Adrenocortical carcinomas secreting aldosterone and progesterone or other steroid sex hormones in cats have been reported.4,5 This case is unusual because the adrenocortical carcinoma secreted at least 3 different types of steroid hormones, and the patient had dermatologic abnormalities (ie, symmetric alopecia, hair coat color change).
Symmetric alopecia has been reported in cats with progesterone-secreting adrenal tumors and in cats treated with progestin injections (ie, medroxyprogesterone acetate).6-8 Carbohydrate intolerance is a common result of progesterone-mediated insulin antagonism in cats and is likely a causal factor for diabetes mellitus.8,9
Lightening of the hair coat from black to red has been observed in some canine endocrinopathies, including Sertoli cell tumors, Cushing’s disease, and hypothyroidism.6 In cats, reddening of the hair coat appears to be less common. The hair coat color change in this patient, which resolved postadrenalectomy, may have been caused by increased estradiol concentration or may have occurred secondary to low ACTH concentration. Estrogen has been reported to cause increased hair pigmentation in mice,10 and a recent case report described a cat with hypocortisolemia and subtle hair coat color changes that resolved with removal of an estrogen-secreting adrenal tumor.2
Alternatively, low ACTH concentration leading to low α-melanocyte-stimulating hormone (MSH) concentration might have been involved in the coat color change. ACTH is a precursor of α-MSH, and both share a common amino acid sequence. A decrease in ACTH production would indirectly decrease the α-MSH concentration. ACTH and α-MSH are both full agonists of the melanocortin-1 receptor (MC1R).11
Activation of MC1R on melanocytes leads to production of eumelanin (black-brown pigment), whereas inhibition of MC1R results in production of pheomelanin (yellow-red pigment). Low concentrations of both ACTH and α-MSH would decrease MC1R binding and subsequently decrease synthesis of eumelanin and increase synthesis of pheomelanin.6,11 The opposite occurs in humans with Addison’s disease; hyperpigmentation caused by increased ACTH concentration is a common finding in these patients.12
The relationship between low ACTH and cortisol concentrations and sex hormone-secreting adrenal tumors is poorly understood. Possible causes include negative feedback of cortisol from increased displacement of free cortisol from cortisol-binding protein by sex hormones and negative feedback of ACTH from progesterone or unmeasured intermediate metabolites.4,7,9 Exogenous progestins such as megestrol acetate have been shown to suppress endogenous ACTH secretion.7,13 All of these sources can result in hypocortisolemia caused by suppression of the hypothalamic–pituitary–adrenal axis.