{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:57:38Z","timestamp":1775523458273,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>So far, only 11 <jats:italic>PTH<\/jats:italic> mutations have been described as causes of familial isolated hypoparathyroidism (FIH). In this report, we describe a family with FIH but with significant elevation of functionally inactive PTH due to a <jats:italic>PTH<\/jats:italic> mutation. We also show a positive therapeutic outcome of recombinant human PTH (teriparatide) therapy in one of the siblings who was not well controlled on large doses of calcitriol and calcium replacement therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case description<\/jats:title><jats:p>The proband is a 34-year-old woman who has a history of chronic severe hypocalcemia (HypoCa) since birth. She and her three brothers (33-year-old male twins, and a 21-year-old male) were diagnosed with pseudohypoparathyroidism type 1b (PHPT 1b) based on the presence of chronic HypoCa (serum Ca 1.6-1.85 mmol\/l) since birth associated with significantly elevated plasma PTH levels in the range of 310-564 pg\/dl (normal range 10-65) and absence of signs of Albright hereditary osteodystrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Molecular studies<\/jats:title><jats:p>WES showed no pathogenic, likely pathogenic or variants of unknown significance in any known calcium-associated genetic disorder but a bi-allelic variant in the <jats:italic>PTH<\/jats:italic> itself ((NM_000315.4:c.128G&amp;gt;A, p.Gly43Glu). This was confirmed by Sanger sequencing in the patient and her affected brothers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Management<\/jats:title><jats:p>Because the patient\u2019s HypoCa was not controlled on large doses of calcitriol and calcium carbonate, a trial of teriparatide 20 mcg SC daily was started and resulted in normalization of calcium, decline in PTH levels and significant improvement in her general wellbeing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>High PTH in the presence of congenital hypocalcemia is not always due to receptor or post-receptor defect and can be due to a biologically inactive mutated PTH. In such cases, treatment with teriparatide may result in stabilization of biochemical profile and improvement in quality of life.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2024.1415639","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T04:37:31Z","timestamp":1728275851000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case report: Familial hypoparathyroidism with elevated parathyroid hormone due to an inactivating PTH 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