下垂体腺腫の病態・治療と最近の動向

Recent Trend of the Pathophysiology and Treatment of Pituitary Adenomas

はじめに

　下垂体前葉には，乳汁分泌刺激ホルモン（prolactin：PRL），成長ホルモン（growth hormone：GH），副腎皮質刺激ホルモン（adenocorticotropic hormore：ACTH），甲状腺刺激ホルモン（thyroid stimulating hormone：TSH），性腺刺激ホルモン（ゴナドトロピン）〔卵胞刺激ホルモン（follicle stimulating hormone：FSH）と黄体形成ホルモン（luteinzing hormone：LH）〕を産生する細胞があり，これらの細胞ないしはその前駆細胞より腫瘍が発生すると考えられている。したがって，下垂体腺腫は次のように分類することができる：①PRL産生腺腫，②GH産生腺腫（先端巨大症，巨人症），③ACTH産生腺腫（クッシング病），④TSH産生腺腫，⑤ゴナドトロピン産生腺腫・臨床的非機能性腺腫，⑥これらの複数のホルモンを産生する多ホルモン産生腺腫。これらの治療を考えるうえではその病態を明らかにする必要がある。そこで本稿では下垂体腺腫の成因と病態，治療，偶然発見されるインシデンタローマ（偶発腫）の治療方針についても言及したい。

Abstract

　Recent molecular pathological investigations have elucidated the cytodifferentiation of pituitary cells and identified several transcriptional factors that regulate this cytodifferentiation of pituitary cells.　The patterns of cytodifferentiation are closely related to the pathogenesis of pituitary adenomas.　Meanwhile, the role of hypothalamic hormones in the development of pituitary adenomas has recently attracted the attention of investigators.　The expression of growth hormone-releasing hormone and corticotrophin releasing hormone in corticotroph adenomas have been demonstrated in somatotroph adenomas and corticotropin adenomas, respectively.　This finding indicates that the endogenous expression of hypothalamic hormones and their receptors in human pituitary adenoma cells has ample significance in the autocrine or paracrine regulation of pituitary hormone production and tumor extension induced by hypothalamic hormones produced by adenoma cells.

　The recent progress in surgical techniques for treatment of pituitary adenomas has provided several alternatives: transsphenoidal surgery vs. transcranial surgery,sublabial approach vs. endonasal approach,and microsurgery vs. endoscopic surgery.　There have also been developments in the medical treatment of pituitary adenomas.　The frequently used dopamine agonist,cabergoline,is very effective for treating prolactin-producing adenoma.　Long-acting octreotide and pegvisomant are now available for the treatment of growth hormone producing adenoma.　Cabergoline is also used for growth hormone producing adenoma.　Temozolomide has recently been used for atypical adenomas or pituitary carcinomas.　Adult growth hormone deficiency sometimes occurs in postoperative patients with pituitary adenomas.　Growth hormone replacement is recommended to maintain the quality of life of these patients.