Cushing syndrome

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Cushing syndrome

Endocrine system


Cushing syndrome


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Cushing syndrome

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A 52-year-old man comes to his physician due to progressive weight gain over the past 6 months. The patient has moderate, persistent bronchial asthma, which is well-controlled with as-needed inhaled corticosteroids and albuterol. His temperature is 37.0°C (98.6°F), pulse is 82/min, and blood pressure is 161/96 mmHg. There are scattered ecchymoses on the extremities and mild proximal muscle weakness is present. Laboratory testing and imaging is performed to confirm the diagnosis. Abdominal CT reveals an adrenal tumor on the right side, with mild atrophy of the left adrenal gland. This patient most likely has which of the following laboratory patterns of hypothalamic-pituitary-adrenal axis activity?  

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Adrenal adenomas

Cushing syndrome p. 354

Adrenal carcinomas

Cushing syndrome p. 354

Adrenal hyperplasia

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Adrenocorticotropic hormone (ACTH)

in Cushing syndrome p. 221, 354


Cushing syndrome p. 354


Cushing syndrome p. 354

Corticotropin-releasing hormone (CRH) p. 335

Cushing syndrome and p. 354

Cortisol p. 337

in Cushing syndrome p. 354

Cushing disease p. 354

Cushing syndrome p. 354

acanthosis nigricans and p. 495

anovulation with p. 669

corticosteroids p. 118

hirsutism p. 354

paraneoplastic syndrome p. 221

small cell lung cancer p. 709


Cushing syndrome diagnosis p. 354


Cushing syndrome diagnosis p. 354


Cushing syndrome p. 354

Hypertension p. 306

Cushing syndrome p. 354

Insulin resistance

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Cushing syndrome p. 354

Osteoporosis p. 472

Cushing syndrome p. 354


Cushing syndrome and p. 354

Weight gain

Cushing syndrome p. 354

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Cushing syndrome, named after the famous neurosurgeon, Harvey Cushing who first described it, is an endocrine disorder with elevated cortisol levels in the blood. In some cases, Cushing syndrome results from a pituitary adenoma making excess ACTH, and in those situations it’s called Cushing disease

Normally, the hypothalamus, which is located at the base of the brain, secretes corticotropin-releasing hormone, known as CRH, which stimulates the pituitary gland to secrete adrenocorticotropic hormone, known as ACTH. ACTH, then, travels to the pair of adrenal glands, on top of each kidney, where it specifically targets cells in the adrenal cortex.

The adrenal cortex is the outer part of the adrenal gland and is subdivided into three layers- the zona glomerulosa, the zona fasciculata, and the zona reticularis. Zona fasciculata is the middle zone and also the widest zone and it takes up the majority of the volume of the whole adrenal gland.

The ACTH specifically stimulates cells in this zone to secrete cortisol, which belongs to a class of steroids, or lipid-soluble hormones, called glucocorticoids. Glucocorticoids are not soluble in water, so most cortisol in the blood is bound to a special carrier protein, called cortisol-binding globulin, and only about 5% is unbound or free. In fact, only this small fraction of free cortisol is biologically active, and its levels are carefully controlled. Excess free cortisol is filtered in kidneys and dumped into the urine. 

Free cortisol in the blood is involved in a number of things and it’s part of the circadian rhythm. Cortisol levels peak in the morning, when the body knows we need to “get up and go” and then drop in the evening, when we’re preparing for sleep. In times of stress, the body needs to have plenty of energy substrates around, so cortisol increases gluconeogenesis, which is the synthesis of new glucose molecules, proteolysis, which is the breakdown of protein and lipolysis, which is the breakdown of fat.


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  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "A Physiologic Approach to Diagnosis of the Cushing Syndrome" Annals of Internal Medicine (2003)
  5. "Cushing's syndrome: update on signs, symptoms and biochemical screening" European Journal of Endocrinology (2015)
  6. "Cushing's disease" Best Practice & Research Clinical Endocrinology & Metabolism (2009)

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