Cushing's+Syndrome


 * Cushing’s Syndrome**


 * Root cause of disease:** Cushing’s syndrome is caused by excess cortisol production. This is often due to a cortisol secreting adenoma in the adrenal gland or the pituitary gland (Cushing’s disease).

Corticotropin releasing hormone (CRH) is released by the hypothalamus which stimulates pituitary release of adrenocorticotropin hormone (ACTH). ACTH stimulates the release of cortisol from the adrenal cortex. Cortisol then invokes a negative feedback mechanism on CRH and ACTH. An adenoma of the adrenal gland results in very high circulating cortisol, and low ACTH. When a pituitary adenoma is present, or too much CRH is produced, ACTH levels are continuously high resulting in high cortisol. These elevated cortisol levels predispose hyperstension, glucose intolerance and increase risk for cardiovascular disease.
 * Physiology**



Cushing’s syndrome was discovered in 1932 by surgeon Harvey Cushing. He originally called it polyglandular syndrome and published a paper reviewing 12 patients with the disease.
 * History:**


 * Common symptoms:** Obesity or weight gain, decreased libido, hypertension, glucose intolerance, osteoperosis, decreased linear growth in children, hypercholesterolemia, insulin resistance, hyponatremia, thin skin, easy bruising.

Medications can be used to reduce cortisol production in the adrenal gland. These medications are not effective in the treatment of Cushing’s disease, oversecretion of corticotropin by the pituitary gland. Depending on the presence and location of adenomas, adrenal and pituitary surgery are viable treatment options. Steroid replacement drugs are often necessary after these surgeries at least until the surrounding tissues have healed and hormone production reaches normal levels. In cases where Cushing’s syndrome is caused by administration of glucocorticoids, the patient is often tapered off these drugs until hormone levels restabilize.
 * Standard treatments:**

A recent study has shown that cortisol levels can be measured in hair. This provides a historical record of the development of hypercortisolism and allows past cortisol exposure to be studied. Comparing current cortisol levels to past levels allows for the estimation of normal cortisol levels specific to that individual (Thompson, et al 2010)
 * Current research:**

Different methods for measuring cortisol have also been studied. One study evaluated the accuracy of plasma, urinary and salivary cortisol levels measured at night in the diagnosis of Cushing’s syndrome. Late-night cortisol levels have historically been considered the best method for Cushing’s syndrome screening because cortisol levels should be lowest at night. High cortisol levels during this time are indicative of Cushing’s syndrome. Urinary cortisol was not shown to be correlated with Cushing’s syndrome. Late-night plasma cortisol and salivary cortisol showed a positive correlation with Cushing’s syndrome, but salivary cortisol was determined to be the most accurate method (Sakihara et. al, 2010).

Another recent study evaluated the use of mifepristone, a glucocorticoid receptor agonist in the treatment of Cushing’s syndrome. During the 24-week trial, participants showed significant improvements in fasting plasma glucose, blood pressure and waist circumference. 87% showed significant clinical improvements. Improvements in insulin resistance, depression, cognition, and quality of life were also observed. These results suggest mifepristone as a promising treatment for Cushing’s syndrome (Fleseriu, et al. 2012).

Bertagna, X., Guignat, L., Groussin, L., and Bertherat, J. (2009). Cushing’s disease. Best Practice & Research Clinical Endocrinology & Metabolism //23//, 607–623.
 * References:**

Fleseriu, M., Biller, B.M.K., Findling, J.W., Molitch, M.E., Schteingart, D.E., Gross, C., Auchus, R., Bailey, T., Biller, B.M.K., Carroll, T., et al. (2012). Mifepristone, a Glucocorticoid Receptor Antagonist, Produces Clinical and Metabolic Benefits in Patients with Cushing’s Syndrome. JCEM //97//, 2039–2049.

Newell-Price, J., Bertagna, X., Grossman, A.B., and Nieman, L.K. (13). Cushing’s syndrome. The Lancet //367//, 1605–1617.

Sakihara, S., Kageyama, K., Oki, Y., Doi, M., Iwasaki, Y., Takayasu, S., Moriyama, T., Terui, K., Nigawara, T., Hirata, Y., et al. (2010). Evaluation of plasma, salivary, and urinary cortisol levels for diagnosis of Cushing’s syndrome. Endocr. J. //57//, 331–337.

Thomson, S., Koren, G., Fraser, L.-A., Rieder, M., Friedman, T.C., and Van Uum, S.H.M. (2010). Hair Analysis Provides a Historical Record of Cortisol Levels in Cushing’s Syndrome. Exp Clin Endocrinol Diabetes //118//, 133–138.