Congenital Adrenal HyperplasiaIn a female most common cause of ambiguous sex is congenital adrenal hyperplasia.
- Infact cases of ambiguity of sex, detected at birth are due to adrenogenital syndrome (congenital adrenal hyperplasia) unless proved otherwise.
- It is an autosomal recessives disorder (if any couple has had one affected child, subsequent baby has 1 in 4 chance of having the same disability).
A point worth nothing is that development of the internal genitalia (i.e mullerian duct and its derivatives) is normal in females with classical CAH because the excess androgen is derived from adrenals and the ovaries are normal so they produce neither antimullerian hormone nor significant amount of androgen.
Physical Characteristics in Females
- Genotype = 46XX
- Gonads = ovaries
- Uterus and vagina are present, as mullerian duct develops normally, but remain infantile therefore failure to menstruates.
- Vulva and introitus are affected. There is clitoromegaly? and the genital folds fuse to form penile urethra rather than labia minora.? Labia majora are fused which appears like scrotum.
- Heterosexual precocious pubertyv: Pubic hair and axillary hair appear and voice deepens by the age of 2-4 years", (since these characteristics are dependent on androgen).
- Associated metabolic abnormalities (d/t decreased aldosterone): Hyponatremia-, hyperkalemiav and hypotension-'.
- USG: shows presence of uterus, vagina, fallopian tubes and ovariesv. (Thus, all patients are pontentially fertile)
- Sex chromatin study: shows positive Barr bodyQ. (Note- whenever a child presents with ambigious genitalia always do karyotyping)
- Serum 17 hydroxy progesterone is elevated (> 800ng/ dl)Q and serum 17-ketosteroid is elevated.
- Level of serum 170HP < 200 ng/ dl virtually rules out the diagnosis of CAH.
- Serum electrolyte studies show salt wastingv.
- Treatment of CAH is aimed at providing sufficient amounts of the deficient hormone, cortisol, to reduce excessive ACTH secretion and to prevent consequences of excessive androgen production.
- DOC is dexamethasone in mothers at risk for having an affected child.
- Dexamethasone should be given to prevent fetal female genital virilisation as dexamethasone is not metabolized by placenta and crosses effectively into fetal circulation.
- Level of serum 170HP < 200 ng/ dl, virtually rules out the diagnosis of CAH.
- For maximum benefit-treatment should begin at 4 to 5 weeks of gestation and not later than 8 weeks
- In younger infants the initial dose of dexamethasone is about 25mg/ day, and in adults 100mg/ day
- In newborn with CAH with defect in electrolyte regulation, it is usually necessary to administer NaCl in amounts of 4-6gm/ day either orally or parenterally in addition to cortisone.
Besides this: -
Phallus should be removed surgically (by age of 5 years).
Me Indoe's vaginoplasty should be done.
Testicular Feminisation Syndrome
- Most common form of male pseudohermaphroditism
- Genotype 46XyQ so gonads will be testis, but testis are found intra abdominalf
There is resistance to androgen.
- Since mullerian inhibiting factor is 'normal in these males mullerian duct regresses so uterus, cervix and vagina are not present and obviously they will not menstruate. These males who are being reared up like females, at puberty have proper breast development and are brought with complain of primary amenorrhea.
- The male baby who is reared like a girl grows tall and attractive with normal breast development (Tanner stage 4)
- No uterus (therefore Primary amenorrheajv and a short vagina
- Scanty pubic and axillary hair?
- Smooth and hairless skinv
- Testosterone levels can be low, normal or high
- LH level is high due to insensitivity of pituitary and hypothalamus to testosterone. Q
- Gonadal biopsy can confirm the diagnosis.
- Seminiferous tubules are small and hyalinized.
- Spermatogenesis is absent.
- Leydig cells and sertoli cells are normal,
Let them be Females
- The testis should be removed after puberty Q(16-18 years) as they have a high potential for malignant change, specially gonadoblastoma and dysgerminoma.
- Bilaterallaparoscopic gonadectomy is the preferred procedure for removal of intra-abdominal testes.
- Estrogen therapy is desirable to prevent osteoporosis.P since when testis are removed the source of testosterone and in turn estroges is also gone.
- Vaginoplasty should be done just before or after marriage.
Klinefelter Syndrome (47XXY)
- The classic form of Klinefelter syndrome (47 XXY) occurs following meiotic nondisjunction of the sex chromosomes during gametogenesis (40% during spermatogenisis, 60% during oogenesis)
- Klinefelter syndrome (KS) is the Mj C cause of primary testicular failure affecting 1 in 1000 males
In addition to these, men with KS exhibit a number of psychosocial abnormalities like.
- Lack of insight
- Poor judgement
- Difficulty with complex speech
- Decreased attention span
In adult life, such males have increased risk of
- Pulmonary diseases
- Mediastinal germ cell tumor
- Antisocial mental disorder
- Breast CA
- Varicose legs
- Diabetes mellitus
Tesicular biopsy shows hyalinised seminifeous tubules and hyperplastic leydig cells.
Pituitary hormones (FSH, LH) are increased and testosterone levels are redused