Cushing Syndrome (Study Outline) For study only—this is not…

Cushing Syndrоme (Study Outline) Fоr study оnly—this is not medicаl аdvice or а substitute for professional care. 1. Background Definition:A disorder caused by prolonged exposure to elevated glucocorticoids (cortisol), whether from endogenous overproduction or exogenous administration. Terminology: Cushing syndrome: the clinical state of cortisol excess (any cause). Cushing disease: specifically from an ACTH-secreting pituitary adenoma. Pathophysiology: ACTH-dependent: Pituitary adenoma (Cushing disease, ~70% of endogenous cases). Ectopic ACTH secretion (e.g., small cell lung carcinoma). ACTH-independent: Adrenal adenoma or carcinoma. Exogenous corticosteroids (most common overall). Cortisol excess → ↑ gluconeogenesis, protein catabolism, lipolysis, and mineralocorticoid activity → metabolic, cardiovascular, and immune effects. Epidemiology: More common in women aged 20–50 years for endogenous disease. Exogenous corticosteroid use is the leading cause overall. 2. History Gradual onset over months to years. Typical Symptoms: Weight gain (central/truncal). Fatigue, weakness, depression, irritability. Menstrual irregularities, decreased libido. Headache or vision changes (pituitary tumor). Metabolic/Endocrine: Glucose intolerance or diabetes. Hypertension, osteoporosis, edema. Physical Appearance (classic triad): Truncal obesity, moon facies, buffalo hump. Other Findings: Purple (>1 cm) abdominal striae, easy bruising, thin skin, poor wound healing. Hirsutism and acne (from adrenal androgens). 3. Exam Findings General: Central obesity with thin limbs, proximal muscle wasting. Skin: Fragile skin, violaceous striae, acne, easy bruising. HEENT: Facial rounding, plethora, supraclavicular fat pads. CV: Hypertension, possible edema. Neuropsych: Depression, insomnia, irritability. Reproductive: Decreased libido, menstrual changes, infertility. 4. Making the Diagnosis Step 1 – Confirm Hypercortisolism (screening): 24-hour urinary free cortisol: elevated. Late-night salivary cortisol: elevated. Low-dose dexamethasone suppression test: failure to suppress cortisol confirms Cushing syndrome. Step 2 – Determine ACTH Dependence: Low ACTH: adrenal tumor or exogenous steroids. High/normal ACTH: pituitary adenoma or ectopic ACTH source. Step 3 – Identify the Source: High-dose dexamethasone suppression test: Pituitary (Cushing disease): partial suppression. Ectopic ACTH: no suppression. CRH stimulation test: Pituitary: ACTH rises. Ectopic: no response. Imaging: Pituitary MRI for suspected adenoma. CT chest/abdomen for ectopic or adrenal tumors. Gold Standard: Demonstration of hypercortisolism via ≥2 positive screening tests, followed by ACTH level determination and localization studies. 5. Management (Exam Concepts) (Conceptual overview only—no dosing or treatment regimens.) Iatrogenic (exogenous steroids): gradual taper of glucocorticoids. Cushing disease (pituitary adenoma): transsphenoidal surgical resection. Adrenal adenoma/carcinoma: adrenalectomy. Ectopic ACTH tumor: surgical resection if possible; medical suppression if unresectable. Medical therapy (for refractory disease): Steroidogenesis inhibitors (ketoconazole, metyrapone, mitotane). Glucocorticoid receptor antagonist (mifepristone). Postoperative care: monitor for adrenal insufficiency and hormone replacement needs. Complications: hypertension, diabetes, osteoporosis, infections, psychiatric symptoms. Exam Tips: Most common cause overall: exogenous corticosteroids. Most common endogenous cause: pituitary adenoma. Ectopic ACTH: severe hypokalemia, rapid onset, hyperpigmentation. Adrenal tumor: low ACTH, unilateral adrenal mass. NBME-Style Practice Question A 39-year-old woman presents with progressive weight gain, fatigue, and easy bruising. She has a rounded face, dorsocervical fat pad, and violaceous abdominal striae. Laboratory testing reveals elevated urinary free cortisol and failure to suppress cortisol on a low-dose dexamethasone suppression test. Plasma ACTH is elevated. Which of the following tests best distinguishes a pituitary from an ectopic source of ACTH? A. Serum DHEA-S levelB. High-dose dexamethasone suppression testC. MRI of the adrenal glandsD. 24-hour urinary metanephrine level