Applied Pathophysiology: Cushing Syndrome

Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease

• This material is adapted from 2017 Wolters Kluwer Health, Lippincott Williams & Wilkins
• It covers Chapter 13: Altered Hormonal and Metabolic Regulation, Module 4: Clinical Models
• The lecture series is MPAT12001 Medical Pathophysiology.
• The presenter is Dr. Romeo Batacan Jr.

Adrenal Cortical Hormone Excess - Cushing Syndrome

• The lecture focuses on the pathophysiology, clinical manifestations, diagnostic criteria, and treatment of Cushing Syndrome.

Adrenal Gland

• The adrenal gland is two glands in one, structurally and functionally.
• The adrenal medulla is part of the sympathetic nervous system, producing epinephrine and norepinephrine.
• The adrenal cortex has three layers:
  • Zona glomerulosa (outer): produces mineralocorticoids (e.g., aldosterone), which regulates sodium and potassium levels.
  • Zona fasciculata (middle): produces glucocorticoids (e.g., cortisol), which regulates metabolism, inflammatory/immune responses, and the stress response.
  • Zona reticularis (inner): produces gonadocorticoids, which contribute to pubic and axillary hair growth in women and minimally impact sexual function.

Cushing Syndrome Pathophysiology

• Cushing syndrome is characterized by excess endogenous or exogenous glucocorticoids (cortisol).
• Cushing disease is specifically related to pituitary tumor-related hypercortisolism.
• Women are five times more likely than men to develop Cushing disease.
• Causes:
  • Excess endogenous glucocorticoids (excess ACTH production by pituitary tumor, pituitary hyperplasia, ectopic ACTH or CRH production by tumors at distant sites).
  • Exogenous glucocorticoids (use of prednisone or similar drugs for chronic inflammatory/autoimmune conditions).
• Effects of Glucocorticoids:
  • Stimulate glucose production, decrease tissue glucose utilization.
  • Increase breakdown/circulation of plasma proteins, mobilization of fats.
  • Inhibit bone formation and immune response.
  • Prevent release of inflammatory mediators, decrease capillary permeability, and inhibit edema formation, stimulate gastric acid secretions and contributes to stress response

Cushing Syndrome Clinical Manifestations

• Metabolic alterations: obesity (truncal, face, upper back), buffalo hump, moon face, striae, protein degradation, weakness, muscle wasting, diabetes mellitus, excessive circulating glucose/glucose intolerance, suppression of inflammation/immunity (increased infection rates), skin ulcerations, and poor wound healing.
• Behavioral changes: impaired stress response, aldosterone overproduction (hypertension, hypokalemia), and androgen overproduction (hirsutism: excessive body and facial hair, changes in hair growth pattern).

Cushing Syndrome Diagnostic Criteria

• Cortisol levels in 24-hour urine: reliable, practical index of cortisol secretion, loss of diurnal pattern, midnight levels elevated.
• Plasma levels of ACTH.
• Dexamethasone suppression test: external hormones provide negative feedback, hormone secretion decrease.
• Imaging studies: detect tumors.

Cushing Syndrome Treatment

• Untreated Cushing syndrome leads to serious morbidity.
• Treatment choices depend on the cause.
• Treatment aims to remove the underlying cause of excess cortisol secretion without permanent damage to the pituitary or adrenal gland.
• Treatment options include:
  • Surgery or radiotherapy: remove tumors.
  • Pharmacologic: block steroid synthesis.