Hypercortisolism Cushing syndrome

Cortisol is a stress hormone released in response to trauma—physical and emotional— that leads to several physiologic changes aimed at reducing the stress associated with this trauma. This process is helpful to the body because the activity of cortisol can limit the harmful effects of stress. However, if too much cortisol is secreted (hypercortisolism) symptoms of Cushing syndrome may appear. 

Cushing syndrome is a rare condition in which elevated levels of cortisol are present in the patient for an extmded period of time (hypercortisolism). Typically, it affects those betweoi the ages of 20 and 50 years. On rare occasions, this disease may result from an inherited condition, which leads to growth of adenomas in endocrine glands, such as the adrenal, parathyroid, pancreas or pituitary glands. 

Cushing syndrome occurs from hypercortisolism over a long period of time. 

Hyperfunction of the adrenal glands occurs in Cushing s syndrome, a disorder caused by excessive secretion of cortisol by the adrenal gland (hypercortisolism). Other causes of adrenal gland hyperfunction include primary and secondary aldosteronism (not discussed in this chapter refer to textbook Chap. 79 for more information on these disorders). 

The goals of treatment for Cushing s syndrome are to limit morbidity and mortality and return the patient to a normal functional state by removing the source of hypercortisolism without causing any pituitary or adrenal deficiencies. 

Treatment with steroids may initially evoke euphoria. This reaction can be a consequence of the salutary effects of the steroids on the inflammatory process or a direct effect on the psyche. The expression of the unpredictable and often profound effects exerted by steroids on mental processes generally reflects the personality of the individual. Psychiatric side effects induced by glucocorticoids may include mania, depression, or mood disturbances. Restlessness and early-morning insomnia may be forerunners of severe psychotic reactions. In such situations, cessation of treatment might be considered, especially in patients with a history of personality disorders. In addition, patients may become psychically dependent on steroids as a result of their euphoric effect, and withdrawal of the treatment may precipitate an emotional crisis, with suicide or psychosis as a consequence. Patients with Cushing s syndrome may also exhibit mood changes, which are reversed by effective treatment of the hypercortisolism. 

Metyrapone is used in the differential diagnosis of both adrenocortical insufficiency and Cushing s syndrome (hypercortisolism). The drug tests the functional competence of the hypothalamic-pituitary axis when the adrenals are able to respond to corticotrophin that is, when primary adrenal insufficiency has been ruled out. 

Ketoconazole can be used as palliative treatment for Cushing s syndrome in patients undergoing surgery or receiving pituitary radiation and in those for whom more definitive treatment is still contemplated. Because surgical treatment is not always well tolerated by elderly patients, ketoconazole 200 to 1,000 mg/day can be a valuable alternative for the control of hypercortisolism. Common side effects include pruritus, fiver dysfunction, and gastrointestinal symptoms. 

Given that the seat of hormonal modulation is in the limbic-hypothalamic-pituitary axis, endocrine changes serve as important correlates to major psychiatric disorders. These changes include basal hormone concentrations, as well as responses to pharmacological challenges. Equally important, endocrine disorders may present with psychiatric symptoms (e.g., manic symptoms in hyperthyroidism, severe depression in hypercortisol ism, psychotic symptoms associated with Cushing s syndrome). Commonly used neuroendocrine tests include the following. 

Overproduction of cortisol by hyperplastic adrenal cortices can result from oversecretion of ACTH (secondary hypercortisolism) due to a defect at the level of the pituitary or median eminence or to ectopic production of ACTH. The former condition is known as Cushing s disease and the latter as ectopic ACTH syndrome. In both conditions, the adrenal cortex functions normally and secretes cortisol in proportion to the level of ACTH. 

To ensure the proper treatment of Cushing s syndrome, diagnostic procedures should (1) establish the presence of hypercortisol ism and (2) discover the underlying etiology of the disease. 

After the development of the method for measuring urinary steroids, Daughaday discovered elevated steroids in the urine of patients with Cushing s disease. Finally, the end product was identified and Cushing s syndrome was correctly explained as an excess of cortisol in the plasma (hypercortisolism). 

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