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Dr. Andrew Rynne
Dr. Andrew Rynne

Family Physician

Exp 50 years

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Article Home Adult and Senior Health Addison Disease

Addison Disease

Addison?s diseaseis a rare endocrine disorder in which the adrenal gland does not produce enough steroid hormones (glucocorticoids and often mineralocorticoids). A problem with your immune system usually causes Addison's disease. The immune system mistakenly attacks your own tissues, damaging your adrenal glands.

Clinical features- symptoms

  • Weight loss
  • Muscle weakness, joint pains
  • Fatigue that gets worse over time
  • Low blood pressure
  • Patchy or dark skin
  • Diarrhea, headache and sweating
  • Changes in mood and personality
  • Patients with diabetes that previously was well-controlled may suddenly develop a marked decrease in insulin requirements and hypoglycemic episodes due to an increase in insulin sensitivity.
  • Impotence and decreased libido may occur in male patients, especially in those with compromised or borderline testicular function.

Clinical features- signs

  • Orthostatic hypotension
  • Signs of conditions that often occur together with Addison's: goiter and vitiligo
  • Hyperpigmentation of hand, nipples, buccal areas, and old scars
  • Calcification of the ear and costochondral junctions is described but is a rare physical finding.


The most common cause of Addison disease is idiopathic autoimmune adrenocortical insufficiency resulting from autoimmune atrophy, fibrosis, and lymphocytic infiltration of the adrenal cortex, usually with sparing of the adrenal medulla.

  • Idiopathic autoimmune adrenocortical atrophy and tuberculosis (TB) account for nearly 90% of cases of Addison disease
  • Idiopathic autoimmune Addison disease may occur in isolation or in association with other autoimmune phenomena
  • Celiac disease
  • Idiopathic hypoparathyroidism
  • Mucocutaneous candidiasis
  • Type 1 diabetes mellitus
  • Hashimoto thyroiditis
  • Graves’s disease
  • Vitiligo
  • Alopecia areata, totalis and universalis
  • Premature ovarian or testicular failure
  • Pernicious anemia
  • Myasthenia gravis
  • Idiopathic hypophysitis
  • Chronic active hepatitis
  • Primary biliary cirrhosis
  • The association of Addison disease and Hashimoto thyroiditis is known as Schmidt syndrome.

Addison disease association

The association of Addison disease with hypoparathyroidism and mucocutaneous candidiasis is described as polyglandular autoimmune syndrome type 1. It may have an autosomal recessive mode of inheritance. It has no human leukocyte antigen (HLA) associations.

The association of Addison disease with type 1 diabetes mellitus and Hashimoto thyroiditis or Graves’s disease is described as polyglandular autoimmune syndrome type 2 and may be associated with HLA-B8 and DR-3.

Additional causes of chronic Addison disease

  • Chronic granulomatous diseases- TB, sarcoidosis, histoplasmosis, blastomycosis, and cryptococcosis could involve the adrenal glands.
  • Hematologic malignancies-Bilateral involvement of the adrenal glands could occur in the setting of metastatic cancer of the lung, breast, or colon or renal cell carcinoma.
  • Infiltrative metabolic disorders - Amylodosis and hemochromatosis could involve the adrenal glands and lead to primary adrenocortical insufficiency.
  • Acquired immunodeficiency syndrome
  • Allgrove syndrome
  • Congenital adrenal Hyperplasia
  • Drug-related causes- Ketoconazole, Aminoglutethimide, Mitotane
  • Abdominal irradiation

Addisonian crisis

Adrenal crisis is a constellation of symptoms that indicate severe adrenal insufficiency.

This may be the result of either previously undiagnosed Addison's disease

Causes for acute adrenal crisis

  • Stress - Acute adrenal crisis precipitated by infection, trauma, surgery, emotional turmoil, or other stress factors.
  • Bilateral adrenal hemorrhage- it may occur as a complication of bacterial infection with Meningococcus or Pseudomonas species, as in Waterhouse-Friderichsen syndrome.
  • Bilateral adrenal artery emboli and bilateral vein thrombosis
  • Bilateral adrenalectomy
  • Untreated, an Addisonian crisis can be fatal. It is a medical emergency, usually requiring hospitalization.

Clinical features

  • Sudden penetrating pain in the legs, lower back or abdomen
  • Severe vomiting and diarrhea, resulting in dehydration
  • Low blood pressure
  • Syncope (loss of consciousness)
  • Hypoglycemia
  • Confusion, psychosis, slurred speech
  • Severe lethargy
  • Hypercalcemia
  • Convulsions
  • Fever

Tests and diagnosis

  • Hypercalcemia
  • Hypoglycemia
  • Hyponatraemia
  • Hyperkalemia
  • Eosinophilia and lymphocytosis
  • Metabolic acidosis
  • Thyroid function tests
  • Imaging studies- CT abdomen may be normal but may show bilateral enlargement of the adrenal glands in patients with Addison disease because of TB, fungal infections, adrenal hemorrhage, or infiltrating diseases involving the adrenal glands.

Specific tests

ACTH test

This is the most specific test for diagnosing Addison's disease.

In this test, blood cortisol, urine cortisol, or both are measured before and after a synthetic form of ACTH is given by injection.

In the so-called short, or rapid, ACTH test, measurement of cortisol in blood is repeated 30 to 60 minutes after an intravenous ACTH injection.

The normal response after an injection of ACTH is a rise in blood and urine cortisol levels.

CRH test

When the response to the short ACTH test is abnormal, a "long" CRH stimulation test is required to determine the cause of adrenal insufficiency.


Treatment of Addison's disease involves replacing, or substituting, the hormones that the adrenal glands are not making.

Cortisol is replaced orally with hydrocortisone tablets, a synthetic glucocorticoid, taken once or twice a day.

If aldosterone is also deficient, it is replaced with oral doses of a mineralocorticoid called fludrocortisone acetate

Patients receiving aldosterone replacement therapy are usually advised by a doctor to increase their salt intake.

Management of Addisonian crisis

During an addisonian crisis, low blood pressure, low blood glucose, and high levels of potassium can be life threatening.

Standard therapy involves intravenous injections of hydrocortisone, saline (salt water), and dextrose (sugar).

When the patient can take fluids and medications by mouth, the amount of hydrocortisone is decreased until a maintenance dose is achieved.

If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.

Special problems


Patients with chronic adrenal insufficiency who need surgery with general anesthesia are treated with injections of hydrocortisone and saline.


Women with primary adrenal insufficiency who become pregnant are treated with standard replacement therapy.
If nausea and vomiting in early pregnancy interfere with oral medication, injections of the hormone may b

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