EQUINE CUSHINGS-SYNDROME

Equine hyperadrenocorticism (Equine Gushing syndrome, equine pituitary pars intermedia dysfunction) represents a relatively rare endocrine d isorder with poor prognosis in the horse, even though recent data sugg est a much higher incidence than has been described in the literature so far. In the horse the condition is caused by honours of the pars in termedia of the pituitary whereas cushing disease of other species is predominantly due to adrenal tumours. ACTH is synthesised exclusively from the precursor pro-opiolipomelanocortin (pro-OLMC) in corticotropi c cells of the anterior pituitary. The melanotropic cells of the pars intermedia also express pro-OLMC, however any formed ACTH is immediate ly cleaved into alpha MSH and CLIP in normal horses. The processing of pro-OLMC peptides appears to be changed in pars intermedia tumours: A CTH formation is greatly enhanced and cleavage to alpha MSH and CLIP a ppears to be inhibited leading to a grossly increased ACTH secretion. In addition, melanotropic cells do not express glucocorticoid receptor s resulting in lack of glucocorticoid negative feedback on ACTH secret ion and thus hyperadrenocorticism. These properties form the basis for a reliable diagnosis of equine pituitary pars intermedia dysfunction: cortisol secretion is not adequately suppressed in horses with pituit ary pars intermedia dysfunction after dexamethasone suppression (40 mu g/kg). In our current study horses with pituitary pars intermedia dys function had elevated basal cortisol levels (68.3 +/- 8.2 ng/ml, mean +/- SE, n = 45), as compared to controls (39.1 +/- 2.4 ng/ml, n = 55). Fifteen (8 AM) and 19 (12 PM) hours after dexamethasone administratio n this test reliably distinguished between affected (39.0 +/- 3.5, 41. 7 +/- 3.6 ng/ml) and control horses (4.3 +/- 0.4, 4.0 +/- 0.4 ng/ml). It is interesting to note that the high ACTH levels do not result in a similar increase in cortisol production. A possible explanation for t his discrepancy could be differences in the biological- and immunoreac tivity of ACTH secreted by pars intermedia adenomas. However these tum ours have been reported to secrete also disproportionately large amoun ts of other peptides such as alpha MSH, beta MSH, CLIP and beta-endorp hin which could modulate the adrenal response to ACTH. Furthermore, so me of the clinical symptoms which are difficult to understand as mere signs of elevated cortisol levels may be attributable to the large amo unts and/or unusual composition of pro-OLMC derived peptides in pars i ntermedia adenomas.