Hirsutism Associated with Adenomas of the Pars Intermedia
Hirsutism is the long, nonshedding hair coat that develops in older horses (typically ≥18 yr old) 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), a factor in the growth of a long hair coat in winter.
Signs of PPID include polyuria and polydipsia (PU/PD), 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 compress the pars nervosa. Horses with PPID may have hyperglycemia (insulin-resistant) and glycosuria. It is not known why some horses with PPID become insulin resistant and others do not. However, cortisol and other hormones that may be present in increased concentrations in horses with PPID are insulin antagonists.
Plasma immunoreactive adrenocorticotropin and alpha-MSH levels may range from modestly to extremely increased. 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 healthy animals.
Hyperglycemia and insulin insensitivity are suggestive of pituitary adenoma in horses, but because they occur in horses with equine metabolic syndrome (see Equine Metabolic Syndrome) or other insulin dysregulation syndromes, they 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 mcg/kg, IM) often will not suppress cortisol levels to at least 30% of baseline or to <1 mcg/dL, as it does in healthy 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. Healthy 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 100% or more of baseline levels 2–4 hr after administration of domperidone at 5 mg/kg, PO, is consistent with PPID. Horses with PPID have an increase in plasma endogenous ACTH concentration 10 min after administration of 1 mg thyroid-releasing hormone (TRH), and the TRH stimulation test is believed to be the most sensitive means to detect a pituitary tumor. Horses experience a seasonal rise in endogenous ACTH in the autumn (August through November in the northern hemisphere). Healthy horses are less likely to have a decreased cortisol concentration in response to dexamethasone administration and may demonstrate an exaggerated response to domperidone or TRH in the autumn as well. For this reason, unless there are season-specific normal values available for the testing being performed, it is recommended to perform diagnostic testing for PPID from January through July.
Differential diagnoses include syndromes resulting in chronic debilitation, eg, poor management and nutrition, parasitism, and chronic systemic diseases. The 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 to 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 found only 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.
Horses with PPID are relatively fragile, with poor immune function. Thus, most require diligent attention to good husbandry. Pergolide, a dopaminergic agonist, is currently the only agent demonstrated to decrease endogenous ACTH concentrations in horses with PPID. Starting dosages are 0.006–0.01 mg/kg/day, PO. This typically results in a dose of 0.5–1 mg/day. If this amount does not result in improvement in clinical signs and endocrinologic testing, it may be increased gradually. Reported adverse effects of pergolide therapy include depression and anorexia. Often, these signs are transitory and resolve over time. If they do not, the dose may be decreased temporarily or split and given twice daily. Although its use has not been documented to result in improvement in clinical signs when given alone, cyproheptadine at a dosage of 0.6–1.2 mg/kg/day, PO, may exert synergistic effects when combined with pergolide, and the combination may result in outcomes better than those achieved with pergolide alone. Trilostane, a competitive 3-β hydroxysteroid dehydrogenase inhibitor, has not been investigated adequately in the horse, although its use has improved clinical results.