Endocrinology · Adrenal Disorders
The facts most likely to be tested
Cushing disease is defined specifically as an ACTH-secreting pituitary adenoma causing secondary hypercortisolism.
The low-dose dexamethasone suppression test or 24-hour urinary free cortisol is the initial screening test for hypercortisolism.
An elevated plasma ACTH level in the setting of hypercortisolism confirms an ACTH-dependent etiology.
The high-dose dexamethasone suppression test demonstrates suppression of cortisol in Cushing disease, distinguishing it from ectopic ACTH production.
Bilateral inferior petrosal sinus sampling (IPSS) is the gold standard diagnostic procedure to confirm a pituitary source of excess ACTH.
Classic physical exam findings include moon facies, dorsocervical fat pad (buffalo hump), abdominal striae, and proximal muscle weakness.
Transsphenoidal resection of the pituitary adenoma is the definitive first-line treatment for Cushing disease.
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A 34-year-old woman presents with a 6-month history of weight gain, fatigue, and irregular menses. Physical examination reveals purple abdominal striae, supraclavicular fat pads, and proximal muscle weakness in the lower extremities. Laboratory evaluation shows an elevated 24-hour urinary free cortisol and an elevated plasma ACTH level. A high-dose dexamethasone suppression test results in a significant decrease in serum cortisol levels.
What is the most appropriate next step in the management of this patient?
MRI of the pituitary gland
The patient has ACTH-dependent Cushing syndrome with suppression on high-dose dexamethasone, which is diagnostic of Cushing disease; therefore, imaging of the pituitary is the next logical step.
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High yield triage
Etiology / Epidemiology
Caused by an ACTH-secreting pituitary adenoma. Most common cause of endogenous Cushing syndrome.
Clinical Manifestations
Moon facies, buffalo hump, and purple striae are pathognomonic. Look for proximal muscle weakness.
Diagnosis
24-hour urinary free cortisol or late-night salivary cortisol are screening tests. High-dose dexamethasone suppression test confirms pituitary source.
Treatment
Transsphenoidal surgery is the definitive first-line treatment. Avoid adrenal insufficiency post-op.
Prognosis
High cure rate with surgery, but requires lifelong monitoring for recurrence and hypopituitarism.
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Epidemiology & Etiology
Cushing disease accounts for 70% of endogenous Cushing syndrome cases. It is significantly more common in women aged 20–50. The primary driver is a benign pituitary adenoma causing autonomous ACTH hypersecretion.
Pertinent Anatomy
The pathology originates in the anterior pituitary gland. Excess ACTH stimulates the adrenal cortex to produce cortisol, leading to bilateral adrenal hyperplasia.
Pathophysiology
The pituitary adenoma loses normal feedback inhibition by cortisol. Chronic hypercortisolism leads to protein catabolism, insulin resistance, and immune suppression. The resulting metabolic derangement manifests as systemic multi-organ dysfunction.
Clinical Manifestations
Patients present with moon facies, buffalo hump, and purple striae >1cm. Proximal muscle weakness and hypertension are classic findings. Psychiatric disturbances and pathologic fractures are critical red flags indicating advanced disease.
Diagnosis
Initial screening requires 24-hour urinary free cortisol or late-night salivary cortisol. If elevated, perform plasma ACTH; low levels suggest adrenal tumor, while high levels suggest Cushing disease. The high-dose dexamethasone suppression test shows >50% suppression of cortisol, confirming a pituitary source.
Treatment
Transsphenoidal resection is the gold-standard treatment. If surgery fails, pituitary irradiation or bilateral adrenalectomy may be required. Ketoconazole is used for medical management to inhibit steroidogenesis, but monitor for hepatotoxicity.
Prognosis
Post-operative adrenal insufficiency is expected and requires temporary hydrocortisone replacement. Lifelong monitoring is mandatory to detect recurrence or the development of Nelson syndrome (pituitary enlargement post-adrenalectomy).
Differential Diagnosis
Exogenous Cushing syndrome: history of chronic glucocorticoid use
Ectopic ACTH syndrome: usually small cell lung cancer with rapid onset and hypokalemia
Adrenal adenoma: low ACTH levels and no suppression on high-dose dexamethasone
Pseudo-Cushing syndrome: alcohol use disorder or severe depression
Adrenal carcinoma: rapid virilization and very high DHEA-S levels