Hypoparathyroidism: Genetics and Diagnosis

Abstract

This narrative report summarizes diagnostic criteria for hypoparathyroidism and describes the clinical presentation and underlying genetic causes of the nonsurgical forms. We conducted a comprehensive literature search from January 2000 to January 2021 and included landmark articles before 2000, presenting a comprehensive update of these topics and suggesting a research agenda to improve diagnosis and, eventually, the prognosis of the disease. Hypoparathyroidism, which is characterized by insufficient secretion of parathyroid hormone (PTH) leading to hypocalcemia, is diagnosed on biochemical grounds. Low albumin‐adjusted calcium or ionized calcium with concurrent inappropriately low serum PTH concentration are the hallmarks of the disease. In this review, we discuss the characteristics and pitfalls in measuring calcium and PTH. We also undertook a systematic review addressing the utility of measuring calcium and PTH within 24 hours after total thyroidectomy to predict long‐term hypoparathyroidism. A summary of the findings is presented here; results of the detailed systematic review are published separately in this issue of JBMR. Several genetic disorders can present with hypoparathyroidism, either as an isolated disease or as part of a syndrome. A positive family history and, in the case of complex diseases, characteristic comorbidities raise the clinical suspicion of a genetic disorder. In addition to these disorders' phenotypic characteristics, which include autoimmune diseases, we discuss approaches for the genetic diagnosis. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Introductory Chapter: A Brief Statement about Parathyroid Glands

“…Hypoparathyroidism occurs for autoimmune or idiopathic or iatrogenic reasons. Autoimmune-related parathyroid gland diseases are observed due to genetic factors [10]. In addition, it should not be forgotten that genetic factors are considered "rare diseases" when looking at parathyroid-gland-related diseases.…”

Hypoparathyroidism: update of guidelines from the 2022 International Task Force

“…In patients with nonsurgical HypoPT who have a positive family history of nonsurgical HypoPT or present with syndromic features, or are younger than 40 years, genetic testing is recommended (3,4,10). In patients with nonsurgical HypoPT who have other clinical features of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, genetic testing for AIRE variants is recommended.…”

“…C are of patients with parathyroid disorders is often challenging due to complexities in the diagnosis, imaging, and surgical or medical management of primary hyperparathyroidism, and inadequacies with conventional management of hypoparathyroidism. This review summarizes recommendations from the 2 nd International Guidelines for Hypoparathyroidism (1) that will soon be published in the Journal of Bone and Mineral Research, along with the supporting systematic and narrative reviews (2)(3)(4)(5). These guidelines summarize information published in the medical literature back as far as 1940, with particular focus on papers published between 1970 and 2020, and emphasizing new information published between 2015 and 2020.…”

The Fifth International Workshop on the Evaluation and Management of Primary Hyperparathyroidism

“…The reports on hypoparathyroidism are published in a contiguous issue of JBMR. (22)(23)(24)(25)(26)(27)(28) In the commentary introducing those reports, we gratefully acknowledge those who were involved in that major effort. (29) Ever mindful of this international effort, we have reached out to many organizations, societies, and patient advocacy groups.…”