Primary adrenal insufficiency

Background

Etiology

• Autoimmune (70-90%)
  • Isolated adrenal insufficiency
  • Polyglandular autoimmune syndrome type I and type II
• Infection: tuberculosis (most common in developing world), histoplasmosis, paracoccidioidomycosis, HIV, CMV, syphilis, African trypanosomiasis
• Infiltrative:
  • Metastatic cancer (lung > stomach > esophagus > colon > breast)
  • Lymphoma
  • Sarcoidosis, amyloidosis, hemochromatosis
• Vascular
  • Bilateral adrenal hemorrhage
  • Sepsis, especially with Neisseria meningitidis
  • Coagulopathy or Waterhouse-Friderichsen syndrome
  • Thrombosis, embolism, adrenal infarction
• Drugs
  • Inhibit cortisol: ketoconazole, etomidate, megesterol acetate
  • Increase cortisol metabolism: rifampin, phenytoin, barbiturates
• Other
  • Adrenoleukodystrophy
  • Congenital adrenal hypoplasia
  • Familial glucocorticoid deficiency or resistance

Risk Factors

• Type 1 diabetes mellitus
• Autoimmune gastritis
• Pernicious anemia
• Vitiligo

Clinical Manifestations

Adrenal Insufficiency

• Fatigue, weight loss, postural dizziness, anorexia, abdominal discomfort
• Hyperpigmentation (primary only), particularly of sun-exposed areas, skin creases, mucosal membranes, scars, and areola, low blood pressure with postural drop, failure to thrive (in children)
• Labs may show hyponatremia, hyperkalemia and, occasionally, hypoglycemia (especially in children) or hypercalcemia

Adrenal Crisis

• Acute adrenal insufficiency typically occurs in patients with known preexisting chronic adrenal insufficiency who develop an intercurrent illness
  • Sometimes can occur without a prior history of adrenal insufficiency, such as tuberculous adrenalitis or Waterhouse-Friderichsen syndrome from meningococcemia
• Severe weakness, syncope, abdominal pain, nausea, vomiting, back pain, confusion
• Hypotension, abdominal tenderness or guarding, altered consciousness, delirium
• Hyponatremia, hyperkalemia, hypoglycemia, hypercalcemia

Differential Diagnosis

• Adrenal suppression with mitotane, ketoconazole, metyrapone, etomidate
• Increased cortisol metabolism with mitotane, phenytoin, carbamazepine, and St. John's wort

Diagnosis

• A single baseline ACTH and cortisol, ideally morning
  • Cortisol is 80% bound to CBG (increased by estrogen, pregnancy, mitotane) and 10-15% bound to albumin
• Corticotropin stimulation test
  • Get ACTH (will tell you if ACTH-dependent or -independent), baseline cortisol, +/-  aldosterone
  • Give Cosyntropin 0.25 mg IM/IV
  • Check cortisol at 30 minutes and 60 minutes
  • A normal test is if cortisol rises to a peak of 500-550 nmol/L by 60 minutes