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Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to glucocorticoids such as cortisol. [4] [9] [10] Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face due to facial plethora, [11] a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals ...
Another diagnostic test used is the urinary free cortisol (UFC) test, which measures the excess cortisol excreted by the kidneys into the urine. Results of 4x higher cortisol levels than normal are likely to be Cushing's disease.
In the alcoholic patient with pseudo-Cushing's, admission to hospital (and avoidance of alcohol) will result in normal midnight cortisol levels within five days, excluding Cushing's [6] Another cause for Cushing's syndrome is adrenocortical carcinoma. This is a rare form of cancer with an incidence of 1-2 per million people annually.
Results indicative of Cushing's disease involve no change in cortisol on low-dose dexamethasone, but inhibition of cortisol on high-dose dexamethasone. If the cortisol levels are unchanged by low- and high-dose dexamethasone, then other causes of Cushing's syndrome must be considered with further work-up necessary.
The inactivating mutation leads to elevated local concentrations of cortisol in the aldosterone sensitive tissues like the kidney. Cortisol at high concentrations can cross-react and activate the mineralocorticoid receptor due to the non-selectivity of the receptor, leading to aldosterone-like effects in the kidney.
In a healthy body, blood cortisone and cortisol levels are roughly equimolar. [7] Cortisone reductase deficiency leads to an elevated level of inert cortisone to active cortisol in adipose tissue. Cortisone reductase deficiency is caused by dysregulation of the 11β-hydroxysteroid dehydrogenase type 1 enzyme, otherwise known as cortisone reductase.
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The long test uses 1 mg tetracosactide (intramuscular). Blood is taken 1, 4, 8, and 24 hours later. Normal plasma cortisol level should reach 1,000 nmol/L by 4 hours. In primary Addison's disease, the cortisol level is reduced at all stages, whereas in secondary corticoadrenal insufficiency, a delayed but normal response is seen.