Cushing’s Syndrome

SOURCE

Source: Hwang AY, Smith SM, Gums JG. Adrenal gland disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=134128262. Accessed March 7, 2017.

CONDITION/DISORDER SYNONYM

• Hypercortisolism.

DEFINITION

• Clinical features resulting from chronic exposure to excess glucocorticoids of any cause.

ETIOLOGY

• Pituitary adenomas (Cushing disease)

• Ectopic adrenocorticotropic hormone (ACTH)-secreting tumors.

• Adrenal adenomas or carcinomas.

PATHOPHYSIOLOGY

• Results from effects of supraphysiologic levels of glucocorticoids caused by exogenous administration or endogenous overproduction by adrenal gland (adrenocorticotropic hormone [ACTH]-dependent) or by abnormal adrenocortical tissues (ACTH-independent)

• Ectopic ACTH syndrome is excessive ACTH production resulting from endocrine or nonendocrine tumor, usually of pancreas, thyroid, or lung.

• ACTH-independent Cushing syndrome usually caused by adrenal adenomas and carcinomas.

EPIDEMIOLOGY

• Annual incidence of Cushing syndrome: 13 cases per million people.

• Approximately 70% of cases due to Cushing disease, 15% to ectopic ACTH-secreting tumors, and 15% to adrenal tumors.

RISK FACTORS

• Chronic corticosteroid use.

• Age 20–50 years.

• Female sex.

CLINICAL PRESENTATION

SIGNS AND SYMPTOMS

• Central obesity and facial rounding (90% of patients)

• Peripheral obesity and fat accumulation (50%)—fat accumulation in dorsocervical area (buffalo hump); moon facies.

• Myopathy (65%) or muscular weakness (58%)

• Striae along lower abdomen that may have red to purple color.

• Hypertension (75–85%)

• Glucose intolerance (60%)

• Psychiatric changes (55%)

• Osteoporosis (50–60%)—typically presenting with back pain.

• Gonadal dysfunction with amenorrhea in up to 75% of women.

• Excess androgen secretion with hirsutism in 80% of women.

DIAGNOSIS

LABORATORY TESTS

• 24-hour urinary free cortisol (UFC), midnight plasma cortisol, late-night (11 PM) salivary cortisol, and/or low-dose dexamethasone suppression test (DST) can identify hypercortisolism.

• Plasma ACTH test; metyrapone stimulation test; corticotropin-releasing hormone (CRH) stimulation test; and inferior petrosal sinus sampling may be performed.

IMAGING

• High-resolution CT and MRI may identify pituitary and adrenal masses.

DIFFERENTIAL DIAGNOSIS

• Primary and secondary aldosteronism.

• Iatrogenic Cushing due to exogenous factors.

• Pseudo-Cushing due to other disease states mimicking Cushing symptoms.

DESIRED OUTCOMES

• Limit morbidity and mortality.

• Return patient to normal functional state by removing source of hypercortisolism without causing pituitary or adrenal deficiencies.

TREATMENT: GENERAL APPROACH

• See Table 1 for treatment plans based on etiology.