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

This quiz covers the structure and function of the adrenal glands, including the adrenal cortex and medulla, and their relationship to the Hypothalamic Pituitary Adrenal axis. It also explores hypersecretory cortisol diseases, such as Cushing syndrome.