1. Cushing’s syndrome
By : (77) Zainab Aleid
March 5, 2014
2. 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.
3. Case scenario B
A 46 year old male
CO Fever& Consistent with
Fatigue& Easy bruising
Weight gain of 5 kg in the past 6 months
4. 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).
5. • Diagnosis is:
6. 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
7. Cushing’s Syndrome:
A disorder that occurs when the body is exposed to high
levels of the hormone cortisol ( increased free circulating
8.  Symptoms and signs:
9. Truncal obesity, Moon face, Buffalo hump
[ Because of fat redistribution]
because of fragile skin
Striae in the abdomen which are purplish
because of fragile skin and fragile capillaries,
&Low collagen because of high protein catabolism.
Because of the abnormal cortisol secretion
More prone to develop infections due to low immunity.
(recall that cortisol has an anti‐inflammatory effect)
Because of Anti‐vitamin D effect of cortisol  Cortisol reduces
calcium absorption in the intestine. Cortisol reduces bone formation.
11. ACTH dependent
Causes of Cushing’s
i.e. steroid therapy
13. Differential Diagnosis cause:
# The classical ectopic ACTH is
- Pigmentation and weight loss
- Unprovoked hypokalaemia
- Clinical or chemical diabetes
- Plasma ACTH levels above 200
Many ectopic tumors are benign.
14. xDD :
• Depression ( because abnormal cortisol affects NTs
which lead to depression, anxiety ) .
• Obesity ( BMI more than 32.5 kg/m2.
16. • 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
• Back: tenderness over L4 & L5 (because of weakened
bone since cortisol has anti vit-D effect).
18.  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
19. What test do we use to make a diagnosis of
 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.
20.  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
 CRH test: An exaggerated ACTH and cortisol response to
exogenous CRH suggests pituitary-dependent Cushing’s disease.