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Objective
Total thyroidectomy is associated with a high risk of postoperative hypoparathyroidism, mainly due to the unintended surgical damage to the parathyroid glands or their blood supply. It is possible that surgeons who also perform parathyroid surgery see lower rates of postoperative hypoparathyroidism. In a single institution, we investigated the effects of restricting total thyroidectomy operations for Graves’ disease to two surgeons who performed both thyroid and parathyroid surgeries. We aimed to evaluate the rates of postoperative hypoparathyroidism in a 10-year period with primary attention toward patients with Graves’ disease.
Design
Retrospective cohort study from a single institution.
Methods
We defined the rate of permanent hypoparathyroidism after total thyroidectomy as the need for active vitamin D 6 months postoperatively. Between 2012 and 2016, seven surgeons performed all thyroidectomies. From January 2017, only surgeons also performing parathyroid surgery carried out thyroidectomies for Graves’ disease.
Results
We performed total thyroidectomy in 543 patients. The rate of permanent hypoparathyroidism decreased from 28% in 2012–2014 to 6% in 2020–2021. For patients with Graves’ disease, the rate of permanent hypoparathyroidism decreased from 36% (13 out of 36) in 2015–2016 to 2% (1 out of 56) in 2020–2021. In cancer patients, the rate of permanent hypoparathyroidism decreased from 30% (14 out of 46) in 2012–2014 to 10% (10 out of 51) in 2020–2021.
Conclusion
Restricting thyroidectomy to surgeons who also performed parathyroid operations reduced postoperative hypoparathyroidism markedly. Accordingly, we recommend centralisation of the most difficult thyroid operations to centres and surgeons with extensive experience in parathyroid surgery.
Significance statement
Thyroid surgery is performed by many different surgeons with marked differences in outcome. Indeed, the risk of postoperative permanent hypoparathyroidism may be very high in low-volume centres. This serious condition affects the quality of life and increases long-term morbidity and the patients develop a life-long dependency of medical treatments. We encountered a high risk of hypoparathyroidism after the operation for Graves’ disease and restricted the number of surgeons to two for these operations. Further, these surgeons were experienced in both thyroid and parathyroid surgeries. We show a dramatic reduction in postoperative hypoparathyroidism after this change. Accordingly, we recommend centralisation of total thyroidectomy to surgeons with experience in both thyroid and parathyroid procedures.
Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
Key Laboratory of TCM Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, China
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Objective
To assess the long-term efficacy and safety of microwave ablation (MWA) in treating low-risk papillary thyroid microcarcinomas (PTMC) and to identify predictive factors for the postoperative local tumor progression of PTMC.
Methods
A total of 154 low-risk PTMC patients treated with MWA who were followed up for at least 3 months were retrospectively recruited. Ultrasonography was performed after MWA to assess the local tumor progression. Adverse events associated with MWA were recorded. The ablated volume (Va) and initial ablation ratio (IAR) were measured to assess their influences on the recurrence risk of PTMC.
Results
The mean tumor volume of PTMC before MWA was 0.071 (0.039, 0.121) cm3, with a maximum diameter of 0.60 ± 0.18 cm. All PTMC patients were followed up for 6 (3, 18) months. Va increased immediately after MWA, then gradually decreased over time, till significantly smaller at 12 months than that before MWA (P < 0.05). The median volume reduction ratio at 24 months reached 100%, which was maintained during a 60-month follow-up. A total of 7 (4.55%) cases of local tumor progression were recorded during the follow-up. Kaplan–Meier survival analysis revealed that the rate of local tumor progression was significantly lower in PTMC patients with a maximum tumor diameter < 0.70 cm than in those with ≥0.70 cm (P = 0.031). A significant better prognosis was achieved in PTMC patients with IAR ≥ 15 than in those with IAR < 15 (P = 0.015). Sex, age (<55 years) and preoperative thyroid-stimulating hormone (>2.0 mU/L) of PTMC patients were not correlated with local tumor progression.
Conclusion
MWA is an effective therapeutic strategy for low-risk PTMC with high safety. The maximum tumor diameter and IAR are predictive factors for the local tumor progression of PTMC after MWA.
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Background
Sarcoidosis is a multiple systemic granulomatous disease, and its main pathological feature is non-caseous necrotic epithelial granuloma. The pathogenesis is not fully understood. The prevalence of thyroid disease is likely higher among individuals with sarcoidosis. However, this association still lacks clinical evidence.
Objective
The aim of this study was to estimate the incidence of thyroid disease in patients with sarcoidosis.
Methods
A literature search was conducted using PubMed, Web of Science, Embase, and China National Knowledge Infrastructure literature databases. Fixed- or random-effects models were used for analysis according to heterogeneity. The results were subjected to meta-analysis with odds ratios (ORs) and corresponding 95% confidence intervals (CIs).
Results
In total, six articles were included in this meta-analysis, which involved 2044 sarcoidosis cases and 5652 controls. The studies found that the incidence of thyroid disease in patients with sarcoidosis was significantly increased compared to the controls (OR 3.28, 95% CI 1.83–5.88).
Conclusions
This systematic review is the first to evaluate the incidence of thyroid disease in sarcoidosis patients, which was increased compared with the controls, suggesting that sarcoidosis patients should be screened for thyroid disease.
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Shanghai Center of Thyroid Diseases, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
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Shanghai Center of Thyroid Diseases, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China
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Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China
Institute of Translational Medicine, Shanghai Jiao Tong University, Shanghai, China
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Thyroid fine needle aspiration biopsy (FNAB) remains indeterminate in 16–24% of the cases. Molecular testing could improve the diagnostic accuracy of FNAB. This study examined the gene mutation profile of patients with thyroid nodules and analyzed the diagnostic ability of molecular testing for thyroid nodules using a self-developed 18-gene test. Between January 2019 and August 2021, 513 samples (414 FNABs and 99 formalin-fixed paraffin-embedded (FFPE) specimens) underwent molecular testing at Ruijin Hospital. Sensitivity (Sen), specificity (Spe), positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. There were 457 mutations in 428 samples. The rates of BRAF, RAS, TERT promoter, RET/PTC, and NTRK3 fusion mutations were 73.3% (n = 335), 9.6% (n = 44), 2.8% (n = 13), 4.8% (n = 22), and 0.4% (n = 2), respectively. The diagnostic ability of cytology and molecular testing were evaluated in Bethesda II and V–VI samples. For cytology alone, Sen, Spe, PPV, NPV, and accuracy were 100%, 25.0%, 97.4%, 100%, and 97.4%; these numbers were 87.5%, 50.0%, 98.0%, 12.5%, and 86.2% when considering positive mutation, and 87.5%, 75.0%, 99.0%, 17.6%, and 87.1% when considering positive cytology or and positive mutation. In Bethesda III–IV nodules, when relying solely on the presence of pathogenic mutations for diagnosis, Sen, Spe, PPV, NPV, and AC were 76.2%, 66.7%, 94.1%, 26.8%, and 75.0%, respectively. It might be necessary to analyze the molecular mechanisms of disease development at the genetic level to predict patients with malignant nodules more accurately in different risk strata and develop rational treatment strategies and definite management plans.
Medical College, Shantou University, Shantou, China
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Medical College, Shantou University, Shantou, China
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Background
Heart failure (HF) is a complex and multifactorial syndrome caused by impaired heart function. The high morbidity and mortality of HF cause a heavy burden of illness worldwide. Non-thyroidal illness syndrome (NTIS) refers to aberrant serum thyroid parameters in patients without past thyroid disease. Observational studies have indicated that NTIS is associated with a higher risk of all-cause mortality in HF. This meta-analysis aimed to investigate the association between NTIS and HF prognosis.
Methods
Medline, Embase, Web of Science, and the Cochrane database were searched for any studies reporting an association between NTIS and HF prognosis from inception to 1 July 2022. A meta-analysis was then performed. The quality of studies was assessed using the Newcastle–Ottawa Scale. The heterogeneity of the results was assessed with I 2 and Cochran's Q statistics. Sensitivity analysis and publication bias analysis were also conducted.
Results
A total of 626 studies were retrieved, and 18 studies were finally included in the meta-analysis. The results showed that NTIS in HF patients was significantly associated with an increased risk of all-cause mortality and major cardiovascular events (MACE), but not with in-hospital mortality. The stability of the data was validated by the sensitivity analysis. There was no indication of a publication bias in the pooled results for all-cause mortality and MACE.
Conclusions
This meta-analysis showed that NTIS was associated with a worse outcome in HF patients. However, the association between NTIS and in-hospital mortality of HF patients requires further investigation.
School of Medicine, Ningbo University, Ningbo, China
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School of Medicine, Ningbo University, Ningbo, China
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School of Medicine, Ningbo University, Ningbo, China
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School of Medicine, Ningbo University, Ningbo, China
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School of Medicine, Ningbo University, Ningbo, China
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Objective
The aim of this study was to elaborate the link of thyroid hormones (THs) and metabolic syndrome (MetS) in a Chinese euthyroid employee population with MetS component(s).
Methods
An annual health checkup was performed on employees in 2019. Anthropometric parameters, metabolic parameters, and thyroid function were measured. A questionnaire was used in conjunction with Zhenhai Lianhua Hospital database to receive employees' medication records and thyroid surgical history records.
Results
A total of 5486 eligible employees were included; the prevalence of MetS was generally higher in males than in females (38.9 vs. 30.4%, P < 0.001). Among employees with central obesity, hypertriglyceridemia, hyperglycemia, hypertension, and low high-density lipoprotein cholesterol (HDL-C), the prevalence of MetS was 68.8, 63.6, 68.2, 48.8, and 60.0% in males and 72.6, 63.3, 61.3, 42.3, and 42.3% in females, respectively. Logistic regression analysis showed that thyroid-stimulating hormone and free thyroxine (FT4) quartiles had no significant impact on MetS. Free triiodothyronine/free thyroxine (FT3/FT4) and free triiodothyronine (FT3)) quartiles were positively associated with the increased odds ratio (OR) for MetS and dyslipidemia (hypertriglyceridemia and low HDL-C), regardless of gender. In males, FT3 and FT3/FT4 quartiles were positively associated with the OR for central obesity, whereas FT4 quartiles were negatively associated; both FT3 and FT4 quartiles were positively associated with increased OR of hyperglycemia, while similar results were not observed in females. Interaction analysis indicated no significant effect of gender and TH interactions on risk of MetS.
Conclusion
High FT3 and FT3/FT4 were strongly linked with MetS and dyslipidemia in our study, even in the euthyroid individuals. Tighter control of thyroid function was necessary for those with preexisting MetS component(s).
The First Affiliated Hospital, Department of Otorhinolaryngology, Hengyang Medical School, University of South China, Hengyang, Hunan, China
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The First Affiliated Hospital, Department of Endocrinology and Metabolism, Hengyang Medical School, University of South China, Hengyang, Hunan, China
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Background
Fibroblast growth factor 1 (FGF1) is extensively amplified in many tumors and accelerates tumor invasion and metastasis. However, the role and precise molecular mechanism by which FGF1 participates in thyroid cancer (TC) are still unclear.
Methods
Quantitative real-time polymerase chain reaction- and western blotting were used to detect the mRNA and protein levels of FGF1, high mobility group A (HMGA1), epithelial-to-mesenchymal transition (EMT)-related factors, and FGFs in both TC tissues and cell lines. Immunohistochemistry was conducted to examine the expression of FGF1 and HMGA1. Immunofluorescence staining was used to detect the coexpression of FGF1 and HMGA1. Transwell and wound healing assays were conducted to evaluate the effects of FGF1 on the capacity of invasion and migration in cells.
Results
FGF1 was upregulated in papillary thyroid carcinoma (PTC) tissues and cell lines and was relatively higher in PTC tissues with cervical lymph node metastasis. Furthermore, FGF1 promotes invasion and metastasis through the EMT pathway. Mechanistically, FGF1 promotes EMT through intracellular function independent of FGF receptors. Interestingly, we demonstrated that FGF1 could upregulate HMGA1 in TC cells, and the correlation of FGF1 and HMGA1 was positive in PTC tissues. FGF1 and HMGA1 had obvious colocalization in the nucleus. We further revealed that FGF1 promotes the invasion and migration of TC cells through the upregulation of HMGA1.
Conclusion
Intracellular FGF1 could promote invasion and migration in TC by mediating the expression of HMGA1 independent of FGF receptors, and FGF1 may be an effective therapeutic target in TC.
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Clinic for Nuclear Medicine, University Hospital of Zürich, Zürich, Switzerland
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Objective
Current staging and risk-stratification systems for predicting survival or recurrence of patients with differentiated thyroid carcinoma may be ineffective at predicting outcomes in individual patients. In recent years, nomograms have been proposed as an alternative to conventional systems for predicting personalized clinical outcomes. We conducted a systematic review to evaluate the predictive performance of available nomograms for thyroid cancer patients.
Design and methods
PROSPERO registration (CRD42022327028). A systematic search was conducted without time and language restrictions. PICOT questions: population, patients with papillary thyroid cancer; comparator prognostic factor, single-arm studies; outcomes, overall survival, disease-free survival, cancer-specific survival, recurrence, central lymph node metastases, or lateral lymph node metastases; timing, all periods; setting, hospital setting. Risk of bias was assessed through PROBAST tool.
Results
Eighteen studies with a total of 20 prognostic models were included in the systematic review (90,969 papillary thyroid carcinoma patients). Fourteen models were at high risk of bias and four were at unclear risk of bias. The greatest concerns arose in the analysis domain. The accuracy of nomograms for overall survival was assessed in only one study and appeared limited (0.77, 95% CI: 0.75–0.79). The accuracy of nomograms for disease-free survival ranged from 0.65 (95% CI: 0.55–0.75) to 0.92 (95% CI: 0.91–0.95). The C-index for predicting lateral lymph node metastasis ranged from 0.72 to 0.92 (95% CI: 0.86–0.97). For central lymph node metastasis, the C-index of externally validated studies ranged from 0.706 (95% CI: 0.685–0.727) to 0.923 (95% CI: 0.893–0.946).
Conclusions
Our work highlights the extremely high heterogeneity among nomograms and the critical lack of external validation studies that limit the applicability of nomograms in clinical practice. Further studies ideally using commonly adopted risk factors as the backbone to develop nomograms are required.
Significance statement
Nomograms may be appropriate tools to plan treatments and predict personalized clinical outcomes in patients with papillary thyroid cancer. However, the nomograms developed to date are very heterogeneous, and their results seem to be closely related to the specific samples studied to generate the same nomograms. The lack of rigorous external validation procedures and the use of risk factors that sometimes appear to be far from those commonly used in clinical practice, as well as the great heterogeneity of the risk factors considered, limit the ability of nomograms to predict patient outcomes and thus their current introduction in clinical practice.
Department of Breast Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China
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Department of Surgery, Second People's Hospital of Guizhou Province, Guiyang, Guizhou, China
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Objective
Thyroid cancer (THCA) is the most common endocrine cancer in the world. Although most patients with THCA have a good prognosis, the prognosis of those with THCA who have an extra-glandular invasion, vascular invasion, and distant metastasis is poor. Therefore, it is very important to find potential biomarkers that can effectively predict the prognosis and progression of highly aggressive THCAs. It has been identified that forkhead box P4 (FOXP4) may be a new biomarker for the proliferation and prognosis for tumor diagnosis. However, the expression and function of FOXP4 in THCA remain to be determined.
Methods
In the present study, the function of FOXP4 in cells was investigated through the comprehensive analysis of data in The Cancer Genome Atlas and combined with experiments including immunohistochemistry (IHC), colony formation, Cell Counting Kit-8 assay, wound scratch healing, and transwell invasion assay.
Results
In the present study, relevant bioinformatic data showed that FOXP4 was highly expressed in THCA, which was consistent with the results of the IHC and cell experiments. Meanwhile, 10 FOXP4-related hub genes were identified as potential diagnostic genes for THCA. It was found in further experiments that FOXP4 was located in the nucleus of THCA cells, and the expression of FOXP4 in the nucleus was higher than that in the cytoplasm. FOXP4 knockdown inhibited in vitro proliferation of the THCA cells, whereas overexpression promoted the proliferation and migration of THCA cells. Furthermore, deficiency of FOXP4 induced cell-cycle arrest.
Conclusion
FOXP4 might be a potential target for diagnosing and treating THCA.
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
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Amsterdam UMC location University of Amsterdam, Department of Endocrinology and Metabolism, Amsterdam, The Netherlands
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Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands
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Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands
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Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
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Introduction
In our hospital, physicians noticed high free thyroxine (fT4) concentrations without complete suppression of thyroid-stimulating hormone (TSH) in blood samples of patients at the outpatient clinic, which appeared to occur more often following the introduction of a new fT4 immunoassay. This discordance may be explained by incorrect reference intervals, analytical issues, or patient-related factors. We aimed to establish the contribution of the possible factors involved.
Methods
Reference intervals of both fT4 immunoassays were re-evaluated using blood samples of healthy volunteers and the new immunoassay’s performance was assessed using internal quality controls and external quality rounds. The frequency of discordant fT4 and TSH pairings obtained from laboratory requests were retrospectively analysed using a Delfia (n = 3174) and Cobas cohort (n = 3408). Last, a literature search assessed whether the time of blood draw and the time of levothyroxine (L-T4) ingestion may contribute to higher fT4 concentrations in L-T4 users.
Results
The original reference intervals of both fT4 immunoassays were confirmed and no evidence for analytical problems was found. The Delfia (n = 176, 5.5%) and Cobas cohorts (n = 295, 8.7%) showed comparable frequencies of discordance. Interestingly, 72–81% of the discordant results belonged to L-T4 users. Literature indicated the time of blood withdrawal of L-T4 users and, therefore, the time of L-T4 intake as possible explanations.
Conclusions
High fT4 without suppressed TSH concentrations can mainly be explained by L-T4 intake. Physicians and laboratory specialists should be aware of this phenomenon to avoid questioning the assay’s performance or unnecessarily adapting the L-T4 dose in patients.
