A 16 years old female with normal pubic hairs and breast presented with primary amenorrhea. On examination, there was blind vagina and absent uterus. Diagnosis is:
47, XYY
Gonadal dysgenesis
Mullerian agenesis
45, XO
Ans. c. Mullerian agenesis (Ref: Shows 14/e p81-83)A 16 years old female with normal pubic hairs and breast presented with primary amenorrhea, with blind vagina and absent uterus. Diagnosis in this case is Mullerian agenesis.Evaluation of Primary Amenorrhea:Primary amenorrhea is evaluated most efficiently by focusing on the presence or absence of:1. Breast Development: It is a marker of estrogen action and therefore function of the ovary2. Presence or absence of uterus: As determined by ultrasound or in more complex cases by MRIEvaluation of Primary AmenorrheaBreast Development:Breast development and other secondary sexual characters are markers of estrogen action and therefore function of the ovaryPresence of breast and other secondary sexual features indicate normal estrogen level and normally functioning ovaryAbsence of Breast:Absence of breast indicates reduced estrogen levelThe cause of reduced estrogen level is then determined by measuring FSHIncreased serum FSH and absent breast indicates primary ovarian failure. This is mostly caused by 'Gondal Dysgenesis' (Turner's syndrome). Elevated FSH is due to absence of ovarian oocytes and follicles leading to reduction in negative feedback on FSH from estradiol and inhibins A and B.Absent breast with decreased serum FSH indicates primary amenorrhea due to hypothalamic or pituitary causes.Presence or absence of uterusFurther testing for a women with primary amenorrhea depends upon the findings on physical examination in particular whether mullerian structures are present or absent (Mullerian structures: Cervix, uterus, vagina, ovarian tube)The single most important step in the evaluation of primary amenorrhea depends upon the findings on physical examination or ultrasonography, whether there are any anatomic abnormalities of the vagina, cervix or uterus.Absence of Uterus:Absence of uterus usually means that Mullerian inhibitory substance was secreted at the time of Wolffian duct development.Mullerian inhibiting substance is usually secreted from the sertoli cells of the testis and it inhibits the development. Wolffian duct or Mullerian duct structures.Absence of uterus suggests presence of MIS and is likely evidence of the presence of testis.For those with absence of the uterus, further evaluation should include a karyotype measurement and measurement of serum testosterone.These tests allow the clinician to distinguish between abnormal Mullerian development and androgen insensitivity syndrome.Absence of Uterus:For patients with normal Mullerian structures and no evidence of an imperforate hymen, vaginal septum, or congenital absence of vagina, an endocrine evaluation should be performed.This includes measurement of serum beta human chorionic gonadotropin to exclude pregnancy and of serum FSH and other hormones.A high serum FSH concentration is indicative of primary ovarian failure.A karyotype is then required to detect the presence of Turner's syndromeTurner's syndrome is characterized by the complete or partial deletion of X chromosome.In addition, evaluation for other diseases associated with specific type of ovarian failure should be performed.Low or normal FSH suggests functional hypothalamic amenorrhea, congenital GnPH deficiency or other disorders of hypothalamic pituitary axis.Serum prolactin is measured if galactorrhoea is present.If there are signs of hyperandrogenism, serum ketosterone and dehydroepiandrosterone sulfate (DHEAS) should be measured.
Genital Differentiation