patient needs stress steroid coverage as described above for significant illness or injury. Other alleles result in even milder degrees of hyperandrogenism that may not even cause problems in males and may not be recognized until adolescence or later in females. Mild androgen effects in young women may include hirsutism, acne, or anovulation (which in turn can cause infertility). Testosterone levels in these women may be mildly elevated, or simply above average. These clinical features are those of polycystic ovary syndrome (PCOS), and a small percentage of women with PCOS are found to have late-onset CAH when investigated. Diagnosis of late-onset CAH may be suspected from a high 17α-hydroxyprogesterone level, but some cases are so mild that the elevation is only demonstrable after cosyntropin stimulation. Treatment may involve a combination of very low dose glucocorticoid to reduce adrenal androgen production and any of various agents to block the androgen effects and/or induce ovulation. Late-onset CAH was originally characterized in 1957 by French biochemist Jacques Decourt, but the association with mild 21-hydroxylase deficiency called nonclassical 21-hydroxylase deficiency, which is characterized by diverse hyperandrogenic symptoms appearing postnatally in males and females, was first described in 1979 by Maria New. New since then have studied ways to reduce androgen excess and found out that treatment with dexamethasone 0.25 mg orally every evening reversed acne and irregular menstruation in 3 months, but hirsutism required up to 30 months. Dexamethasone has glucocorticoid activity, and potent ACTH-suppression properties within the hypothalamic–pituitary–adrenal axis. Lower ACTH leads to reduced production of all the steroids, including androgens. According to 2018 Clinical Practice Guideline, glucocorticoid treatment is not recommended in asymptomatic individuals, however, if the symptoms of androgen excess are sufficient, dexamethasone treatment may be prescribed. Another treatment option is oral contraceptive pills. Genetics The CYP 21A2 gene for the P450c21 enzyme (also known as 21-hydroxylase) is at 6p21.3, amid genes HLA B and HLA DR coding for the major human histocompatibility loci (HLA). CYP21A2 is paired with a nonfunctional pseudogene CYP21A1P. Scores of abnormal alleles of CYP21A2 have been documented, most arising from recombinations of homologous regions of CYP21A2 and CYP21A1P. The 21-hydroxylase deficiency may be caused by macrodeletions of about 30 Kb, which includes not only most of the 5′ region of the CYP21A2 gene, but also all of the C4B gene and 3′ regions of the CYP21A1P pseudogene. Duplications of CYP21A1P pseudogene and C4B gene are often