Cushing disease
Cushing disease is hypercortisolism caused specifically by an ACTH-secreting pituitary adenoma, diagnosed after confirming ACTH-dependent Cushing syndrome and then localizing the pituitary source with MRI and, when needed, inferior petrosal sinus sampling. First-line treatment is transsphenoidal resection of the adenoma, with steroidogenesis inhibitors, radiotherapy, or bilateral adrenalectomy reserved for persistent or recurrent disease.
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What this article covers
- Overview
Cushing disease is hypercortisolism caused specifically by excess ACTH secretion from a pituitary corticotroph adenoma, distinguishing it from the broader term "Cushing syndrome," which describes hypercortisolism regardless of cause.
- Epidemiology
Cushing disease is rare overall, consistent with the rarity of endogenous Cushing syndrome in the general population.
- Risk factors
Sporadic corticotroph adenoma with no identifiable predisposing condition is the risk profile in the great majority of patients.
- Pathophysiology
A corticotroph adenoma secretes ACTH autonomously, escaping the normal negative feedback that cortisol exerts on the hypothalamus and pituitary, so ACTH secretion continues despite already-elevated cortisol.
- Clinical features
The clinical phenotype does not differ from other causes of Cushing syndrome: central obesity, wide (greater than 1 cm) violaceous striae, proximal muscle weakness, facial plethora, and easy bruising are the most discriminating findings.
- Differential diagnosis
Ectopic ACTH-secreting tumor (bronchial carcinoid, small cell lung cancer, or other neuroendocrine tumor): produces an identical ACTH-dependent biochemical picture, but is distinguished from Cushing…
- Diagnosis
The diagnosis requires two sequential confirmations: first that Cushing syndrome (hypercortisolism) is present, then that it is ACTH-dependent and localized to the pituitary; a pituitary MRI should…
- Management
First action after ACTH-dependent, pituitary-localized disease is confirmed is referral for transsphenoidal resection of the corticotroph adenoma, the treatment of choice for essentially all patients with Cushing disease.
- Complications
Cardiovascular disease from chronic hypertension, hyperglycemia, and dyslipidemia is a leading cause of morbidity and mortality, both before and, to a lesser extent, after cure.
- Prognosis
Transsphenoidal surgery achieves biochemical remission in the majority of patients with a microadenoma, with lower cure rates for macroadenomas or tumors with cavernous sinus invasion.
- Prevention
There is no primary prevention for sporadic corticotroph adenoma formation; prevention efforts focus on early detection, appropriate diagnostic sequencing, and prevention of treatment complications.
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Related articles
- Cushing syndrome
Cushing syndrome is the clinical state of chronic glucocorticoid excess from any cause, most often exogenous glucocorticoid use, diagnosed by demonstrating loss of normal cortisol suppression or diurnal rhythm with at least two of three screening tests. Treatment targets the underlying source: withdrawal or tapering of exogenous steroid, transsphenoidal surgery for a pituitary cause, or adrenalectomy for an adrenal or ectopic tumor, with steroidogenesis inhibitors reserved for persistent or unresectable disease.
- Pituitary carcinoma
Pituitary carcinoma is an exceptionally rare pituitary tumor, accounting for about 0.1% of all pituitary tumors, in which hormone hypersecretion is more common than hormone deficiency and mass effect on the optic chiasm or cavernous sinus can occur. Treatment follows standard pituitary tumor management with transsphenoidal surgery and hormone-specific medical therapy, escalating to radiation therapy and temozolomide chemotherapy when the tumor proves aggressive or resistant to surgical and medical treatment.
- Nonfunctioning pituitary adenoma
A nonfunctioning pituitary adenoma is a benign pituitary tumor, usually of gonadotroph origin, that does not secrete a clinically excessive hormone and presents through mass effect (visual field loss, headache) or hypopituitarism rather than a hypersecretory syndrome. Diagnosis requires excluding hormone excess and screening for hypopituitarism; treatment is observation for a small asymptomatic incidentaloma or transsphenoidal surgery for mass effect, apoplexy, or growth on follow-up.