Precocious pseudo-puberty in a 2-year-old girl, presenting with bilateral ovarian enlargement and progressing to unilateral juvenile granulosa cell tumour

Abstract

Ovarian causes of precocious pseudo-puberty (PPP) include McCune-Albright syndrome (MAS) and juvenile granulosa cell tumour (JGCT). We describe a case of PPP in which bilateral ovarian enlargement with multiple cysts progressed to unilateral JGCT. A girl aged 2.17 years presented with 3 months of breast development, and rapid growth. Examination showed tall stature, height + 2.6 standard deviations, Tanner stage B3P2A1. A single cafe au lait patch was noted. Bone age was advanced at 5 years. Pelvic ultrasound showed bilaterally enlarged ovaries (estimated volumes 76 ml on the left, 139 ml on the right), each containing multiple cysts. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) values before/after gonadotrophin administration were 0.43/0.18 and < 0.1/<0.1 mUI/ml, serum estradiol 130 pg/ml, (prepubertal range < 20). PPP of ovarian origin was diagnosed, and Tamoxifen 20 mg daily started. However, after only 7 weeks height velocity escalated and breast development increased to B3-4 with menorrhagia. Basal/stimulated LH and FSH were still suppressed at 0.13/0.25 and <0.1/<0.1 mUI/ml, serum estradiol 184 pg/ml. Repeat imaging now showed normal right ovary (volume 1.8 ml) and a large left-sided vascular solid/cystic ovarian tumour which was excised (weight 850g). Histology showed JGCT, FIGO stage IA. DNA from tumour tissue showed no mutation in GNAS, exon 3 of AKT1 (which contains a mutational hotspot) or FOXL2. The observation that bilateral ovarian activity progressed to unilateral development of JGCT in this patient is novel. This case highlights current uncertainties in the ontology of JGCT, and its possible relationship with MAS.