Equine Cushing's Disease: Plasma Immunoreactive Proopiolipomelanocortin Peptide and Cortisol Levels Basally and in Response to Diagnostic Tests*

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Abstract
Equine Cushing's disease is almost invariably caused by ACTH hypersecretion by adenomas of pars intermedia (PI), rather than pars distalis (PD), as in man. Therefore, PI proopiolipomelanocortin (proOLMC) peptides, such as αMSH, βMSH, corticotropin-like intermediate lobe peptide (CLIP), and β-endorphin (βEND), are also secreted. In two horses with Cushing's disease, basal plasma immunoreactive ACTH was elevated about the same as in human Cushing's disease, but αMSH, βMSH, CLIP, and βEND were disproportionately increased. Neither they nor the modestly elevated plasma cortisol demonstrated a diurnal rhythm. In the mare with more severe disease, neither low nor high dose dexamethasone suppressed hormone levels; in the less affected mare, high dose dexamethasone suppressed peptide levels only modestly, and cortisol never fell below normal. Both mares had glucose intolerance. Insulin (0.8 U/kg) did not lower blood glucose in the mare with severe Cushing's disease and diabetes mellitus; in the other, there was little response of peptides or cortisol, although blood glucose fell to 34 mg/dl. The adrenal cortices of both animals responded to exogenous ACTH. The less affected mare was studied further. Vasopressin was followed by only a modest increase in hormone levels at 60 min or later, which may have represented a spontaneous fluctuation in secretion. Dopamine infusion caused a prompt fall in hormone levels, followed by a rebound after it was stopped. Bromocriptine and pergolide, dopaminergic agonists, caused prompt and sustained decreases in hormone levels, but not to less than normal. Combined pergolide and dexamethasone lowered hormone levels still further, supporting the concept that dexamethasone had suppressed residual PD secretion. The results suggest that proOLMC peptide secretion by a PI adenoma causing equine Cushing's disease is under similar control as normal PI in other species. Glucocorticoids, which suppress PD but not PI secretion, and vasopressin and hypoglycemia, which stimulate PD but not PI secretion, had little or no effect on PI tumor proOLMC secretion; in contrast, dopamine, which inhibits PI but not PD proOLMC peptide secretion, also inhibited PI tumor secretion and thereby provides a potential rationale for treating Cushing's disease in horses.