Endocrine Abstracts

Introduction: Children with long-standing primary hypothyroidism usually have growth retardation, neurodevelopmental impairment, and delayed puberty. However, paradoxical precocious puberty, namely Van Wyk-Grumbach syndrome (VWGS), has been described. The postulated mechanism is high levels of TSH stimulate gonadal FSH receptors, resulting in ovarian over-stimulation and precocious puberty. Since the enlarged ovarian cyst is commonly found in VWGS, malignancy is often suspected. Non-recognition can lead to misdiagnosis and unnecessary surgery. Here we report a girl with long-standing hypothyroidism and gonadotropin-independent precocious puberty (GIPP) who was first misdiagnosed with ovarian tumors.

Case report: A 9-year and 10-month-old girl presented with slow-progressive abdominal distension, heavy vaginal bleeding, and pelvic pain for a month. Her thelarche and menarche occurred at the age of nine years with regular periods and cycle length of 4 weeks, suggesting precocious puberty. Physical examination showed breast Tanner stage IV with no pubic or axillary hair. A midline cystic mass was palpated at the lower abdomen. A pelvic ultrasound found a pubertal-size uterus with endometrial thickness and large bilateral ovarian cysts (8.5*4.2*7 cm and 8.1*4.7*8 cm in right and left ovary, respectively) with multiple internal septations. The bilateral ovarian tumors were initially suspected. However, no tumor markers were elevated, except slightly increased LDH (266 IU/l (135-214)). In addition, the patient was disproportionately short (height at -4.5SDS with upper/lower ratio of 1.39:1 and weight at -2.0 SDS) and had signs of hypothyroidism, including mild pallor, puffy eyelids, flat nasal bridge, dry skin, gross motor and speech delays, and muscular pseudohyperthrophy. Her skeletal age was markedly delayed (5 years). Severe primary hypothyroidism was diagnosed by high TSH and low FT4 (TSH 621 uIU/ml (0.60-4.84), FT4 0.13 ng/dL (0.97-1.67), TPOAb 6.9 IU/ml (<40), TGAb 37.6 IU/ml (<125), thyroglobulin level 1.1 ng/ml (5-40)). Baseline LH was below 0.1, FSH 6.62 IU/l, and estradiol 6.22 pg/ml, indicating GIPP. Thyroid scan revealed an ectopic lingual thyroid. VWGS was diagnosed based on the concurrence of severe primary hypothyroidism, GIPP, and delayed bone age. After levothyroxine replacement, she had no further episode of vaginal bleeding, and bilateral ovarian cysts were gradually resolved.

Conclusion: VWGS is an unusual presentation of long-standing primary hypothyroidism. The combination of precocious puberty, short stature, and delayed skeletal maturation is a clue for diagnosis. Ovarian cysts progressively regress with LT4 replacement. Physicians need to be aware of this condition to avoid unnecessary surgery due to suspected ovarian tumors.