Insulinomas are very common in ferrets >2–3 yr old. These functional tumors of the pancreatic β cells cause increased insulin levels, resulting in hypoglycemia and its associated clinical signs such as weakness, lethargy, posterior paresis, hypersalivation, bruxism, and seizures. Diagnosis is based on demonstration of hypoglycemia and corresponding normal or increased insulin levels. Other blood tests are usually normal. Ultrasonography is only occasionally useful in demonstrating these pancreatic masses. Medical and surgical treatments are possible, but there is no cure, and owners should be made aware of the chronic and progressive nature of this disease. Surgical treatment involves removing discrete tumors via nodulectomies or partial pancreatectomy. Microscopic tumors within the entire pancreas are common; therefore, removal of the entire tumor is unlikely. A period of euglycemia occurs after surgery in some cases, but most cases require continued medical treatment. Major benefits of surgery are decreased severity of signs, ease of management, and moderately increased survival time. Medical management includes use of prednisone (0.5–2 mg/kg, PO, bid) and diazoxide (5–30 mg/kg, PO, bid) to counteract the effects of the tumor; however, this does not affect the tumor directly. Prednisone increases resting blood glucose levels and down-regulates peripheral insulin receptors, whereas diazoxide decreases insulin release from the β cells and competes at peripheral insulin receptors. These drugs can be used independently or synergistically. Typically, prednisone is used first until the dosage approaches 2 mg/kg and then diazoxide is added. Medical treatment is lifelong, and glucose levels should be monitored 5–7 days after changing doses and at least every 3 mo afterward.
Hyperadrenocorticism in ferrets is caused by excessive secretion of the sex hormones progesterone, testosterone (in the form of androstenedione), and estrogen by the zona reticularis of the adrenal gland. It can be seen in ferrets as young as 1.5 yr old. The most common clinical sign is hair loss beginning on the tail and rump and progressing up the flank and head. In females, a swollen vulva and enlarged mamillae may also be seen, whereas males may develop aggression and stranguria secondary to prostatic enlargement. Bone marrow suppression may be seen in either sex, with severe hyperestrogenemia. A presumptive diagnosis is made after history and physical examination. The enlarged adrenal glands are often palpable cranial to either kidney. CBCs and chemistry panels are typically normal. Radiographs are not useful, because the masses do not calcify as commonly as in other species. Ultrasonography can demonstrate enlargement of the gland(s). Definitive diagnosis requires measurement of the three sex hormones, which can be performed in a panel (at University of Tennessee).
Medical and surgical treatments exist. Surgical removal of the adrenal gland(s) is more likely to be curative than medical management, but there is still a recurrence rate of ~40% after surgery. The left gland is easier to remove, because the right gland is closely associated with the caudal vena cava. If both sides are affected, a subtotal adrenalectomy can be performed. Histology of these glands may reveal hyperplasia, adenoma, or adenocarcinoma. Functionally, all three grades are similar, and metastasis is unlikely. Hypoadrenocorticism may develop if both adrenal glands are completely or partially removed. This may be treated with mineralocorticoid and glucocorticoid supplementation. Medical management of hyperadrenocorticism is aimed at reducing the clinical signs but does not affect the adrenal tumor itself. Leuprolide acetate is the most common drug used. The mechanism is not completely understood but is probably related to down-regulation of peripheral hormone receptors. Leuprolide is a repositol formulation of a GnRH agonist that is formulated in 1-mo (100–400 mcg, IM) and 4-mo (2–4 mg, IM) preparations. Owners should be advised that this is a lifelong treatment to control the clinical signs of the disease. Recently, some clinicians have treated hyperadrenocorticism medically only during breeding months, typically November to March. Deslorelin acetate, a similar GnRH agonist, is also available. This is a longer-acting implant that lasts 10–17 mo. This drug is well tolerated by ferrets. Melatonin can also be used at 1 mg per ferret per day, orally or in an injectable, repositol formulation, which is reported to last 4 mo. This drug counteracts the alopecia and may help with other signs as well, but, like leuprolide, is only symptomatic treatment. Drugs used to control sex hormone levels in people are beginning to be used in ferrets and show promise in controlling clinical signs.