An Atypical Presentation of Turner Syndrome in an Adolescent Female

Primary amenorrhea is defined by absence of menarche by age 13 in an adolescent who has normal growth and secondary sexual development or by age 15 in an adolescent with abnormal growth and secondary sexual development. When evaluating for primary amenorrhea one must consider three major systems that could be responsible for absence of menstruation. Uterine anatomic abnormalities such as an imperforate hymen, Mullerïan dysgenesis, vaginal agenesis, or a transverse vaginal septum. Neuroendocrine regulation via the hypothalamic-pituitary-ovarian (HPO) axis and adrenal synthesis pathways responsible for both the menstrual and uterine cycles could be involved and absence, underactivity, or overactivity in different checkpoints of this system may be the culprit. Hormonally responsive endometrial tissue which differentiates and sheds in the presence of the appropriate hormones if absent, as seen in Asherman syndrome, may be responsible. The most common cause of primary amenorrhea is Turner syndrome. Turner syndrome is a genetic disorder characterized by a 45,XO (monosomy), 46,XX/45,XO (mosaic), or 46,Xi,(Xq) (isochromosome) karyotype. Half of patients present with the monosomic form in which all cell lines are derived from a 45,XO cell lineage while most others present with mosaicism with at least 1 cell line being derived from a non-45,XO karyotype. A smaller subset of patients presents with an isochromosome or duplication of the long arm of the X chromosome. The pathogenesis of karyotype abnormalities in Turner syndrome commonly results from paternal meiotic nondisjunction in monosomy and mitotic errors in mosaicism. Isochromosome presentation can result from either meiotic or mitotic duplication of a long or short arm of the X chromosome, though most commonly the long arm. Not all patients will present with the same constellation of symptoms. In neonates the most common finding is edema of the hands and feet, though not always present. Turner syndrome is commonly diagnosed in adolescent patients presenting with post-pubertal height of less than 5ft. Consideration for diagnostic testing is supported by at least 2 of the somatic findings: short stature, metabolic abnormalities (overweight, hypertension), craniofacial abnormalities (high palate, micrognathia, prominent epicanthal folds, low-set ears), musculoskeletal abnormalities (osteoporosis, shield chest), dermatologic/lymphoreticular abnormalities (nail hypoplasia, pigmented moles, lymphedema, cutis laxa, keloids), cardiac abnormalities (coarctation of the aorta, bicuspid aortic valve), intellectual disability, intestinal telangiectasia, and deafness. Diagnostic imaging classically reveals streak ovaries, resulting from premature ovarian failure, and potentially other genitourinary abnormalities. Lab values typically reveal an elevated total gonadotropin level with an FSH of greater than 50mIU/mL and LH of greater than 90mIU/mL. Urinary estrogen is low due to insufficient ovarian production and lower filtered load. A 17-year-old nulligravid female presented to an obstetrician-gynecologist for evaluation of primary amenorrhea. She had never experienced a menstrual period, spotting, vaginal bleeding or discharge. Past medical history revealed headaches, recurrent otitis externa prompting 5 ear surgeries including myringotomies and cochlear implant placement. Family history was significant for short stature. On sexual history, the patient had never had sexual intercourse. Physical examination was negative for cervical and axillary lymphadenopathy. Pelvic examination revealed normal pubic hair distribution and external female genitalia. A pediatric speculum was inserted, though cervical examination proved difficult for this patient, thus examination was terminated early. Laboratory evaluation of TSH, free T3, free T4, anti-Mullerian hormone, testosterone, prolactin, luteinizing hormone, FSH, estradiol, DHEAS, and 17-hydroxyprogesterone and diagnostic imaging with a transabdominal ultrasound were planned. Transvaginal ultrasound of the internal pelvic organs was not preferred given the patients inability to tolerate pelvic examination. Laboratory values revealed an elevated TSH (5.36 IU/mL), free T3 (5.06 pg/mL) and FSH (27.1 mIU/mL) and low estradiol (<15 pg/mL), testosterone (11 ng/dL), and anti-Mullerian hormone (<0.03 ng/dL). Transabdominal ultrasound showed a small uterus, endometrial thickness of 3mm, and adnexa without separately identifiable ovaries. These findings suggest premature ovarian failure prompting genetic testing. A Mayo clinic CHCRB test for Chromosome Analysis, Congenital Disorders, Blood was ordered to assess for congenital chromosome abnormalities. Results showed 20 chromosomes in metaphase, 16 revealing monosomy (45,XO) and 4 showing disomic (46,X,r(X)) with a ringed X chromosome. These findings align with the mosaic form. This case highlights subtle findings that may prompt investigation for Turner syndrome in patients with primary amenorrhea. Though the only typical findings in this case were short stature (though positive in family history) and primary amenorrhea. The history of recurrent otitis media with subsequent hearing loss may represent maldevelopment of the cervical lymphatics. In many typical cases this abnormality may cause the constitutional webbed neck finding. Mosaicism represents a small subset of Turner syndrome patients, though identification proves important for support and management.