Adrenocortical Hyperfunction (Cushing Disease, Cushing Syndrome)

Key Features

Essentials of Diagnosis

• Truncal adiposity, thin extremities, moon facies, muscle wasting, weakness, plethora, easy bruising, purple striae, decreased growth rate, and delayed skeletal maturation

• Hypertension, osteoporosis, and glycosuria

• Elevated urinary free cortisol, elevated midnight salivary cortisol

General Considerations

• May result from

  • Excessive autonomous secretion of adrenal steroids (adrenal adenoma or carcinoma)

  • Excessive pituitary ACTH secretion (Cushing disease)

  • Ectopic ACTH or CRH secretion

  • Long-term exposure to exogenous glucocorticoids

• Less commonly due to

  • Adrenal tumor

  • Adrenal hyperplasia

  • Pituitary adenoma

  • Extrapituitary ACTH-producing tumor

• Usually iatrogenic in children younger than 12 years

Clinical Findings

• Excess glucocorticoid

  • Adiposity, most marked on the face, neck, and trunk—a fat pad (buffalo hump) in the interscapular area is characteristic but not diagnostic

  • Fatigue

  • Plethoric facies

  • Purplish striae

  • Easy bruising

  • Osteoporosis and back pain

  • Hypertension and glucose intolerance

  • Muscle wasting and weakness

  • Retardation of growth and skeletal maturation

• Excess mineralocorticoid

  • Hypokalemia and mild hypernatremia

  • Increased blood volume

  • Edema

  • Hypertension

• Excess androgen

  • Hirsutism

  • Acne

  • Virilization

  • Menstrual irregularities

Laboratory Findings

• Plasma cortisol values

  • Generally elevated with loss of normal diurnal variation

  • Measuring level at the expected nadir between midnight and 2 am is a sensitive indicator of the loss of diurnal variation

• Serum electrolytes

  • Serum sodium and bicarbonate are mildly elevated, with metabolic alkalosis

  • Potassium may be low

• Morning ACTH concentration is decreased in adrenal tumors and increased with ACTH- or CRH-producing pituitary or extrapituitary tumors.

• Salivary cortisol obtained at midnight is a noninvasive but highly specific and sensitive test

• 24-Hour urinary free cortisol excretion

  • Measurement of urinary free cortisol/creatinine ratio is a useful way to document hypercortisolism

  • However, midnight salivary cortisol is considered a more practical and specific alternative

• Dexamethasone suppression testing

  • Suppression of adrenal function by a small dose (0.5–1.0 mg) of dexamethasone is seen in children who may have elevated urinary free cortisol excretion due to obesity, but not in children with an ACTH-secreting tumor or adrenal tumor

  • Larger doses (4–16 mg/d in four divided doses) of dexamethasone cause suppression of adrenal activity when the disease is due to ACTH hypersecretion by a pituitary tumor, whereas hypercortisolism due to adrenal adenomas or adrenal carcinomas is rarely suppressed

• CRH stimulation test, in conjunction with petrosal sinus sampling, is used to

  • Distinguish pituitary and ectopic sources of ACTH excess

  • Assess lateralization prior to surgery

Imaging

• Pituitary imaging may demonstrate a pituitary adenoma

• Adrenal imaging by CT scan may demonstrate adenoma or bilateral hyperplasia

• MRI and nuclear medicine studies of the adrenals may be useful in complex cases

Treatment

• If possible, surgical removal is indicated in all cases of primary adrenal hyperfunction due to tumor

• Glucocorticoids should be administered parenterally in pharmacologic doses during and after surgery until the patient is stable

• Supplemental oral glucocorticoids, potassium, ...