Nonclassical Congenital Adrenal Hyperplasia (NCAH) usually due to 21 Hydroxylase deficiency (21OHD) is an autosomal recessive disease, occurring in upto 1/200 of Caucasians and more often in certain ethnic groups. Common CYP21A2 mutations from most severe to mildest are; null, I2 splice, I172N, P30L, and V281L. Mutations leaving 2070% of enzyme activity is responsible for NCAH, mostly caused by V281L mutation. About 2550% of patients are homozygous or compound heterozygous for two mild (nonclassical) alleles. Remaining have one severe (classical) and one mild mutation. Carrier frequency for a severe CAH mutation is about 1/60, whereas mild mutations are detected ranging from 1/5 to 1/16 of the population. Thus, preconception counseling is very important for avoiding birth of classical CAH babies to NCAH mothers. Probability of a NCAH mother having an infant affected by classic CAH is about 1/480. Following confirmation with dynamic hormone testing, analysis for 21-hydroxylase gene can determine the underlying mutation and disease risk for the fetus. Male partner of a NCAH female carrying a severe mutation should also be genetically examined. There is an overlap between the stimulated serum 17OHP levels of heterozygotes for 21OHD and unaffected subjects. Although heterozygotes do not need medical treatment, they should have genetic counselling. In adults, first symptoms of NCAH are usually acne, hirsutism, oligo-menorrhea. Symptoms of a NCAH individual with one classic allele is more severe and 17OHP level is more elevated than the one with homozygous mild mutations. Infertility is the presenting symptom in only 13%. Glucocorticoid (GC) therapy is the treatment of choice for hyperandrogenism and infertility. It usually takes about three months for the reversal of complaints. This treatment also seems to shorten the time to conceive and reduce miscarriage rates. Ovulation induction with clomiphene citrate or aromatase inhibitors can be performed for selected NCAH females.
18 - 21 May 2019
European Society of Endocrinology