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 three months of breast development, and rapid growth. Examination showed tall stature, height +2.6 standard deviations, Tanner stage B3P2A1. A single café 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 pg/mL). PPP of ovarian origin was diagnosed, and tamoxifen 20 mg daily started. However, after only seven 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 and, 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 850 g). Histology showed JGCT, International Federation of Gynecology and Obstetrics 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.

Abstract Fibrous Dysplasia (FD) is a rare bone disease which usually presents to Endocrinologists as part of McCune Albright Syndrome or as precocious puberty. A variety of other co-morbidities have been described for FD including renal phophate wasting secondary to an excess of FGF23; abnormal thryoid and growth hormone production and abnormal cortisol production.A large number of children are referred to the Regional Sarcoma Service with lytic lesions, many of which are diagnosed as FD. There is currently no screening programme in place for children with this diagnosis, as is recommended by the FD Foundation. We therefore audited all patients diagnosed with FD since 2009. Of the over 1100 patients suspected to have FD, we were able to conclusively arrive at the diagnosis in 86 patients, 53 Males and 33 females; 24/86 (28%) had polyostotic disease and 57/86(67%) had monostotic FD. Only 5 patients had extra skeletal signs leading to a diagnosis of McCune Albright Syndrome. 6 patients had non skeletal symptoms at presentation: 2 had frank rickets, 2 had very extensive cafe au lait patches, and 2 had skeletal malformations. Using the FD Foundation recommendations, patients were screened by Whole Body MRI(WBMRI). 37/57 monostotic and 17/24 polyostic patients were screened with 11/57 and 8/24 patients, respectively, diagnosed with 'additional' lesions. Therefore 11 patients labelled as monostotic were in fact polyostotic. None of the additional lesions found, in either group, has resulted in a change to planned management but has increased the ares of ongoing surveillance 49/86 patients have thus far undergone blood testing. 6/49 (12%) were found to have one or more abnormalities, 3 had already manifested clinically. 3/49(6%) abnormalities found were in previously undiagnosed patients. Although borderline hypophosphataemia was observed in 7 patients, Phosphaturia was noted in 14 patients and rickets in only 3 patients. FGF 23 levels were evaluated but were not useful in discriminating which patients were more likely to have significant phosphate wasting.Conclusion: Although patients with FD can have co-morbidities, the prevalence reported in the literature(of about 40%) appears to be a significant over-reporting and is likely to represent the cohort of patients who present to endocrinologists rather than orthopaedic surgeons. Our analysis suggests that testing for phosphate wasting and endocrinopathy is worthwhile but that routine WBMRI is of questionable value in both monostotic and polyostotic patients.

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)