Endocrine Disorders: Addison's Disease and Cushing's Syndrome

Introduction

• Lecturer: Eddie Watson
• Platform: ICU Advantage
• Focus: Differences between Addison's Disease and Cushing's Syndrome
• Importance: Both are related to corticosteroid production issues

General Anatomy and Physiology Review

• Hypothalamus releases Corticotropin-releasing hormone (CRH)
• Pituitary Gland releases Adrenocorticotropic hormone (ACTH)
• Adrenal Glands produce corticosteroids from the adrenal cortex
  • Hormones: Cortisol, Aldosterone, Androgens (sex hormones)

Addison's Disease

Definition

• Chronic adrenal insufficiency leading to Addison’s crisis
• Inadequate secretion of glucocorticoids (cortisol) and mineralocorticoids (aldosterone)

Causes

• Primary: Damage to adrenal cortex (e.g., autoimmune diseases, cancer, trauma, sepsis, drugs)
• Secondary: Interference with ACTH secretion (e.g., pituitary tumors, hypothalamic disorders)
• Tertiary: Long-term steroid use leading to adrenal gland failure to produce cortisol

Pathophysiology

• Decreased Cortisol Levels: Leads to decreased glucose production, decreased metabolism, appetite, intestinal motility, vascular tone, and catecholamine effectiveness, causing stress intolerance and potential cardiovascular collapse
• Decreased Aldosterone Levels: Results in sodium and fluid loss, potassium retention, decreased blood volume, high risk for cardiovascular collapse

Signs and Symptoms

• Nonspecific: Headache, fatigue, anorexia, depression, nausea, vomiting, fever, hair loss
• Hyperpigmentation, hypotension, shock, decreased sodium, increased potassium, unresponsive hypoglycemia

Diagnosis

• Lab Tests: CBC, CMP, ABG, cortisol, aldosterone (looking for hypoglycemia, hyponatremia, hyperkalemia, decreased cortisol)
• Cosyntropin Stimulation Test: Lack of rise in cortisol after dose confirms adrenal insufficiency

Treatment

• Steroid Replacement: Glucocorticoids (e.g., hydrocortisone)
• Fluid Volume Replacement: Up to 5 liters in 12-24 hours (normal saline or normal saline with 5% dextrose)
• Glucose Replacement: Ensure adequate glucose levels

Cushing's Syndrome

Definition

• Condition characterized by excessive corticosteroid production (hypercoriticolism)

Causes

• Adrenal Cortex Tumor: Adenomas causing excess corticosteroid production
• Pituitary Tumor: Excess ACTH release, stimulating adrenal cortex
• Ectopic ACTH Production: Tumors producing ACTH independently (e.g., ovarian or pulmonary neoplasms)
• Prolonged Steroid Use

Pathophysiology

• Increased Cortisol Levels: Elevated glucose, increased liver glycogen, decreased protein synthesis, protein catabolism
• Alpha-1 receptor activation: Elevated blood pressure, inhibition of bone formation, anti-inflammatory effect, immune system reduction, glucogenesis, lipolysis, proteolysis

Signs and Symptoms

• Physical: Hypertension, osteoporosis, immune suppression, muscle weakness (thin extremities), moon face, buffalo hump, truncal obesity, weight gain, hyperglycemia, abdominal striae, hypernatremia, hypokalemia, hirsutism, bruising

Diagnosis

• 24-hour Urine Free Cortisol Test: Gold standard
• Dexamethasone Suppression Test
• Imaging: MRI of head, chest, or abdomen

Differentiating Adrenal vs. Pituitary vs. Ectopic Causes

• Low ACTH: Adrenal origin
• High ACTH: Pituitary or ectopic origin
• High-Dose Dexamethasone Test: Suppression indicates pituitary origin; no suppression indicates ectopic origin

Treatment

• Adjust Steroid Use: Gradually decrease if due to long-term use
• Surgery: Remove ectopic ACTH source, adrenalectomy, transsphenoidal surgery for pituitary tumor
• Radiation Therapy: For inoperable pituitary tumors

Conclusion

• Addison's Disease: Insufficient corticosteroids, leading to cardiovascular concerns and thin, weak appearance
• Cushing's Syndrome: Excessive corticosteroids, leading to hypertensive, obese, potentially hirsute appearance
• Next Lesson: Hypoglycemia, hyperglycemia, and diabetes