Diagnosis of disorders of sexual development

The main principle of diagnostic studies for congenital pathology of sexual development is to determine the anatomical and functional state of all links that make up the concept of sex.

Examination of the genitals. At birth, the doctor determines the sex of the child based on the structure of the external genitalia ("obstetric sex"). In case of gonadal agenesis and complete testicular feminization, the structure of the external genitalia is always female, so the question of choosing the female civil sex is decided unambiguously, despite the genetic and gonadal sex, which in the latter case will be male. In case of testicular feminization syndrome, the diagnosis can in some cases be established at prepubertal age in the presence of testicles in the "large labia" or inguinal hernias. Palpation of the extra-abdominal testicles allows us to determine their size, consistency, and to assume the possibility of tumor changes.

In abdominal cryptorchidism in boys and severe forms of congenital dysfunction of the adrenal cortex in children with female genetic and gonadal sex, the structure of the penis may be normal, which often leads to an erroneous assessment of a newborn girl as a boy with cryptorchidism. In Klinefelter syndrome, the structure of the external genitalia at birth is normal male, which does not allow a diagnosis to be made based on a routine examination. Intersexual structure of the external genitalia in a newborn requires a more in-depth examination to establish the form of pathology and select the sex. Probing of the vagina (urogenital sinus) allows us to identify its absence or sharp shortening in testicular feminization syndrome and incomplete masculinization. Probing of the vagina is necessary in all cases of primary amenorrhea to exclude its aplasia. Rectal digital examination allows to establish the presence and size of the uterus, which is determined in case of agenesis and dysgenesis of the gonads, as well as congenital dysfunction of the adrenal cortex in girls and absent in case of incomplete masculinization and testicular feminization. Ultrasound examination allows to clarify the condition of the uterus and gonads.

Somatic examination includes identification of characteristic signs of development of the skeleton, muscular system, and fatty tissue. Already at birth, examination allows identifying characteristic signs of Shereshevsky-Turner syndrome (short stature, pterygoid skin folds of the neck, shortening of the IV-V metacarpal and metatarsal bones, swelling (lymphostasis) of the extremities, etc.).

Tall stature in puberty with the formation of eunuchoid proportions of the skeleton is one of the signs of hypogonadism. On the contrary, with early saturation of the child's body with an inadequately large amount of sex hormones, a characteristic skeletal structure is formed: shortening of the tubular bones of the limbs creates the impression of "chondrodystrophic" proportions. Such a skeletal structure is characteristic of congenital dysfunction of the adrenal cortex. In puberty, the nature of the development of secondary sexual characteristics is of particular importance. Early manifestation of male sexual characteristics with an indefinite structure of the external genitalia confirms the diagnosis of congenital dysfunction of the adrenal cortex in a girl. The absence of sexual hair growth and menstruation with the timely development of the mammary glands and feminine features of the figure is characteristic of testicular feminization syndrome. Insufficient pubic hair growth in false male hermaphroditism indicates the degree of insufficiency of the androgenic function of the testicles (or tissue insensitivity to androgens). Development of mammary glands in boys is common in Klinefelter syndrome. It should be remembered that some forms of congenital pathology of sexual development are accompanied by characteristic malformations of internal organs. Thus, in testicular feminization syndrome, there are developmental anomalies of the kidneys and ureters, in Shereshevsky-Turner syndrome - congenital malformations of the heart and blood vessels, kidneys.

The absence of gonads in agenesis or their insufficiency in dysgenesis already from puberty, according to the principle of "feedback", causes activation of the hypothalamic-pituitary system, which often leads to the development of hypothalamic pathology of the type of "castration syndrome" (vegetative-vascular dystonia, metabolic disorders, trophism). Therefore, such patients require systematic monitoring of fluctuations in blood pressure, body weight, signs of the appearance of dystrophic "striae" on the skin. If necessary, an electroencephalographic study is prescribed. Normalization of the hypothalamic-pituitary system is an indirect indicator of compensation for the deficiency of sex hormones.

Genetic testing is necessary, and in the neonatal period it is one of the main diagnostic methods. The introduction of sex chromatin (SC) determination in practice for all newborns will allow to identify such diseases as Klinefelter syndrome, pure gonadal agenesis with male genetic sex, testicular feminization syndrome, Shereshevsky-Turner syndrome already at birth, and will allow to differentiate congenital dysfunction of the adrenal cortex and idiopathic intrauterine virilization of the external genitalia in girls (positive SC) from abdominal cryptorchidism in boys and forms of false male hermaphroditism (negative SC). The study of Y-chromatin by the fluorescent method makes it possible to detect the presence of the Y-chromosome, which is especially important for resolving the issue of removing the rudiments of the intraperitoneally located gonads in patients with Shereshevsky-Turner syndrome (mosaic form) and "pure" agenesis of the gonads, since their rudiments in patients with the XY karyotype are especially dangerous in terms of oncology. In doubtful cases, it is necessary to determine the chromosome set (karyotype).

X-ray and ultrasound examination. Dynamic X-ray of the hands with wrist joints allows monitoring the rate of skeletal maturation and assessing the adequacy of replacement therapy, and also reveals characteristic anomalies in skeletal development (shortening of the metacarpal bones, Madelung's deformity, etc.). X-ray of the skull and sella turcica allows characterizing the condition of the pituitary gland, identifying endocraniosis or symptoms of increased intracranial pressure, osteoporosis of the skull bones. X-ray contrast methods (pneumopelvigraphy, sinus-vaginography, intravenous pyelography) are necessary to clarify the condition of the genitals and exclude concomitant malformations of the urinary system. At the same time, ultrasound examination is also highly informative.

Hormonal examination of the content of 17-ketosteroids (17-KS) and 17-hydroxycorticosteroids (17-OCS), 17-hydroxyprogesterone (17-OP) is necessary if congenital dysfunction of the adrenal cortex is suspected: an increased level of 17-KS and 11-OP with a normal or reduced content of 17-OCS speaks in favor of this pathology. A test with suppression of the function of the adrenal cortex with dexamethasone and simultaneous stimulation of the gonads with chorionic gonadotropin allows us to determine their source (adrenal or gonadal), assess the ability of the gonads to respond to stimulation, and provides certain information for the diagnosis of tumor processes in the adrenal glands or gonads. The functional activity of the latter is characterized by the results of a study of testosterone and estradiol.

The study of gonadotropins (LH and FSH in the blood and/or urine) allows to differentiate hypo- and hypergonadotropic hypogonadism from primary gonadal lesions (agenesis, dysgenesis). In puberty and post-puberty, an increase in the level of gonadotropic hormones, especially FSH, is typical.

Histological examination of the gonads is the final stage of the examination. It is necessary to exclude tumor changes in the gonads, which are often found in congenital pathology of sexual development. This is especially important when identifying the Y chromosome in patients with "pure" agenesis of the gonads, with Shereshevsky-Turner syndromes and gonadal bisexuality, as well as with all forms of false male hermaphroditism with intraperitoneal location of the gonads. In addition, it gives a clear idea of the prognosis of the functional activity of the gonad.

Differential diagnostics of disorders of sexual development

Differential diagnostics of Shereshevsky-Turner syndrome is carried out with a phenotypically similar Noonan syndrome, described in 1963, which usually occurs without gross chromosomal abnormalities. Noonan syndrome occurs in patients of both sexes. The characteristic symptom complex in male patients was previously called Shereshevsky-Turner syndrome in men. It is assumed that the disease is caused by an autosomal gene mutation transmitted in a dominant way. There are observations of familial forms of the disease in several generations, in particular with transmission through the male line. Noonan syndrome is characterized by all the anomalies of somatic development observed in Shereshevsky-Turner syndrome, however, sexual development is not impaired in most patients. Sometimes fertility may be preserved. Some patients have a karyotype of 46,XX/45,X or 46,XY/45,X, sometimes - a deletion of the short arm of the X chromosome. This is accompanied by manifestations of ovarian or testicular dysgenesis of varying severity, cryptorchidism, etc.

Turner syndrome must also be differentiated from the “Turneroid” form of testicular dysgenesis syndrome by the presence of a normal male karyotype or 46,XY/45,X mosaicism (which is rare in Turner syndrome), satisfactory development of the testicles and, as a rule, more pronounced masculinization of the external genitalia.

"Pure" gonadal agenesis is differentiated from hypogonadotropic hypogonadism by the level of gonadotropins (elevated in the first and decreased in the second form of pathology), from the eunuchoid form of testicular dysgenesis syndrome and incomplete masculinization by satisfactory development of the testicles, and from the syndrome of incomplete masculinization - also by the absence of Müllerian derivatives in the latter.

The main method of diagnosis and differential diagnosis of true hermaphroditism - the rarest form of pathology of sexual development - is histological evidence of gonadal bisexuality.

Differential diagnostics of incomplete masculinization syndrome is carried out with testicular dysgenesis syndrome and congenital dysfunction of the adrenal cortex. Unlike testicular dysgenesis syndrome, in incomplete masculinization syndrome the uterus is absent, the vagina is a shortened blind sac. Unlike congenital dysfunction of the adrenal cortex in girls, patients with incomplete masculinization syndrome have negative sex chromatin, do not have a uterus and ovaries, and in puberty their bone age is not ahead of the actual age, but behind it, and they develop male secondary sexual characteristics.

Differential diagnostics of testicular feminization syndrome should be carried out with incomplete masculinization syndrome, testicular dysgenesis syndrome and congenital aplasia of the vagina and uterus (Rokitansky-Küster-Meyer syndrome). In prepuberty, it is clinically impossible to distinguish the first two syndromes from each other. However, in puberty, unlike incomplete masculinization syndrome, testicular feminization is characterized by spontaneous development of the mammary glands. The main differential diagnostic sign from testicular dysgenesis syndrome is the absence of the uterus. In Rokitansky-Küster-Meyer syndrome, the vagina and uterus are absent, female secondary sexual characteristics develop spontaneously in a timely manner, there is positive sex chromatin and normal ovaries.

Idiopathic congenital virilization of the external genitalia must be differentiated from congenital dysfunction of the adrenal cortex in girls: in both cases, the genetic, gonadal sex and internal genitalia are female, while the external genitalia are gender-indeterminate. Only hormonal diagnostics (excess adrenal androgens, 11-OP, increased levels of 17-KS in urine) and, in older age, accelerated skeletal maturation and premature sexual development of the heterosexual (male) type allow differential diagnosis.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ]