原発性副甲状腺機能亢進症の病因と病態

Update on drugs acting on calcium-sensing receptor. Etiology and pathogenesis of primary hyperparathyroidism.

　原発性副甲状腺機能亢進症（pHPT）は頻度の高い内分泌疾患で，カルシウム（Ca）調節機構の異常により高Ca血症をきたす。pHPTの原因は腺腫が最も多く８割以上を占め，約15％が過形成，１％以下～５％が癌とされる。多くは散発性に生じるが，ごく一部は家族性に発症するなど遺伝性を示し，これを家族性副甲状腺機能亢進症と呼ぶ。pHPTの病因・病態には，サイクリンD1シグナル（CCND1，CDC73，CDKN1Bなど）や，Wnt/βカテニンシグナル（MEN1など），Ca感知受容体（CaSR，GNA11，AP2S1）のシグナル伝達に影響を及ぼす遺伝子異常が関わる。また，ビタミンＤ不足・欠乏やCa感知受容体（CaSR）の機能低下などが疾患重症度に関与する。pHPTの病因・病態の解明は日々進歩しており，新たな治療薬の開発やCa調節機構のさらなる解明につながると考えられる。

　Primary hyperparathyroidism（pHPT）is a frequent endocrine disease in which abnormal calcium（Ca）regulation leads to hypercalcemia. The most frequent cause of pHPT in more than 80％ of patients is an adenoma, followed by hyperplasia in about 15％, and cancer in 1～5％. Although most cases of pHPT are sporadic, a few are familial（hereditary）, and this is known as familial hyperparathyroidism（FHPT）. 　Gene abnormalities that affect cyclin D1 signaling（CCND1, CDC73, CDKN1B）, Wnt/β-catenin signaling（MEN1）, and calcium-sensing receptor signaling（CaSR, GNA11, AP2S1）play a role in the etiology and pathogenesis of pHPT. Vitamin D insufficiency/deficiency and CaSR dysfunction also play a role in pHPT severity. Continued elucidation of the etiology and pathogenesis of pHPT may lead to development of new treatments for pHPT as well as further understanding of Ca regulation.