Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline

Metyrapone has been given occasionally with no apparent adverse effects to mother or offspring.

We recommend transsphenoidal selective adenomectomy (TSS) by an experienced pituitary surgeon as the optimal treatment.

Bilateral adrenalectomy is indicated if aggressive and life threatening.

Clinicians may consider medical therapy.

Administering human GH for GH deficiency is indicated if linear growth potential exists.

We recommend normalizing cortisol levels or action at its receptors to eliminate the signs and symptoms of CS and treating comorbidities associated with hypercortisolism.

We recommend against treatment to reduce cortisol levels or action

We suggest against treatments designed to normalize cortisol or its action. The benefit of treating to normalize cortisol is not established in this setting.

We recommend providing education to patients and their family/caretaker(s) about their disease, treatment options, and what to expect after remission.

We recommend that all patients receive monitoring and adjunctive treatment for cortisol-dependent comorbidities (psychiatric disorders, diabetes, hypertension, hypokalemia, infections, dyslipidemia, osteoporosis, and poor physical fitness).

We recommend that a multidisciplinary team, including an experienced endocrinologist, takes patient values and preferences into consideration and provides education about the treatment options to the patient.

We suggest evaluating CS patients for risk factors of venous thrombosis.

We suggest perioperative prophylaxis for venous thromboembolism.

We recommend that clinicians discuss and offer age-appropriate vaccinations to CS patients—particularly influenza, Herpes zoster, and pneumococcal vaccinations—due to an increased risk of infection.

We recommend initial resection of primary lesion(s) underlying Cushing's disease (CD), ectopic and adrenal (cancer, adenoma, and bilateral disease) etiologies

We recommend unilateral resection by an experienced adrenal surgeon

We recommend localizing and resecting ectopic ACTH-secreting tumors with node dissection as appropriate.

We recommend transsphenoidal selective adenomectomy (TSS) by an experienced pituitary surgeon as the optimal treatment

We recommend measuring serum sodium several times.

We recommend assessing free T4 and prolactin, to evaluate for overt hypopituitarism.

We recommend obtaining a postoperative pituitary magnetic resonance imaging (MRI) scan.

We recommend surgical resection.

We suggest medical therapy to block aberrant hormone receptors.

We suggest an individualized management approach based on whether the serum cortisol values categorize the patient's condition as hypocortisolism, hypercortisolism, or eucortisolism.

We recommend additional treatments.

We recommend measuring late-night salivary or serum cortisol.

We recommend using tests to screen for hypercortisolism to assess for recurrence.

We recommend that hypocortisolemic patients receive glucocorticoid replacement and education about adrenal insufficiency.

We recommend follow-up morning cortisol and/or ACTH stimulation tests or insulin-induced hypoglycemia.

We also recommend discontinuing glucocorticoid.

We recommend re-evaluating the need for treatment of other pituitary hormone deficiencies.

We suggest a shared decision-making approach because there are several available second-line therapies (eg, repeat transsphenoidal surgery, radiotherapy, medical therapy, or bilateral adrenalectomy).

We suggest bilateral adrenalectomy.

We recommend regularly evaluating for corticotrope tumor progression using pituitary MRIs and ACTH levels.

We suggest repeat transsphenoidal surgery.

We recommend confirming that medical therapy is effective in normalizing cortisol because this will be needed while awaiting the effect of radiation.

We suggest RT/radiosurgery.

We recommend using RT.

We recommend measuring serum cortisol or urine free cortisol (UFC) off-medication at 6- to 12-month intervals.

We recommend steroidogenesis inhibitors.

We suggest pituitary-directed medical treatments.

We suggest administering a glucocorticoid antagonist.

We suggest targeted therapies to treat ectopic ACTH syndrome.

We recommend treating the specific comorbidities associated with CS (eg, cardiovascular risk factors, osteoporosis and psychiatric symptoms) in all patients with CS.

We also recommend testing for recurrence throughout life.

We recommend educating patients and families about the clinical features of remission.

We suggest follow-up tests for the specific comorbidities associated with CS.

We suggest evaluating for malignancy using imaging.

We recommend that patients with Carney complex have lifelong follow-up tests for cardiac myxoma and other associated disease (testicular tumors, acromegaly, thyroid lesions).

We recommend urgent treatment (within 24–72 h) of hypercortisolism.

Dose interruption or reduction should be considered when adrenal insufficiency is suspected.

Close monitoring of liver function is needed.

Clinicians should correct hypokalemia and hypomagnesemia and administer tests for baseline liver function tests, thyroid function, IGF-1, fasting glucose/glycated hemoglobin, gallbladder ultrasounds and electrocardiograms.

Clinicians should monitor glucose, liver enzymes, and QT interval at a minimum at 3–4 months after initiating treatment and after any dose increase.