Adrenal Glands and Endocrine Function

Adrenal Glands and Their Functions

• Composed of two functionally distinct endocrine units: adrenal cortex and medrenal medulla
• Essential for normal physiologic functioning

Hypersecretory Cortisol Diseases (Cushing Syndrome)

• Classification:

  • ACTH-dependent: excessive ACTH secretion
    • Pituitary corticotroph adenoma (Cushing disease)
    • Ectopic ACTH syndrome (extrapituitary tumor)
  • ACTH-independent: excessive cortisol secretion or exogenous steroids
    • Unilateral adrenocortical tumors
    • Bilateral adrenal hyperplasia or dysplasia
    • Exogenous steroid administration

• Diagnosis and Clinical Presentation

  • Presence of hypercortisolism through 24-hour urinary free cortisol concentration
  • Differentiate etiology (key to treatment options)

Clinical Presentation of Cushing Syndrome

• Central obesity and facial rounding
• Peripheral obesity and fat accumulation
• Myopathies
• Osteoporosis, back pain, compression fracture
• Abnormal glucose tolerance or diabetes
• Amenorrhea and hirsutism in women
• Lower abdominal pigmented striae (red to purple)
• Hypertension (principal cause of morbidity and mortality)

Therapy Goals for Cushing Syndrome

• Reduce morbidity and mortality and eliminate cause
• Reverse clinical features
• Normalize biochemical changes (when possible)
• Achieve long-term control without recurrence (remission when possible)

Therapeutics for Cushing Syndrome

• Inhibit ACTH secretion:
  • Pasireotide: somatostatin analog (better selectivity to pertinent somatostatin receptors than octreotide)
  • Cabergoline (off-label): dopamine agonist
• Inhibit cortisol synthesis:
  • Osilodrostat: hinders cortisol production by blocking the 11-β-hydroxylase enzyme
  • Ketoconazole: inhibits 11- and 17-hydroxylase
  • Mitotane: inhibits 11-hydroxylase and has direct adrenolytic activity
  • Etomidate: inhibits 11-hydroxylase (intravenous route of administration reserved for rapid control of cortisol concentrations)
  • Metyrapone (compassionate use only): hinders secretion of cortisol by blocking final step in cortisol synthesis by inhibiting 11-hydroxylase activity

Hyperaldosteronism: Primary Aldosteronism

• Classification:

  • Bilateral adrenal hyperplasia (70% of cases)
  • Aldosterone-producing adenoma (30% of cases)

• Diagnosis and Clinical Presentation:

  • Elevated plasma aldosterone/renin ratio
  • Hypernatremia, hypokalemia, hypomagnesemia, glucose intolerance
  • Clinical presentation:
    • Hypertension
    • Muscle weakness or fatigue
    • Headache
    • Polydipsia
    • Nocturnal polyuria

Therapeutics for Hyperaldosteronism

• Spironolactone (drug of choice): mineralocorticoid receptor antagonist
• Eplerenone and amiloride are alternatives to spironolactone

Hyposecretory Adrenal Disorders

• Classification:

  • Primary adrenal insufficiency (Addison disease): autoimmune disorder, infection, or infarction
  • Secondary adrenal insufficiency: any process that involves the pituitary and interferes with corticotropin (ACTH) secretion

• Diagnosis and Clinical Presentation (focus on Addison disease):

  • Abnormal rapid cosyntropin (synthetic ACTH) stimulation test
  • Clinical presentation:
    • Hyperpigmentation (caused by elevated ACTH concentrations)
    • Weight loss
    • Dehydration
    • Hyponatremia, hyperkalemia

Therapeutics for Hyposecretory Adrenal Disorders

• Steroid replacement: replace cortisol loss
• Hydrocortisone: 15 mg/day (oral administration commonly dosed to mimic normal cortisol production circadian rhythm)
• Cortisone acetate: 20 mg/day
• Prednisone: 2.5 mg/day
• Dexamethasone: 0.25–0.75 mg/day
• Fludrocortisone (replaces loss of mineralocorticoid): 0.05–0.2 mg/day by mouth