Testicular feminization syndrome (TFS), also known as androgen insensitivity syndrome (AIS), is an X-linked recessive genetic disorder in which males have testes and are partially or completely feminized. TFS is the most common male pseudohermaphroditism, divided into complete and incomplete types, with complete type being the most common, and all four cases in this group were complete.
The four cases in this group are all complete. We are now discussing the pathogenesis, clinical manifestations, diagnosis and treatment of this disease, taking into account the four patients admitted to the Department of Urology of our hospital in the past year and the related literature.
1.Data and methods
1.1 Case data
The four patients in this group, aged 13-25 (average 19) years old. four cases are all female in social gender, presenting female appearance, and raised with female gender from childhood. All four cases were unmarried. Two patients presented with inguinal masses and two patients presented with primary amenorrhea.
On examination, all patients had no laryngeal nodes, fine skin, breast development, sparse pubic and axillary hair, and tough, chicken egg-sized masses were palpated in the inguinal region bilaterally. Female vulvar manifestations; there was a vagina, which was blind-ended.
1.1.1. Auxiliary examination: ultrasound: there was no uterus, ovaries and fallopian tubes, and oval hypoechoic areas were palpated in the bilateral inguinal walkways.
1.1.2. Cytogenetic examination: karyotype diagnosis: 46, XY and SRY genes were positive.
1.1.3. Sex hormone examination: serum testosterone (Testosterone, T) was 7.29-29.11 pmol/L in four cases (the normal value of our hospital was 0.77-33.03 pmol/L), and estrogen examination was within the normal range of female hormones.
1.2 Treatment and results
All four patients in this group underwent surgical treatment under continuous epidural anesthesia after admission, and an inguinal incision was made, and the swelling was seen to be smooth with an intact envelope, which was testicular tissue. After surgery, estrogen and auxiliary psychotherapy were given appropriately, and the patients recovered well.
2. Discussion
2.1, Etiology.
TFS is the most common male pseudohermaphroditism, which is an X-linked recessive genetic disorder. The patient’s karyotype is 46, XY, and the testis determine gene (TDG) is located on the short arm of Y chromosome, which controls the synthesis of cytosolic histocompatibility Y antigen, causing the embryonic gonads to develop into testes and secrete androgens and paramedian tubular hormones. The development of secondary sexual characteristics in the male organism depends on androgens synthesized by the testes and their interaction with receptors in order to exert their biological effects.
The androgen receptor is an intracellular protein (encoded by the Tfm gene) and is a member of the steroid hormone superfamily, which must bind to specific receptors in target tissues to produce biological effects. Androgens depend on androgen receptors within the body, and without them, even if sufficient androgens are available, they cannot function and produce normal physiological effects, i.e., they affect the process of embryonic masculinization.
Testicular development secretes sufficient amounts of paramedian tubular degeneration factor since the embryonic stage, which inhibits the development of paramedian tubules into female reproductive organs, such as uterus and ovaries. The androgen secretion is normal or higher than normal, but the Tfm gene mutation causes the absence or reduction of androgen receptors, so that the paramedian tubules cannot develop into male reproductive organs such as epididymis, so the external genitalia appear feminized.
2.2. Clinical manifestations.
Patients have a female phenotype with puberty slightly earlier than normal males and close to normal females. Some patients have a height between the average height of normal males and females, with longer limbs and larger hands and feet. Patients with the complete phenotype have normal breast development, but the areola is pale and dysplastic, and the pubic and axillary hairs are sparse, which may not be noticed by the patient and his family.
The main difference between the incomplete type and the complete type is the partial defect of androgen receptors, the presence of androgen biological effects in the body, and the presence of different degrees of masculinization of the external genitalia, such as clitoral enlargement and hypospadias.
The serum hormone levels of patients are age-related. A physiological peak of luteinizing hormone (LH) and testosterone occurs at 6-8 weeks in normal male infants, but there is no such peak in patients with testicular feminization, and testosterone and gonadotropin are normal before puberty; after puberty, gonadotropin rises and testosterone reaches normal levels or higher. Conversion to large amounts of estradiol in the peripheral tissues, the absence of androgen action and the increase of estrogen lead to feminization of the patient’s physical appearance, and the female body shape is obvious after puberty, including breast development.
2.3. Diagnosis.
Most patients present with the finding of bilateral inguinal goiter swellings or amenorrhea as the main complaint, and should be admitted to the hospital with the aid of relevant tests to determine whether the syndrome is testicular feminization. The main diagnosis of the disease relies on the patient’s history, signs and chromosomal examination. If the patient has a karyotype of 46, XY, palpable swelling in the inguinal walkway area and on examination: the vagina is blind-ended, the diagnosis of the disease should be considered.
The diagnosis should also exclude other types of male pseudohermaphroditism, such as: LH receptor abnormalities, testosterone synthesis disorders, 5α-reductase abnormalities, and masculinization due to adrenal hyperplasia. To clarify the diagnosis, molecular biology techniques can be used to identify whether the androgen receptor gene is normal.
2.4. Treatment.
The treatment of TFS should take into account the patient’s gender, endocrine status, external genital orthopedic trend and other related issues to determine the treatment plan comprehensively.
2.4.1 Gender selection
During the patient’s growth, social gender is more practical than biological gender, and changing the patient’s social gender may cause serious psychiatric consequences and social problems. Therefore, the selection of the patient’s social gender during infancy is crucial and should be decided under the guidance of a physician, based on the patient’s vulvar phenotype and the correctable trend of surgery.
2.4.2 Gonadectomy
The greatest complication of TFS is the ectopic testis and the damage it causes, and most scholars now believe that both testes should be removed, especially in those who choose the female gender. Testicular malignancy is rare until the end of puberty, and the testes can cause secondary female sexual characteristics during this period, so surgery can be performed after puberty is well developed [7]. testicular malignancy is rare until the age of 20 years, but the rate of malignancy increases gradually afterwards, and about 20-30% of testes in TFS patients eventually develop tumors.
Reference criteria for early removal of the testis in complete patients.
①The testis descends into the groin or labia to form a hernia;
②Patients and their family members have abnormal fear of testicular malignancy;
(3) Patients and family members cannot accept the presence of testes in female phenotype patients. Incomplete patients, the rate of testicular malignancy is higher than that of complete patients, and the patients will develop masculinization during puberty. In order to avoid the trend of masculinization and the psychological barriers caused by hermaphroditism, the timing of surgery should be before puberty.
2.4.3 Vulvar reconstruction
In patients with this disease, the external genitalia should be reconstructed to conform to the dependent sex. Patients with the complete form of the disease, who are female, do not need vulvoplasty. Incomplete patients with varying degrees of vulvar deformity should undergo appropriate reconstructive surgery according to the patient’s physical appearance in order to keep the patient in a good frame of mind and close to the physiological characteristics of the dependent sex. Vaginal dilatation may be performed in cases of short vagina. For those who choose male as the dependent gender, cryptorchidism surgery and penile orthopedic surgery should be performed.
2.4.4 Hormone therapy
After orchiectomy, most patients should be treated with estrogen supplementation to maintain female secondary sexual characteristics and to prevent the corresponding complications of estrogen deficiency, usually in small continuous doses. Estrogen promotes the deposition of calcium in bone and can cause epiphyseal closure under the influence of estrogen, and should not be supplemented prematurely if the patient is young.
2.4.5 Psychological treatment
Patients may out loneliness, depression, pessimism, anxiety and other psychological reactions due to congenital physical defects. Health care personnel should take appropriate psychological interventions to improve the quality of life of patients.
The following interventions can be taken.
1.Protect the patient’s self-esteem.
2. Provide coping skills to reduce emotional reactions.