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

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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.