Adrenocortical Insufficiency (Adrenal Crisis, Addison Disease)

Key Features

Essentials of Diagnosis

• Primary adrenal insufficiency

  • Hereditary enzyme defects (congenital adrenal hyperplasia)

  • Autoimmune destruction of the glands (Addison disease)

    • May be familial

    • Can be isolated or associated with hypoparathyroidism, mucocutaneous candidiasis, hypothyroidism, pernicious anemia, hypogonadism, and diabetes mellitus

  • Destruction of the gland by tumor, calcification, or hemorrhage (Waterhouse-Friderichsen syndrome)

  • Adrenal disease secondary to opportunistic infections (fungal or tuberculous) is reported in immunocompromised patients

• Central adrenal insufficiency

  • Intracranial neoplasm or its treatment

  • Congenital midline defects associated with optic nerve hypoplasia (septo-optic dysplasia)

  • Chronic iatrogenic exposure to exogenous glucocorticoids

General Considerations

• Acute illness, surgery, trauma, or hyperthermia may precipitate an adrenal crisis in patients with adrenal insufficiency

• Patients with primary adrenal insufficiency are at greater risk for life-threatening crisis than patients with central ACTH deficiency because mineralocorticoid secretion and low-level autonomous cortisol secretion remain intact in central ACTH deficiency

Clinical Findings

Symptoms and Signs

• Acute form (adrenal crisis)

  • Nausea, vomiting, diarrhea, abdominal pain

  • Dehydration

  • Fever (sometimes followed by hypothermia)

  • Weakness

  • Hypotension and circulatory collapse

  • Confusion and coma

• Chronic form

  • Fatigue

  • Hypotension

  • Weakness

  • Weight loss or failure to gain weight

  • Salt craving (primary insufficiency)

  • Vomiting and dehydration

  • Recurrent hypoglycemia

  • Diffuse tanning occurs with increased pigmentation over pressure points, scars, and mucous membranes

Differential Diagnosis

• Sepsis diabetic coma

• CNS disturbances

• Acute poisoning

• In the neonatal period, may be clinically indistinguishable from respiratory distress, intracranial hemorrhage, or sepsis

• Anorexia nervosa

• Certain muscular disorders (myasthenia gravis)

• Salt-losing nephritis

• Chronic debilitating infections

Diagnosis

Laboratory Findings

• Primary adrenal insufficiency

  • Decreased serum sodium, serum bicarbonate, arterial partial pressure of carbon dioxide, blood pH, and blood volume

  • Increased serum potassium, urea nitrogen levels

  • Urinary sodium and the ratio of urinary sodium to potassium are inappropriate for the degree of hyponatremia

  • Eosinophilia and moderate lymphopenia

  • Plasma cortisol < 18 mcg/dL 30 and 60 minutes after 250 μg of cosyntropin given intravenously and aldosterone fails to rise above baseline

  • Baseline serum ACTH concentration

    • Elevated in primary adrenal failure

    • Low in central adrenal insufficiency

  • Decreased urinary free cortisol

• Central adrenal insufficiency

  • Serum sodium levels may be mildly decreased as a result of impaired water excretion

  • Eosinophilia and moderate lymphopenia

  • Plasma cortisol < 18 mcg/dL 30 and 60 minutes after 1 μg of cosyntropin given intravenously

  • Baseline serum ACTH concentration

    • Elevated in primary adrenal failure

    • Low in central adrenal insufficiency

  • Decreased urinary free cortisol

Treatment

• Acute insufficiency (adrenal crisis)

  • Hydrocortisone sodium succinate

    • 50 mg/m2 intravenously over 2–5 minutes or intramuscularly) is given initially followed by 12.5 mg/m2 every 4–6 hours until stabilization is achieved and oral therapy can be tolerated

    • Cortisol replacement is critical because vasopressor agents may be ineffective in adrenal insufficiency

  • Fluids and electrolytes

    • In primary adrenal ...