Rokitansky-Kuster-Hauser Syndrome (Inadequate Mullerian Development)


Question

I am an endocrinology intern form india,this my second case to the ask the expert section.firstly i would thank u for the advice given for the last case.

The case is 18/F, h/o primary amenorrhoea, Fourth child of a nonconsanguinus marriage,family history- Elder sister had periods at 16 yrs, normal pernatal events,normal developmental milestones,normal intelligence.No history of growth spurt but was growing normally. Thelarche at 12 yrs and pubarche at 14 yrs.No history of virilization at pubertal age.Normal prenatal events.Normal developmental milestones.Normal intelligence. No history of growth spurt but was growing nornally.Thelarche at 12 yrs and pubarche at 14 yrs.No history of virilization at pubertal age.No history of inguinal hernia.H/O infertility in paternal aunt. No history of acne,hirsutism.No history of maternal abortions or neonatal deaths.No history of short stature.

H/o attempted withdrawal to progesterone : no bleeding,. Mother's height: 158 cm. Father is short. Height : 153cm Weight : 48.5kg Height is at 5 th centile.Upper segment : 74 cm Lower segment: 78 cm. Arm span : 153 cm

Thyroid:Normal. Other findings:Smell normal. Pubic hair stage 4, Breast stage 4 Axillary hair has been shaved off.

Local Examination : Labia Majora - normal, labia minora - fused together. Small blind vagianal opening / pouch. P/R - could not get Uterus. Systems :Normal

Investigations: TSH/FT4,PROLACTIN,-NORMAL LEVELS. Testosterone; total 0.097 (ng/ml)(F-< 0.1). FSH-2.43 (mIU/ml)(1-8). LH-<0.1(mIU/ml). Estradiol 154.8 pg/ml. Sonogram of pelvis: Uterus Measures 32.6x8.2mm (CC x AP). Endometrium not visualised. Bilateral ovaries :Not visualised. No obvious pelvic mass seen. : Hypoplastic uterus.No obvious pelvic mass

The question is how to further proceed about the case? any further investigations? management? Arun Kannan:, India < mailto:drarunkannan@gmail.com >

Response

This 18 year old has genital outflow tract obstruction and perhaps uterine abnormalities and probably represents a variant of Rokitansky-Kuster-Hauser Syndrome. The workup of this patients indicates:

1. Normal progression of pubertal events including thelarche and adrenarche.

2. Adequate growth given the history of short stature in the father.

3. Normal thyroid and prolactin function.

4. Low or normal FSH with ovulatory levels of estradiol.

5. Failure to withdraw bleed with progesterone due to no endometrial compartment.

Thus, this individual has proceeded through puberty, has adequate secondary sex characteristics that are estrogen driven, has a normal XX karyotype but is unable to respond to estrogens due to inadequate development of the Mullerian system and the upper parts of the vagina with a blind vaginal pouch.

To complete her workup, I would probably perform a transrectal ultrasound which may provide further anatomic details such as an absence of a cervix and no endometrium and the presence of ovaries (I disagree that there are absent ovaries since the estradiol levels are too high for peripheral conversion of estradiol).

She can be treated with vaginal dilators to achieve a functional vagina using the approach proposed by Frank.

James H. Liu, M.D. Case School of Medicine, Cleveland, OH

Detecting Ovulation by Progesterone Level


Question

Traditionally (often a euphemism for "We've always done it though we don't have the evidence") serum progesterone has been used in the UK to assess the likelihood of ovulation having occurred on day 21 of a day 28 day cycle (or 7 days before next period if cycle >28 days). A cut-off of >30 nmol/L ( = 943 ng/dL) is quoted as indicating a likely ovulatory cycle by some. My own response has been that this indicates "evidence of adequate luteal activity".

My understanding of the events leading to ovulation is that an ovarian follicle matures, and that if ovulation occurs, a corpus luteum develops which is responsible for progesterone production. If pregnancy ensues, the placenta takes over. If fertilisation does not occur, the CL regresses and progesterone falls.

I therefore have a question as follows:

If a serum progesterone is measured on day 21, and the result is <30 nmol/L, but, say, in double figures - 10-15 nmol/L - the UK perspcetive in many quarters would be that ovulation had not occurred. However, that being the case, where is the progesterone coming from ? Is it the case that ovulation has occurred but that the ovum is produced, is non-viable with rapid "failure" ensuing, and thus a brief burst of progesterone occurs but which peaks below 30 nmol/L ? Philip Hyde, Pilgrim Hospital, Lincolnshire, United Kingdom

Response

Progesterone is produced from both the adrenal gland and the corpus lutuem. Progesterone production from the adrenal gland is fairly stable and contributes approximately 1-1.5 ng/mL when measured in the serum of women during the follicular phase. Following ovulation, there is increasing production of progesterone from the corpus luteum and the progesterone levels gradually rises from a baseline of 1.5 to 3 ng/mL by the first day after ovulation. Levels then continue to rise until it reaches a peak 7 days after ovulation reaching levels of approximately 10-20 ng/mL. Levels of progesterone are secreted in a pulsatile pattern during the luteal phase and thus levels can vary depending on the timing of the blood draw. (See Filicori et al. J Clin Invest 1984;73(6):1638-47).

In this case, where progesterone is lower than the normal D21 peak probably suggests that the timing of the blood draw was either 3 or 4 days before the peak (i.e. the ovulation was occurring later) or 3 or 4 days after the peak ( i.e. the ovulation was occurring earlier). In the U.S. a level of 4 ng/mL is considered ovulatory. However, the most reliable clinical indicator for ovulation is regular menstrual cycles between 25-35 day intervals. Thus, reproductive endocrinologists seldom measure progesterone levels to confirm ovulation. James H. Liu, M.D. Case School of Medicine