cushing’s syndrome
TRANSCRIPT
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Cushing’s syndromeBy : (77) Zainab AleidMarch 5, 2014
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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.
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Case scenario B
A 46 year old male
C\O Fever& Consistent with erysipelas.
Fatigue& Easy bruising
Weight gain of 5 kg in the past 6 months
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Moon face
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).
A dorsal fat pad in the neck
Abdominal purple striae
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• Diagnosis is:
Cushing's syndrome
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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
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Cushing’s Syndrome:
A disorder that occurs when the body is exposed to high
levels of the hormone cortisol ( increased free circulating
glucocorticoid).
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Symptoms and signs:
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Truncal obesity, Moon face, Buffalo hump
skin Bruises
Striae in the abdomen which are purplish stretch marks
[ Because of fat redistribution]
because of fragile skin
because of fragile skin and fragile capillaries, &Low collagen because of high protein catabolism.
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Hypertension
Fever& erysipelas
Because of the abnormal cortisol secretion
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.
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Causes of Cushing’s syndrome:
Endogenous
ACTH dependent
ACTH independent
Exogenous“iatrogenic”
Cushing syndrome i.e. steroid therapy
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ACTH-Dependent
Cushing’s disease. (pituitary adenoma)
Ectopic corticotropinsyndrome (ACTH-secreting pulmonary small-cell carcinoma, bronchial carcinoid).
ACTH-Independent
Adrenal Adenoma , Adrenal Carcinoma.
Macronodularhyperplasia
Endogenous causes:
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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.
# Severe hirsutism/ virilizationsuggest an
adrenal tumor.
Cushing’s disease
(pituitary adenoma)
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• Depression ( because abnormal cortisol affects NTs which lead to depression, anxiety ) .
• Obesity ( BMI more than 32.5 kg/m2.
xDD :
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Laboratory investigations recommend ?
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Physical examination:
• BMI (usually overweight or obese). • Vital signs (elevated blood pressure) .• Severe acne and abnormal hair on upper lip & chin.
(because of androgens).
• 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).
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• complete blood count CBC ( Hb , lymphocyte count decreased, eosinophylia, Acidosis, Hypercalciuria).
• Blood chemistry ( glucose, hypokalemia, cholesterol, triglycerides).
• 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}.
Lab
investigations
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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.
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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.
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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.
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A 46 YO male C\O: Lab Investigations:
• Fever.• Fatigue• Easy bruising.• weight gain. • HTN.• BMI=32.5kg/m2.• Moon face.• buffalo hump.• abdominal purple striae.
• Full blood count.• Blood chemistry:( glucose, cholesterol, triglycerides) • Hormonal assay: cortisol , {DHEA} ,
ACTH levels .
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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/diseasemanagement/endocrinology/diseases-of-the-adrenal-gland/
http://www.nlm.nih.gov/medlineplus/ency/article/000348.htm
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Any Questions ?
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