Which type of abnormality in sexual development has best prognosis?
Ans. a. Congenital adrenal hyperplasia (Ref: Navak's 15/e p1029. 14/e p1023-1026)Congenital adrenal hyperplasia is a type of abnormality in sexual development, which has best prognosis.'Congenital adrenal hyperplasia can be managed by supplying enough glucocorticoids to suppress excess androgen production. The deformity in genitalia (enlarged clitoris, fusion of labia minora) can be corrected surgically. Newborn screening methods to detect CAH and efforts to treat CAH in utero have improved the prognosis. Women with CAH can get pregnant and have healthy infants.'21-Hydroxylase Deficiency (Congenital Adrenal Hyperplasia)The classic form of 21 -hydroxylase deficiency (21-OHD) is the most common cause of CAH.It has an incidence between 1 in 10.000 and 1 in 15,000 and is the most common cause of androgenization in chromosomal 46,XX females.Affected individuals are homozygous or compound heterozygous for severe mutations in the enzyme 21-hydroxylase (CYP21A2).This mutation causes a block in adrenal glucocorticoid and mineralocorticoid synthesis, increasing 17-hydroxyprogesterone and shunting steroid precursors into the androgen synthesis pathwayQ.Increased androgen synthesis in utero causes androgenization of the female fetus in the first trimesterQ.Ambiguous genitalia are seen at birth, with varying degrees of clitoral enlargement and labial fusionQ.Excess androgen production causes gonadotropin-independent precocious puberty in males with 21-OHDQ.Presymptomatic diagnosis of classic 21-OHD is now made by neonatal screening tests forincreased 17-hydroxy progesteroneQ in many centers.Treatment: Congenital Adrenal Hyperplasia:Acute salt-wasting crises require fluid resuscitation, IV hydrocortisone, and correction of hypoglycemia.Once the patient is stabilized, glucocorticoids must be given to correct the cortisol insufficiency and suppress ACTH stimulation, thereby preventing further virilization, rapid skeletal maturation, and the development of polycystic ovariesQ.Girls with significant genital androgenization due to classic 21-OHD usually undergo vaginal reconstruction and clitoral reductionQ (maintaining the glans and nerve supply).Androgen insensitivity syndrome (AIS):A condition that results in the partial or complete inability of the cell to respond to androgensQ.The unresponsiveness of the cell to the presence of androgenic hormones can impair or prevent the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does not significantly impair female genital or sexual developmentQ.As such, the insensitivity to androgens is clinically significant only when it occurs in genetic malesQ (i.e. individuals with a Y-chromosome, or more specifically, an SRY gene).Clinical phenotypes in these individuals range from a normal male habitus with mild spermatogenic defect or reduced secondary- terminal hair, to a full female habitus, despite the presence of a Y-chromosome.Androgen insensitivity syndrome is the largest single entity that leads to 46, XY undermasculinized genitaliaQ.Management of AIS is currently limited to symptomatic management; no method is currently available to correct the malfunctioning androgen receptor proteins produced by AR gene mutationsQ.Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, genetic counseling, and psychological counseling.Mixed Gonadal Dysgenesis:A condition of unusual and asymmetrical gonadal development leading to an unassigned sex differentiation.A number of differences have been reported in the karyotype, most commonly a mosaicism 45, X/ 46, XY.The phenotypical expression may be ambiguous, intersex, or male, or female pending the extent of the mosaicism.It has been pointed out that the gonads may not be symmetrical, thus the development of the Mullerian duct and Wolffian duct may be asymmetrical, too.Because of the presence of dysgenetic gonadal tissue and Y chromosome material, there is a high risk of the development of a gonadoblastoma, thus removal of the gonads is usually indicated.True hermaphroditism:A medical term for an intersex condition in which an individual is born with ovarian and testicular tissue.There may be an ovary underneath one testicle or the other, but more commonly one or both gonads is an ovotestis containing both types of tissue.There are no documented cases in which both types of gonadal tissue function.Encountered karyotypes are 47XXY, 46XX/46XY, or 46XX/47XXY, and various degrees of mosaicism.There has yet to be a documented case where both gonadal tissues function (Bad reproductive potential); contrary to rumors of hermaphrodites being able to impregnate themselves.
Congenital adrenal hyperplasia
Mixed gonadal dysgenesis
Androgen insensitivity syndrome
True hermaphroditism
Sex Intersexuality