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Kenneth Ka Hei Lai Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Fatema Mohamed Ali Abdulla Aljufairi Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Department of Ophthalmology, Salmaniya Medical Complex, Government Hospitals, Bahrain

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Jake Uy Sebastian Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Department of Ophthalmology, Vicente Sotto Memorial Medical Center, Cebu City, Philippines

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Yingying Wei Department of Statistics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Ruofan Jia Department of Statistics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Karen Kar Wun Chan Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

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Elaine Yuen Ling Au Division of Clinical Immunology, Department of Pathology, Queen Mary Hospital, Hong Kong Special Administrative Region, China

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Alan Chun Hong Lee Division of Endocrinology and Metabolism, Department of Medicine, Queen Mary Hospital, Hong Kong Special Administrative Region, China

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Chiu Ming Ng Department of Medicine, Queen Elizabeth Hospital, Hong Kong Special Administrative Region, China

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Hunter Kwok Lai Yuen Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China

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Wilson Wai Kuen Yip Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

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Alvin Lerrmann Young Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China

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George Pak Man Cheng Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Clement Chee Yung Tham Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China

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Chi Pui Pang Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China

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Kelvin Kam Lung Chong Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Special Administrative Region, China
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China

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Purpose

This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients.

Methods

A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI.

Results

A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60–0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP.

Conclusion

TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

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Véronique Raverot Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Centre de biologie et de pathologie Est, Lyon, France

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Stéphanie Metrat Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Centre de biologie et de pathologie Est, Lyon, France

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Pauline Perrin Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Centre de biologie et de pathologie Est, Lyon, France

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Juliette Abeillon Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Lyon, France

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Hélène Lasolle Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Lyon, France

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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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Stan R Ursem Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands

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Anita Boelen Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam Reproduction & Development, Amsterdam, The Netherlands

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Jacquelien J Hillebrand Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands

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Wendy P J den Elzen Department of Laboratory Medicine, Laboratory Specialized Diagnostics & Research, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Public Health, Amsterdam, The Netherlands

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Annemieke C Heijboer Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam Reproduction & Development, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC Location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands

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Objective

International guidelines concerning subclinical hyperthyroidism and thyroid cancer advice absolute cut-off values for aiding clinical decisions in the low range of thyroid-stimulating hormone (TSH) concentrations. As TSH assays are known to be poorly standardized in the normal to high range, we performed a TSH assay method comparison focusing on the low range.

Methods

Sixty samples, selected to cover a wide range of TSH concentrations (<0.01 to 120 mIU/L) with oversampling in the lower range (<0.4 mIU/L), were used for the method comparison between three TSH immunoassays (Cobas, Alinity and Atellica). In addition, 20 samples were used to assess the coefficient of variation from duplicate measurements in these three methods.

Results

The TSH immunoassays showed standardization differences with a bias of 7–16% for the total range and 1–14% for the low range. This could lead to a different classification of 1.5% of all measured TSH concentrations <0.40 mIU/L measured in our laboratory over the last 6 months, regarding the clinically important cut-off value of TSH = 0.1 mIU/L. As the imprecision of the immunoassays varied from 1.6–5.5%, this could lead to a similar reclassification as the bias between immunoassays.

Conclusions

We established the standardization differences of frequently used TSH assays for the total and low concentration ranges. Based on the proportional bias and the imprecision, this effect seems to have limited clinical consequences for the low TSH concentration range. Nevertheless, as guidelines mention absolute TSH values to guide clinical decision-making, caution must be applied when interpreting values close to these cut-offs.

Open access
Ilaria Muller Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan, Italy

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Anita Daturi Department of Clinical Sciences and Community Health, University of Milan, Italy

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Matteo Varallo Department of Clinical Sciences and Community Health, University of Milan, Italy

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Tiziana E Re Internal Medicine - High Intensity of Care Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Davide Dazzi Casa di Cura Val Parma SRL, Langhirano (Parmigiano: Langhiràn), Italy

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Sara Maioli Department of Clinical Sciences and Community Health, University of Milan, Italy

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Erica Crivicich Department of Clinical Sciences and Community Health, University of Milan, Italy

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Francesco Di Marco Department of Clinical Sciences and Community Health, University of Milan, Italy

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Virgilio Longari Nuclear Medicine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Beatrice Dazzi Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Massimo Castellani Nuclear Medicine Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Giovanna Mantovani Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan, Italy

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Maura Arosio Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan, Italy

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Mario Salvi Endocrinology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

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Objective

We have previously observed thyroid dysfunction, i.e. atypical thyroiditis (painless thyrotoxicosis associated with non-thyroidal illness syndrome), in patients with severe acute respiratory syndrome coronavirus 2 disease (Covid-19). This study aimed to analyse the evolution of thyroid dysfunction over time.

Methods

One hundred eighty-three consecutive patients hospitalised for severe Covid-19 without known thyroid history were studied at hospital admission (baseline). Survivors were offered 12-month longitudinal follow-up including assessment of thyroid function, autoantibodies and ultrasound scan (US). Patients showing US focal hypoechoic areas suggestive of thyroiditis (focal hypoechogenicity) also underwent thyroid 99mTc or 123I uptake scan.

Results

At baseline, after excluding from TSH analysis, 63 out of 183 (34%) Covid-19 patients commenced on steroids before hospitalisation, and 12 (10%) showed atypical thyroiditis. Follow-up of 75 patients showed normalisation of thyroid function and inflammatory markers and no increased prevalence of detectable thyroid autoantibodies. Baseline US (available in 65 patients) showed focal hypoechogenicity in 28% of patients, of whom 82% had reduced thyroid 99mTc/123I uptake. The presence of focal hypoechogenicity was associated with baseline low TSH (P = 0.034), high free-thyroxine (FT4) (P = 0.018) and high interleukin-6 (IL6) (P = 0.016). Focal hypoechogenicity persisted after 6 and 12 months in 87% and 50% patients, respectively, but reduced in size. After 9 months, thyroid 99mTc/123I uptake partially recovered from baseline (+28%) but was still reduced in 67% patients.

Conclusions

Severe Covid-19 induces mild transient thyroid dysfunction correlating with disease severity. Focal hypoechogenicity, associated with baseline high FT4, IL6 and low TSH, does not seem to be related to thyroid autoimmunity and may persist after 1 year although decreasing in size. Long-term consequences seem unlikely.

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Federica D’Aurizio Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy

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Alessia Biasotto Department of Medicine, University of Udine, Udine, Italy

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Claudia Cipri Endocrinology, Metabolism and Clinical Nutrition Unit, University Hospital of Udine, Udine, Italy

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Franco Grimaldi Endocrinology, Metabolism and Clinical Nutrition Unit, University Hospital of Udine, Udine, Italy

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Jessica Zucco Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy

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Stefania Marzinotto Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy

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Francesco Curcio Department of Laboratory Medicine, Institute of Clinical Pathology, University Hospital of Udine, Udine, Italy
Department of Medicine, University of Udine, Udine, Italy

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Salvatore Benvenga Department of Clinical and Experimental Medicine, Endocrinology Section, University of Messina, Messina, Italy

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Introduction

Thyroid function tests (TFT) are extensively used in daily clinical practice. Here, we described a case of incongruent TFT both in a pregnant woman and in her newborn.

Case presentation

A 32-year-old woman, diagnosed with autoimmune thyroiditis during her first pregnancy, was monitored during her second gestation. At week 5 + 2 days, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) values (Dimension VISTA 1500, Siemens Healthineers) were within normal limits. At week 19 + 5 days, TSH remained normal while FT4 increased approximately by three-fold. FT4 inconsistency was with both TSH and the clinical status since she continued to be clinically euthyroid. On the same serum sample, thyroid autoantibodies were negative. At week 25 + 4 days, the patient complained of palpitations and dyspnea, with tachycardia. Even though TSH was normal, high levels of both FT4 and free triiodothyronine (FT3) were interpreted as evidence of thyroid overactivity and methimazole was started. TFT of the pregnant woman continued to be monitored throughout gestation. Postpartum FT4 and FT3 gradually returned to normal. TFT, performed on the daughter’s serum, 3 days after birth, showed the same inconsistency as her mother but without clinical signs of congenital hyperthyroidism. Based on the clinical and laboratory setting, the presence of circulating autoantibodies against T3 and T4 (THAb) was suspected and demonstrated by radioimmunoprecipitation.

Conclusion

Analytical interferences should be supposed when TFT do not fit with the clinical picture and despite their infrequency, THAb must also be considered. To our knowledge, this is the first case describing the passage of THAb to the newborn.

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Eijun Nishihara Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Yoshitaka Hobo ASKA Pharmamedical Co., Ltd. Fujisawa, Japan

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Akira Miyauchi Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Yasuhiro Ito Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Miyoko Higuchi Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Mitsuyoshi Hirokawa Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Mitsuru Ito Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Shuji Fukata Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Mitsushige Nishikawa Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Takashi Akamizu Kuma Hospital, Center for Excellence in Thyroid Care, Kobe, Japan

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Objective

This study aimed to elucidate disproportionately low serum thyroglobulin (Tg) values in Tg antibody (TgAb)-positive patients with structural recurrence of papillary thyroid carcinoma (PTC) using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Design

A retrospective study was performed on 176 patients in whom Tg and TgAb levels were measured between 2016 and 2021. Several comprehensive analyses of Tg-LC-MS/MS with an electrochemiluminescence immunoassay for Tg (Tg-ECLIA) were conducted using serum samples.

Methods

TgAb-positive patients who underwent total thyroidectomy with multiple lung metastases due to PTC were evaluated using Tg-LC-MS/MS and Tg-ECLIA. Tg expression in lymph node metastases and metastatic lesions was evaluated by immunohistochemistry and Tg levels of aspiration washouts were also evaluated. Two in vitro assays were performed to elucidate TgAb interference.

Results

Tg concentrations of negative TgAb in both assays were similar (R2= 0.99; n  = 52). Patients with structural recurrence showed higher Tg values with Tg-LC-MS/MS than with Tg-ECLIA. The undetectable proportion was significantly lower with Tg-LC-MS/MS (31.6%, 6/19) than with Tg-ECLIA (68.4%, 13/19; P  = 0.023). The spike-recovery rate and Tg concentrations determined by the serum mixture text (n  = 29) were significantly reduced to 75.0% (118.3–88.7%) and 81.3% (107.0–87.0%), respectively, with TgAb using Tg-ECLIA (both P  < 0.001) confirming assay interference but not using Tg-LC-MS/MS (91.8–92.3%, P  = 0.77 and 98.4–100.8%, P  = 0.18, respectively).

Conclusions

TgAb had no effect on the Tg-LC-MS/MS assay but yielded 19–25% lower values in Tg-ECLIA. Tg-LC-MS/MS is preferable for monitoring serum Tg levels in TgAb-positive patients, although those with structural recurrence often had disproportionally low Tg values.

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