Monday, April 12, 2010

Adrenal Insufficiency

Clinical Background

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

Epidemiology

  • Incidence – estimated at 5/100,000
  • Sex – M:F, equal

Classification

  • Primary or secondary insufficiency

Etiology

  • Causes of primary adrenal insufficiency
    • Autoimmune  (Addison disease)
      • Frequent association with other endocrine diseases
        • Autoimmune polyendocrine syndromes
          • Epidemiology
            • Incidence – 1-2/100,000
            • Age – usually in 30s
            • Sex – M<F, 1:3
          • Most frequent endocrine abnormality is adrenal insufficiency
          • Type 1
            • Addison disease
            • Chronic mucocutaneous candidiasis
            • Hypoparathyroidism
          • Type 2
            • Diabetes mellitus type 1 (DM1)
            • Addison disease with hypothyroidism – Schmidt syndrome
        • Both types 1 and 2 may also include:
          • DM1
          • Other autoimmune disorders – vitiligo, chronic atrophic gastritis, alopecia
      • Autoantibodies to 21-hydroxylase are frequently present
    • Anatomic destruction of the gland
      • Surgical removal
      • Bilateral hemorrhage into the gland
        • Associated with anticoagulant therapy
      • Invasion of the gland
        • Metastatic cancer is extremely rare
    • Infection
      • Bacterial
        • Tuberculosis
        • Meningococcus (Waterhouse-Friderichsen) – rare
        • Pseudomonas – rare
      • Fungal – histoplasmosis, coccidioidomycosis
      • Viral – cytomegalovirus (CMV), AIDS
    • Congenital adrenal hyperplasia (CAH)
  • Causes of secondary adrenal insufficiency
    • Hypopituitarism
      • Postpartum hemorrhage – Sheehan syndrome
      • Pituitary radiation
      • Pituitary surgery
      • Acute interruption of prolonged corticosteroids
      • Pituitary infiltrative disease – tuberculosis, sarcoidosis, Wegener granulomatosis
    • Exogenous glucocorticoid administration
    • Lymphocytic hypophysitis – may be part of autoimmune polyendocrine syndrome

Pathophysiology

  • Primary – glucocorticoid and mineralocorticoid deficiency
  • Secondary – only glucocorticoid deficiency

Clinical Presentation

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

Treatment

  • Primary – glucocorticoids and mineralocorticoids in primary
  • Secondary – glucocorticoids only
  • Increase glucocorticoid dosing during acute illness

Diagnosis

  • Indications for testing – presence of disease process associated with adrenal insufficiency and other symptoms consistent with adrenal insufficiency
  • Laboratory testing
    • Initial testing
      • First, measure early morning serum cortisol
        • Cortisol ≥5 µg/dL makes primary adrenal insufficiency less likely; however, if serious consideration is given to this diagnosis, perform stimulation testing
      • Follow with adrenocorticotropic hormone (ACTH) testing
        • If ACTH >300 pg/dL – adrenal failure likely
        • If ACTH <10 pg/dL – pituitary failure likely
        • If ACTH between 10 pg/dL and 300 pg/dL – administer ACHT (cosyntropin) stimulation test
    • Stimulation
      • ACTH stimulation test – cortisol response to cosyntropin (250 µg followed by serial cortisol measures at 30 and 60 minutes)
        • Cortisol <5 µg/dL – adrenal failure
        • Cortisol >20 µg/dL – normal
        • Cortisol ≤20 µg/dL but ≥5 µg/dL – evaluate for pituitary failure
      • Pituitary failure stimulation testing
        • Insulin tolerance testing (ITT)
        • Metyrapone overnight testing
        • CT/MRI anatomic location based on cortisol ratios (see Adrenal Insufficiency Testing Algorithm)
  • Imaging studies
    • MRI/CT based on stimulation testing
    • If stimulation testing or absolute cortisol suggests adrenal failure – MRI/CT of adrenal glands
    • If stimulation testing suggests pituitary failure – MRI/CT of pituitary

Differential Diagnosis

  • Bronchogenic carcinoma
  • Hemochromatosis
  • Peutz-Jeghers syndrome
  • Tuberculosis
  • Congenital adrenal hyperplasia
  • Malnutrition

 

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