Cushing syndrome

Cushing syndrome, or hypercortisolism, is an endocrine disorder that is most often caused iatrogenically by
the exogenous administration of glucocorticoids. Less commonly, Cushing syndrome can result from
endogenous overproduction of cortisol. Primary hypercortisolism is the result of autonomous overproduction of
cortisol by the adrenal gland (e.g., adrenal adenoma, adrenal carcinoma). Secondary hypercortisolism, on the other
hand, is the result of increased production of adrenocorticotropic hormone (ACTH), either by pituitary
microadenomas (Cushing disease) or by ectopic, paraneoplastic foci (e.g., small cell lung cancer).
Etiology
Exogenous (iatrogenic) Cushing syndrome Endogenous Cushing syndrome

• Prolonged glucocorticoid therapy → hypercortisolism

→ decreased ACTH → bilateral adrenal atrophy
• Most common cause of hypercortisolism

• While the term “Cushing syndrome” can be applied to any

cause of hypercortisolism, “Cushing disease” refers
speci cally to secondary hypercortisolism that results
from excessive production of ACTH by pituitary adenomas.

Clinical Features
adrenal adenomas occur more commonly
in adults, adrenal carcinomas occur more
commonly among children.

Hypertension Caused by the following pathophysiological effects:

1. Mineralocorticoid effect of cortisol (increased water and sodium
retention with increased potassium excretion);
2. Enhanced sympathetic activity;
3. Ampli ed response to catecholamines;
4. Secretion of prehormones with mineralocorticoid effect;
5. Activation of the renin-angiotensin-aldosterone system (RAAS)

Due to inhibition of
calcitriol synthesis by
cortisol Hypercortisolism
results in inhibition of
Necrosis of the gonadotropin release.
femoral head!

Diagnosis
General laboratory ndings [4]
• Hypernatremia, hypokalemia, metabolic alkalosis
• Hyperglycemia: due to stimulation of gluconeogenesis enzymes (e.g.,
glucose-6-phosphatase) and inhibition of glucose uptake in peripheral tissue
• Hyperlipidemia (hypercholesterolemia and hypertriglyceridemia)
• Leukocytosis (predominantly neutrophilic), eosinopenia

Serum cortisol is lowest

The most accurate around midnight and highest
screening test in the morning (∼ 8 a.m.).
Therefore, midnight samples
are preferred for screening
tests and early morning
fasting serum samples for
dexamethasone suppression
tests in the diagnosis of
hypercortisolism.