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

Introduction

• Lecture Series: Differences between Addison’s and Cushing’s Syndrome
• Presenter: Eddie Watson, ICU Advantage
• Focus: Corticosteroid production disorders

Basic Anatomy Recap

• Components:
  • Hypothalamus
  • Pituitary gland
  • Adrenal glands
• Hormone Pathway:
  • Hypothalamus releases corticotropin-releasing hormone (CRH)
  • CRH stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH)
  • ACTH stimulates the adrenal cortex to release:
    • Cortisol
    • Aldosterone
    • Androgens (sex hormones)

Addison’s Disease

Overview

• Definition: Acute adrenal insufficiency, can lead to Addison’s crisis
• Hormones Affected: Insufficient cortisol (glucocorticoid) & aldosterone (mineralocorticoid)

Causes

1. Primary Causes: Damage to the adrenal cortex

• Idiopathic autoimmune diseases
  • Metastatic cancer
  • Trauma, sepsis, AIDS
  • Drugs (e.g., phenytoin, barbiturates)

2. Secondary Causes: Interference with ACTH secretion

• Pituitary tumors, radiation, hemorrhage, trauma, surgery
  • Hypothalamic disorders

3. Tertiary Causes: Long-term steroid use

• Failure of adrenal gland to resume cortisol production

Pathophysiology

• Decreased Cortisol: Reduced stress response, leading to
  • Decreased glucose production
  • Decreased metabolism (fats, proteins), appetite, intestinal motility, vascular tone, catecholamine effectiveness
  • Increased risk for cardiovascular collapse
• Decreased Aldosterone: Fluid regulation issues, leading to
  • Sodium & fluid loss, potassium retention
  • Decreased blood volume, increased cardiovascular risk

Signs and Symptoms

• General: Headache, fatigue, anorexia, depression, nausea, vomiting, fever, hair loss
• Specific: Hyperpigmentation, hypotension, shock
• Lab Findings: Hyponatremia, hyperkalemia, hypoglycemia, decreased cortisol

Diagnostic Tests

• Laboratory Work: CBC, CMP, ABG, cortisol, and aldosterone levels
• Stimulation Test: Cosyntropin stimulation test (diagnostic if no rise in cortisol)

Treatment

1. Steroids: Hydrocortisone (glucocorticoid replacement)
2. Fluids: Normal saline or saline with 5% dextrose

• Up to 5 liters in the first 12-24 hours
  • May require vasopressors

3. Glucose: Dextrose added if necessary

Cushing’s Syndrome

Overview

• Definition: Overproduction of cortisol and aldosterone
• Also Known As: Hypercortisolism

Causes

1. Adrenal Cortex Tumors: Adenomas
2. Pituitary Tumors: Excess production of ACTH
3. Long-term Steroid Use
4. Ectopic ACTH Production: Rare tumors (ovarian, pulmonary neoplasms)

Pathophysiology

• Increased Cortisol: Causes exaggerated stress response
  • Stimulates gluconeogenesis, glycogenolysis
  • Decreases protein synthesis, increases catabolism
  • BIG Acronym:
    • B: Blood pressure (elevated; alpha-1 receptor activation)
    • I: Inhibition of bone formation
    • I: Anti-inflammatory (immune suppression)
    • G: Gluconeogenesis, lipolysis, proteolysis
• Increased Aldosterone: Fluid retention, hypertension

Signs and Symptoms

• General: Weight gain, hyperglycemia
• Specific: Hypertension, osteoporosis, immune suppression (slow wound healing), muscle weakness (thin extremities)
• Characteristic Signs:
  • Moon face
  • Buffalo hump
  • Truncal obesity
  • Abdominal striae

Diagnostic Tests

• Gold Standard: 24-hour urine free cortisol test
• Dexamethasone Suppression Test
• Imaging: MRI (head, chest, abdomen)
• Hormone Level Tests: Serum cortisol and ACTH levels
  • Helps differentiate adrenal, pituitary, ectopic sources
  • High-dose dexamethasone test for further differentiation

Treatment

1. Address Underlying Cause

• Gradually decrease steroid dose (if due to steroid use)
  • Surgery for tumor removal (adrenalectomy, transsphenoidal surgery)
  • Radiation therapy for pituitary tumors

2. Lifelong Hormone Replacement: May be necessary post-surgery

Conclusion

• Addison’s Disease: Insufficient corticosteroids, thin weak patients
• Cushing’s Syndrome: Excess corticosteroids, large possibly hairy patients
• Next Lesson: Hypoglycemia and hyperglycemia (diabetes)