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  • Title: Therapy with PTH 1-34 or calcitriol and calcium in diverse etiologies of hypoparathyroidism over 27 years at a single tertiary care center.
    Author: Winer KK, Ye S, Ferré EMN, Schmitt MM, Zhang B, Cutler GB, Lionakis MS.
    Journal: Bone; 2021 Aug; 149():115977. PubMed ID: 33932619.
    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.
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