Endocrine Abstracts

Introduction

We report a case of severe thyrotoxicosis due to a metastatic testicular tumor secreting human chorionic gonadotropin (hCG), known to have a TSH-mimicking effect due to alpha-subunits’ structural similarity.

Case report

In November 2020 a 38-year-old man was referred to our Department for thyrotoxicosis of unknown etiology. He had no family history of thyroid disease and his medical history had been unremarkable until August 2020, with normal thyroid function. He denied alcohol or substance abuse, was a nonsmoker and was taking no medication. One month before, a lumbosacral MRI performed because of recurrent back pain incidentally discovered multiple lesions in the aortocaval region. A CT scan showed fourty-seven bilateral solid lung lesions and extensive retroperitoneal and iliac chain lymphadenopathy. Tumor markers panel showed 180-fold increase of alpha 1-fetoprotein levels and a subsequent testicular US revealed multiple nodules with calcifications in the left testis. Pulmonary and pelvic lesions biopsies and left orchifunicolectomy were performed, with histological diagnosis of metastatic nonseminomatous germ-cell tumor (AJCC stage IIIC; 75% Embryonal carcinoma, 15% Teratoma, 10% Yolk sac carcinoma, <1% Choriocarcinoma). Clinical examination revealed tachycardia (HR 104 bpm), but no neck pain or ocular signs. The patient complained of agitation and weight loss. Laboratory tests showed suppressed TSH levels, a marked rise in free-thyroxine (FT4 36.1 pg/ml, normal range 9.3–17) and free-triiodothyronine (FT3 10.9 pg/ml, range 2–4.4) levels, with no serological evidence of thyroid autoimmunity (AbTg, AbTPO, TRAb); dramatically increased hCG levels (745.506 mU/ml, range 0–2) were detected. Thyroid US revealed normal volume, homogeneous isoechogenic echotexture (vascular pattern not available), without solid nodules. A diagnosis per exclusionem of HCG-induced hyperthyroidism was established and treatment with Methimazole 20 mg/day and Propranolol 40 mg/day was initiated. One week later, FT4 levels improved (FT4 26 pg/ml) and FT3 levels normalized (FT3 3.33 pg/ml). Concurrently, chemotherapy with cisplatin, etoposide and bleomycin (PEB) was started, then shifted to cisplatin, etoposide and ifosfamide (VIP) because of respiratory failure. After a sharp rise (>1.000.000 mU/ml), HCG levels progressively decreased to almost physiological levels and the thyroid function normalized as well; Methimazole treatment was tapered to 5 mg/day.

Conclusions

HCG overproduction by germ cell tumor represents a rare cause to consider in differential diagnosis of hyperthyroidism; the presence of misdiagnosed paraneoplastic thyrotoxicosis could negatively impact on clinical and pharmacological management and on patient’s QoL.

References

Amin MB et al, eds. AJCC Cancer Staging Manual. 8th ed. New York: Springer; 2017: 727–735.