Effect of mitotane on pituitary corticotrophs in clinically normal dogs.
Author(s): Taoda T, Hara Y, Takekoshi S, Itoh J, Teramoto A, Osamura RY, Tagawa M
Affiliation(s): Department of Veterinary Science, Division of Veterinary Surgery, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Musasino-shi, Tokyo 180-8602, Japan.
Publication date & source: 2006-08, Am J Vet Res., 67(8):1385-94.
Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't
OBJECTIVE: To evaluate the effects of mitotane administration on the function and morphology of pituitary corticotrophs in clinically normal dogs. ANIMALS: 12 clinically normal adult Beagles. PROCEDURES: Dogs were randomly assigned to the control group or the mitotane treatment group. In mitotane treatment group dogs, mitotane was administered for 1 month. In both groups, ACTH stimulation testing and corticotrophin-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 the pituitary gland and adrenal glands were excised for gross and histologic examination. RESULTS: ACTH concentrations in mitotane treatment group dogs were significantly higher than in the control group dogs following CRH stimulation. Magnetic resonance imaging 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. CONCLUSIONS AND CLINICAL RELEVANCE: 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.