Adrenal Gland Disorders

Introduction

• Hyperfunction of the adrenal glands involves excess production of the adrenal hormones cortisol (resulting in Cushing syndrome) or aldosterone (resulting in hyperaldosteronism).
• Adrenal gland hypofunction is associated with primary (Addison disease) or secondary adrenal insufficiency

CUSHING SYNDROME

Originating from either exogenous administration or endogenous overproduction by the adrenal gland (adrenocorticotropic hormone [ACTH]-dependent) or by abnormal adrenocortical tissues (ACTH-independent).

CLINICAL PRESENTATION

• The most common findings in Cushing syndrome are central obesity and facial rounding (90% of patients). Peripheral obesity and fat accumulation occur in 50% of patients. Fat accumulation in the dorsocervical area (buffalo hump) is nonspecific, but increased supraclavicular fat pads are more specific for Cushing syndrome. Patients are often described as having moon facies and a buffalo hump.
• Other findings may include myopathy or muscular weakness, abdominal striae, hypertension, glucose intolerance, psychiatric changes, gonadal dysfunction, and amenorrhea and hirsutism in women.
• Up to 60% of patients develop Cushing-induced osteoporosis; ~40% present with back pain, and 20% progress to spinal compression fractures.

DIAGNOSIS

Hypercortisolism can be established with a 24-hour urinary free cortisol (UFC), midnight plasma cortisol, late-night (11 pm) salivary cortisol, and/or low-dose dexamethasone suppression test (DST).

• Other tests to determine etiology are plasma ACTH test; adrenal vein catheterization; metyrapone stimulation test; adrenal, chest, or abdominal computed tomography (CT); corticotropin-releasing hormone (CRH) stimulation test; inferior petrosal sinus sampling; and pituitary magnetic resonance imaging (MRI).
• Adrenal nodules and masses are identified using high-resolution CT scanning or MRI.

TREATMENT

Goals of Treatment: Limit morbidity and mortality and return the patient to a normal functional state by removing the source of hypercortisolism while minimizing pituitary or adrenal deficiencies.

Steroidogenic Inhibitors

• Ketoconazole inhibits cytochrome P-450 enzymes, including 11 β-hydroxylase and 17 α-hydroxylase. It is effective in lowering serum cortisol levels after several weeks of therapy. Ketoconazole (Nizoral) 200 mg tablets, 200–1,200 mg/day, divided twice daily.

Glucocorticoid-Receptor Blocking Agents

• Mifepristone (RU-486) is a progesterone- and glucocorticoid-receptor antagonist that inhibits dexamethasone suppression and increases endogenous cortisol and ACTH levels in normal subjects. Evidence suggests that mifepristone is highly effective in reversing the manifestations of hypercortisolism. Its use for treatment of Cushing syndrome remains investigational.

Neuromodulators of Acth Release

• Cyproheptadine can decrease ACTH secretion in some patients with Cushing disease. However, side effects such as sedation and weight gain significantly limit its use.
• Pasireotide is a somatostatin analogue that binds and activates somatostatin receptors, thereby inhibiting ACTH secretion, leading to decreased cortisol secretion. It is approved for treatment of adults with Cushing disease for whom pituitary surgery is not an option or has not been curative.