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Objective
The management of thyroid eye disease (TED) has undergone significant changes for decades. The study sought to investigate current clinical practice on the management of TED in China.
Methods
An online questionnaire survey was conducted from April to May 2023. The questionnaire involved diagnostic criteria for TED, multidisciplinary treatment (MDT) collaboration, and treatment preference for mild, moderate, and severe TED.
Results
A total of 289 questionnaires were collected, with 165 from endocrinologists and 124 from ophthalmologists. Only 36.7% of participants claimed there was an MDT clinical pattern for TED in their institutions. The coverage of biological agents was around 10% or lower. These were distinctly lower than in Western countries. About 62.6% of participants believed the incidence of TED has increased in recent years. Imaging techniques were used widely to assist in the diagnosis of TED. However, there was still controversy regarding the definition of proptosis in the Chinese population. Most doctors managed risk factors and provided orbital supportive treatments of artificial tears and glasses. For mild active TED, endocrinologists (39.4%) were inclined to recommend therapy for hyperthyroidism alone, while ophthalmologists (43.6%) preferred orbital corticosteroid injections. Currently, the most widely used treatment for moderate to severe active TED was high-dose intravenous corticosteroid (94.8%), while orbital radiotherapy combined with immunosuppressive agents was the most recognized second-line therapy (43.6%).
Conclusion
The study documented the consistency and differences between current clinical practices in the management of TED in China and the recently updated guidelines. There was a remarkable difference between ophthalmology and endocrinology departments, warranting management optimization.
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Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Department of Internal Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
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Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild–moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program – as IF – is initiated.
Department of Pathology, General University Hospital of Ciudad Real, Ciudad Real, Spain
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Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain
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The Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA-BIONAND Platform), University of Malaga, Malaga, Spain
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The Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA-BIONAND Platform), University of Malaga, Malaga, Spain
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Department of Pathology, Virgen de la Victoria University Hospital, Málaga, Spain
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Department of Pathology, Virgen de la Victoria University Hospital, Málaga, Spain
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Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Málaga, Spain
The Biomedical Research Institute of Malaga and Platform in Nanomedicine (IBIMA-BIONAND Platform), University of Malaga, Malaga, Spain
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Graphical abstract
Abstract
Objective
The objective of this study was to analyze the evolution in the diagnosis and management of indeterminate thyroid nodules over three time periods.
Methods
In total, 3020 patients with thyroid nodules underwent cytological evaluation during three periods (2006–2008, 2012–2014, 2017–2019). The distribution of diagnostic cytology, risk of malignancy, diagnostic performance indices of fine needle aspiration (FNA), and cytologic–histologic correlation in indeterminate cytology were analyzed.
Results
Only 2.2% of cytology tests were insufficient for a diagnosis. About 86.9% cytology was benign, 1.7% malignant, and 11.4% indeterminate. Indeterminate cytology rates were 15.9% (2006–2008), 10.1% (2012–2014), and 10% (2017–2019). Surgery was performed in 13% of benign cytology, resulting in malignant histology in 2.7%. All malignant and suspicious cytology underwent surgery, with malignancy confirmed in 98% and 77% of cases, respectively.
All ‘indeterminate with atypia’ cytology (2006–2008) and Bethesda IV (2012–2014; 2017–2019) underwent surgery, with malignancy confirmed in 19.6%, 43.8%, and 25.7%, respectively. In the ‘indeterminate without atypia’ category (2006–2008) and Bethesda III (2012–2014; 2017–2019), diagnostic surgery was performed in 57.7%, 78.6%, and 59.4%, respectively, with malignancy confirmed in 3.3%, 20.5%, and 31.6%. The FNA sensitivity was 91.6%, with a negative predictive value greater than 96% in all periods. The specificity exceeded 75% in the last two periods.
Conclusion
The Bethesda system reduces indeterminate cytology and improves the accuracy of FNA diagnosis. We reported a higher proportion of malignancy than expected in Bethesda III, underscoring the importance of having institution-specific data to guide decision-making. However, there is a need for risk stratification tools that allow for conservative management in low-risk cases.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy
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Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Background
Fatigue is a frequent adverse event during systemic treatments for advanced thyroid cancer, often leading to reduction, interruption, or discontinuation. We were the first group to demonstrate a correlation between fatigue and primary adrenal insufficiency (PAI).
Aim
The objective was to assess the entire adrenal function in patients on systemic treatments.
Methods
ACTH, cortisol and all the hormones produced by the adrenal gland were evaluated monthly in 36 patients (25 on lenvatinib, six on vandetanib, and five on selpercatinib). ACTH stimulation tests were performed in 26 cases.
Results
After a median treatment period of 7 months, we observed an increase in ACTH values in 80–100% of patients and an impaired cortisol response to the ACTH test in 19% of cases. Additionally, dehydroepiandrosterone sulphate, ∆-4-androstenedione and 17-OH progesterone levels were below the median of normal values in the majority of patients regardless of the drug used. Testosterone in females and oestradiol in males were below the median of normal values in the majority of patients on lenvatinib and vandetanib. Finally, aldosterone was below the median of the normal values in most cases, whilst renin levels were normal. Metanephrines and normetanephrines were always within the normal range. Replacement therapy with cortisone acetate improved fatigue in 14/17 (82%) patients with PAI.
Conclusion
Our data confirm that systemic treatments for advanced thyroid cancer can lead to impaired cortisol secretion. A reduction in the other hormones secreted by the adrenal cortex has been first reported and should be considered in the more appropriate management of these fragile patients.
University of Geneva, Faculty of Medicine, Rue Michel Servet, Geneva, Switzerland
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University of Geneva, Faculty of Medicine, Rue Michel Servet, Geneva, Switzerland
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University of Geneva, Faculty of Medicine, Rue Michel Servet, Geneva, Switzerland
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University of Geneva, Faculty of Medicine, Rue Michel Servet, Geneva, Switzerland
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University of Geneva, Faculty of Medicine, Rue Michel Servet, Geneva, Switzerland
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University of Geneva, Faculty of Medicine, Rue Michel Servet, Geneva, Switzerland
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Service of Hematology and Laboratory of Hematology, Institut Central des Hôpitaux, Hôpital du Valais, Av. du Grand-Champsec, Sion, Switzerland
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University of Geneva, Faculty of Medicine, Rue Michel Servet, Geneva, Switzerland
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Langerhans cell histiocytosis (LCH) may present as unifocal disease of the suprasellar region, with symptoms and signs of hypopituitarism, arginine vasopressin deficiency (AVP-D), and weight gain. Transcranial biopsy is necessary to define diagnosis and guide treatment decisions, but it is associated with significant morbidity. We describe a patient with Hashimoto thyroiditis and a single hypothalamic mass in whom LCH diagnosis was made by thyroid fine-needle aspiration cytology (FNAC) performed despite nonspecific findings in thyroid imaging, on the basis of a slightly elevated [18F]-fluorodeoxyglucose (FDG) avidity on PET/CT and volume increase during follow-up.
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Background
Current guidelines recommend different postpartum approaches for patients started on levothyroxine (LT4) during pregnancy.
Objective
We studied the postpartum management of these patients and determined factors associated with long-term hypothyroidism.
Methods
A retrospective study was conducted at a tertiary center between 2014 and 2020, with LT4 initiation according to 2014 ETA recommendations. We performed multivariate logistic regression (MVR) and a receiver operating characteristic curve analysis to determine variables associated with long-term hypothyroidism and their optimal cutoffs.
Results
LT4 was initiated in 177 pregnant women, and 106/177 (60%) were followed at long-term (at least 6 months post partum) (28.5 (9.0–81.9) months). LT4 could have been stopped in 45% of patients who continued it immediately after delivery. Thirty-six out of 106 (34%) patients were long-term hypothyroid. In them, LT4 was initiated earlier during pregnancy than in euthyroid women (11.7 ± 4.7 vs 13.7 ± 6.5 weeks, P = 0.077), at a higher thyroid-stimulating hormone (TSH) level (4.1 (2.2–10.1) vs 3.5 (0.9–6.9) mU/L, P = 0.005), and reached a higher dose during pregnancy (62.8 ± 22.2 vs 50.7 ± 13.9 µg/day, P = 0.005). In the MVR, only the maximal LT4 dose during pregnancy was associated with long-term hypothyroidism (odds ratio (OR) = 1.03, 95% CI: 1.00–1.05, P = 0.003). The optimal cutoffs for predicting long-term hypothyroidism were an LT4 dose of 68.75 µg/day (87% specificity, 42% sensitivity; P = 0.013) and a TSH level ≥ 3.8 mU/L (68.5% specificity, 77% sensitivity; P = 0.019).
Conclusion
One-third of the patients who started on LT4 during pregnancy had long-term hypothyroidism. The TSH level at treatment initiation and the LT4 dose during pregnancy could guide the decision for continuing long-term LT4.
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MacroTSH still interferes with TSH assays. We present here a case report illustrating the difficulties that can arise in such conditions and attempt to discuss the steps involved in diagnosis.
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Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
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Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, Freiburg, Germany
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Academic Center for Thyroid Diseases, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
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Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
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DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
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Introduction
Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the hypothalamic–pituitary–thyroid (HPT) axis and have a heritable component. Using genetic information, we applied tissue-specific transcriptome-wide association studies (TWAS) and plasma proteome-wide association studies (PWAS) to elucidate gene products related to thyrotropin (TSH) and free thyroxine (FT4) levels.
Results
TWAS identified 297 and 113 transcripts associated with TSH and FT4 levels, respectively (25 shared), including transcripts not identified by genome-wide association studies (GWAS) of these traits, demonstrating the increased power of this approach. Testing for genetic colocalization revealed a shared genetic basis of 158 transcripts with TSH and 45 transcripts with FT4, including independent, FT4-associated genetic signals within the CAPZB locus that were differentially associated with CAPZB expression in different tissues. PWAS identified 18 and ten proteins associated with TSH and FT4, respectively (HEXIM1 and QSOX2 with both). Among these, the cognate genes of five TSH- and 7 FT4-associated proteins mapped outside significant GWAS loci. Colocalization was observed for five plasma proteins each with TSH and FT4. There were ten TSH and one FT4-related gene(s) significant in both TWAS and PWAS. Of these, ANXA5 expression and plasma annexin A5 levels were inversely associated with TSH (PWAS: P = 1.18 × 10−13, TWAS: P = 7.61 × 10−12 (whole blood), P = 6.40 × 10−13 (hypothalamus), P = 1.57 × 10−15 (pituitary), P = 4.27 × 10−15 (thyroid)), supported by colocalizations.
Conclusion
Our analyses revealed new thyroid function-associated genes and prioritized candidates in known GWAS loci, contributing to a better understanding of transcriptional regulation and protein levels relevant to thyroid function.
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Context
Two-thirds of metastatic differentiated thyroid cancer (DTC) patients have radioiodine (RAI)-resistant disease, resulting in poor prognosis and high mortality. For rare NTRK and RET fusion-positive metastatic, RAI-resistant thyroid cancers, variable success of re-induction of RAI avidity during treatment with NTRK or RET inhibitors has been reported.
Case presentation and results
We report two cases with RAI-resistant lung metastases treated with larotrectinib: an 83-year-old male presenting with an ETV6::NTRK3 fusion-positive tumor with the TERT promoter mutation c.-124C>T, and a 31-year-old female presenting with a TPR::NTRK1 fusion-positive tumor (and negative for TERT promoter mutation). Post larotrectinib treatment, diagnostic I-123 whole body scan revealed unsuccessful RAI-uptake re-induction in the TERT-positive tumor, with a thyroid differentiation score (TDS) of −0.287. In contrast, the TERT-negative tumor exhibited successful I-131 reuptake with a TDS of −0.060.
Conclusion
As observed for RAI-resistance associated with concurrent TERT and BRAF mutations, the co-occurrence of TERT mutations and NTRK fusions may also contribute to re-sensitization failure.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
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Background
Radiofrequency ablation (RFA) is effective in the treatment of thyroid nodules, leading to a 50–90% reduction with respect to baseline. Current guidelines indicate the need for a benign cytology prior to RFA, though, on the other side, this procedure is also successfully used for the treatment of papillary microcarcinomas. No specific indications are available for nodules with an indeterminate cytology (Bethesda III/IV).
Aim
To evaluate the efficacy of RFA in Bethesda III nodules without genetic alterations as verified by means of a custom panel.
Methods
We have treated 33 patients (mean delivered energy 1069 ± 1201 J/mL of basal volume) with Bethesda III cytology, EU-TIRADS 3-4, and negative genetic panel. The mean basal nodular volume was 17.3 ± 10.7 mL.
Results
Considering the whole series, the mean volume reduction rate (VRR) was 36.8 ± 16.5% at 1 month, 59.9 ± 15.5% at 6 months, and 62 ± 15.7% at 1-year follow-up. The sub-analysis done in patients with 1 and 2 years follow-up data available (n = 20 and n = 5, respectively) confirmed a progressive nodular volume decrease. At all-time points, the rate of reduction was statistically significant (P < 0.0001), without significant correlation between the VRR and the basal volume. Neither cytological changes nor complications were observed after the procedure.
Conclusion
RFA is effective in Bethesda III, oncogene-negative nodules, with reduction rates similar to those obtained in confirmed benign lesions. This procedure represents a good alternative to surgery or active surveillance in this particular class of nodules, regardless of their initial volume. A longer follow-up will allow to evaluate further reduction or possible regrowth.
