Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
J Bone Miner Res. 2018 Jan;33(1):27-31. doi: 10.1002/jbmr.3339. Epub 2017 Dec 11.
Familial hypocalciuric hypercalcemia (FHH) causes lifelong hypercalcemia with features that overlap with typical primary hyperparathyroidism (PHPT). The incompleteness of this overlap has led to divergent nomenclatures for FHH. I compare two nomenclatures. One sets FHH as an entity distinct from PHPT. The other groups FHH with PHPT but conditions FHH as atypical PHPT. I analyzed selected articles about calcium-sensing receptors, FHH, PHPT, CASR, GNA11, and AP2S1. FHH usually results from a heterozygous germline inactivating mutation of the CASR, and less frequently from mutation of GNA11 or AP2S1. The CASR encodes the calcium-sensing receptors. These are highly expressed on parathyroid cells, where they sense serum calcium concentration and regulate suppression of PTH secretion by serum calcium. Their mutated expression in the kidney in FHH causes increased renal tubular reabsorption of calcium (hypocalciuria). Many FHH features are shared with PHPT and thus support FHH as a form of PHPT. These include a driver mutation expressed mainly in the parathyroid cells. The mutation causes a parathyroid cell insensitivity to extracellular calcium in vivo and in vitro, a right-shift of the set point for suppression of PTH secretion by calcium. Serum PTH is normal or mildly elevated; ie, it is not appropriately suppressed by hypercalcemia. Total parathyroidectomy causes hypoparathyroidism and durable remission of hypercalcemia. Some other features are not shared with PHPT and could support FHH as a distinct entity. These include onset of hypercalcemia in the first week of life, frequent persistence of hypercalcemia after subtotal parathyroidectomy, and hypocalciuria. The features supporting FHH as a form of PHPT are stronger than those favoring FHH as a distinct entity. Classifying FHH as an atypical form of PHPT represents compact nomenclature and supports current concepts of pathophysiology of FHH and PHPT. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
家族性低钙血症性高钙血症 (FHH) 导致终生高钙血症，其特征与典型原发性甲状旁腺功能亢进症 (PHPT) 重叠。这种重叠的不完整性导致了 FHH 的不同命名法。我比较了两种命名法。一种将 FHH 设定为与 PHPT 不同的实体。另一种将 FHH 与 PHPT 分组，但将 FHH 归类为非典型 PHPT。我分析了一些关于钙敏感受体、FHH、PHPT、CASR、GNA11 和 AP2S1 的文章。FHH 通常是由于 CASR 的种系失活突变引起的杂合子，较少是由于 GNA11 或 AP2S1 的突变引起的。CASR 编码钙敏感受体。这些受体在甲状旁腺细胞中高度表达，在那里它们感知血清钙浓度，并调节血清钙对 PTH 分泌的抑制作用。它们在 FHH 中的肾脏中的突变表达导致肾小管对钙的重吸收增加（低钙尿症）。许多 FHH 特征与 PHPT 共享，因此支持 FHH 作为 PHPT 的一种形式。这些特征包括主要在甲状旁腺细胞中表达的驱动突变。该突变导致甲状旁腺细胞对体内和体外细胞外钙不敏感，钙抑制 PTH 分泌的设定点右移。血清 PTH 正常或轻度升高；即，它不能被高钙血症适当抑制。甲状旁腺全切除术导致甲状旁腺功能减退和高钙血症的持久缓解。其他一些特征与 PHPT 不共享，这可能支持 FHH 作为一个独立实体。这些特征包括高钙血症在生命的第一周开始，甲状旁腺次全切除术后高钙血症频繁持续存在，以及低钙尿症。支持 FHH 作为 PHPT 一种形式的特征强于支持 FHH 作为独立实体的特征。将 FHH 归类为 PHPT 的一种非典型形式代表了紧凑的命名法，并支持 FHH 和 PHPT 的病理生理学的当前概念。2017 年出版。本文是美国政府的作品，在美国属于公有领域。
