Cushing syndrome

Cushing

syndrome • Hypothalamic pituitary axis (illustration) - Ganzer Fall bei Radiopaedia

Gaillard, F. Hypothalamic pituitary axis (illustration). Case study, Radiopaedia.org. (accessed on 20 Oct 2022) https://doi.org/10.53347/rID-36193 • CC by-nc-sa 3.0 (modified)

Cushing

syndrome • Acquired adrenal hyperplasia - due to thymic carcinoid tumor - Ganzer Fall bei Radiopaedia

Niknejad, M. Acquired adrenal hyperplasia - due to thymic carcinoid tumor. Case study, Radiopaedia.org. (accessed on 20 Oct 2022) https://doi.org/10.53347/rID-21269 • CC by-nc-sa 3.0 (modified)

Imaging

spectrum of abnormal subcutaneous and visceral fat distribution. A 52-year-old man with Cushing disease. a Lateral skull radiography shows “buffalo hump” on the posterior neck (asterisk). Note the enlarged sella due to pituitary macroadenoma (arrowhead). b Frontal skull radiograph shows a rounded shape of the face, “moon face” (double arrows). c CT scanogram shows characteristic central obesity. d CT image at the level of bilateral renal hilum shows marked visceral fat deposition, in contrast to subcutaneous fat thinning (boxed arrows)

insightsimaging.springeropen.com • CC-by-4.0

Radiopaedia • CC-by-nc-sa 3.0 • de

Cushing syndrome is due to the effects of excessive glucocorticoids which may be exogenous or endogenous.

Terminology

Cushing disease refers to glucocorticoid excess solely due to an adrenocorticotropic hormone-secreting pituitary adenoma, while Cushing syndrome encompasses all etiologies of glucocorticoid excess .

Clinical presentation

Typically, patients have the following clinical features :

rounded face, sometimes described as 'moon-shaped'
progressive centripetal obesity and weight gain
prominent supraclavicular fat pad, sometimes known as a 'buffalo hump'
purple skin striae
easy skin bruising
acanthosis nigricans
proximal myopathy
depression and other mood disorders
osteoporosis
hypertension
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 . Features of androgen excess are not present in men as the adrenal glands are not a major source of androgens in men .

Furthermore, certain patient groups may demonstrate additional or atypical clinical features depending on the etiology of Cushing syndrome :

patients with Cushing disease:
- hyperpigmentation, because melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) share the same precursor molecule, proopiomelanocortin (POMC)
- clinical features as a result of an intracranial mass (see: pituitary adenoma)
patients with ectopic ACTH secretion (e.g. secondary to small cell lung cancer):
- cachexia
- hyperpigmentation, because ACTH has an alpha MSH sub-unit as part of its structure
patients with an adrenal carcinoma:
- cachexia

Pathology

In modern Western populations, iatrogenic steroid administration for treatment of inflammatory condition is the most common cause, e.g. asthma, rheumatoid arthritis.

Endogenous sources of excess cortisol production include:

adrenal adenoma: 20%
primary pigmented nodular adrenal dysplasia (PPNAD): rare
ACTH-secreting tumor: 80%
- pituitary adenoma: 85% (i.e. Cushing disease)
- ectopic production: 15%
  - lung cancer: small cell lung cancer, bronchial carcinoid
  - small cell cancers of the thymus
  - pancreatic neuroendocrine tumor
  - pheochromocytoma
  - benign ovarian tumors
adrenocorticotropin (ACTH)-independent macronodular adrenocortical hyperplasia (AIMAH): rare cause of ACTH-independent Cushing syndrome
corticotropin-releasing hormone-secreting tumor: very rare
- hypothalamic tumors
- ectopic production

The workup of Cushing syndrome requires measurement both of cortisol as well as ACTH. Measuring cortisol typically needs to be over a 24 hour period because release is intermittent.

Radiographic features

Imaging of the suspected region is then required:

CT or MRI for adrenal glands
MRI (or CT) for pituitary gland

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 unapparent on imaging in 40-50% of cases.