISSN: 1873-2763 [Electronic] United States
• PMID: 33932619 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Elsevier Inc.

Chemical References

• Parathyroid Hormone
• Phosphorus
• Calcitriol
• Calcium

Topics

• Adolescent
• Adult
• Aged
• Calcitriol (therapeutic use)
• Calcium
• Child
• Child, Preschool
• Humans
• Hypoparathyroidism (drug therapy)
• Middle Aged
• Parathyroid Hormone
• Phosphorus
• Tertiary Care Centers
• Young Adult