Adrenal insufficiency is defined as hypofunction of the adrenal gland with decreased or absent cortisol secretion.

Epidemiology

• Incidence
  • Estimated at 5/100,000
• Gender - no predominance

Classification

• Primary or secondary insufficiency

Etiology

• Primary adrenal insufficiency
  • Autoimmune  (referred to as Addison disease)
    • Frequent association of Addison disease with other endocrine diseases
      • Autoimmune polyendocrine syndromes
        • Epidemiology
          • Incidence - 1-2/100,000
          • Age - most commonly 30-40 years
          • Gender - F:M; 3:1
        • Most frequent endocrine abnormality is adrenal insufficiency
        • Type I
          • Addison disease
          • Chronic mucocutaneous candidiasis
          • Parathyroid disease
        • Type II
          • Addison disease and hypothyroidism
            • Also called Schmidt syndrome
      • May also include:
        • Diabetes mellitus type I
        • Other autoimmune disorders such as vitiligo, chronic atrophic gastritis, alopecia
    • Occurs in >50% of Addison disease associated with autoimmunity
    • Autoantibodies to 21-hydroxylase are frequently present
  • Anatomic destruction of the gland
    • Hemorrhage into the gland
      • Anticoagulant therapy
    • Surgical removal
    • Invasion of the gland
      • Metastatic cancer is extremely rare
  • Infection
    • Bacterial
      • Meningococcus (Waterhouse-Friderichsen)
      • Pseudomonas
      • Tuberculosis
    • Fungal - histoplasmosis, coccidioidomycosis
    • Viral - cytomegalovirus, AIDS
  • Congenital adrenal hyperplasia
• Secondary adrenal insufficiency
  • Hypopituitarism
    • Postpartum hemorrhage - Sheehan syndrome
    • Pituitary radiation
    • Pituitary surgery
    • Acute interruption of prolonged corticosteroids
  • Exogenous glucocorticoid administration

Pathophysiology

• Primary
  • Glucocorticoid and mineralocorticoid deficiency
• Secondary
  • Only glucocorticoid deficiency

Clinical Presentation

• Insidious onset of fatigability, weakness, anorexia, nausea and emesis
• Cutaneous hyperpigmentation - diffuse tan, brown or bronzing
  • Does not usually occur in secondary insufficiency
• Orthostatic hypotension
• Diarrhea, abdominal pain
• Acute presentation may occur in patients with mild adrenal insufficiency who are stressed (e.g., critical illness, surgery)
  • Mainly attributable to mineralocorticoid deficiency
  • Hypotension which is unresponsive to fluids

Treatment

• Treatment with glucocorticoids and mineralocorticoids in primary; only glucocorticoids in secondary
• Increase glucocorticoid dosing during acute illness

Diagnosis

• Laboratory testing
  • Screening
    • Measuring early morning serum cortisol and ACTH are initial testing
  • Stimulation
    • Adrenocorticotropic hormone (ACTH) stimulation test - cortisol response to cosyntropin (250µg followed by serial cortisol measures)
    • Measuring ACTH/plasma aldosterone differentiates primary from secondary