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Cushing's syndrome definition
Results from chronic glucocorticoid excess
(LOW incidence - 2-4 persons per million each year)
Types of Cushing's syndrome
Usually iatrogenic from tx with glucocorticoid drugs
Endogenous Cushing's is usually caused by overproduction of adrenocorticotropic hormone (ACTH) by pituitary gland adenomas
Clinical presentation of Cushing's syndrome
Obesity (moonface, neck, trunk, abdomen), hypertension, hirsutism, acne, amenorrhea, depression, thin skin, easy bruising, diabetes, osteopenia
Pathophysiology of Cushing's syndrome
The hypothalamus produces cortocotropin-releasing hormone --> stimulates the anterior pituitary gland to release ACTH. Circulating ACTH stimulates the adrenal cortex to produce cortisol.
Diagnosis of Cushing's syndrome
Based on s/sx of Cushing's
Deamethasone suppression test or 24-hour urine cortisol measurement may be used
Treatment principles of Cushing's syndrome
1. Minimize corticosteroid exposure
2. Pharmacotherapy aimed at reducing production of cortisol
Inhibits conversion of cholesterol to pregnenolone --> blocks synthesis of adrenal steroids.
It induces P450 enzymes!
Ketoconazole pt counseling
Notify MD if ab pain, yellow skin, plae stool
Space w/antacids by 2 hours
Drowsiness, rash, weakness, hypotension, N, loss of appetite, hypothyroidism, blood dyscrasias
Major ketonazole drug interactions
Increases serum concentrations of cyclosporine, warfarin, cisapride, and triazolam.
Drugs that lower gastric acidity will lower ketoconazole absorption
Rifampin reduces ketoconazole levels
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