Neurosurgical Treatment of Cushing Disease

Cushing disease (CD) is caused by overproduction of adrenocorticotropin by a pituitary adenoma (or, rarely, carcinoma). The diagnosis of CD requires distinguishing it from other hypercortisolemic states with a thorough endocrine workup. CD remains a primarily surgical disease, with remission rates of 70% to 95% following microscopic or endoscopic transsphenoidal surgery.

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Cushing syndrome (CS) refers to the clinical and metabolic effects of excess systemic glucocorticoids; Cushing disease (CD), or adrenocorticotropin (ACTH) overproduction by an adrenal adenoma or carcinoma, is the most common cause of endogenous CS.
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CD is largely a surgical disease, with microscopic and endoscopic transsphenoidal surgery enjoying similar success rates and relatively low complication rates.
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Remission rates following surgery are 70% to 95%, although the literature demonstrates significant variability in the definition of remission.
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Recurrence following surgery occurs 2% to 20% of the time, after 2 to 10 years.
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Recurrences may be treated with reoperation, radiosurgery, or radiation therapy; interim medical therapy is required in the latter 2 cases.

Key Points

Introduction

Cushing syndrome (CS) refers to the constellation of physiologic effects of excess systemic glucocorticoids, including impaired glucose tolerance, skin and bone fragility, compromised immunity, and cardiovascular complications, to name a few. Untreated CS is associated with mortality rates greater than 5 times that of matched controls, whereas proper treatment normalizes mortality risk.

Whereas the most common cause of CS is the administration of exogenous steroids, endogenous CS is a consequence of adrenocorticotropin (ACTH) overproduction by a pituitary adenoma or an ectopic tumor, or cortisol overproduction by autonomous adrenal abnormalities. Overproduction of ACTH by a pituitary adenoma (or, rarely, carcinoma) is the most common of these, and is known as Cushing disease (CD).

Diagnosis

Patients who should be considered for evaluation of possible CS/CD include those with unusual features for their age (including early-onset hypertension, low bone mineral density for age, fractures after minimal trauma, oligomenorrhea in premenopausal-aged women, to name a few), those who manifest multiple features suggestive of cortisol excess over time (including central adiposity, hyperglycemia, spontaneous ecchymoses, wide or darkly pigmented striae, proximal muscle weakness, edema, hypokalemia, thromboembolic events, psychiatric manifestations, and recurrent, opportunistic, or atypical infections), children with delay in linear growth, and patients with incidentally found adrenal or pituitary masses.

Once the diagnosis of CS/CD is considered, laboratory testing is aimed at establishing (or refuting) the presence of pathologic hypercortisolism ( Fig. 1 ). After the diagnosis of CS is established on a biochemical basis, a thorough, systematic approach is required to identify the underlying cause (pathologic lesion) with the goal of curative resection, if possible.

Establishing the Diagnosis of Cushing Syndrome

Laboratory testing is needed to confirm the presence of CS, and distinguish it from other conditions ( Box 1 ). The physiologic principles underlying laboratory testing for CS include excessive cortisol secretion leading to increased cortisol excretion in the urine (24-hour urine free cortisol [UFC]), blunting of the normal circadian rhythm of cortisol secretion leading to high nocturnal (nadir) cortisol levels (measured in the blood or saliva), and decreased sensitivity of the hypothalamic-pituitary-adrenal axis to negative feedback exerted by glucocorticoids, leading to lack of suppression of early-morning serum cortisol after the oral administration of dexamethasone (dexamethasone suppression testing).

Box 1

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