Abstract
Hyperadrenocorticism is a common disease in ferrets. In recent years evidence has accumulated that this disease differs from hyperadrenocorticism in humans, dogs, and cats, in that adrenocortical sex steroids, rather than cortisol play, an important role in the pathogenesis. In this study attention was focused on the possible pathogenetic role
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of high plasma concentrations of gonadotropic hormones as a result of neutering.
First, plasma concentrations of ACTH and a-MSH in ferrets with hyperadrenocorticism were not found to be significantly different from those of healthy neutered ferrets. Therefore, this disease should be regarded as a normocortisolemic and corticotropin-independent condition. In contrast, a distinct seasonal variation in the UCCR was observed in healthy intact ferrets, and in two neutered hyperadrenocorticoid ferrets, and an increased UCCR was measured in privately owned ferrets with hyperadrenocorticism. However, no seasonal fluctuation in the UCCRs was seen in healthy neutered ferrets. Sexual arousal may play a role in healthy ferrets and in the hyperadrenocorticoid ferrets with an elevated UCCR during the breeding season. One has to assume, however, that only small amounts of cortisol are produced, insufficient to cause suppression of ACTH.
Two of ten ferrets with hyperadrenocorticism studied had a pituitary tumor. These tumors did not stain for any of the pituitary hormones, but had characteristics of clinically non-functional gonadotrope tumors. Gonadal feedback on hypothalamic GnRH, as a result of neutering, may have initiated pituitary tumor development.
In a survey held among Dutch ferret owners, a prevalence of hyperadrenocorticism (0.55%: 95% confidence interval: 0.2 1.1%) was found. Also a linear correlation between age at neutering and age at time of diagnosis of hyperadrenocorticism was found, indicating that neutering, and possibly gonadotropic hormones, play a role in the development of hyperadrenocorticism in ferrets.
The next step was to study the presence and function of gonadotropin receptors in the adrenal glands of healthy ferrets and of ferrets with hyperadrenocorticism. Positive immunohistochemical staining with a luteinizing hormone receptor (LH-R) antibody was found in adrenal glands from young, healthy, intact ferrets. In addition, adrenal hyperplasias and neoplasias from ferrets with hyperadrenocorticism stained positive for the LH-R. To investigate the functionality of the LH-Rs, in vivo GnRH stimulation tests were performed with healthy neutered ferrets and neutered ferrets with hyperadrenocorticism. These studies showed that although LH-Rs are present in the adrenals of young healthy ferrets, they are not functional. Based on in vitro stimulation test, performed with adrenal cells suspended in culture medium, it became clear that neither GnRH nor FSH had a significant influence on the production of adrenocortical steroids, whereas hCG induced the production of these hormones.
Since surgical neutering seems to be a major risk factor in the development of hyperadrenocorticism in ferrets, the literature was reviewed for current and future alternatives for surgical neutering of ferrets. Of the alternatives, the use of progestagens seems the most practical in jills, but the effect of these drugs in hobs is uncertain. Other potential alternatives for the future may be slow-release GnRH implants, GnRH antagonists, or immunization against GnRH
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