The Mystery of Elevated β-hCG in GnRH-Independent Precocious Puberty without a Detectable Tumor: A Six-Year Diagnostic Odyssey

Background: β-human chorionic gonadotrophin (β-hCG) secreting tumors causing gonadotropin-independent precocious puberty (GIPP) are rare. This case underscores the diagnostic difficulties presented by these tumors. Case Presentation: A 10.8-year-old boy referred with rapidly advancing puberty. He had Tanner stage 5 pubic hair, macropenis, accelerated growth and bone age. Suppressed gonadotropins with elevated testosterone and β-hCG levels led to diagnosis of GIPP. Cranial imaging for the source of β-hCG identified a 6 mm pituitary adenoma, however, resection of the pituitary lesion and petrosal sinus and cerebrospinal fluid β-hCG measurements did not support this. A testicular biopsy and spermatic venous β-hCG levels due to testicular calcifications indicated no evidence of testicular secretion. PET/CT demonstrated mild fluorodeoxyglucose (FDG) uptake in the thymic region. Excisional biopsy was consistent with thymic hyperplasia. During follow-up, β-hCG levels fluctuated between 100 and 154 mIU/ml, with serial imaging (cranial, thoraco-abdomino-pelvic MRIs) remaining unremarkable. At sixth-year of follow-up, β-hCG surged to 2039 mIU/ml, at which time, thoracic CT revealed a 5 cm mass in the mediastinum. The mass was resected and pathology was consistent a mixed germ cell tumor. Conclusion: The source of β-hCG may remain obscure for a long time in β-hCG-mediated GIPP. Ongoing surveillance is essential in similar cases.