Mayo Test Catalog, (Sorted By Test Name) - Mayo Medical ...

OH21
81970
CYPSP
89081
21-hydroxylase deficiency. J Clin Endocrinol Metab 2006;91:2179-2184
21-Hydroxylase Antibodies, Serum
Clinical Information: Chronic primary adrenal insufficiency (Addison's disease) is most
commonly caused by the insidious autoimmune destruction of the adrenal cortex and is characterized by
the presence of adrenal cortex autoantibodies in the serum. It can occur sporadically or in combination
with other autoimmune endocrine diseases, that together comprise Type I or Type II autoimmune
polyglandular syndrome (APS). The microsomal autoantigen 21-hydroxylase (55 kilodalton) has been
shown to be the primary autoantigen associated with autoimmune Addison's disease. 21-Hydroxylase
antibodies are markers of autoimmune Addison's disease, whether it presents alone, or as part of Type I
or Type II (APS).
Useful For: Investigation of adrenal insufficiency Aid in the detection of those at risk of developing
autoimmune adrenal failure in the future
Interpretation: Positive results (> or =1 U/mL) indicate the presence of adrenal autoantibodies
consistent with Addison's disease.
Reference Values:
90% of CAH cases, the affected enzyme is 21-steroid
hydroxylase, encoded by the CYP21A2 gene located on chromosome 6 within the highly recombinant
human histocompatibility complex locus. Since sex steroid production pathways branch off proximal to
this enzymatic step, affected individuals will have increased sex steroid levels, resulting in virilization
of female infants. If there is some residual enzyme activity, a nonclassical phenotype results, with
variable degrees of masculinization starting in later childhood or adolescence. On the other end of the
severity spectrum are patients with complete loss of 21-hydroxylase function. This leads to both cortisol
and mineral corticosteroid deficiency and is rapidly fatal if untreated due to loss of vascular tone and
salt wasting. Because of its high incidence rate, testing for 21-hydroxylase deficiency included in most
US newborn screening programs, typically by measuring 17-hydroxyprogesterone concentrations in
blood spots by immunoassay. Confirmation by other testing strategies (eg, LC-MS/MS, CAHBS/84113
Congenital Adrenal Hyperplasia [CAH] Newborn Screening, Blood Spot), or retesting after several
weeks, is required for most positive screens because of the high false-positive rates of the
immunoassays (due to physiological elevations of 17- hydroxyprogesterone in premature babies and
immunoassay cross-reactivity with other steroids). In a small percentage of cases, additional testing will
fail to provide a definitive diagnosis. In addition, screening strategies can miss many nonclassical cases,
which may present later in childhood or adolescence and require more extensive steroid hormone
profiling, including testing before and after adrenal stimulation with adrenocorticotropic hormone
(ACTH)-1-24. For these reasons, genetic diagnosis plays an important ancillary role in classical cases,
and is even more important in nonclassical cases. In addition, the high carrier frequency (approximately
1:50) for CYP21A2 mutations makes genetic diagnosis important for genetic counseling. Finally,
genetic testing may play a role as an adjunct to biochemical testing of amniotic fluid in the antenatal
diagnosis of 21-hydroxylase deficiency. However, accurate genetic diagnosis continues to be a
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