HCG induced hyperthyreosis in germ cell cancer

Human germ cell tumors have the unique capacity for totipotential different iation. AFP (the product of normal yolk sac) and HCG (produced by trophobla stic tissues) are frequently produced by germ cell tumors. The a-subunit of the glycoprotein. HCG is identical to that of several pituitary glycoprote in hormones (e.g. TSH, LH, FSH), whereas the b-subunit of HCG, TSH, LH and FSH is homologous but distinct in the terminal amino acid sequence suggesti ng that HCG is part of a superfamily of gestational hormones. However; the role of TSH within this hormone superfamily is still not yet established. A 24-year old patient was admitted to our clinic because of a widespread rec urrence of a germ cell tumor (stage IIIC, Lugano classification). The routi ne hematologic and blood chemical tests were normal, yet, an elevated HCG w as found. In addition, increased levels of the thyroid hormones FT3 and FT4 were seen although, this was not associated with clinical symptoms of a hy perthyreosis. There was no history of hyperthyreosis and thyroidal autoanti body screening revealed normal titers. An ultrasound examination of the thy roid gland showed no abnormalities and no iodine exposure had occured durin g the last months. To mobilize peripheral stem cells (PBSC) he was initiall y treated with paclitaxel (175 mg/m(2)) and ifosfamide (8.000 mg/m(2))) fol lowed by apheresis of PBSC. The patient was then entered in our phase-II-st udy for relapsing germ cell carcinomas using a high-dose chemotherapy regim e (paclitaxel 175 mg/m(2) ifosfamide 9.000mg/m(2), carboplatin 900 mg/m(2), etoposide 900 mg/m(2)) with subsequent retransfusion of collected stem cel ls. Doe to cranial metastases an cranial irradiation was also performed Aft er three courses of this protocol an excellent pal tial I emission of the t umor lesions was achieved and the HCG value dramatically decreased. Due to elevated thyroidal hormones, the patient was initially treated with thiamaz ole (20 mg) resulting in decrease of the thyroidal hormones. Thus, the thia mazole dose was reduced to 5 mg and then omitted. The dea ease of the thyro idal hormones FT3 and FT4 strongly correlated with the reduction of HCG val ues (r(2) 0.91 and 0.77 p<0.0008). To date there is only slight evidence th at enhanced HCG levels may cause, at least in part, a hyperthyreosis (e.g. gestational hyperthyreosis), however; the underlying biochemical mechanism still remains unclear: In this case report we have demonstrated a clear pos itive correlation between HCG levels and thyroidal hormones in a patient wi th germ cell tumor suggesting a direct stimulation of hormone producing thy roidal cells by HCG, however; this was not associated with clincal symtoms of hyperthyreosis. Currently, several in vitro studies are underway in our laboratory to further elucidate the biochemical mechanisms of HCG induced h yperthyreosis.