Cushing’s syndrome

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Information about Cushing’s syndrome
Health & Medicine

Published on March 4, 2014

Author: Zainab1861


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.  ment/endocrinology/diseases-of-the-adrenal-gland/ 

Any Questions ?

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