OVERVIEW
Androgen resistance is a group of clinical syndromes caused by abnormal binding of androgen receptor and ligand or abnormal post-receptor signaling, resulting in the underactivation of androgen action. Depending on the degree of androgen resistance in peripheral tissues, the syndrome is divided into complete androgen resistance and partial androgen resistance (PARS). Complete androgen resistance syndrome is also known as testicular feminization syndrome. The term testicular feminization was first advocated by Morris, and these patients can present with varying degrees of male pseudohermaphroditism or even a completely feminized appearance. After puberty, the patient presents with primary amenorrhea, well-developed breasts, and the absence of a female uterus and adnexa in the pelvis; in patients with partial deficiency of the androgen receptor, the external genital phenotype is essentially close to that of a normal male appearance, which is also referred to as Reifenstein’s syndrome.
Etiology
Mutations in the androgen receptor. The gene encoding the human androgen receptor is located on chromosome Xq11-22, approximately 90 KB, and contains 8 exons. The androgen receptor is composed of 3 functional domains: a variable N-terminal transcriptional activation region, a highly conserved DNA-binding region, and a moderately conserved C-terminal ligand-binding region. After testosterone enters the cell, it is converted to dihydrotestosterone by 5α-reductase and binds to the receptor. Although testosterone itself can bind to the receptor and produce an effect, dihydrotestosterone produces a stronger activation, three times that of testosterone. After binding to dihydrotestosterone, the receptor enters the nucleus and binds to the androgen response element (ARE), which regulates androgen target genes.
Symptoms
The patient has a normal male karyotype (46, XY) and gonads with normal functioning testes. The external genitalia are of normal female type with poorly developed labia majora, blind pouch vagina, absence of uterus and fallopian tubes in 2/3 of the patients, and only vestigial remains in the remaining 1/3. The epididymis and vas deferens were usually absent. The testes were located in the labia majora, inguinal canal, or abdominal cavity. Histologic examination of the testes was normal before puberty, with narrowing of the seminiferous tubules, sparse spermatogonia, no spermatogenesis, and adenomatous hyperplasia of the Rheumatoid cells after puberty. The testes have a tendency to develop malignant tumors.
At puberty, female secondary sexual characteristics develop, breast development is the same as in normal females, female physique, sparse pubic and axillary hair, primary amenorrhea, and normal intelligence.
Examination
1. Characteristic changes in plasma hormone profiles: increased levels of LH and testosterone, normal or mildly increased levels of FSH, and generally lower than normal levels of DHT. HCG excitability test is optional for prepubertal patients.
2. Regular ultrasound to monitor testicular and breast development.
3. Chromosomal genetic examination.
Diagnosis
Confirmation is based on clinical manifestations and laboratory tests as well as chromosomal tests.
Treatment
Children diagnosed before puberty should have regular ultrasound to monitor testicular development, and the testicles should be removed after full breast development at puberty, followed by estrogen replacement therapy. Mold dilation is sometimes sufficient to enlarge and lengthen the vagina in cases of short vaginas, and if mold dilation fails, vaginoplasty is indicated.
Prognosis
The testes have a tendency to develop malignant tumors, with an incidence of 4% to 9% in adulthood.