21-Hydroxylase Antibodies

21-hydroxylase antibodies are markers of autoimmune Addison disease, which may manifest alone or as part of type I or type II polyglandular autoimmune syndrome.

Normal findings: < 1 U/mL ^[1]

A test result of 21-hydroxylase antibodies at 1 U/mL or higher indicates the presence of adrenal autoantibodies, which is consistent with Addison disease. ^[2]

Collection details are as follows:

• Collection container/tube - Red top preferred, serum gel acceptable

• Submission container/tube - Plastic vial

• Specimen volume - 1 mL

• Specimen minimum volume - 0.19 mL

• Reject due to gross hemolysis or gross lipemia

• Serum specimen stability - Frozen (preferred), 14 days; refrigerated, 7 days

Description

In the United States, autoimmune destruction of the adrenal cortex most commonly causes chronic primary adrenal insufficiency (Addison disease). The presence of adrenal cortex autoantibodies in the serum is associated with Addison disease. ^{[3, 4]} It can occur sporadically or in combination with other autoimmune endocrine diseases; these together comprise type I or type II polyglandular autoimmune syndrome. ^[5]

The 3 major components of type I polyglandular autoimmune syndrome are as follows: ^[6]

• Chronic mucocutaneous candidiasis

• Hypoparathyroidism

• Autoimmune adrenal insufficiency

Less common manifestations include the following:

• Hypergonadotropic hypogonadism

• Type 1 diabetes mellitus

• Asplenia

• Keratoconjunctivitis

• Cholelithiasis

• Malabsorption

• Alopecia

• Vitiligo

• Interstitial nephritis

• Autoimmune thyroid disease (not including Graves disease)

• Pernicious anemia

• Chronic atrophic gastritis

• Chronic active hepatitis

• Enamel hypoplasia, which occasionally precedes the onset of hypoparathyroidism

Polyglandular autoimmune syndrome type II consists of the following:

• Pernicious anemia

• Celiac disease

• Primary biliary cirrhosis

• Hypogonadism (usually autoimmune oophoritis)

• Hypopituitarism

• Addison disease

• Autoimmune thyroid disease

• Type 1 diabetes mellitus

• Idiopathic thrombocytopenic purpura

• Vitiligo

• Alopecia

• Seronegative arthritis

• Myasthenia gravis

• Parkinson disease

The primary autoantigen associated with autoimmune Addison disease has been shown to be the microsomal autoantigen 21-hydroxylase (55 kilodalton).

The incidence of antiadrenal and other autoantibodies by tissue type in patients with autoimmune adrenal insufficiency is as follows:

• Adrenal: 60%-70%

• Thyroid peroxidase: 50%

• Parathyroid: 26%

• Islet cell: 8%

• Ovary: 22%

• Testes: 5%

• Parietal cell: 30%

• Intrinsic factor: 9%

Indications/Applications

21-hydroxylase antibodies are markers of autoimmune Addison disease, which may manifest alone or as part of type I or type II polyglandular autoimmune syndrome. These antibodies may be present even before the endocrine function is reduced.

Autoimmune adrenal disease is divided into stages. Initially, the adrenal glands may be enlarged and have extensive lymphocytic infiltration. With chronic disease, the glands can be small and sometimes difficult to locate. A thickened and fibrotic capsule is seen, and the cortex is completely destroyed, although some small clusters of adrenocortical cells surrounded by lymphocytes may exist, and the medulla is relatively spared. Adrenal insufficiency is clinically apparent only after 90% or more of the cortex has been destroyed.

Considerations

Healthy subjects rarely have antibodies against other endocrine glands, but this is common in patients with autoimmune adrenal insufficiency. Over half of patients with autoimmune adrenal insufficiency have high serum antithyroid peroxidase antibody concentrations; nearly half of these patients have overt hypothyroidism. Many others have subclinical hypothyroidism (increased thyroid-stimulating hormone with normal serum thyroxine concentrations); these patients are at risk for developing overt hypothyroidism (Schmidt syndrome). ^[7]

The incidence of serum antiadrenal antibodies in patients with normal adrenal function but other autoimmune endocrine diseases is low (2%); the exception is those patients with hypoparathyroidism (16%).

The incidence of antiadrenal antibodies in patients with autoimmune disease of other endocrine glands is as follows:

• Hypoparathyroidism: 16%

• Goitrous autoimmune thyroiditis: 1.9%

• Atrophic autoimmune thyroiditis: 1.7%

• Hyperthyroidism: 1.9%

• Diabetes mellitus: 1.2% ^{[8, 9]}

• Pernicious anemia: < 1%

Autoimmune adrenal insufficiency can be classified as either familial or nonfamilial. When the condition occurs alone, it is somewhat less likely to be familial in origin. Approximately one-third of such patients have affected family members, versus about half of patients who have adrenal insufficiency as part of polyglandular autoimmune syndrome type I or II.