Morphological and functional changes of pituitary corticotrophs in the experimental dog under inhibition of the adrenal cortex.

随机分为对照组和米托坦治疗组。米托坦治疗组给予米托坦治疗1个月。两组患者均行促ACTH刺激试验和促肾上腺皮质激素释放激素（CRH）刺激试验。对米托坦治疗组大鼠给予米托坦前后进行脑垂体和脑磁共振成像（MRI）检查。经CRH刺激试验和MRI后，对犬实施安乐死，切除垂体、肾上腺进行大体和组织学检查。CRH刺激后，米托坦治疗组犬ACTH浓度显著高于对照组犬。MRI显示，给药后治疗组犬垂体较给药前明显增大。大体和组织学检查显示肾上腺皮质明显萎缩。免疫组化结果显示米托坦治疗组犬垂体皮质因子肥大。这些结果表明，在临床正常犬中，持续给药米托坦抑制肾上腺皮质可导致促肾上腺皮质激素的功能扩增和形态增强。在促皮质腺瘤的情况下，米托坦诱导的单个促皮质细胞肥大可能极大地促进垂体增大和促ACTH分泌增加。

Dogs were randomly assigned to the control group or the mitotane treatment group. In mitotane treatment group dogs, mitotane were administered for 1 month. In both groups, ACTH stimulation testing and corticotropin releasing hormone (CRH) stimulation testing were performed. Magnetic resonance imaging (MRI) of the pituitary gland and brain was performed in mitotane treatment group dogs before and after administration of mitotane. After CRH stimulation testing and MRI, dogs were euthanatized and pituitary gland and adrenal glands were excised for gross and histologic examination. ACTH concentrations in mitotane treatment group dogs were significantly higher than in the control group dogs following CRH stimulation. MRI revealed that pituitary glands were significantly larger in treatment group dogs after administration of mitotane compared with before administration. On gross and histologic examinations, the adrenal cortex was markedly atrophied. Immunohistochemistry revealed hypertrophy of corticotrophs in pituitary glands of mitotane treatment group dogs. These findings indicate that inhibition of the adrenal cortex by continuous administration of mitotane leads to functional amplification and morphologic enhancement of corticotrophs in clinically normal dogs. In instances of corticotroph adenoma, hypertrophy of individual corticotrophs induced by mitotane may greatly facilitate enlargement of the pituitary gland and increases in ACTH secretion.