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Cushing syndrome is due to the effects of excessive glucocorticoids, which may be exogenous or endogenous.
Cushing disease refers to glucocorticoid excess solely due to an adrenocorticotropic hormone-secreting pituitary adenoma, while Cushing syndrome encompasses all etiologies of glucocorticoid excess 6.
Typically, patients have the following clinical features 6:
rounded face, sometimes described as 'moon-shaped'
progressive centripetal obesity and weight gain
prominent supraclavicular and dorsocervical fat pads (the latter is sometimes known as a 'buffalo hump')
purple skin striae
easy skin bruising
depression and other mood disorders
hyperglycemia and development of overt diabetes mellitus
immunosuppression and recurrent infections
Female patients with Cushing syndrome may also have signs of androgen excess (e.g. hirsutism, acne, changes in libido, virilisation) and menstrual changes 6. Features of androgen excess are not present in men as the adrenal glands are not a major source of androgens in men 6.
Furthermore, certain patient groups may demonstrate additional or atypical clinical features depending on the etiology of Cushing syndrome 6:
hyperpigmentation, because melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) share the same precursor molecule, pro-opiomelanocortin (POMC)
clinical features as a result of an intracranial mass (see: pituitary adenoma)
ectopic ACTH secretion (e.g. secondary to small cell lung cancer):
hyperpigmentation, because ACTH has an alpha MSH subunit as part of its structure
adrenal carcinoma: cachexia
Endogenous sources of excess cortisol production include:
adrenal adenoma: 20%
ACTH-secreting tumor: 80%
adrenocorticotropin (ACTH)-independent macronodular adrenocortical hyperplasia (AIMAH): rare cause of ACTH-independent Cushing syndrome 4
corticotropin-releasing hormone-secreting tumor: very rare
The workup of Cushing syndrome requires measurement of cortisol and ACTH. Measuring cortisol typically needs to be over a 24-hour period because release is intermittent.
Imaging of the suspected region is then required:
If ACTH is elevated but no microadenoma can be identified, and no ectopic source can be found, then inferior petrosal sinus sampling can be undertaken. Bilateral adrenal hyperplasia is one of the most common findings on abdominal CT.
ACTH-secreting pituitary microadenomas may be inapparent on imaging in 40-50% of cases.
Treatment and prognosis
Management depends on the specific etiology 6.
bilateral adrenalectomy in a patient with Cushing disease may lead to the development of Nelson syndrome
History and etymology
It is named after Harvey Williams Cushing (1869-1939), a pioneering American neurosurgeon, who first described a patient with hypercorticism 7.
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- 7. Harvey Cushing. The Pituitary Body and Its Disorders. (2015) ISBN: 9781331948223 - Google Books