testicular feminization
Introduction
Introduction to testicular feminization The term testicular feminization is first advocated by Morris to express a group of genetic sexes for males, testes, no Müllerian tubes, and phenanthrene-derived organs. The genitourinary sinus differentiates into a full female type. A patient with normal breast development and lacking or scarring pubic hair. In patients with primary amenorrhea, the disease ranks third in gonadal dysplasia and congenital absence of vagina, accounting for about 10% of patients with primary amenorrhea. basic knowledge The proportion of illness: 0.001% Susceptible people: no specific population Mode of infection: non-infectious Complications: small penis
Cause
Testicular feminization
(1) Causes of the disease
The study of collecting genital skin fibroblasts in the 1970s found that fibroblasts are androgen-resistant and cannot bind to androgens. Later studies have shown that some patients have the ability of genital skin fibroblast serous and nuclear-binding androgen. Normal, but androgen-receptor conjugates are unstable: increased dissociation rate, defective upregulation of the receptor, decreased affinity for binding to the ligand, short nuclear retention time of the ligand, and instability to conditions such as temperature.
(two) pathogenesis
The AR gene is located at Xq11~12, encoding 910-919 amino acids with 8 exons. Exon 1 is at the N-terminus, which is related to the transcriptional function of the gene. Exons 2 and 3 each encode a zinc finger. , which constitutes a highly conserved DNA binding region, which, after binding of the receptor to the ligand, unblocks the heat shock protein, binds to a hormone response element (transcription enhancer nucleotide series), activates the transcription process, and exon 4 is a hinge The region contains a nuclear localization signal, which is necessary for the receptor-ligand complex to be fixed in the nucleus. The exons 5 to 8 are the androgen-binding region, which is a binding site with high affinity for androgen, and binds to androgen. Afterwards, the receptor is allosteric, phosphorylated, dimerized, nuclear localized and activated.
The general rule is that the clinical manifestation of the patient is related to the severity of the AR defect. The receptor is completely incapable of binding to androgen, and there is almost no masculine expression. The receptor has partial binding ability and may be partially masculine. The AR gene mutation occurs most frequently. Proton 5-7, arginine only accounts for 4% of all amino acid residues in the receptor, while arginine mutations account for 40% of all mutations, and 4 arginine residues at 774, 831, 840 and 855. And the 866 proline residue is the site with the highest probability of mutation. The AR gene mutation causes the receptor to lose or lose the ability to bind androgen, or the receptor-ligand complex is unstable, easily at temperature or other environmental factors. Dissociation under the influence of the effect, the final result is that androgen can not play a normal physiological role in the target tissue.
Prevention
Testicular feminization prevention
The disease is an X-linked recessive genetic disease with no clear prevention data.
Complication
Testicular feminization complications Complications small penis
Complications mainly include genital malformations, small penis, perineal hypospadias, blind pocket vagina, lack of prostate or hypoplasia, testis in the inguinal canal or labia scrotum pleats, testicular dysplasia without normal sperm, unable to breed the next generation . Secondly, the breast enlargement can be concurrently presented with a feminine appearance. And other secondary sexual changes due to the reduction of androgen, relative increase in estrogen, such as: no beard, no pubic hair, no throat.
Symptom
Testicular feminization symptoms Common symptoms Amenorrhea blind bag Vaginal gonadal dysplasia Female sexual organ response lacks no whisker hair and pubic hair
The karyotype of the patient is normal male type (46, XY), the gonad is a normal testis, the external genitalia is normal female type, the labia majora is poorly developed, the blind pocket is vagina, 2/3 of the patients have no uterus and fallopian tubes, and the remaining 1/ 3 remains of remains, epididymis and vas deferens are generally absent, rare examples may have dysplastic Wolff tube-derived organs, testis located in the labia majora, inguinal canal or abdominal cavity, testicular histology is normal before puberty, after puberty The seminiferous tubules are shrunk, the spermatogonial cells are sparse, no sperm is produced, the Lyd cells are adenomatous hyperplasia, and the testes have a tendency to develop malignant tumors. The incidence rate after adulthood is 4% to 9%.
In adolescence, women develop secondary sexual characteristics, breast development is the same as normal women, female body, pubic hair and mane are sparse, about 1/3 of patients have no pubic hair and mane growth, clitoris small or normal, labia minora dysplasia, primary Sexual amenorrhea, normal intelligence.
The characteristic changes in plasma hormonal spectrum are elevated levels of LH and testosterone, but this does not necessarily manifest in infancy. By the time of puberty, the androgen's feedback to the hypothalamic-pituitary is lost, resulting in increased LH pulse frequency and amplitude, LH secretion. Increased amount, stimulates Lydi cells to synthesize and secrete more testosterone, increases testicular secretion of E2, plus testosterone and 4A in peripheral tissues through the conversion of aromatase to E2, the result is increased plasma concentration of E2, causing high androgen conditions Feminization, FSH levels are normal or slightly elevated, due to E2 stimulation, SHBG levels are increased, DHT levels are generally lower than normal, because testosterone is reduced by 5-reductase to DHT in target tissues, if patients are double Lateral orchiectomy, plasma LH and FSH levels will be further elevated, indicating that in the case of androgen resistance, E2 has a feedback regulation of gonadotropins.
Examine
Testicular feminization
Characteristic changes in plasma hormone profiles: elevated LH and testosterone levels, normal or slightly elevated FSH levels, generally lower than normal DHT levels, and pre-pubertal patients may choose HCG stimulation test.
Regular B-ultrasound, monitoring testicles, breast development, and chromosomal gene examination.
Diagnosis
Testicular feminization diagnosis
diagnosis
Post-pubertal patients have a female phenotype, good breast development, lack or sparse pubic hair and pubic hair, testicular mass in the inguinal canal, primary amenorrhea, blind vaginal and no uterus and other typical clinical manifestations and karyotype 46, XY can determine the diagnosis of testicular feminization. Similarly, prepubertal girls or female infants, karyotype 46, XY, may touch the testicular mass or have inguinal hernia in the labia majora.
Plasma LH and testosterone levels are elevated, but can be normal during infancy, and pre-pubertal patients sometimes require an HCG stimulation test to reveal elevated testosterone levels.
Differential diagnosis
Incomplete testicular feminization should be differentiated from steroid 5-reductase B deficiency,
