Session: SAT 498-531-Female Repro Endocrinology & Case Reports
Poster Board SAT-499
Clinical Case: A 19-year-old female presented with primary amenorrhea. Thelarche and pubarche had occurred at age 13. She had dysarthria since childhood, and absence of the mandibular second bicuspids and two supernumerary teeth under her secondary mandibular incisors. On examination, she had Tanner stage 5 breast and pubic hair development. Neurological evaluation revealed nystagmus, a mildly ataxic gait, and mild spasticity of the upper limbs.
Laboratory investigations included: LH <1 (1-13 IU/L), FSH 5 (2-10 IU/L), estradiol 62 (Prepubertal range: 0-130 pmol/L), prolactin 25 (0-25 ug/L), and Free T4 14.9 (8.0-22.0 pmol/L). She did not menstruate after a progesterone challenge, but did with the oral contraceptive. Pelvic ultrasound showed a small uterus. MRI of the sella revealed mildly decreased pituitary bulk, and diffuse hypomyelination with cerebellar hypoplasia. 4H syndrome was diagnosed. Subsequent DNA sequencing revealed that the patient is compound heterozygous for POLR3B mutations.
She later wished to become pregnant and failed to show any biochemical or radiological response to pulsatile GnRH, but achieved normal follicular growth and ovulation with subcutaneous gonadotropin therapy.
Clinical Lesson: Patients with 4H syndrome might initially present with hypogonadotrophic hypogonadism, particularly if their neurological and dental manifestations are subtle. Our results indicate that ovulation induction in women with 4H syndrome can be achieved with subcutaneous gonadotropin therapy, but not with pulsatile GnRH. Given this patient’s known POLR3B mutations, we suggest that the hypogonadotrophic hypogonadism in 4H syndrome may be a result of defective translation of the GnRH receptor protein. This is now undergoing characterization.
Nothing to Disclose: EB, GB, WG, BC
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