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Cushing’s syndrome

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    Cushing’s syndrome Cushing’s syndrome Presentation Transcript

    • Cushing’s syndrome By : (77) Zainab Aleid March 5, 2014
    • Learning objectives • • • • • • Anatomy and physiology of adrenal gland. Pathology of adrenal gland. Definition of Cushing's syndrome. Symptoms and signs of Cushing's syndrome. Causes of Cushing's syndrome with xDD. Laboratory tests recommended.
    • Case scenario B A 46 year old male CO Fever& Consistent with erysipelas. Fatigue& Easy bruising Weight gain of 5 kg in the past 6 months
    • Moon face A dorsal fat pad in the neck Abdominal purple striae Blood pressure is 160 mm Hg systolic and 104 mm Hg diastolic Central obesity (body mass index 32.5 kg/m2, waist circumference 115 cm).
    • • Diagnosis is: Cushing's syndrome
    • Adrenal gland Three layers in the cortex: Glomerulosa, fasiculata, reticularis.  Three types of steroids: (1) Mineralocorticoids (aldosterone) (2) Glucocorticoids (principally cortisol) (3) Sex steroids (estrogens and androgens) The adrenal medulla has chromaffin cells .  epinephrine & norepinephrine
    • Cushing’s Syndrome: A disorder that occurs when the body is exposed to high levels of the hormone cortisol ( increased free circulating glucocorticoid).
    •  Symptoms and signs:
    • Truncal obesity, Moon face, Buffalo hump [ Because of fat redistribution] skin Bruises because of fragile skin Striae in the abdomen which are purplish stretch marks because of fragile skin and fragile capillaries, &Low collagen because of high protein catabolism.
    • Hypertension Because of the abnormal cortisol secretion Fever& erysipelas More prone to develop infections due to low immunity. (recall that cortisol has an anti‐inflammatory effect) Osteoporosis Because of Anti‐vitamin D effect of cortisol  Cortisol reduces calcium absorption in the intestine. Cortisol reduces bone formation.
    • ACTH dependent Endogenous ACTH independent Causes of Cushing’s syndrome: Exogenous “iatrogenic” Cushing syndrome i.e. steroid therapy
    • Endogenous causes: ACTH-Dependent ACTH-Independent Cushing’s disease. (pituitary adenoma) Adrenal Adenoma , Adrenal Carcinoma. Ectopic corticotropin syndrome (ACTH-secreting pulmonary small-cell carcinoma, bronchial carcinoid). Macronodular hyperplasia
    • Differential Diagnosis cause: # The classical ectopic ACTH is distinguished by: - Pigmentation and weight loss - Unprovoked hypokalaemia - Clinical or chemical diabetes - Plasma ACTH levels above 200 mg/L. Many ectopic tumors are benign. Cushing’s disease # Severe hirsutism/ virilization suggest an adrenal tumor. (pituitary adenoma)
    • xDD : • Depression ( because abnormal cortisol affects NTs which lead to depression, anxiety ) . • Obesity ( BMI more than 32.5 kg/m2.
    •  Laboratory investigations recommend ?
    • • BMI  (usually overweight or obese). • Vital signs  (elevated blood pressure) . • Severe acne and abnormal hair on upper lip & chin. (because of androgens). Physical examination: • Few bruises on arms & legs  (because of fragile skin). • Abdominal examination: truncal obesity, striae. • Lower limbs examination: thin thighs, proximal muscles weakness . • Back: tenderness over L4 & L5 (because of weakened bone since cortisol has anti vit-D effect).
    • • complete blood count CBC ( Hb , lymphocyte count decreased, eosinophylia, Acidosis, Hypercalciuria). • Blood chemistry ( glucose, hypokalemia, cholesterol, triglycerides). Lab investigations • Hormonal assay: ( cortisol by 24h urine free cortisol, dehydroepiandrosterone {DHEA}, ACTH levels vary depending on the cause {ectopic ACTH tumor, adrenal tumor or pituitary problem}.
    •  48 hour low dose dexamethasone test: which strongly decrease the pituitary-adrenal axis. Normal individuals suppress plasma cortisol to <50nmol/l, patients with Cushing’s syndrome fail to do this. Sensitivity of 97%.  High-dose dexamethasone test: Failure of significant plasma cortisol suppression suggests an ectopic source of ACTH or an adrenal tumor.
    • What test do we use to make a diagnosis of Cushing’s syndrome?  Low-‐dose dexamethasone suppression test. What test do we use to locate an ACTH-‐producing adenoma?  High-‐dose dexamethasone suppression test.  If cortisol level is suppressed = Pituitary adenoma  If not = Adrenocortical adenoma or ectopic origin.
    •  Plasma potassium levels: Hypokalaemia is common with ectopic ACTH secretion. (All diuretics must be stopped.)  Plasma ACTH levels: Low or undetectable ACTH levels (< 10 mg/L) on two or more occasions are a reliable indicator of ACTH independent disease.  CRH test: An exaggerated ACTH and cortisol response to exogenous CRH suggests pituitary-dependent Cushing’s disease.
    • A 46 YO male CO: • • • • • • • • • Fever. Fatigue Easy bruising. weight gain. HTN. BMI=32.5kg/m2. Moon face. buffalo hump. abdominal purple striae. Lab Investigations: • Full blood count. • Blood chemistry: ( glucose, cholesterol, triglycerides) • Hormonal assay: cortisol , {DHEA} , ACTH levels .
    • REFERENCES:  Guyton and Hall Textbook of medical physiology, 12th edition. Pages: 935-936  Kumar and Clark's Clinical Medicine, 8th Edition. Pages:957-959.  http://www.clevelandclinicmeded.com/medicalpubs/diseasemanage ment/endocrinology/diseases-of-the-adrenal-gland/  http://www.nlm.nih.gov/medlineplus/ency/article/000348.htm
    • Any Questions ?