Primary Amenorrhea with Normal Breast Development: Müllerian Agenesis (Mayer-Rokitansky-Küster-Hauser Syndrome)
The most likely diagnosis is Müllerian syndrome (Mayer-Rokitansky-Küster-Hauser syndrome), as normal breast development indicates functioning ovaries with adequate estrogen production, ruling out gonadal and pituitary causes. 1
Diagnostic Reasoning
Why Normal Breast Development is the Key Finding
- Breast development requires estrogen from functioning ovaries, which means this patient has normal ovarian function and normal estrogen production 2
- Normal breast development excludes gonadal agenesis (option B) and pituitary hormone deficiency (option C), as both would result in absent or minimal breast development due to lack of estrogen 2, 1
- Pituitary deficiency causes low FSH/LH levels, low estradiol, and delayed or absent puberty with no breast development 1
- Gonadal agenesis (gonadal dysgenesis) causes elevated FSH/LH levels and absent secondary sexual characteristics including absent breast development 2
Why Müllerian Agenesis is the Answer
- Müllerian agenesis (MRKH syndrome) is the second most common cause of primary amenorrhea and presents with normal breast development and secondary sexual characteristics due to normal ovarian function 3, 4, 5
- The syndrome is characterized by congenital absence of the uterus, cervix, and upper two-thirds of the vagina in otherwise phenotypically normal 46,XX females with normal secondary sexual characteristics 3, 4
- It is critical to avoid assuming functional hypothalamic amenorrhea or PCOS in primary amenorrhea with normal breast development without first ruling out anatomic causes like Müllerian agenesis 1
Diagnostic Workup Required
Initial Assessment
- Pregnancy test must be performed first to rule out pregnancy 6
- Pelvic examination to assess for outflow tract obstruction is essential 6
- Physical examination should assess for normal secondary sexual characteristics, which would be present in MRKH 4
Imaging Studies
- Pelvic ultrasound is mandatory to evaluate uterine presence and anatomy 1, 6
- Magnetic resonance imaging (MRI) is the gold standard for confirming Müllerian agenesis, revealing complete uterine agenesis and vaginal abnormalities 4
- MRI can detect associated renal and skeletal abnormalities seen in MRKH type II 4
Laboratory Evaluation
- FSH, LH, estradiol, and testosterone levels should be measured and will be normal or low-normal with normal breast development 1
- Karyotype should be obtained to confirm 46,XX and exclude other chromosomal abnormalities 4
Clinical Subtypes and Associated Anomalies
- MRKH type I affects only the upper vagina, cervix, and uterus 3
- MRKH type II is associated with renal and skeletal malformations, including unilateral renal agenesis and vertebral anomalies 7, 3, 4
- The incidence is approximately 1 in 4,500-5,000 newborn females 3
Common Pitfalls to Avoid
- Do not assume functional hypothalamic amenorrhea in a patient with primary amenorrhea and normal breast development without imaging to exclude structural causes 1
- Do not overlook the need for pelvic ultrasound and potentially MRI, as these are essential to diagnose Müllerian agenesis 6, 4
- Recognize that most cases are sporadic, though familial cases suggest autosomal dominant inheritance with incomplete penetrance 3
Management Considerations
- Neovagina creation can be achieved through non-surgical methods (Frank's dilators) or surgical approaches (laparoscopic Vecchietti method) depending on initial vaginal length 5
- Psychological counseling and multidisciplinary support are important given the impact on fertility and sexual function 5
- Patients require evaluation for associated renal and skeletal abnormalities, particularly in MRKH type II 4