Addison Disease

Snapshot

A 25-year-old man presents to the clinic for an annual check-up. He is otherwise healthy and has no significant concerns. Basic laboratory studies demonstrate a sodium level of 129 mg/dL and potassium level of 5.9 mg/dL. A physical examination demonstrates hyperpigmentation of the oral mucosa. Review of systems were positive for generalized fatigue, 5-lbs unintentional weight loss, and some headaches.

Introduction

Clinical definition
- disorder characterized by the loss of adrenal gland function leading to the deficiency of glucocorticoids, mineralocorticoids, and adrenal androgens
- can be either acute or chronic depending of the etiology
Epidemiology
- demographics
  - autoimmune causes (which accounts for 70-90% of cases in the U.S.) occur predominantly within the female population
- risk factors
  - other autoimmune endocrinopathies
Pathogenesis
- any process that damages the adrenal cortices and leads to a deficiency of aldosterone, catecholamines, and cortisol
- autoimmune adrenalitis (Addison disease)
  - most common cause in the U.S.
  - both humoral and cell-mediated immune mechanisms against the adrenal cortex
  - a small percentage of patients may have polyglandular autoimmune syndrome
- infectious adrenalitis
  - tuberculosis (most common cause in the developing world)
  - disseminated fungal infections (e.g., histoplasmosis)
  - HIV infection
- hemorrhagic infarction
  - Waterhouse-Friderichsen syndrome associated with meningococcemia (Neisseria meningitidis)
  - anticoagulant drug or heparin therapy (e.g., heparin-induced thrombocytopenia)
- metastatic disease
  - commonly associated with lung, breast, and melanoma cancers
Associated conditions
approximately 1/2 of patients with autoimmune adrenal insufficiency have other autoimmune endocrine disorders (e.g., hypothyroidism)

Presentation

Symptoms
- fatigue
- weight loss
- nausea/vomiting
- abdominal pain
- muscle/joint pain
- salt craving
- adrenal crisis
Physical exam
- skin and mucosal hyperpigmentation (if longstanding)
  - due to increased production of proopiomelanocortin (POMC), a prohormone that is cleaved into ACTH and melanocyte-stimulating hormone (MSH)
- hypotension
- auricular-cartilage calcification
vitiligo

Imaging

Studies

Serum cortisol concentration (e.g., morning serum cortisol)
- best initial test
- low serum cortisol (e.g., < 5 ug/dL) strongly suggests adrenal insufficiency
Plasma ACTH concentration
- best initial test but often not quickly available
- high plasma ACTH concentration with low serum cortisol suggests primary adrenal insufficiency
ACTH stimulation test
- will have low response to ACTH stimulation
Plasma aldosterone and renin levels
- will have low aldosterone and high renin levels
Chemistry panel
- hyperkalemia
hyponatremia

Differential

Secondary adrenal insufficiency
- distinguishing factors
  - will not have hyperpigmentation on physical examination
will have low levels of ACTH

Treatment

Glucocorticoid replacement therapy
- e.g., hydrocortisone or dexamethasone
- stress doses indicated at times of stress (e.g., surgery)
- significant adverse effects with chronic use (e.g., osteoporosis)
Mineralcorticoid replacement therapy
- e.g., fludrocortisone
- prevents sodium loss, intravascular volume depletion, and hyperkalemia
Androgen replacement therapy
- e.g., dehydroepiandrosterone (DHEA)
- appears to improve mood and psychological well-being
adverse effects include hirsutism, acne, and increased sweating/odor

Complications