adrenal insufficiency

• Adrenal cortex produces primary hormones: cortisol, aldosterone, and androgens (specifically dehydroepiandrosterone)
• Anatomy of adrenal cortex:

  • Zona glomerulosa (blue): produces aldosterone
  • Zona fasciculata (red): produces cortisol
  • Zona reticularis (black): transition to adrenal medulla
• Causes of adrenal insufficiency:

  • Autoimmune disease (most common in the US): autoimmune polyglandular syndrome type 1 or type 2
  • Infectious etiology: tuberculosis (TB) or HIV
  • Metastatic cancer: tumors spread to adrenal cortex, must damage 90% of both adrenal cortices
  • Drugs inhibiting cortisol synthesis: Ketoconazole, phenytoin, Rifampin
• Diagnostic features:

  • Low levels of cortisol trigger increased ACTH production
  • ACTH levels rise, but cortisol levels remain low
  • Deficiency in cortisol, aldosterone, and DHEA
• Adrenal cortex hemorrhage can lead to adrenal crisis or metastatic lesions
• 90% of the adrenal cortex needs to be destroyed bilaterally to lose hormone production ability
• Secondary adrenal insufficiency involves a healthy adrenal cortex but diseased hypothalamus or pituitary
• Hypothalamus produces CRH, which stimulates the pituitary to produce ACTH, which then stimulates cortisol and dihydroepiandrosterone production
• Tertiary adrenal insufficiency is rare and usually due to a hypothalamic lesion
• Secondary adrenal insufficiency can be caused by pituitary lesions or chronic glucocorticoid therapy
• Chronic steroid therapy can suppress ACTH production, leading to adrenal cortex atrophy and cortisol deficiency
• Discontinuation of chronic steroids can lead to adrenal crisis due to atrophied adrenal cortex
• Adrenal crisis can be precipitated by stressors like infections, trauma, surgery, or steroid discontinuation
• Adrenal crisis can lead to shock and is fatal
• Low cortisol and aldosterone levels in primary adrenal insufficiency, low cortisol only in secondary adrenal insufficiency
• Effects of low cortisol include decreased response to adrenergic receptors, bradycardia, decreased contractility, hypotension, and shock
• Low cortisol affects sodium and water balance, leading to hyponatremia
• Primary adrenal insufficiency results in low cortisol production
• ACTH levels increase in response to low cortisol levels
• Increased ACTH levels can lead to the production of ADH
• ADH increases water retention in the bloodstream
• Increased water retention can lead to hyponatremia
• Hyperpigmentation can occur due to increased Alpha melanocyte stimulating hormone in primary adrenal insufficiency
• Low cortisol levels lead to a pro-inflammatory state
• Pro-inflammatory state can cause fever and fatigue
• Low cortisol levels result in hyper eosinophilia
• Hypoglycemia can develop due to inhibited gluconeogenesis, glycogenolysis, and lipolysis
• Low cortisol levels can inhibit gastric and pancreatic enzyme production, affecting digestion
• Abdominal pain can be a sign of adrenal crisis in adrenal insufficiency
• Aldosterone levels are low in primary adrenal insufficiency
• Low aldosterone levels can lead to hyponatremia and hyperkalemia
• Water retention decreases due to low aldosterone levels
• Bicarbonate levels drop due to inhibited reabsorption in intercalated cells
• Negative effects of adrenal insufficiency:

  • Low sodium (hyponatremia)
  • Can be due to low cortisol or low aldosterone and primary adrenaline sufficiency
  • Hyperkalemia can also occur, leading to a high risk of cardiac arrhythmias
  • Low bicarb leads to metabolic acidosis, specifically non-anion gap metabolic acidosis
• Effects of low sodium:

  • Decreased water retention due to decreased sodium reabsorption
  • Decreased blood volume, leading to low preload, stroke volume, cardiac output, and blood pressure
  • Resulting in hypotension
• Androgens in adrenal insufficiency:

  • Low androgens affect female sex hormones more significantly
  • Decreased pubic and axillary hair, libido in females
• Diagnostic approach for adrenal insufficiency:

  • Morning cortisol level test to indicate adrenal insufficiency
  • ACTH level test to differentiate between primary and secondary causes
  • ACTH co-centropin stimulation test to confirm primary vs secondary adrenal insufficiency
  • Plasma bastrum levels to check for low aldosterone in primary adrenal insufficiency
• Increase renin production to increase Angiotensin II levels
• Increased Angiotensin II levels hopefully trigger an increase in aldosterone production
• Resulting in high renin levels and low aldosterone levels supporting primary adrenal insufficiency