Letter to the Editor
Paraneoplastic hyperthyroidism secondary to chorionic gonadotrophin-producing testicular tumor
Hipertiroidismo paraneoplásico secundario a tumor testicular productor de gonadotrofina coriónica
a Servicio de Endocrinología y Nutrición, Hospital Universitario de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain
b Instituto de Investigación Biomédica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain
c CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
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The CBC showed TSH 0.01<span class="elsevierStyleHsp" style=""></span>mIU/l (normal: 0.57–5.51), T4 32.1<span class="elsevierStyleHsp" style=""></span>pmol/l (normal: 12–22), T3 8.1<span class="elsevierStyleHsp" style=""></span>pmol/l (normal: 3.1–6.8) and anti-TSI 1.2<span class="elsevierStyleHsp" style=""></span>mIU/l (normal: <1.75). Examination revealed a heart rate of 110 beats/minute, absence of exophthalmos and normal cervical palpation. The disproportion between symptoms and thyroid hormone levels, low back pain, absence of goitre and negative anti-TSI antibodies were significant. Targeted examination showed a lesion in the right testicle and ultrasound confirmed two nodules suspicious for malignancy. Serum human chorionic gonadotropin (HCG) was 828,300<span class="elsevierStyleHsp" style=""></span>mIU/l (normal: <2.6). X-ray and CT scan showed multiple bilateral pulmonary nodules, bilobar liver metastases, and enlarged thoracic, abdominal and retroperitoneal node collections.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Treatment with beta-blockers was started and a right orchiectomy was performed. Histological study confirmed a non-seminomatous germ cell tumour with choriocarcinoma (50%), teratoma (45%) and endodermal sinus tumour (<5%) component. Subsequently, chemotherapy with etoposide and cisplatin was started. On day 5, serum HCG was 1,807,037 mIU/l and the patient developed acute respiratory failure with bilateral lung infiltrates. Antibiotic therapy (piperacillin-tazobactam) and respiratory support were started, and improvement was observed in the following 7<span class="elsevierStyleHsp" style=""></span>days. Chemotherapy was resumed with paclitaxel and ifosfamide, followed by carboplatin and etoposide. Thyroid function was normal at one month, and tumour stability and normal HCG levels were observed over the next 5 months. However, the disease worsened and the patient died 12 months after diagnosis from neurological complications due to metastatic spread.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Testicular germ cell tumours are the most common solid neoplasms in males aged 25−35<span class="elsevierStyleHsp" style=""></span>years.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> These tumours can produce HCG, which is a glycoprotein hormone structurally homologous to TSH.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> This feature gives the TSH receptor an intrinsic biological activity that increases in parallel with the level of the hormone.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> A study in 144 patients with non-seminomatous testicular tumours found a prevalence of paraneoplastic hyperthyroidism (PH) of 3.5%, with HCG above 50,000<span class="elsevierStyleHsp" style=""></span>IU/l in all cases.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Our patient's PH improved after chemotherapy, similar to others described in the medical literature. However, the cytotoxic effect of chemotherapy leads to increased HCG, presumably due to tumour lysis, and PH<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> may occur. As PH can be difficult to detect in the context of oncological disease and chemotherapy, TSH monitoring is recommended before and after chemotherapy in patients with HCG-secreting tumours4.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Choriocarcinoma syndrome (CS) is another HCG-related paraneoplastic syndrome.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> It usually occurs in patients with metastatic disease and choriocarcinoma histology and is characterised by acute respiratory distress and/or alveolar haemorrhages.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> CS can occur spontaneously or after initiation of chemotherapy, and HCG levels are often greater than 50,000<span class="elsevierStyleHsp" style=""></span>IU/l).<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The pathophysiology of CS is not known, although it may be related to the massive release of cytokines by tumour destruction.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The role of HCG in CS is not fully understood and the syndrome does not appear to be unique to cases with choriocarcinoma histology.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">In conclusion, PH in HCG-secreting testicular tumours should be suspected in young males, especially when there is clinical-hormonal disproportion, atypical symptoms, normal cervical examination and negative anti-TSI antibody results. The disease usually reverses with oncological treatment, and other therapeutic measures (antithyroid drugs, radioactive iodine) are usually not necessary. CS is another potentially serious paraneoplastic condition related to HCG that should be kept in mind in these patients. Clinical surveillance in the first days after the start of treatment is essential for early detection.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Ethical considerations</span><p id="par0035" class="elsevierStylePara elsevierViewall">Informed consent has been obtained, and confidentiality has been protected in accordance with applicable regulations.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0040" class="elsevierStylePara elsevierViewall">The authors have not received any funding for this work.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Ethical considerations" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hyperthyroidism: aetiology, pathogenesis, diagnosis, management, complications, and prognosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "W.M. 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