Early Clinical Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, United States.
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Front Endocrinol (Lausanne). 2021 Feb 25;12:623667. doi: 10.3389/fendo.2021.623667. eCollection 2021.
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.
人类血清钙水平的调节是通过甲状旁腺的内分泌作用与维生素 D 以及一组关键的靶细胞和组织（包括成骨细胞、破骨细胞、肾小管和小肠）协同作用来实现的。甲状旁腺是位于甲状腺后面的小型高度血管化内分泌器官，会根据需要将甲状旁腺激素（PTH）分泌到全身循环中，以保持血清游离钙浓度在严格的生理范围内。原发性甲状旁腺功能亢进症（HPT）是一种矿物质代谢紊乱的疾病，通常与异常升高的血清钙有关，是由于一个或多个异常甲状旁腺不受控制地释放 PTH 引起的。尽管在绝大多数情况下 HPT 是一种散发性疾病，但它也可能表现为家族综合征的一种表现。许多良性和恶性散发性甲状旁腺肿瘤是由肿瘤抑制基因的功能丧失突变引起的，这些基因最初是通过研究表现为遗传性综合征的 HPT 患者的基因组 DNA 而被鉴定出来的。某些原癌基因的体细胞和遗传性突变也会导致甲状旁腺肿瘤的发生。在已经缺乏已知 HPT 易感性基因种系变异的家族中对家族性 HPT 的临床和遗传研究，代表了发现与甲状旁腺肿瘤发展相关的新基因的一个有前途的未来方向。
