Cushing’s syndromeBy : (77) Zainab AleidMarch 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

C\O Fever& Consistent with erysipelas.

Fatigue& Easy bruising

Weight gain of 5 kg in the past 6 months

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

• 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

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.

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.

Causes of Cushing’s syndrome:

Endogenous

ACTH dependent

ACTH independent

Exogenous“iatrogenic”

Cushing syndrome i.e. steroid therapy

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:

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)

• Depression ( because abnormal cortisol affects NTs which lead to depression, anxiety ) .

• Obesity ( BMI more than 32.5 kg/m2.

xDD :

Laboratory investigations recommend ?

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).

• 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

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 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 .

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

Any Questions ?