Cushing syndrome | Cushing disease | endocrine and metabolic syndromes | human body syndrome

endocrine and metabolic syndromes clinical scenario questions Cushing's Syndrome: A Comprehensive Guide 1. Introduction: Brief Overview of the Syndrome Definition: Cushing's Syndrome is a hormonal disorder caused by prolonged exposure to high levels of cortisol, a steroid hormone produced by the adrenal glands. It can result from endogenous overproduction of cortisol or exogenous administration of glucocorticoids. Epidemiology: Prevalence: Affects approximately 10-15 people per million annually. Age: Most commonly diagnosed in adults aged 20-50 years. Gender: More common in women (female-to-male ratio of 3:1). Relevance: Cushing's Syndrome is a classic example of hypercortisolism and is frequently tested in medical exams. Understanding its pathophysiology, clinical features, and management is crucial for diagnosing and treating endocrine disorders. Key Points: In this lecture, we’ll cover: The pathophysiology of Cushing's Syndrome. Its clinical features and how to recognize them. Diagnostic criteria and tests. Management strategies, including surgical and pharmacological options. A case study to reinforce learning. 2. Pathophysiology: Underlying Mechanisms Primary Cause: Cushing's Syndrome can be caused by: Endogenous Causes: ACTH-Dependent (80%): Pituitary adenoma (Cushing's Disease): Most common cause (70%). Ectopic ACTH production: Seen in small cell lung cancer or carcinoid tumors. ACTH-Independent (20%): Adrenal adenoma or carcinoma. Adrenal hyperplasia. Exogenous Causes: Prolonged use of glucocorticoids (e.g., prednisone). Mechanism: Excess cortisol leads to: Protein breakdown: Causes muscle wasting and thin skin. Fat redistribution: Results in central obesity, moon face, and buffalo hump. Insulin resistance: Leads to hyperglycemia and diabetes. Mineralocorticoid effects: Causes hypertension and hypokalemia. Key Pathways: Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: In Cushing's Disease, a pituitary adenoma secretes excess ACTH, stimulating cortisol production. In adrenal tumors, cortisol is produced autonomously, suppressing ACTH. Complications: If untreated, Cushing's Syndrome can lead to: Cardiovascular disease: Hypertension, heart failure. Metabolic syndrome: Diabetes, dyslipidemia. Osteoporosis: Increased fracture risk. Infections: Due to immunosuppression. 3. Clinical Features: Signs and Symptoms Common Symptoms: Weight gain (central obesity). Moon face, buffalo hump, and supraclavicular fat pads. Purple striae (abdominal stretch marks). Muscle weakness (proximal myopathy). Mood changes (depression, anxiety). Menstrual irregularities in women. Physical Examination Findings: Thin, fragile skin with easy bruising. Hirsutism (excessive hair growth) in women. Acne and oily skin. Hypertension. Osteoporosis (vertebral fractures). Systemic Effects: Metabolic: Hyperglycemia, dyslipidemia. Cardiovascular: Hypertension, edema. Musculoskeletal: Osteoporosis, muscle wasting. Immune: Increased susceptibility to infections. Red Flags: Rapid onset of symptoms. Severe hypertension or hypokalemia. Signs of adrenal carcinoma (e.g., abdominal mass). 4. Diagnosis: Diagnostic Criteria and Tests Initial Workup: 24-hour urinary free cortisol: Elevated in Cushing's Syndrome. Late-night salivary cortisol: High sensitivity and specificity. Low-dose dexamethasone suppression test: Failure to suppress cortisol confirms hypercortisolism. Confirmatory Tests: High-dose dexamethasone suppression test: Differentiates ACTH-dependent (pituitary vs. ectopic) causes. ACTH levels: High ACTH: Pituitary or ectopic source. Low ACTH: Adrenal source. Imaging: MRI of the pituitary: To detect adenomas. CT/MRI of the adrenal glands: To identify adrenal tumors. Differential Diagnosis: Obesity, metabolic syndrome. Polycystic ovary syndrome (PCOS). Depression or chronic fatigue syndrome. 5. Management: Treatment Options and Guidelines First-Line Treatment: Cushing's Disease: Transsphenoidal surgery: Removal of pituitary adenoma (cure rate: 70-90%). Adrenal Tumors: Adrenalectomy: Surgical removal of the tumor. Pharmacological Options: Ketoconazole: Inhibits cortisol synthesis. Metyrapone: Blocks 11-beta-hydroxylase, reducing cortisol production. Pasireotide: Somatostatin analog for Cushing's Disease. Lifestyle Modifications: Monitor blood pressure and blood sugar regularly. Calcium and vitamin D supplementation for bone health. Follow-Up: Regular monitoring of cortisol levels. Assess for recurrence or complications (e.g., adrenal insufficiency post-surgery). 6. Case Studies: Real-Life Examples to Reinforce Learning Case Presentation: A 45-year-old woman presents with weight gain, fatigue, and irregular periods. She reports easy bruising and mood swings. Clinical Findings: Moon face, buffalo hump, and thin skin with purple striae. Blood pressure: 150/95 mmHg. Proximal muscle weakness.