Equine Cushing's Disease
History. You are called to examine a 15-year-old mare whose owner complains that the mare has had stiffness in her legs for the past 9 months. The mare has been used as a broodmare and delivered a foal the past spring (and for the 7 previous years’.
She failed to conceive last spring, and now, in the early summer of the next year, she has yet to exhibit normal estrous cycles.Clinical Examination. As you gain a general perspective on the mare, you notice that she appears to have been clipped recently. She is not a show mare, and because it is early summer, you inquire why she has been clipped. The owner indicates that the mare has been slow to shed this spring, and she is tired of seeing the mare with a rough hair coat. The finding of a long hair coat out of season prompts you to ask about the water consumption of the mare; the owner indicates that the mare drank more water (and urinated accordingly) than would be expected. You examine the feet and find that the soles appear slightly "dropped”; you find a small abscess in the sole of one of the feet.
Comment. The main clue regarding the nature of the disease is the presence of a long hair coat out of season; this is the sine qua non of the disease. The usual complaints of owners of horses with Cushing’s disease are related to chronic processes, such as pneumonia, Iaminitis, or weight loss, the latter often associated with parasitism and an inability to masticate properly because of tooth problems. Broodmares progressing into Cushing’s disease often have a recent history of infertility after a successful broodmare career. Although the cause of infertility is not known, a disturbance of gonadotropin secretion is likely, along with a perturbation of the pro-opiomelanocortin system.
The disease represents a classic case of loss of control of the intermediate lobe of the pituitary gland by the hypothalamus, in this case the loss of dopaminergic control.
Under normal conditions, melanotropes of the intermediate lobe process proopiomelanocortin to α-MSH and acetylated β-endorphin, residues 1 to 31, and nonopiate active carboxy-terminally shortened 1 to 26, or 1 to 27, endorphin. In the absence of dopamine, the melanotropes produce α-MSH, as well as β- endorphin, 1 to 31 (the active form), and small amounts of corticotropin; the latter stimulates glucocorticoid production by the adrenal cortex. The negative-feedback control system fails in this situation because the melanotropes do not have glucocorticoid receptors, even under normal conditions. The result is unchecked synthesis and secretion of melano- trope products, including corticotropin, and unchecked glucocorticoid secretion. Activity of the Corticotropes in the pars distalis is decreased because of negativefeedback inhibition by the glucocorticoids. One of the longterm effects of excess glucocorticoid secretion is muscle wasting, a common finding in these animals. Also, typical manifestations of the disease include polydipsia and polyuria, which result from compression of the pars nervosa by the enlarging pars intermedia and reduction in ADH synthesis.Although there is hyperplasia of the intermediate lobe in Cushing’s disease, it has not been established whether this disease occurs because of autonomous hyperplasia of the intermediate lobe or, conversely, whether the hyperplasia occurs because of gradual loss of dopaminergic control by the hypothalamus. One theory is that chronic stress, such as that occurring with Iaminitis, could affect dopamine secretion by the hypothalamus, leading to loss of control of the intermediate lobe and the development of hyperplasia.
Treatment. At present the only proven treatment is to provide the best possible husbandry for animals with Cushing’s disease. This care includes parasite control, floating of teeth, providing good nutrition, and taking proper care of the feet.