Background: Van WykGrumbach syndrome (VWGS) is characterized by breast development, uterine bleeding and multi-cystic ovaries in the presence of long-lasting primary hypothyroidism.
Objective and hypotheses: The pathophysiology of VWGS involves a complex mechanism, which is at least partly mediated by the direct action of TSH and FSH receptors.
Method: We present a girl with Down syndrome having typical features of VWGS. The girl, aged 9 years and 7 months, was referred to our endocrinology department with the suspicion of precocious puberty after having had first episode of vaginal bleeding lasting 4 days. Her poor growth and inactivity were previously thought to be due to her Down syndrome.
Results: On examination, her height was 117 cm (<3p) and weight was 30 kg (50p). She had breast development at Tanners stage 3, but no pubic and axillary hair development. Baseline LH was 0.15 U/l, FSH 5.4 U/l, oestradiol was 94 mIU/ml and prolactin was 140 mU/l. Morning cortisol, 17-hydroxyprogesteron, and androgens were normal. Primary hypothyroidism was demonstrated by a free T4<2 pmol/l and TSH>100.000 mU/l. Positive thyroid peroxidase antibodies confirmed autoimmune thyroiditis. LHRH test showed FSH dominated prepubertal response. A pelvic ultrasound showed a pubertal uterus in size and appearance, and large cystic ovaries with multiple follicles. Cardiac echography yielded moderate pericardial effusion. Her bone age was compatible with 6 years. Her clinic and laboratory findings were in agreement with VWGS. T4 replacement was started at a very low dose, 25 mg, because of pericardial effusion, and was increased gradually. She had no further episodes of vaginal bleeding.
Conclusion: The combination of delayed bone age with vaginal bleeding is one of the important diagnostic clues of the VWGS.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology