Familial Hyperparathyroidism.

Jenny E Blau,William F Simonds

doi:10.3389/fendo.2021.623667

Abstract

Regulation of the serum calcium level in humans is achieved by the endocrine action of parathyroid glands working in concert with vitamin D and a set of critical target cells and tissues including osteoblasts, osteoclasts, the renal tubules, and the small intestine. The parathyroid glands, small highly vascularized endocrine organs located behind the thyroid gland, secrete parathyroid hormone (PTH) into the systemic circulation as is needed to keep the serum free calcium concentration within a tight physiologic range. Primary hyperparathyroidism (HPT), a disorder of mineral metabolism usually associated with abnormally elevated serum calcium, results from the uncontrolled release of PTH from one or several abnormal parathyroid glands. Although in the vast majority of cases HPT is a sporadic disease, it can also present as a manifestation of a familial syndrome. Many benign and malignant sporadic parathyroid neoplasms are caused by loss-of-function mutations in tumor suppressor genes that were initially identified by the study of genomic DNA from patients who developed HPT as a manifestation of an inherited syndrome. Somatic and inherited mutations in certain proto-oncogenes can also result in the development of parathyroid tumors. The clinical and genetic investigation of familial HPT in kindreds found to lack germline variants in the already known HPT-predisposition genes represents a promising future direction for the discovery of novel genes relevant to parathyroid tumor development.

Highlights

Evidenced by elevated serum calcium, primary hyperparathyroidism (HPT) is a disorder of mineral metabolism caused by the inappropriate or excessive secretion of parathyroid hormone (PTH) from one or several abnormal parathyroid glands [1]
Since the release of parathyroid hormone (PTH) from parathyroid chief cells is tightly regulated by the calcium-sensing receptor (CASR), a cell surface-expressed G protein-coupled receptor (GPCR) belonging to GPCR family C [2], mutation in the germline of CASR or other genes transducing and propagating the CASR signal can result in
Even though inherited forms of HPT represent only a small proportion of total cases (< 5%), investigation into the molecular basis of these rare familial syndromes has resulted in considerable insight into the genetics and pathophysiology of both sporadic and familial HPT and spotlighted the importance of genes such as Multiple endocrine neoplasia type 1 (MEN1), CDC73, CASR, GNA11, AP2S1, CDKN1B, and GCM2

Summary

Introduction

Evidenced by elevated serum calcium, primary hyperparathyroidism (HPT) is a disorder of mineral metabolism caused by the inappropriate or excessive secretion of parathyroid hormone (PTH) from one or several abnormal parathyroid glands [1]. Following careful clinical and genetic analysis, the majority of FIHP kindreds have been shown to lack germline mutation in the established HPT-susceptibility genes (Figure 2) [20, 119, 123].

Results

Conclusion