CUSHING’S SYNDROME

Cushing’s syndrome is the clinical condition resulting from

chronic exposure to excessive circulating levels of
glucocorticoids

It is called hyperadrenocorticalism, hyperadrenal

corticalism, or hypercortisolism
 I- ETIOLOGY

A- Cushing disease:
- Pituitary adenoma (90%)
- Diffuse hyperplasia of pituitary corticotroph cells (less
commonly)

B-Ectopic ACTH syndrome

- A non pituitary tumor
- Small cell carcinoma of the lung

C- Functonning adrenocortical tumors

- Both adrenocortical adenomas and carcinomas
 II- PATHOGENESIS

A- Cushing disease
- Over production of ACTH by the pituitary adenoma
- A 24 hours urine free cortisol measurement confirms
hypercortisolism
- Despite ACTH hypersecretion, the pituitary and adrenal
fail to respond normally to stress

B- Ectopic ACTH syndrome

ACTH is quantitatively greater than in patients with
Cushing’s disease

C- Adrenal tumors
 III- CLINICAL MANIFESTATION

Cortisol excess:
- Gluconeogenesis
- Antagonizes the action of insulin
- Muscle wasting
- Obesity and redistribution of fat: the face, neck, trunk,
and abdomen
- The characteristic moon facies, buffalo hump,
supraclavicular fat pads, truncal obesity and abdominal striae
 III- CLINICAL MANIFESTATION

Cortisol excess:
- Inhibits fibroblasts: loss of collagen and connective
tissue
- Thinning of the skin, abdominal striae, easy
bruisability, poor wound healing and frequent skin infection
- In the ectopic ACTH syndrome: hyperpigmentation of
the skin
- In bone and calcium metabolism: inhibits bone
formation and accelerates bone resorption
 III- CLINICAL MANIFESTATION

Cortisol excess:
- Decreases intestinal calcium absorption and
increases urinary calcium excretion (hypercalciuria)
- Alters the normal inflammatory response to infection
or injury
- Suppresses manifestations of allergic disorders
- Hypertension (75%-85% of patients)
 III- CLINICAL MANIFESTATION

Cortisol excess:
- Gonadal dysfunction is the result of increased
secretion of adrenal androgens (in female) and cortisol ( in
male and female);

Hirsutism from increased secretion of adrenal androgens

(80% of female patients)

- Inhibits growth in children:

 IV- DIAGNOSIS

- Measurement of free cortisol in a 24 hours urine specimen

- The overnight dexamethasone suppression test
 Pathophysiology of Disease
An Introduction to Clinical Medicine

Stephen J. McPhee
Vishwanath R. Lingappa
William F. Ganong
Jack D. Lange

a LANGE medical book