What is the evaluation and treatment approach for a patient presenting with signs of Cushing's syndrome, such as moon facies and buffalo hump?

From the Guidelines

The evaluation and treatment of Cushing's syndrome, characterized by signs such as moon facies and buffalo hump, begins with biochemical confirmation of hypercortisolism, followed by determining its cause, as recommended by the most recent guidelines 1. The initial step involves screening tests including 24-hour urinary free cortisol, late-night salivary cortisol, and the overnight dexamethasone suppression test to confirm hypercortisolism. Once hypercortisolism is confirmed, ACTH levels are measured to distinguish between ACTH-dependent (pituitary or ectopic source) and ACTH-independent (adrenal) causes. For ACTH-dependent disease, an MRI of the pituitary and possibly inferior petrosal sinus sampling may be necessary, while for ACTH-independent disease, adrenal imaging with CT or MRI is indicated. Treatment depends on the cause and may include transsphenoidal surgery for pituitary adenomas, adrenalectomy for adrenal tumors, and resection of the source for ectopic ACTH. Medical therapy, such as steroidogenesis inhibitors like ketoconazole (400-1200 mg/day) or metyrapone (500-6000 mg/day), may be used when surgery is delayed or contraindicated, as supported by recent studies 1. Glucocorticoid replacement is necessary after successful surgery until the hypothalamic-pituitary-adrenal axis recovers, typically with hydrocortisone 15-25 mg daily in divided doses. Patients require close monitoring for complications, including diabetes, hypertension, osteoporosis, and psychiatric symptoms, throughout treatment, emphasizing the importance of a multidisciplinary approach in managing Cushing's syndrome, as highlighted in recent consensus guidelines 1.

Some key points to consider in the evaluation and treatment of Cushing's syndrome include:

• The importance of biochemical confirmation of hypercortisolism before proceeding with further diagnostic tests or treatment.
• The need to determine the cause of hypercortisolism to guide appropriate treatment.
• The role of imaging studies, such as MRI and CT scans, in identifying the source of ACTH-dependent or ACTH-independent Cushing's syndrome.
• The potential benefits and risks of surgical and medical therapies, including the need for glucocorticoid replacement after surgery.
• The importance of close monitoring for complications and adjusting treatment as necessary to optimize patient outcomes.

Overall, the management of Cushing's syndrome requires a comprehensive approach that takes into account the underlying cause, the presence of any complications, and the need for ongoing monitoring and adjustment of treatment, as emphasized in recent studies and guidelines 1.

From the FDA Drug Label

High doses of supplemental glucocorticoids may be needed to overcome the glucocorticoid receptor blockade produced by mifepristone. Factors considered in deciding on the duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hours). Treatment with mifepristone at a lower dose can be resumed after resolution of adrenal insufficiency Patients should also be evaluated for precipitating causes of hypoadrenalism (infection, trauma, etc.).

The evaluation and treatment approach for a patient presenting with signs of Cushing's syndrome, such as moon facies and buffalo hump, may involve the use of medications like mifepristone.

• Key considerations include the potential need for supplemental glucocorticoids to overcome the glucocorticoid receptor blockade produced by mifepristone.
• Treatment duration should take into account the long half-life of mifepristone (85 hours).
• Dose adjustment may be necessary to minimize the risk of adverse effects, such as hypokalemia or QT interval prolongation 2.
• Monitoring for signs of adrenal insufficiency, hypokalemia, and other potential adverse effects is crucial during treatment with mifepristone.

From the Research

Evaluation Approach

• The evaluation of a patient presenting with signs of Cushing's syndrome, such as moon facies and buffalo hump, begins with ruling out exogenous steroid use 3.
• Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose 3.
• Plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism (suppressed corticotropin) and corticotropin-dependent forms of hypercortisolism (midnormal to elevated corticotropin levels) 3.

Treatment Approach

• Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production 3.
• Medication, including adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers, may be used in addition to surgery 3.
• For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate 3.

Clinical Features

• Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders 3.
• Characteristic skin changes include facial plethora, easy bruising, and purple striae, as well as metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs 3.
• Moon facies and buffalo hump are common features of Cushing syndrome, resulting from excess fat deposition in the face and dorsocervical region 4, 5, 6, 7.