Pediatric androgen insensitivity syndrome

　　It has been confirmed that androgen insensitivity syndrome (AIS) belongs to a sex-linked genetic disease, and it is believed that whether there is a lack of androgen receptor numbers or dysfunction, both are due to gene mutations, and they may be allelic. At least three mechanisms are known to cause the occurrence of AIS:
　　In normal circumstances, the action of androgens on target organs depends on the sensitivity of target cells, which is expressed through the interaction between androgens and their receptors. The androgen receptor can bind to dihydrotestosterone (DHT) and also to testosterone (T) in the form of non-covalent bonds, with high affinity. Testosterone and dihydrotestosterone are the most biologically active steroids in androgens, essential for the development of male accessory sex organs and their normal physiological functions. If the receptors within the cell are lacking or in reduced numbers, it will inevitably affect the action of androgens. The cause of most CAIS and a few PAIS is the lack of androgen receptors.
　　Some patients with gene mutations in the androgen receptor gene, leading to functional abnormalities, have no significant change in the number of androgen receptors but have defects in receptor function, mainly reflected in the binding障碍 between androgens and receptors. This may be due to the impairment of the activation or conversion of the androgen receptor complex caused by gene mutations. Many researchers have used specific monoclonal antibodies and CDNA probes to analyze the androgen receptor gene in patients and confirmed that the molecular basis of androgen insensitivity syndrome is the gene mutation of the androgen receptor.
　　The lack of 3,5α-reductase requires two proteins, namely the androgen receptor and 5α-reductase, for the binding of androgens to target cells. The 5α-reductase, by binding to testosterone and its receptor, converts testosterone into the more active dihydrotestosterone. If this enzyme is lacking or its activity is weakened, it will affect the conversion of testosterone to dihydrotestosterone.

　　The position of the testicles is not fixed, and they can be in the abdominal cavity or inguinal canal. The risk of testicular malignancy is high after 25 years old, most commonly in the third and fourth decades. The incidence of testicular cancer in cryptorchid patients is much higher than that in patients with incomplete descent of the testicles, which indicates that long-term exposure to a higher temperature is harmful to the testicles. Although testicular malignant tumors are relatively rare, accounting for only 1.5% of male malignant tumors, due to the high mortality rate of patients, and significant impact on fertility and sexual function, this disease is highly valued.

　　The clinical manifestations of androgen insensitivity syndrome are various, ranging from phenotypic females to almost normal males. The complete androgen insensitivity syndrome (CAIS) with a normal female phenotype is often found due to primary amenorrhea, and a few are diagnosed unexpectedly due to the discovery of testicles in the hernia sac or inguinal canal during hernia surgery. The external genitalia of patients are of normal female type, but the vagina is short and blind-ended, without female internal genitalia. During puberty, the body shape is female, with breast development, but without pubic hair and axillary hair. The partial androgen insensitivity syndrome (PAIS) has different degrees of phenotypes, with possible female-type perineal clitoris, hypospadias, labial fusion, large clitoris, and cryptorchidism. Or it may appear as a normal male appearance, with only breast enlargement during puberty, or as a male without reproductive ability. The common phenomenon of all types of AIS is the absence of the Müllerian duct (due to the action of testicular-Müllerian inhibitory substance), and the poor development of the Wolffian duct.

　　Androgen insensitivity syndrome belongs to a class of X-linked genetic diseases, and preventive measures should be implemented from pre-pregnancy to prenatal. Pre-marital physical examination plays a positive role in preventing birth defects, and its effectiveness depends on the items and content of the examination, mainly including serological tests (such as hepatitis B virus, syphilis spirochete, HIV), reproductive system examination (such as cervical inflammation screening), general physical examination (such as blood pressure, electrocardiogram), and inquiries about family history of diseases and personal medical history, etc. Good genetic counseling work should be done. Pregnant women should try to avoid harmful factors, including staying away from smoke, alcohol, drugs, radiation, pesticides, noise, volatile harmful gases, and toxic heavy metals. During the process of prenatal health care during pregnancy, a systematic screening for birth defects should be carried out, including regular ultrasound examinations, serological screenings, and chromosomal examinations when necessary.

　　The laboratory examination of androgen insensitivity syndrome in children found that the karyotype of complete androgen insensitivity syndrome (CAIS) is 46,XY, and the concentration of testosterone, estradiol, and follicle-stimulating hormone in the plasma of AIS patients is normal or at the upper limit of normal, while luteinizing hormone can be elevated. Auxiliary examinations showed bilateral primary optic atrophy, mild sensorineural hearing loss, bilateral pelviureteral dilatation, B-ultrasound showed a short blind-ended vagina, without cervix, uterus, and female reproductive tract, and abnormal position of testicles.

　　Patients with pediatric androgen insensitivity syndrome should eat foods that have antibacterial and anti-inflammatory properties, clear heat and detoxify, and enhance human immunity. They should avoid eating foods rich in fats such as butter, chicken fat, and duck fat. Patients should also avoid eating spicy and irritating foods such as chili, white wine, and Sichuan pepper. They should also avoid eating unfermented foods such as salted eggs, salted fish, and salted meat.

　　There have been no new developments in the treatment of pediatric androgen insensitivity syndrome. It is still believed that ectopic testes are prone to malignant tumors, and patients are recommended to have the testes removed, and then estrogen replacement therapy is given during puberty. For patients with partial androgen insensitivity syndrome (PAIS) who are expected to achieve complete normal masculinization after puberty, it is still recommended to maintain their male gender, otherwise, the same treatment as CAIS should be performed. There have been reports that PAIS patients, after receiving tamoxifen (an estrogen receptor antagonist), showed a significant increase in sperm count and their wives became pregnant. This change is reversible, and the patient's sperm count will decrease again once the treatment is stopped..

　　Regarding the age of orchidectomy, it was previously believed that patients with complete androgen insensitivity syndrome (CAIS) had a very low chance of developing malignant tumors before the age of 25, with an incidence rate of about 2% to 5% after the age of 25, and PAIS patients rarely developed tumors. However, recent research results have raised objections to this. Cassio et al. conducted histological studies on the gonadal tissues of 11 PAIS patients with no clinical suspicion of tumors, and found that 8 cases showed intratubular spermatocytoma, including 5 cases (62.5%) who were not yet in puberty. Based on this, researchers believe that it is necessary to reconsider the previous argument that orchidectomy should not be performed before puberty.