Interference against a newly labeled substance with ruthenium sulfonate complexes showing discrepant thyroid function test results.

We report here two patients exhibiting a combination of falsely elevated serum levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin receptor antibodies (TRAb), measured using Elecsys assay kits (Roche Diagnostics GmbH). The first patient was a 74-year-old man misdiagnosed with Graves' disease and treated with methimazole. The second patient was a 48-year-old woman whose serum FT4 and FT3 concentrations were found to be high during a blood test. These patients denied taking biotin or any other supplements. Further detailed examination, including a heterophilic blocking tube test, revealed the presence of serum antibodies. The abnormal reactions were observed only using the improved assay kits using ruthenium (Ru) sulfonate instead of Ru as a chemiluminescent agent. Therefore, serum antibodies to the Ru sulfonate complex caused the pseudo-high levels of FT4, FT3, and TRAb. To our knowledge, this is the first report showing that antibodies to the Ru sulfonate complex in the electrochemiluminescence immunoassay can cause falsely elevated levels of the combination, leading to discrepant thyroid function test results. We emphasize that in cases of abnormal test results, alternative assay methods should be considered for further examination; unusual test results should not be impulsively interpreted, even when using revised assay kits.

Sorafenib and Lenvatinib Treatment for Metastasis/Recurrence of Radioactive Iodine-refractory Differentiated Thyroid Carcinoma.

BACKGROUND/AIM: Radioactive iodine-refractory differentiated thyroid carcinoma (RR-DTC) has been treated with multi-kinase inhibitors (MKIs), e.g., sorafenib (SOR) and lenvatinib (LEN). We analyzed the outcomes of RR-DTC patients who underwent SOR or LEN treatment at Kuma Hospital. PATIENTS AND METHODS: We enrolled 21 and 18 patients treated with SOR and LEN, respectively. RESULTS: The incidence of partial response in the LEN group was significantly higher than that in the SOR group. Serum thyroglobulin significantly decreased from the beginning of treatment to 1 month later in the LEN group (not in the SOR group). The neutrophil-lymphocyte ratio (NLR) was significantly decreased at 1 month later in both groups. An NLR ≥3 at the start of MKI treatment had a prognostic impact. CONCLUSION: For RR-DTC, LEN could be more effective than SOR, at least in the short term. The first-line drug should be selected based on other factors (e.g., adverse events, patient background).

Successful treatment switch from lenvatinib to sorafenib in a patient with radioactive iodine-refractory differentiated thyroid cancer intolerant to lenvatinib due to severe proteinuria.

Sorafenib and lenvatinib showed efficacy for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) in pivotal phase 3 clinical trials. Although the efficacy of lenvatinib in patients who received previous treatment with multi-target kinase inhibitors (m-TKIs), including sorafenib, was reported, the efficacy of sorafenib in patients who previously received lenvatinib remains unknown. A 75-year-old woman diagnosed as RAI-refractory poorly differentiated carcinoma with multiple lung metastases and started treatment with lenvatinib. She continued to receive lenvatinib but with repeated dose interruptions and reductions due to continuous proteinuria. Because of severe and persistent proteinuria as well as newly developed renal impairment, lenvatinib was suspended after two years of treatment. After the 7-month suspension, her proteinuria and renal impairment were partially improved, but her lung metastases progressed. Because she was unable to tolerate previous treatment with lenvatinib, sorafenib was started. At 7 months of treatment with sorafenib, her lung metastases shrank and she could continue sorafenib without exacerbation of proteinuria or renal impairment. This case may suggest that sorafenib does not exacerbate the proteinuria or renal impairment induced by lenvatinib, and may be an effective treatment option for RAI-refractory DTC patients who are unable to tolerate lenvatinib.

Benefit of short-term iodide supplementation to antithyroid drug treatment of thyrotoxicosis due to Graves' disease.

OBJECTIVE: Combined treatment with anti-thyroid drugs (ATDs) and potassium iodide (KI) has been used only for severe thyrotoxicosis or as a pretreatment before urgent thyroidectomy in patients with Graves' disease. We compared methimazole (MMI) treatment with MMI + KI treatment in terms of rapid normalization of thyroid hormones during the early phase and examined the later induction of disease remission. DESIGN AND PATIENTS: A total of 134 untreated patients with Graves' disease were randomly assigned to one of four regimens: Group 1, MMI 30 mg; Group 2, MMI 30 mg + KI; Group 3, MMI 15 mg and Group 4, MMI 15 mg + KI. For easy handling, KI tablets were used instead of saturated solution of KI. KI was discontinued when patients showed normal free thyroxine (FT4) levels but MMI was continued with a tapering dosage until remission. Remission rate was examined during a 4- to 5-year observation. MEASUREMENTS: Serum FT4, FT3 and TSH were measured by chemiluminescent immunoassays. TSH receptor antibody (TRAb) was assayed with TRAb-ELISA. Goitre size was estimated by ultrasonography. RESULTS: After 2 weeks of treatment, normal FT4 was observed in 29% of patients in Group 1 and 59% (P < 0.05) of patients in Group 2. Furthermore, normal FT4 after 2 weeks of treatment was observed in 27% of patients in Group 3 and 54% (P < 0.05) of patients in Group 4. Similarly, FT3 normalized more rapidly in Groups 2 and 4 than in Groups 1 and 3. None of the patients showed an increase in thyroid hormones or aggravation of disease during combined treatment with MMI and KI. The remission rates in Groups 1, 2, 3 and 4 were 34%, 44%, 33% and 51%, respectively, and were higher in the groups receiving combined therapy but differences among four groups did not reach significance. CONCLUSIONS: Combined treatment with MMI and KI improved the short-term control of Graves' hyperthyroidism and was not associated with worsening hyperthyroidism or induction of thionamide resistance.

Thyrotoxicosis caused by weight-reducing herbal medicines.

The weight-reducing herbal medicines "Dream Shape" and "Ever Youth" became available in Japan in 2000. Herein, we describe 12 patients who developed thyrotoxicosis after taking them. The thyroid hormone content of 1 capsule or tablet of herbal medicine, measured following Pronase digestion and ethanol extraction, was approximately 1 mug of triiodothyronine and 3 to 4 mug of thyroxine. Two of us took 10 capsules or tablets of Dream Shape or Ever Youth, and changes in thyroid hormone levels were observed during the first 24 hours. Serum free triiodothyronine levels began to rise 2 hours after ingestion and reached peak levels at 4 to 8 hours; changes in free thyroxine and thyrotropin levels were small during the first 24 hours. Similar herbal medicines may have been distributed to other countries via the Internet. Resultant factitious thyrotoxicosis can create diagnostic and therapeutic confusion, particularly in patients with thyroid disease.

[Bronchospasm during upper gastrointestinal endoscopy under sedation].

We experienced a case of bronchospasm during upper gastrointestinal endoscopy under sedation. An 80-year-old man came to our hospital with abdominal distension with pain, nausea and vomiting. He has the history of splenectomy, cholecystectomy for hemolytic anemia and thyroidectomy for thyroid cancer, surgery for bilateral shoulder joints and diabetes. Abdominal X-ray suggested obstruction of the small intestine. On the third hospital day, gastrointestinal endoscopy was scheduled for insertion of a long ileus tube. Under sedation with diazepam 10 mg and local anesthesia of the pharynx with lidocaine spray 24 mg, the endoscope was inserted and when it reached the esophageal-gastrojunction, respiratory rate increased to 30 breaths.min-1 with expiratory stridor. The endoscope was removed immediately. He was oro-tracheally intubated and artificially ventilated. On the fourth hospital day, he was extubated under bronchoscopy. No abnormalities were observed in the trachea, vocal cord, pharynx and larynx. Later, it was revealed that he had a history of hoarseness and dysphasia. His left recurrent nerve and cervical nerve had been resected with thyroid and right cervical nerve anastomosed to the rest of the left recurrent nerve. The insertion of upper gastrointestinal endoscope might have induced bronchospasm stimulating distal esophageal afferent vagal reflex partly by regurgitation of gastric acid under sedation.