A Case of HCG-Mediated Hyperthyroidism Related to Metastatic Choriocarcinoma

Introduction: We present a clinical case of a non-seminomatous germ cell choriocarcinoma producing human chorionic gonadotrophin (HCG) and inducing hyperthyroidism. Clinical Case: A 21-year-old male with recently diagnosed metastatic non-seminomatous germ cell choriocarcinoma presented with persistent tachycardia and anxiety. At diagnosis, his β- human chorionic gonadotrophin (β-HCG) was elevated to 6,435 mIU/mL (normal <1 in male) and thyroid-stimulating hormone (TSH) was within normal limits. At presentation, however, his β-HCG increased to 103,229 mIU/mL, TSH was suppressed <0.02 mcIU/mL (normal 0.3-4.7), and free thyroxine was elevated (FT4) 2.6 ng/dL (normal 0.8-1.7). His thyrotoxicosis improved with initiation of methimazole; however, his TSH remained undetectable due to persistently elevated β-HCG levels. His course was complicated by hemorrhagic shock and acute liver injury in the setting of a presumed intraluminal gastric metastasis, necessitating the discontinuation of methimazole. He was continued on steroids to try to minimize T4 to T3 conversion, but ultimately his thyroid hormones uptrended. He became stable enough to tolerate 5 days of chemotherapy, after which his FT4 quickly normalized. Unfortunately, he continued to suffer from vasodilatory shock and ultimately passed away. Discussion: It has been demonstrated that HCG can bind to the TSH receptor and has thyrotropic activity. The development of hyperthyroidism requires HCG levels >200,000 mIU/mL that are sustained for several weeks (1). It is unknown what the prevalence of hyperthyroidism is in choriocarcinoma, but it has been shown to greatly increase when serum HCG levels are greater than >50,000 mIU/mL (2). Conclusion: Hyperthyroidism can be difficult to recognize in patients suffering from cancer as many of the typical symptoms can also be seen with active malignancy. Patients with HCG-secreting tumors should be evaluated for hyperthyroidism and may benefit from treatment until the underlying cause can be managed. References: (1) Hershman, Jerome M. “Physiological and Pathological Aspects of the Effect of Human Chorionic Gonadotropin on the Thyroid.” Best Practice & Research Clinical Endocrinology & Metabolism, Baillière Tindall, 19 May 2004, www.sciencedirect.com/science/article/abs/pii/S1521690X0400020X.(2) Oosting, S F et al. “Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non-seminomatous germ-cell tumors.” Annals of oncology: official journal of the European Society for Medical Oncology vol. 21,1 (2010): 104-8. doi:10.1093/annonc/mdp265