Hirsutism develops in older horses (typically 18 yr and over) and is associated with pituitary pars intermedia dysfunction (PPID) caused by an adenoma of the cells of the pars intermedia of the pituitary gland. Such adenomas often severely compress the overlying hypothalamus, which is the primary center for homeostatic regulation of body temperature, appetite, and cyclic shedding of hair. In addition, pars intermedia adenomas secrete increased amounts of alpha melanocyte stimulating hormone (MSH), which is a factor in the growth of a long hair coat in winter.

Cushing's disease, hirsutism

Clinical Findings and Lesions

Signs of PPID include polyuria, polydipsia, poor muscle tone, weakness, somnolence, abnormal distribution of adipose tissue, swelling of the periorbital fossa, laminitis, increased susceptibility to infections, intermittent hyperpyrexia, and generalized hyperhidrosis. Hirsutism often becomes evident because of failure of the cyclic seasonal shedding of hair. Before generalized hirsutism is observed, horses may have longer hair on the legs, ventral abdomen, and throat latch. Eventually, the hair over most of the trunk and extremities becomes long (up to 4–5 in. [10–12 cm]), abnormally thick, wavy, and often matted.

Pars intermedia adenomas are the most common pituitary tumors in horses. They are yellow to white, multinodular, and incorporate the pars nervosa. Horses with PPID may have hyperglycemia (insulin-resistant) and glycosuria, probably because of increase concentration of cortisol and other hormones that are insulin antagonists.

Plasma immunoreactive adrenocorticotropin and alpha-MSH levels may range from modestly increased to extremely elevated. Blood cortisol concentrations generally remain in the normal range but lack normal diurnal rhythm and escape suppression by administration of dexamethasone much more quickly than in normal animals.

Diagnosis

Hyperglycemia and insulin insensitivity are suggestive of pituitary adenoma in horses, but because they occur in horses with equine metabolic syndrome, are not diagnostic of PPID. Other nonspecific findings include an absolute or relative neutrophilia, eosinopenia, and lymphopenia; lipemia; hypercholesterolemia; and a mild, normochromic, normocytic anemia. Liver enzymes may be increased. Electrolytes are usually normal. Urinalysis is normal except for occasional glycosuria and a low to normal specific gravity.

Definitive diagnosis is based on evocative testing or measurement of resting endogenous ACTH concentrations. Dexamethasone (40 μg/kg, IM) often will not suppress cortisol levels to at least 30% of baseline or to <1 μg/dL, as it does in normal horses 6–15 hr after administration. In addition, cortisol concentrations return to within 80% or greater of baseline values 24 hr after dexamethasone administration in horses with PPID. Normal horses have suppressed cortisol levels 24 hr after dexamethasone administration. Horses with PPID react with an exaggerated response to domperidone administration. Increase in plasma endogenous ACTH to 200% or more of baseline levels 2–4 hr after 5.0 mg/kg domperidone administration PO is consistent with PPID.

Differential diagnoses include syndromes resulting in chronic debilitation, eg, poor management and nutrition, parasitism, and chronic systemic diseases. The polyuria and polydipsia (PU/PD) must be differentiated from that due to chronic renal disease or diabetes insipidus. The hyperglycemia, glycosuria, and PU/PD must be differentiated from that caused by primary diabetes mellitus. High insulin concentrations or an increased glucose:insulin ratio must be differentiated from primary hyperinsulinemia (equine metabolic syndrome). Pheochromocytomas (see Neuroendocrine Tissue Tumors) may cause hyperhidrosis, hyperglycemia, and tachypnea, although they usually are nonfunctional and only found incidentally at necropsy. Differential diagnosis for hirsutism includes being of the Bashkir Curly breed or having a congenital curly coat abnormality. There is no other recognized condition in which adult horses acquire a long, curly hair coat. For this reason, hirsutism can be considered a positive diagnostic test for PPID.

Treatment

Horses with PPID are relatively fragile, with poor immune function. Thus, most require diligent attention to normal husbandry. Pergolide, a dopaminergic agonist, is currently the only agent that has been demonstrated to decrease endogenous ACTH concentrations in horses with PPID. Starting dosages are 0.006–0.01 mg/kg, PO, sid. This typically results in a dose of 0.5–1 mg per day. If this amount does not result in improvement in clinical signs and endocrinologic testing, it may be increased gradually. Reported side effects from pergolide therapy include depression and anorexia. Often these signs are transitory and resolve over time. If they do not, the dose may be decreased or split and given twice daily. Although its use has not been documented to result in improvement in clinical signs, cyproheptadine at a dose of 0.6–1.2 mg/kg, PO, sid has been described to treat PPID. There are anecdotal reports that cyproheptadine and pergolide exert synergistic effects, and that the combination results in superior outcomes compared to pergolide alone. Trilostane, a competitive 3-β hydroxysteroid dehydrogenase inhibitor, may be beneficial in horses, but its cost prohibits its use.

Last full review/revision July 2011 by Janice E. Kritchevsky