An Unusual Cause of Primary Amenorrhea

Background: Müllerian agenesis is the most common cause of primary amenorrhea in patients with typical thelarche and adrenarche. Most of the time, this diagnosis is made at the age of 10-13 years. Clinical Case: We present a case of a 18 year-old Vietnamese female who was referred to the endocrine clinic for primary amenorrhea. She stated that pubic hair developed at age 15 years. Patient is sexually active and uses condoms. She has 10 siblings (7 sisters, 3 brothers), 6 older sisters with menarche at ages 12-16 and a younger sister of 10 years old who has not yet had menarche. In addition, her older sister has 3 biological children and there was no reported infertility in her family. She stated that a pelvic ultrasound had been done at age of 17 years that showed no uterus. Oral contraceptives had been previously trialed and failed to induce withdrawal bleeding. HT 157.48 cm, WT 55.34 kg. The patient had a normal female phenotype with normal bilateral breast development, and no hirsutism. She was not concerned with this issue, which questioned her personality and coping skills. Laboratory testing-cortisol 13.0 ug/dL (5.3- 2.5), ACTH 29 pg/mL (0-47), estradiol 46.04 pg/mL), total testosterone 39 ng/dL (2-45), free testosterone 4.2 pg/mL (0.1-6.4), TSH 1.80 uIU/mL (0.358- .74), free T4 0.99 ng/dL(0.76- .46), FSH 4.4 mIU/mL (Follicular Phase:2.3 - 12.6, Midcycle Peak:5.2-17.5 mIU/mL, Luteal Phase:1.7-12.9 mIU/mL), Progesterone <0.5 ng/mL (follicular -less than 0.8 ng/ml, luteal=4.1- 3.7 ng/ml, mid-luteal= 4.5-25.2 ng/ml), LH 3.7 mIU/mL (follicular phase = 1.9-26.2 mIU/mL, Midcycle = 22.8 - 6.1 mIU/mL, Luteal phase = 0.6-16.6 mIU/mL). Transvaginal ultrasound-uterus not visualized; ovaries were unremarkable. DXA scan-normal Z scores. She refused to have a karyotype analysis. Differential diagnoses included müllerian agenesis, 5-alpha-reductase deficiency and complete androgen insensitivity syndrome. Unfortunately, our patient declined karyotype testing. Based on clinical presentation, which showed normal female genitalia, absence of uterus and normal laboratory finding, the most likely diagnosis was müllerian agenesis (Mayesr-Rokitansky-Kuster-Hauser syndrome). This syndrome has an incidence of 1/4,500-5,000 females and is caused is caused by embryologic underdevelopment of the müllerian duct, with resultant agenesis or atresia of the vagina, uterus, or both. Patients with müllerian agenesis usually are identified when they are evaluated for primary amenorrhea with otherwise typical growth and pubertal development, as in our patient. Psychosocial and genetic counseling, as well as offering options for pregnancy are important. In addition, certain personality traits, such as higher neuroticism, depression, and decreased coping styles may be observed. References: Obstetrics and Gynecology, Müllerian agenesis: Diagnosis, management, and treatment. Vol.131, NO.1, January 2018