6793 The Potential Of Melatonin As A Treatment Option For Cushing’s Syndrome In Humans Based On Observations In Cushingoid Dogs

Abstract

Abstract Disclosure: K. Fecteau: None. It is known that the secretion of cortisol and melatonin is circadian, with the former increasing during morning hours and the latter increasing during the dark hours of night. Studies investigating melatonin concentrations in patients with Cushing’s syndrome have reported differing results, with some having low melatonin concentrations, and others normal or high concentrations. Interestingly, adrenal glands have been shown to express melatonin receptors, and in vitro studies with human adrenal cells have shown a decrease in cortisol, as well as other adrenocortical steroids, when treated with melatonin. In human adrenal gland explants, melatonin reportedly inhibited ACTH stimulated circadian clock genes, as well as cortisol and progesterone production. Melatonin is often used as a first-line of treatment in dogs with atypical Cushing’s, where cortisol is normal, other adrenocortical steroids are elevated, and typical clinical signs of Cushing’s are present. Retrospective data collected in our diagnostic laboratory from dogs that had at least two submissions (before & during treatment), showed 34 percent of dogs on melatonin improved clinically. Of the 34 percent, 26.4 percent experienced either similar or more aberrant steroid concentrations, and 7.6 percent experienced lower steroid concentrations. Approximately 40 percent of dogs had significantly lower androstenedione when retested on melatonin. In humans, Cushing’s disease is a rare cause of androgen excess, with one study reporting occurrence of less than 4 percent in women. Adrenocortical carcinoma is also rare, however, women with this type of tumor may exhibit clinical signs of androgen excess due to adrenal androgen hypersecretion, and up to 25 percent of women with clinical signs had normal testosterone and elevated androstenedione. Therefore, based on the effectiveness of melatonin on lowering androstenedione concentrations and improving clinical signs associated with increased androgens and glucocorticoids in dogs, it may be an inexpensive and conservative option, especially for patients presenting with clinical signs but diagnostic testing is either negative of equivocal for Cushing’s. Presentation: 6/2/2024