Adrenal Gland
The adrenal gland is an endocrine gland that sits above the kidneys.
It is divided into a cortex and a medulla.
The main responsibility of the adrenal gland is to regulate the stress response through the synthesis of corticosteroids, such as cortisol, and catecholamines, such as adrenaline.
Adrenal Cortex
The adrenal cortex is divided into 3 zones:
Zona glomerulosa: main site for production of mineralocorticoids, namely aldosterone.
Zona fasciculate: mainly responsible for producing glucocorticoids, cortisol.
Zona reticularis: produces androgens, estrogen and testosterone.
Stages of Adrenocortical Disease in Ferrets
Adrenal Hyperplasia
Adrenal hyperplasia is an increase in the size of the adrenal cells resulting in an increase in the amount of hormones produced by the adrenal cortex.
Adrenal Adenoma
Adrenal adenoma is a benign tumor arising from the cortex of the adrenal gland.
Adenocarcinoma
Adenocarcinoma is a malignant, cancerous, tumor arising from the cortex of the adrenal gland.
Causes of Adrenocortical Disease
The exact causes of the changes in adrenal glands that lead to adrenocortical disease is unknown.
Several possible hypotheses include:
Early age of sterilization, typically between 4–6 weeks of age.
Prolonged photoperiods.
Genetic component due to inbreeding.
Diet.
Signs of Adrenocortical Disease
Hair loss, alopecia.
Vulva swelling in females.
Enlarged prostate in males and urethral obstruction.
Increased sexual aggression. Males often grab and drag females by the nape of the neck.
Muscle atrophy.
Pruritus, itchiness.
Thinning of the skin.
Lethargy.
Enlarged adrenal glands.
GnRH Feedback Loop
Negative Feedback of GnRH
The absence of normal gonadal secretion of estrogen and other androgens in neutered or spayed ferrets results in a lack of negative feedback on the hypothalamus, causing continuous secretion of GnRH and continuous stimulation of the hormonal cascade.
The continuously secreted GnRH in turn stimulates the pituitary gland, which consequently secretes Luteinizing Hormone, LH, and Follicle Stimulating Hormone, FSH.
If ferrets incorporate gonadal cells into the adrenal gland, LH and FSH will stimulate an increased secretion of sex hormones by the adrenal gland, thus resulting in the adrenal gland changes that result in adrenocortical disease.
Photoperiod
Ferrets are descended from the European polecat, who inhabit a region of the world where there are long periods of darkness.
Ferrets in the United States are exposed to less definitive seasonal photoperiods.
Ferrets kept at light cycles longer than 8 hours have been reported to have increased GnRH and LH production, increasing the risk of adrenal disease.
Melatonin
Melatonin’s exact mechanism of action is poorly understood, but it does inhibit GnRH secretion from the hypothalamus.
Melatonin is produced by the pineal gland within the brain during dark hours.
It is thought that ferrets experiencing artificially prolonged photoperiods may become deficient in melatonin, increasing their likelihood of development of adrenal disease.
Keeping your ferret in a dark room will increase their melatonin production and reduce the risk of adrenal disease development.
Treatment Options for Adrenal Disease
Ferretonin
Ferretonin is a melatonin implant about the size of a grain of rice that is injected under the skin of your ferret between the shoulder blades.
Melatonin
Melatonin is a natural inhibitor of GnRH.
By inhibiting GnRH, the production of LH and FSH is reduced, preventing their negative effect on the adrenal gland.
The implant is broken down by the body and eliminated, and must be administered repeatedly with the return of adrenal disease signs, such as hair loss.
Lupron
Lupron is a long-acting GnRH analog.
It can relieve clinical symptoms of adrenal disease for 2–8 months.
Lupron is administered by injection every 1 or 4 months.
Lupron functionally imitates GnRH, stimulating the release of FSH and LH from the pituitary gland and ultimately the production of estrogen and testosterone which negatively inhibits any further release of GnRH from the hypothalamus.
Consequently, Lupron in the long-term will decrease the production of the sex hormones that facilitate adrenal disease.
Deslorelin
Deslorelin is a GnRH-agonist that stops the production of sex hormones, testosterone and estrogen.
Deslorelin is an implant that is injected under the skin of the ferret between the shoulder blades, allowing the continuous, low-level release of the drug.
Unlike Lupron and Ferretonin, Deslorelin only has to be administered every 18 months to 2 years.
Deslorelin works by inhibiting the synthesis and release of LH and FSH by the pituitary gland, decreasing the effect of these hormones on the adrenal gland.
Surgery
Surgical removal of the adrenal gland is the only definitive treatment for adrenal disease but is performed only if the other treatment approaches are no longer effective.
Removal of the right adrenal gland is considered more challenging because it is found attached to the caudal vena cava, the great vessel which transports the bulk of deoxygenated blood back to the heart.
Removal often results in significant blood loss.
Most veterinarians in turn debulk the majority of the right adrenal gland.
This often leaves hormone-secreting tissue and the tumor in turn often continues to grow and produce clinical signs.
The use of drugs, including mitotane, ketoconazole, or streptozocin, currently utilized to treat hyperadrenocorticism in humans, dogs, and cats is unsuccessful in ferrets as it targets a different layer in the adrenal cortex that is not affected with ferret adrenal disease.
