Propylthiouracil (PTU)-induced otitis media with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) is an extremely rare adverse event associated with anti-thyroid drugs and is ...not well recognized. A 42-year-old woman with Graves’ disease undergoing PTU therapy for 8 years visited our hospital because of earache and congested feeling in her left ear. Blood tests, a computed tomography scan and pure tone audiometry revealed otitis media and moderate mixed hearing impairment. Antibiotics, ear drops with antibiotics and painkillers were administered. However, her earache and hearing loss gradually got worse and symptoms of facial nerve palsy appeared. At several weeks after initiation of the treatment, a high serum level of myeloperoxidase (MPO)-ANCA, 75.6 U/mL, was revealed. After excluding other causes, she was diagnosed with OMAAV. PTU was suspected as the cause of her OMAAV and was immediately discontinued, and prednisolone was started. Hearing impairment in her left ear gradually got better and showed substantial improvement. Facial nerve palsy disappeared. Although PTU-induced OMAAV is an extremely rare disease, it is important to recognize the disease, as delayed treatment can lead to irreversible hearing loss, hypertrophic pachymeningitis, and subarachnoid hemorrhage. When patients taking anti-thyroid drugs, especially PTU, are diagnosed with refractory otitis media or hearing loss, it is possible that OMAAV might be the cause and thus serum ANCA levels should be evaluated.
Background Because lenvatinib is well known to induce proteinuria by blocking the vascular endothelial growth factor (VEGF) pathway, renal function is a concern with long-term administration of ...lenvatinib. The long-term effects of lenvatinib on renal function in patients with advanced differentiated thyroid carcinoma (DTC) were analyzed. Method This study involved 40 DTC patients who continued lenvatinib therapy for greater than or equai to6 months. Estimated glomerular filtration rate (eGFR) was calculated as an indicator of renal function. The temporal course of eGFR, effects of baseline eGFR on eGFR changes, and factors affecting renal impairment were investigated. Results The overall cohort showed sustainable decreases in eGFR, with decreased values of 11.4, 18.3, and 21.0 mL/min/1.73 m.sup.2 at 24, 36, and 48 months after starting treatment, respectively. No differences in eGFR decrease every 6 months were seen for three groups classified by baseline eGFR greater than or equai to90 mL/min/1.73 m.sup.2 (n = 6), < 90 but greater than or equai to60 mL/min/1.73 m.sup.2 (n = 26), or < 60 but greater than or equai to45 mL/min/1.73 m.sup.2 (n = 8). Grade 3 proteinuria was associated with declines in eGFR (p = 0.0283). Long observation period was also associated with decreases in eGFR (p = 0.0115), indicating that eGFR may decrease in a time-dependent manner. Conclusion Lenvatinib can induce declines in eGFR, particularly with treatment duration > 2 years, regardless of baseline eGFR. Proteinuria is a risk factor for declines in eGFR. Patients who start lenvatinib with better renal function show a renal reserve capacity, prolonging clinical outcomes. Decision-making protocols must balance the benefits of lenvatinib continuation with acceptable risks of harm. Keywords: Lenvatinib, Advanced thyroid carcinoma, Renal function, eGFR, Proteinuria
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Differentiated thyroid carcinoma (DTC) is generally indolent in nature and, even though it metastasizes to distant organs, the prognosis is normally excellent. In contrast, the overall survival (OS) ...of patients with radioactive iodine (RAI)-refractory and progressive metastases is dire, because no effective therapies have been available to control the metastatic lesions. However, recently, administration of tyrosine-kinase inhibitors (TKIs) has become a new line of therapy for RAI-refractory and progressive metastases. Previous studies have reported significant improvement regarding the progression-free survival rates of patients with metastatic lesions. However, TKIs cause various severe adverse events (AEs) that damage patients’ quality of life and can even be life-threatening. Additionally, metastatic lesions may progress significantly after stopping TKI therapy. Therefore, it is difficult to determine who is a candidate for TKI therapy, as well as how and when physicians start and stop the therapy. The present review, created by Committee of pharmacological therapy for thyroid cancer of the Japanese Society of Thyroid Surgery (JSTS) and the Japan Association of Endocrine Surgeons (JAES) describes how to appropriately use TKIs by describing what we do and do not know about treatment using TKIs.
Background
The aim of this study was to analyze the clinical features and clinical outcomes of papillary thyroid carcinoma (PTC) in the pediatric and adolescent population treated in our institution.
...Methods
The subjects were 227 PTC patients 20 years of age or under treated initially between 1979 and 2012. Their mean age at diagnosis was 18-year old (range 7–20 years). Patient characteristics and outcomes in the period before 1999 and the period after 2000 were compared. Cause-specific survival (CSS) rates and disease-free survival (DFS) rates were calculated by the Kaplan–Meier method.
Results
Two patients died of their disease and 45 patients had recurrent disease (36 in lymph node, seven in a remnant thyroid, and 11 in the form of distant metastasis). The 10-, 20-, and 30-CSS rates were 99.3, 99.3, and 96.5 %, respectively, and the 10-, 20-, and 30-DFS were 83.6, 70.7, and 64.0 %, respectively. Gender and preoperative lymph node metastasis were identified as significant factors related to DFS in the multivariate analysis. After the year 2000, there were significantly more patients with a small primary tumor size, significantly more patients without distant metastasis at presentation and significantly more patients without extrathyroidal invasion.
Conclusion
The number of patients with advanced cancer has been declining in recent years. Lobectomy with prophylactic unilateral central neck dissection is considered acceptable for patients without the risk factors for recurrence.
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EMUNI, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UL, UM, UPUK, VKSCE, ZAGLJ
The purpose of this study was to examine the postoperative clinical course of parathyroid carcinoma to determine factors that predict postoperative recurrence and distant metastasis.
In this ...retrospective study, we included 38 patients with parathyroid carcinoma who received surgical intervention at Itoh Hospital between 1979 and 2020. Clinicopathologic characteristics (age, sex, intact PTH, serum Ca level, operation type, parathyroid weight, parathyroid size, histopathologic findings: vascular invasion, capsular invasion, necrosis, histological type, and Ki-67 staining) were used. The median follow-up observation period was 63.7 months.
Postoperatively, 5 patients (13.2%) developed distant metastasis or had localized recurrence, and 3 patients died (7.9%). The results of the univariate analysis revealed three factors affecting distant metastasis and recurrence, which were Ki-67 (p = 0.0041), the presence or absence of necrosis (p = 0.0163), and tumor weight (p = 00,189). Using the cutoff values obtained by ROC analysis, which were 4.1 for Ki-67 (sensitivity of 80% and specificity of 96.9%) and 4890 mg for tumor weight (sensitivity of 100% and specificity of 60.9%), we calculated the cumulative incidence of recurrence and distant metastasis by the three factors retained. We found that the presence of the three factors was associated with a high possibility of distant metastasis or recurrence during the 5-year follow-up period.
Three factors, Ki-67, necrosis, and tumor weight in parathyroid carcinoma, may predict outcomes of postoperative recurrence and distant metastasis.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The extent of thyroidectomy in Graves’ disease remains controversial. In our institution, long-term euthyroidism without thyroxin replacement therapy has been the aim, and it has long been the ...standard surgical procedure used to treat Graves’ disease in many institutions, including our hospital. Based our several clinical studies, it was concluded that subtotal thyroidectomy is not suitable as a standard surgical procedure for the treatment of Graves’ disease. In 2009, the surgical strategy for Graves’ disease was changed from subtotal thyroidectomy to total thyroidectomy in our hospital. In this study, how surgical complications have changed after this modification was examined. The subjects were 1,476 patients with Graves’ disease treated by thyroidectomy between 2006 and 2014. There were 1,119 females and 357 males with a median age of 39 years. A total of 660 patients underwent bilateral subtotal thyroidectomy (ST group), and 816 patients underwent total thyroidectomy (TT group). Both transient hypocalcemia and prolonged hypocalcemia were observed significantly more frequently in the TT group than in the ST group (p < 0.001). Total thyroidectomy was identified as risk factors for prolonged hypocalcemia on multivariate analysis. In conclusion, total thyroidectomy is a reliable and effective therapy for controlling hyperthyroidism in terms of controlling of hyperthyroidism. However, it should be noted that total thyroidectomy resulted in increased rate of prolonged hypocalcemia. Surgeons should try to reduce the surgical complication rate as much as possible.
Activity of Graves’ disease (GD) is known to improve during gestation, as values of thyrotropin (TSH) receptor antibody (TRAb) also improve. However, the risk of neonatal hyperthyroidism increases ...when maternal TRAb values are high in the second to third trimester. A 29-year-old woman who had undergone radioactive iodine (RAI) therapy for GD 10 years earlier visited our hospital at 17 weeks of gestation, showing subclinical hypothyroidism and a positive TRAb value of 2.6 IU/L (reference range, <2.0 IU/L). Thyroid hormone replacement therapy was commenced and thyroid function normalized within 4 weeks, although TRAb was elevated at the time (3.8 IU/L). Prenatal check-up showed normal growth development and no irregularities. At 29 weeks of gestation, serum TRAb was extremely elevated, up to 16.8 IU/L. Since the risk of neonatal hyperthyroidism was of great concern, delivery was planned at an advanced-care medical center. At 38 weeks 5 days of gestation, she delivered a female neonate without any complications, although blood testing of the neonate showed subclinical hyperthyroidism with positive TRAb and TSH receptor stimulating antibody (TSAb). According to the American Thyroid Association guidelines, the TRAb value should be checked in the third trimester if mothers show a TRAb elevation between the initial visit after pregnancy and 18–22 weeks of gestation. However, if the mother has a history of RAI therapy for GD, regardless of thyroid function during gestation, the possibility of TRAb values elevating over time even years after the definitive therapy must be considered.
Objective This study assessed the efficacy of machine learning in predicting thyrotoxicosis and hypothyroidism thyroid-stimulating hormone (TSH) >10.0 mIU/L by leveraging age and sex as variables and ...integrating biochemical test parameters used by the Japan Society of Health Evaluation and Promotion (JHEP) and the Japan Society of Ningen Dock (JND). Subjects and Methods Our study included 20,653 untreated patients with Graves' disease, 3,435 untreated patients with painless thyroiditis, 4,266 healthy individuals, and 18,937 untreated patients with Hashimoto's thyroiditis. Machine learning was conducted using Prediction One on three distinct datasets: the Ito dataset (age, sex, and 30 blood tests and biochemical test data), the JHEP dataset (age, sex, and TP, T-Bil, AST, ALT, γGTP, ALP, CRE, UA, and T-Cho test data), and the JND dataset (age, sex, and AST, ALT, γGTP, CRE, and UA test data). Results The results for distinguishing thyrotoxicosis patients from the healthy control group showed that the JHEP dataset yielded substantial discriminative capacity with an area under the curve (AUC) of 0.966, sensitivity of 92.2%, specificity of 89.1%, and accuracy of 91.7%. The JND dataset displayed similar robustness, with an AUC of 0.948, sensitivity of 92.0%, specificity of 81.3%, and accuracy of 90.4%. Differentiating hypothyroid patients from the healthy control group yielded similarly robust performances, with the JHEP dataset yielding AUC, sensitivity, specificity, and accuracy values of 0.864, 84.2%, 72.1%, and 77.4%, respectively, and the JND dataset yielding values of 0.840, 83.2%, 67.2%, and 74.3%, respectively. Conclusions Machine learning is a potent screening tool for thyrotoxicosis and hypothyroidism.
The efficacy of potassium iodide (KI) for Graves’ disease (GD) has been reported, although few clinical reports have examined the long-term efficacy of treatment. The objective of this study was to ...investigate the efficacy and limitations of KI treatment for GD. This study enrolled patients newly diagnosed with mild GD, defined as free thyroxine (FT4) <5.0 ng/dL, between July 2014 and June 2016. KI was started at a dose of 50 mg/day, and if FT4 values did not decrease after initiation of treatment, doses were increased to 100 mg/day. Patients for whom thyroid hormone levels could not be controlled with KI at 100 mg/day were regarded as non-responders. Of the 122 patients (13 males, 109 females) included in this study, 71 (58.2%) responded to KI therapy. The remaining 51 patients (41.8%) were non-responders. The median duration required to judge non-responsiveness was 5.9 months. Multiple logistic regression analysis performed on parameters measured at the initial visit indicated FT4 (odds ratio (OR) 2.19, 95% confidence interval (CI) 1.28–3.75; p = 0.0007) and male sex (OR 3.58, 95%CI 1.04–12.3; p = 0.04) were significantly associated with KI responsiveness. Receiver operating characteristic (ROC) curve analysis of the relationship between FT4 and KI responsiveness indicated an FT4 cut-off of 2.76 ng/dL was optimal for differentiating between responders and non-responders. KI therapy was effective and safe for about 60% of patients with mild GD.
Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant condition and is the most commonly inherited euthyroid hyperthyroxinemia in Caucasians. However, it is extremely rare in Asian ...populations. A 30-year-old Japanese woman, who was incidentally found to have apparent thyroid dysfunction, was admitted to our hospital in 2004. She had extremely elevated serum free thyroxine (FT4), moderately elevated free triiodothyronine (FT3), and normal thyroid-stimulating hormone (TSH). Clinical thyroid examination revealed no abnormalities other than small goiter. Anti-thyroglobulin antibody titer was positive, but titers of other anti-thyroid antibodies, including antithyroid peroxidase antibody, TSH receptor antibodies, and thyroid-stimulating antibody, were negative. Levels of FT3, FT4, and TSH were similar when measured by three different laboratory kits, and FT4 was still high when measured by equilibrium dialysis. By affinity chromatography, FT4, TT4, and albumin were extracted to the same fraction, and the levels of FT4 and TT4 were extremely high. By combination of reversed phase liquid chromatography and mass spectrometry techniques, the amino acid sequence of human serum albumin was determined. The patient was found to be a heterozygote for p.R218P mutation in the gene for human serum albumin and was diagnosed as FDH. This patient, who harbored the p.R218P mutation in the albumin gene, is the fifth case report of FDH in Japan. This condition is characterized by extremely high serum FT4 and moderately high serum FT3 levels. Although rare, FDH should be considered in the differential diagnosis for syndrome of inappropriate secretion of TSH (SITSH) in Japan.
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