Adrenal Insufficiency

Adrenal Insufficiency

 

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

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

Treatment

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

See Also