Sorted By Test Name - Mayo Medical Laboratories

CYPSP
89081
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 challenge because most of the
mutations arise from recombination events between CYP21A2 and its highly homologous pseudogene,
CYP21A1P (transcriptionally inactive). In particular, partial or complex rearrangements (with or without
accompanying gene duplication events), which lead to reciprocal exchanges between gene and
pseudogene, can present severe diagnostic challenges. Comprehensive genetic testing strategies must
therefore allow accurate assessment of most, or all, known rearrangements and mutations, as well as
unequivocal determination of whether the observed changes are located within a potentially
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