Everything You Wanted to Know about Adrenal Disease in Ferrets

Adrenal disease can refer to changes to the adrenal cortex and/or to the adrenal medulla. The most common form of adrenal medulla pathology is a pheochromocytoma. These rare tumors are usually much larger than tumors of the adrenal cortex and can remain unnoticed for a long time. Although cases have been reported where pheochromocytomas have been diagnosed based on histologic characteristics of the adrenal tumor, measurement of urinary metanefrine is necessary to confirm the diagnosis. To the author’s knowledge this type of confirmation has not yet been performed in ferrets. The most common form of adrenal disease in ferrets is hyperadrenocorticism, also referred to as adrenocortical disease, in which the adrenal cortex is affected. The outermost layer of the adrenal cortex is the zona glomerulosa, which produces mineralocorticoids (primarily aldosterone). The zona fasciculata consists of an outer and inner part, and produces glucocorticoids (cortisol and corticosterone) and androgens. The most interior zone is the zona reticularis, which is extremely variable in its prominence and cellular composition. This zone contains the smallest cells of the adrenal cortex and produces primarily androgens. Thus, in principle, three distinct syndromes may arise in adrenocortical hyperfunction: hyperaldosteronism, hypercortisolism, and hyperandrogenism. Primary hyperaldosteronism or Conn’s syndrome is the most common form of hyperadrenocorticism in cats, usually due to excessive secretion of mineralocorticoids by an adrenocortical neoplasia or bilateral adrenocortical hyperplasia. The exact pathogenesis of primary hyperaldosteronism remains to be elucidated. Hypercortisolism or Cushing’s syndrome is the most common form of hyperadrenocorticism in dogs, and also occurs frequently in humans. In these species, hypercortisolism most frequently results from excessive secretion of adrenocorticotropic hormone (ACTH) by a pituitary adenoma. ACTH-independent hypercortisolism may be due to excessive secretion of glucocorticoids by a benign or malignant adrenocortical tumor. However, ACTH-independent hypercortisolism may also occur as a result of expression of aberrant or overactive eutopic hormone receptors. In humans, various membranebound receptors, functionally coupled to steroidogenesis, have been reported, including gastric inhibitory polypeptide, catecholamine, vasopressin, serotonin, and luteinizing hormone (LH) receptors. LHdependent hypercortisolism has been reported in several women. In addition to LH-dependent hypercortisolism, virilizing and feminizing LH-dependent adrenal tumors have been reported in humans. HYPERADRENOCORTICISM In neutered pet ferrets hyperandrogenism is the most common form of hyperadrenocorticism. In ferrets, plasma androstenedione, 17-hydroxyprogesterone and estradiol concentrations are increased. It has been reported that approximately 85% of ferrets with hyperadrenocorticism have enlargement of one adrenal gland without atrophy of the contralateral adrenal gland. In the other 15% of cases bilateral enlargement is present. After surgical removal of a unilateral adrenal tumor, the disease commonly recurs due to involvement of the contralateral adrenal gland. The adrenal glands have been histologically classified as (nodular) hyperplasia, adenoma and adenocarcinoma. The histologic diagnosis, however, does not provide information on functionality of the tumor, nor does it provide any prognostic information. No relationship has been found between pituitary and adrenal tumors in ferrets. At this stage, pituitary tumors should be regarded as incidental findings. Different etiologies have been suggested for the high occurrence of hyperadrenocorticism in ferrets. These include (early) neutering of ferrets, housing ferrets indoors, and genetic background. In recent years, evidence has been gathered that increased concentrations of gonadotropins, which occur after neutering (due to the loss of negative feedback), stimulate the adrenal cortex, eventually leading to an adrenocortical neoplasm.