Cushing syndrome and Cushing disease: Clinical sciences

Cushing syndrome refers to a combination of clinical features and symptoms that arise as a result of long-term exposure to high glucocorticoid levels in the blood. Based on the underlying cause, Cushing syndrome can be iatrogenic, which occurs from exogenous administration of glucocorticoids; ACTH-independent, which is specific to adrenal cortisol hypersecretion; and ACTH-dependent, which can be due to either ectopic ACTH secretion by non-pituitary tumors or excessive pituitary ACTH secretion.

Moreover, Cushing syndrome caused by excessive secretion of ACTH by pituitary adenoma is called Cushing disease!

Now, if your patient presents with a chief concern suggesting Cushing syndrome, the first step is to obtain a focused history and physical examination as well as labs, including a basic metabolic panel or BMP.

High glucocorticoid levels in the blood affect almost every system in the body, so your patient will have various clinical manifestations. For example, history will often reveal central nervous system symptoms, such as irritability and depressed mood; as well as metabolic conditions, like glucose intolerance or diabetes mellitus. Next, high glucocorticoid levels can suppress gonadotropin secretion, so your patients might report symptoms involving the reproductive system, like decreased libido and amenorrhea.

The physical exam reveals the glucocorticoid effects on fat redistribution and findings like central obesity, moon facies or round face, and “buffalo hump”, which refers to fat accumulation on the back of the neck. Additionally, you might notice skin changes, such as thin skin, acne, hirsutism, and purple and broad abdominal striae!

Next, let’s take a look at cardiovascular findings! Normally, the kidneys inactivate cortisol by converting it into cortisone, which cannot bind mineralocorticoid receptors and exert cardiovascular effects.