Cushing’s Syndrome

KEY FEATURES

ESSENTIALS OF DIAGNOSIS

• Excess cortisol in the circulation

• Central obesity

• Hypertension

• Hyperlipidemia

• Hyperglycemia

GENERAL CONSIDERATIONS

• Cushing’s syndrome can be caused by an adrenocorticotropic hormone (ACTH)-producing pituitary tumor (Cushing’s disease); ACTH production by other tumors, such as small-cell carcinoma of the bronchus; glucocorticoid-secreting adrenal tumors; or exogenous steroid use

• Because of associated central obesity, hypertension, hyperglycemia, and hyperlipidemia, affected patients are at risk for coronary artery disease

CLINICAL PRESENTATION

SYMPTOMS AND SIGNS

• Fatigue, dyspnea, and chest pain

PHYSICAL EXAM FINDINGS

• Central obesity, dorsal hump, plethoric facies, striae

• Signs of cardiac dysfunction

DIFFERENTIAL DIAGNOSIS

• Pseudo-Cushing’s syndrome: patients appear cushingoid but have normal screening laboratory tests

• Other causes of obesity, hypertension, hyperlipidemia, and hyperglycemia

DIAGNOSTIC EVALUATION

LABORATORY TESTS

Screening tests

• Twenty-four-hour urine for free cortisol

• Overnight dexamethasone suppression test

Confirmatory tests

• Two-day dexamethasone suppression test

• Corticotropin-releasing factor test

Determine cause of abnormal ACTH

• ACTH level

  • – Elevated ACTH indicates pituitary tumor or ectopic production

  • – Low ACTH indicates adrenal disease

• High-dose dexamethasone suppression test and corticotropin-releasing hormone stimulation test will differentiate pituitary from ectopic sources

• Inferior petrosal sinus sampling when hormone tests unclear but a pituitary tumor is seen on imaging or an ectopic source is suspected

ELECTROCARDIOGRAPHY

• Signs of myocardial ischemia/infarction may be present

IMAGING STUDIES

• CT scan usually identifies the tumor(s)

TREATMENT

CARDIOLOGY REFERRAL

• Suspected cardiac disease

HOSPITALIZATION CRITERIA

• Acute coronary syndrome

• Planned surgery

MEDICATIONS

• If surgery is not feasible, adrenolytic (eg, mitotane) or adrenocortical-blocking pharmacologic agents (eg, glutethimide, metyrapone, or ketoconazole) can be used

SURGERY

• Surgical removal of the pituitary, adrenal, or ectopic tumor is usually definitive

MONITORING

• ECG monitoring in hospital as appropriate

DIET AND ACTIVITY

• Low-fat diet

• Restricted activity if heart disease is present

ONGOING MANAGEMENT

HOSPITAL DISCHARGE CRITERIA

• Resolution of problem

• Successful surgery

FOLLOW-UP

• Depends on condition

COMPLICATIONS

• Myocardial infarction

• Heart failure

• Cardiovascular death

PROGNOSIS

• Good with recognition and treatment. The longer the condition persists, the more likely coronary artery disease ...