(134) Van Wyk-Grumbach Syndrome: A Case of Elevated Inhibins with Normal Ovarian Pathology

Background: This case describes a likely diagnosis of Van Wyk-Grumbach syndrome presenting as age-appropriate pubertal changes, a benign ovarian mass, and elevated tumor markers.

Case: An 11-year-old female presented to the emergency department with acute abdominal pain. Past gynecologic history was notable for thelarche in the past year and menarche occurring two weeks prior to presentation. Physical exam demonstrated diffuse lower abdominal tenderness. Pelvic ultrasound revealed a 6.4 cm simple left ovarian cyst with features concerning for ovarian torsion. The patient underwent an emergent diagnostic laparoscopy and evacuation of hemoperitoneum for a suspected ruptured left hemorrhagic ovarian cyst. No ovarian torsion was identified.

Her postoperative course was notable for recurrence of abdominal pain. Repeat ultrasonography demonstrated a persistent 6 cm cyst with internal debris and thin septations, which was confirmed with magnetic resonance imaging (Figure 1). Serum tumor markers were notable for elevated LDH (263 U/L) and inhibin B (474 pg/mL) that remained markedly elevated on repeat assessment. The case was reviewed by an interdisciplinary tumor board, which recommended surgical removal of the ovary due to concern for an ovarian malignancy. An uncomplicated laparoscopic left oophorectomy and pelvic washings were performed. Pathology yielded benign cytology and ovarian parenchyma with multiple follicular cysts.

Inhibin B levels continued to rise postoperatively (Figure 2) despite normal imaging of the remaining ovary. Workup for secondary amenorrhea was performed given the patient had no menses postoperatively. Serum hormone levels revealed elevated prolactin (129 ng/mL) and thyroid stimulating hormone (TSH) (>1000 mIU/L ) with undetectable free thyroxine. Further workup demonstrated positive anti-TPO and anti-thyroglobulin antibodies. The patient was referred to endocrinology for further evaluation of suspected Van Wyk-Grumbach syndrome. Thyroid hormone replacement was initiated with subsequent normalization of the TSH, prolactin and inhibin B levels.

Comments: Van Wyk-Grumbach syndrome is usually characterized by severe hypothyroidism, cystic ovaries, and precocious puberty thought secondary to hyperstimulation by TSH on ovarian FSH receptors. This patient presented with normal pubertal progression, and workup of subsequent menstrual irregularity revealed a unifying diagnosis. This is the first known case report demonstrating normal ovarian pathology with this rare syndrome. In the setting of an ovarian mass with elevated inhibin B, evaluation of thyroid function could prevent inadvertent oophorectomy.