Adrenal Insufficiency, Primary (Addison Disease)

Key Features

Essentials of Diagnosis

• Weakness, fatigue, weight loss; nausea, vomiting, diarrhea; abdominal pain, arthralgias; amenorrhea

• Sparse axillary hair; increased skin pigmentation, especially of creases, pressure areas, and nipples

• Hypovolemic hypotension

• Hyponatremia; potassium, calcium, and BUN elevated; mild anemia and relative neutropenia, lymphocytosis, and eosinophilia

• Plasma adrenocorticotropic hormone (ACTH) level elevated; cosyntropin unable to stimulate serum cortisol to ≥ 20 mcg/dL (550 nmol/L)

• Acute adrenal crisis: above manifestations become critical, along with fever, shock, confusion, coma, death

General Considerations

• Addison disease refers to a chronic deficiency of cortisol caused by adrenocortical insufficiency; plasma ACTH and α- melanocyte-stimulating hormone (MSH) levels are consequently elevated, causing pigmentation that ranges from none to strikingly dark

• Can present acutely but usually presents gradually over months or years

• Acute adrenal (Addisonian) crisis

  • An emergency caused by insufficient cortisol

  • May occur in the course of treatment of chronic adrenal insufficiency

  • May be the presenting manifestation of adrenal insufficiency

• Causes of primary adrenal insufficiency

  • Autoimmunity

    • Accounts for about 90% of spontaneous cases

    • Over half the cases of autoimmune Addison disease occur as part of autoimmune polyendocrine syndrome type-I, also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

  • Infection

    • Relatively rare cause of primary adrenal insufficiency

    • Tuberculosis is the most common infection of the adrenals

    • Coccidioidomycosis and other infections are rare

  • Bilateral adrenal hemorrhage

  • Adrenoleukodystrophy

  • Congenital adrenal insufficiency occurs in several conditions

    • Familial glucocorticoid deficiency

    • Triple A (Allgrove) syndrome

    • Congenital adrenal hypoplasia

• Rare causes of primary adrenal insufficiency

  • Lymphoma, metastatic carcinoma

  • Coccidioidomycosis, histoplasmosis, cytomegalovirus infection (more frequent in patients with AIDS)

  • Syphilitic gummas

  • Systemic sclerosis (scleroderma)

  • Amyloidosis

  • Hemochromatosis

• Medications that cause primary adrenal insufficiency

  • Mitotane

  • Abiraterone acetate

• Patients with treated chronic adrenal insufficiency appear to be more prone to develop pneumonia and gastrointestinal and urinary tract infections

Demographics

• Prevalence is about 90–140 cases per million

• Annual incidence is about 5–6 per million in the United States

Clinical Findings

Symptoms and Signs

• Abdominal pain, nausea, and vomiting; diarrhea can occur

• Fevers and lymphoid tissue hyperplasia may also occur

• Arthralgias, myalgias, chest pain, abdominal pain, back pain, leg pain, or headache

• Psychiatric symptoms: anxiety, irritability, and depression

• Low and orthostatic blood pressure

• Skin hyperpigmentation due to increased pituitary secretion of α-MSH and scant axillary and pubic hair

• Anovulation and reduced fertility

• Recurrent hypoglycemia and reduced insulin requirements in patients with preexisting type 1 diabetes mellitus

Differential Diagnosis

• Adrenal insufficiency secondary to other causes

• Hemochromatosis

• Acute adrenal crisis must be distinguished from other causes of shock

  • Sepsis

  • Cardiogenic

  • Hemorrhagic

• Hyperkalemia due to other cause (see Hyperkalemia)

• Hyponatremia due to other cause (see Hyponatremia)

• Abdominal pain due to other cause

• Intrinsic gastrointestinal disease

• Multiple sclerosis