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Background
This study aimed to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine-to-free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), thyroid-stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with all-cause mortality in euthyroid adults.
Methods
The study included 6243 euthyroid adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2012. FT3/FT4 ratio, TFQIFT4, TSHI, and TT4RI were calculated. The multivariable Cox proportional hazard regression, restricted cubic spline (RCS), and subgroup analysis were conducted.
Results
Individuals in fourth quartile (Q4) had lower all-cause mortality than those in first quartile (Q1) of FT3/FT4 ratio (hazard ratio (HR): 0.70, 95% CI: 0.51, 0.94). Regarding TFQIFT4, individuals in Q4 of TFQIFT4 had a 43% higher all-cause mortality than those in Q1 (HR: 1.43, 95% CI: 1.05, 1.96) (P < 0.05, all). Compared with participants in Q1, no associations of TSHI and TT4RI with mortality were found. TFQIFT4 was linearly and positively associated with mortality. However, the FT3/FT4 ratio showed a U-shaped association with mortality.
Conclusions
Increased risk for all-cause mortality was positively associated with TFQIFT4, suggesting that increased risk for all-cause mortality was associated with decreased central sensitivity to thyroid hormones. Furthermore, the FT3/FT4 ratio showed a U-shaped association with mortality, with an inflection point at 0.5. However, more cohort studies are needed to validate the conclusions.
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Objective
Anaplastic thyroid cancer (ATC) is an aggressive disease associated with poor outcomes and resistance to therapies. Our study aim was to evaluate the activity of a combinatorial regimen of sandwich sequencing of pembrolizumab immunotherapy and hypofractionated radiotherapy (RT).
Methods
In this case series, patients with ATC received hypofractionated RT (QUAD-shot) and intravenous pembrolizumab 200 mg every 3–4 weeks. Pembrolizumab was continued until disease progression or up till 24 months. Concurrent lenvatinib treatment was allowed. Primary endpoint was best overall response (BOR) and progression-free survival (PFS). Additionally, we performed immune profiling of circulating T cells in a responder to investigate the immune response to our combinatorial treatment.
Results
At median follow-up of 32.6 months (IQR: 26.4–38.8), of a cohort of five patients, BOR was 80%; with two complete responses (CR) and two partial responses (PR). Patients who achieved CR remained disease-free at last follow-up. Median PFS was 7.6 months (IQR: 6.2–NR), and 1-year PFS and overall survival rate was 40% (95% CI: 13.7–100) for both. Treatment was well-tolerated, with mostly grade 1–2 adverse events. Immune profiling of one partial responder revealed an increase in activated CD4 and CD8 T cells post-QUAD-shot RT, which was further enhanced during the maintenance phase of pembrolizumab.
Conclusion
Herein, we report a case series of five patients with ATC, with two long-term survivors who were treated with surgical debulking followed by QUAD-shot RT and pembrolizumab, possibly due to synergy of local and systemic treatments in activating anti-tumour immunogenic cytotoxicity. This regimen warrants further investigation in a larger cohort of patients.
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Objective
This study aims to analyze the diagnostic utility of multiple repeat FNA on thyroid nodules with initially benign diagnosis.
Methods
In a 5-year period, 1658 thyroid nodules with initially benign FNAs were retrospectively reviewed and followed for subsequent resection and repeat biopsy.
Results
Out of 2150 thyroid nodules, 1658 (77.1%) were diagnosed as benign on FNAs. The average age at diagnosis was 57.4 years (range: 11–93 years), and most were females (83.8%). Repeat FNA was performed on 183 benign nodules, of which 141 (8.5%) were sampled a second time and 42 (2.5%) had two or more repeat samplings. For the benign nodules without repeat FNAs, 124 had benign resection. Of cases with one-time repeat FNA, most (n = 101) remained benign on repeat FNAs, 13 of which were benign on resection. Eleven had atypical repeat FNAs, five were resected, four of which were benign and one was atypical follicular neoplasm with HRAS and TERT promoter mutations. Of cases with multiple repeat FNA, most (n = 35) were still benign on repeat FNAs, one had benign resection. Two had atypical repeat biopsies, one was PTC on resection with CCD6::RET fusion. The positive predictive value significantly decreased from 41.1% on single FNA to 8.3% on one-time repeat (P < 0.001) and 16.7% on multiple repeat (P = 0.002). The total cost for the work-up of previously benign nodules was $285,454.
Conclusions
Repeat FNA biopsies did not provide an additional diagnostic value in the evaluation of benign thyroid nodules, and often led to unwarranted follow-up procedures and significantly increased health-care cost.
Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, China
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Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, China
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Objective
It is crucial to diagnose lymph node (LN) metastases (LNM) before or during thyroid carcinoma surgery. Measurement of thyroglobulin (Tg) in the fine needle aspirate washout (FNA-Tg) is useful to assist in the diagnosis of LNM for papillary thyroid carcinoma (PTC). This study aimed to assess the diagnostic performance of a new technique based on a colloidal gold-based immunochromatographic assay (GICA) for intraoperative FNA-Tg in diagnosing LNM.
Clinical trial information
This study is registered with chictr.org.cn, ID: ChiCTR2200063561 (registered 11 September, 2022).
Methods
This prospective study enrolled 51 PTC patients who underwent cervical LN dissection. A total of 150 LNs dissected from the central and lateral compartments were evaluated by FNA-Tg-GICA at three different time points and compared with frozen sections and the conventional Tg measurement method electrochemiluminescence immunoassay (ECLIA). Receiver operating characteristic curve (ROC) and area under the curve (AUC), cutoff value to discriminate benign and malignant LNs, sensitivity, specificity, and accuracy were provided.
Results
The cutoff value of FNA-Tg to predict LNM was 110.83 ng/mL for ECLIA and 13.19 ng/mL, 38.69 ng/mL, and 77.17 ng/mL for GICA at 3, 10, and 15 min, respectively. There was no significant difference between the AUCs of GICA at different time points compared to using ECLIA and frozen sections. Besides, the diagnostic performance of GICA and ECLIA showed no significant difference in evaluating LNM from central and lateral compartments or between the TgAb-positive subgroup and TgAb-negative subgroup.
Conclusion
GICA is a promising method for intraoperative FNA-Tg measurement and has high value in predicting LNM. It may be a novel alternative or supplementary method to frozen section or ECLIA.
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Graphical abstract
Abstract
In 2022, the European Chemicals Agency (ECHA) made a statement concluding that iodine is an endocrine disruptor (ED). We stress the fact that the ECHA opinion ECHA/BPC/357/2022 is based on their misguidedly zooming in on exclusively the biocidal products (e.g. hand disinfectants, disinfection of animals’ teats/udder, embalming fluids before cremation) that contain molecular iodine (I2), entirely neglecting the 2013 ECHA Regulation (EU) no. 528/2012 describing iodine as being of ‘great importance for human health’. Clearly, the current sweeping and erroneous classification of ‘iodine’ as an endocrine disruptor is ill-advised. We moreover call upon the scientific and medical community at large to use the accurate scientific nomenclature, i.e. iodide or iodate instead of ‘iodine’ when referring to iodized salts and food prepared there with. Drugs, diagnostic agents, and synthetic chemicals containing the element iodine in the form of covalent bonds must be correctly labeled ‘iodinated’, if possible, using each time their distinctive and accurate chemical or pharmacological name.
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Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada
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Objective
Loss of function mutations in the insulin receptor substrate 4 (IRS4) gene cause a rare form of X-linked congenital central hypothyroidism in boys and men. Affected individuals show decreased thyroid-stimulating hormone (TSH) secretion. Members of the IRS family canonically act as scaffold proteins between tyrosine kinase receptors and downstream effectors. How loss of IRS4 affects TSH synthesis or secretion is unresolved. We therefore assessed IRS4’s role in the hypothalamic–pituitary–thyroid axis of Irs4 knockout mice.
Methods
We generated two global Irs4 knockout mouse lines harboring either two or four base-pair deletions that result in frameshifts and loss of most of the IRS4 protein.
Results
Under normal laboratory conditions, Irs4 knockout males did not exhibit impairments in pituitary expression of TSH subunit genes (Tshb or Cga) or in the thyrotropin-releasing hormone (TRH) receptor. Additionally, their serum thyroid hormone, triiodothyronine (T3) and thyroxine (T4), and hypothalamic Trh expression levels were normal. When Irs4 knockouts were rendered hypothyroid with a low-iodine diet supplemented with propylthiouracil for 3 weeks, their serum TSH increased similarly to wild-type males.
Conclusion
Overall, Irs4 knockout mice do not exhibit central hypothyroidism or otherwise appear to phenocopy IRS4 deficient patients. Compensation by another IRS protein may explain euthyroidism in these animals.
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Objective
Tumor molecular genotyping plays a key role in improving the management of advanced thyroid cancers. Molecular tests are classically performed on formalin-fixed, paraffin-embedded (FFPE) carcinoma tissue. However alternative molecular testing strategies are needed when FFPE tumoral tissue is unavailable. The objective of our study was to retrospectively assess the performance of targeted DNA and RNA-based next-generation sequencing (NGS) on the fine needle aspirate from thyroid cancer cervical recurrences to determine if this strategy is efficient in clinical practice.
Design/Methods
A retrospective study of 33 patients who had had DNA and/or RNA-based NGS on ultrasound (US)-guided fine needle aspirates of cervical thyroid cancer recurrences in our Department from July 2019 to September 2022.
Results
In total, 34 DNA and 32 RNA-based NGS analyses were performed. Out of the 34 DNA-based NGS performed, 27 (79%) were conclusive allowing the identification of an oncogenic driver for 18 patients (53%). The most common mutation (n = 13) was BRAF c.1799T>A. Out of the 32 RNA-based NGS performed, 26 were interpretable (81%) and no gene fusion was found. The identification of a BRAFV600E mutation was decisive for one patient in our series, who was prescribed dabrafenib and trametinib.
Conclusion
NGS performed on fine needle aspirates of neck lymph node metastases enabled the identification of an oncogenic driver alteration in 53% of the cases in our series of advanced thyroid cancer patients and could significantly alter patient management.
Significance statement
This paper shows that thyroid cancer genotyping on the fine needle aspirate (FNA) of a metastatic neck lymph node recurrence can be performed efficiently. This strategy of genotyping appears particularly effective and safe when FFPE tissue is unavailable and when the spread of the disease requires systemic treatment. To the best of our knowledge, our data regarding DNA and RNA next generation sequencing on FNA of metastatic neck recurrences are the first ever published.
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Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Purpose
The aim was to determine the combined value of serological lipid metabolism and an orbital MRI quantitative parameter in predicting the effectiveness of glucocorticoid (GC) therapy in patients with thyroid eye disease (TED).
Methods
This study retrospectively enrolled 46 patients with active and moderate-to-severe TED (GC-effective group, n = 29; GC-ineffective group, n = 17). Serological lipid metabolism, the orbital MRI-based minimum signal intensity ratio of extraocular muscles (EOM-SIRmin), as well as other clinical parameters before GC therapy were collected and compared between the two groups. Multivariate logistic regression and receiver operating characteristic curve analysis were adopted to identify independent predictable variables and assess their predictive performances.
Results
Compared to the GC-ineffective group, the GC-effective group showed lower serum total cholesterol levels (P = 0.006), lower serum low-density lipoprotein cholesterol levels (P = 0.019), higher EOM-SIRmin values (P = 0.005), and shorter disease durations (P = 0.017). Serum total cholesterol and EOM-SIRmin were found to be independent predictors of GC-effective TED through multivariate analysis (odds ratios = 0.253 and 2.036 per 0.1 units, respectively) (both P < 0.05). The integration of serum total cholesterol ≤4.8 mmol/L and EOM-SIRmin ≥ 1.12 had a better predictive efficacy (area under the curve, 0.834) than EOM-SIRmin alone, with a sensitivity of 75.9% and a specificity of 82.4% (P = 0.031).
Conclusion
Serological lipid metabolism, combined with an orbital MRI-derived parameter, was a useful marker for predicting the effectiveness of GCs in patients with active and moderate-to-severe TED.
Institute of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
Wallenberg’s Centre of Molecular and Translational Medicine, Region Västra Götaland, Sweden
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Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden
Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden
Gothenburg Centre for Person Centred-Care (GPCC), Göteborg, Sweden
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Background
Mood disorders are common in Graves’ disease despite treatment. The pathogenic mechanisms involved are unknown and so is whether previous psychiatric disease influences these symptoms.
Methods
This is a longitudinal study conducted in Sweden on 65 women with newly diagnosed Graves’ disease and 65 matched controls. Participants were examined during hyperthyroidism and after 15 months of treatment. Examinations included blood sampling, and psychiatric testing with the Comprehensive Psychopathological Rating Scale for Affective Syndromes and the Structured Clinical Interview for DSM-IV – Axis I Disorders. We also performed two analyses of a national population-based registry to determine previous psychiatric diagnoses and previous prescriptions of psychoactive drugs in (i) all patients we asked to participate and (ii) all Swedish women given a diagnosis of hyperthyroidism during 2013–2018, comparing them to matched controls.
Results
There was no increased previous psychiatric comorbidity in Graves’ patients compared to controls. There was no higher prevalence of psychiatric diagnoses and prescriptions of psychoactive drugs between (i) included GD patients compared to those who declined participation and (ii) women with a hyperthyroidism diagnosis in 5 years prior to their diagnosis, compared to matched controls. Depression scores and anxiety scores were higher in patients compared to controls both during hyperthyroidism (depression (median (IQR): 7.5 (5.0–9.5) vs 1.0 (0.5–2.5) P < 0.001), anxiety: 7.7 (5.0–11) vs 2.5 (1.0–4.0) P < 0.001) and after treatment (depression: 2.5 (1.5–5.0) vs 1.5 (0.5-3.5) P < 0.05), anxiety: 4.0 (2.5–7.5) vs 3.0 (1.5-5.0) P < 0.05). Patients with a previous psychiatric condition, mild eye symptoms, and a younger age had more anxiety at 15 months compared to patients without these symptoms and a higher age (all p<0.05).
Conclusion
Graves’ disease affects patients’ mood despite treatment. A previous psychiatric condition, mild eye symptoms, and a younger age increase the vulnerability for long-lasting symptoms and require specific attention.
