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Open access

Paolo Cavarzere, Laura Palma, Lara Nicolussi Principe, Monica Vincenzi, Silvana Lauriola, Rossella Gaudino, Virginia Murri, Luigi Lubrano, Giuliana Rossi, Alessia Sallemi, Ermanna Fattori, Marta Camilot, and Franco Antoniazzi

Introduction

Infants of mothers with autoimmune hypothyroidism (AH) are at risk of developing late-onset hypothyroidism, often escaping at newborn screening. This condition might be caused both by the action of maternal antibodies and/or by maternal treatment.

Objectives

The aim of this study is to evaluate the prevalence of AH in the mothers of children born in Veneto region, Italy, and to define what is the most appropriate management for these newborns.

Methods

Newborns of six different hospitals with a mother suffering from AH and with negative neonatal screening for congenital hypothyroidism (CH) were included in the study. Between 15 and 20 days of life, we collected a serum sample for the evaluation of thyroid function (thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3)) and anti-thyroid antibodies. On the same occasion, a capillary blood sampling was performed for a second screening test.

Results

Maternal AH has a prevalence of 3.5%. A total of 291 newborns were enrolled from November 2019 to May 2021. Whereas the 11.4% of infants had a slight elevated serum TSH (>6 mU/L) and required a follow-up, only 2 children presented an elevated TSH level at the second screening test. One of these, with the gland in situ, showed persistently elevated serum TSH levels and required treatment with levothyroxine.

Conclusions

Maternal AH rarely caused neonatal thyroid dysfunction. We suggest to reassess newborns from mothers with AH 15 days after birth by means of a second neonatal screening test. This procedure avoids false negatives due to maternal thyroid status, is less invasive and cheaper than the serum TSH evaluation, and prevents a long follow-up.

Open access

Juan Antonio Vallejo Casas, Marcel Sambo, Carlos López López, Manuel Durán-Poveda, Julio Rodríguez-Villanueva García, Rita Joana Santos, Marta Llanos, Elena Navarro-González, Javier Aller, Virginia Pubul, Sonsoles Guadalix, Guillermo Crespo, Cintia González, Carles Zafón, Miguel Navarro, Javier Santamaría-Sandi, Ángel Segura, Pablo Gajate, Marcelino Gómez-Balaguer, Javier Valdivia, Manel Puig-Domingo, Juan Carlos Galofré, Beatriz Castelo, María José Villanueva, Iñaki Argüelles, and Lorenzo Orcajo-Rincón

Background

Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS).

Objective

The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal.

Methods

A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated.

Results

Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3–15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7–16.2) years; log-rank test P = 0.4737). Age at diagnosis being <55 years was associated with a lower risk of death (Wald chi-square (Wc-s) P < 0.0001), while a poor response to RAI to a higher risk of death ((Wc-s) P < 0.05). In the eDTC cohort, median (RP)FS (95% CI) was of 1.7 (1.0–2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ((Wc-s) P < 0.05).

Conclusion

Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.

Open access

Annamaria Erdei, Annamaria Gazdag, Bernadett Ujhelyi, Edit B Nagy, Ervin Berenyi, Eszter Berta, Zita Steiber, Sandor Barna, Emese Mezosi, Miklos Bodor, and Endre V Nagy

Introduction

Dysthyroid optic neuropathy (DON) is a rare, severe form of thyroid eye disease, in which decreased visual acuity is accompanied by characteristic MRI findings. The treatment of DON has always been a challenge.

Case presentation

In a patient in whom visual acuity deteriorated on the left eye, mannitol 20% 200 mL followed by furosemide 40 mg 6 h later, administered daily, were initiated on the day of admission. Visual function by ophthalmology methods, and orbital compartment volumes and water content by MRI were followed. Intravenous diuretics resulted in an immediate therapeutic response. Visual acuity improved from 20/50 to 20/25 after 2 days of treatment. MRI revealed decreasing water content of both the muscle and connective tissue compartments without any volume changes. Subsequently, corticosteroids and orbital irradiation were started. Orbital decompression surgery was not required.

Discussion/conclusion

Edematous swelling of orbital tissues is an established contributor of local pressure increase in thyroid eye disease. Diuretics reduce orbital pressure and, if confirmed by others, may be useful additions to the standard of care in sight-threatening DON.

Open access

Jihwan Yoo, Hee Jun Kim, Seok Mo Kim, and Hun Ho Park

Introduction

Brain metastasis in differentiated thyroid cancer (DTC) is rare (frequency < 1%) and has a poor prognosis. Treatment strategies for brain metastasis are not well established.

Objectives

We conducted a retrospective analysis to identify predictive factors for patient outcomes and verify surgical indications for patients with brain metastasis and DTC.

Methods

The study included 34 patients with pathologically confirmed DTC with brain metastasis from March 2008 to November 2020. The associations between overall survival (OS) and clinical factors were evaluated. Cox regression analysis was used to determine the relationship between clinical factors and OS. To assess the survival benefit of craniotomy, Kaplan–Meier survival analysis was performed for each variable whose statistical significance was determined by Cox regression analysis.

Results

The median OS of the entire patient sample was 11.4 months. Survival was affected by the presence of lung metastasis (P = 0.033) and the number of brain metastases (n  > 3) (P = 0.039). Only the subgroup with the number of brain metastases ≤3 showed statistical significance in the subgroup analysis of survival benefit following craniotomy (P = 0.048).

Conclusions

The number of brain metastases and the existence of lung metastasis were regarded more essential than other clinical factors in patients with DTC in this study. Furthermore, craniotomies indicated a survival benefit only when the number of brain metastases was ≤3. This finding could be beneficial in determining surgical indications in thyroid cancer with brain metastasis.

Open access

Sofia Macedo, Ana Pestana, Liliana Santos, Celestino Neves, Susana Guimarães, Amaro Duarte-Neto, Marisa Dolhnikoff, Paulo Saldiva, Georgina Alves, Rute Oliveira, Didier Cabanes, Fátima Carneiro, Manuel Sobrinho-Simões, and Paula Soares

Objective

To understand whether thyroid cells can be directly infected by the SARS-CoV-2 virus and to establish a putative correlation with the expression of the host entry machinery: ACE-2, TMPRSS2, and furin.

Methods

We assessed the presence of SARS-CoV-2 virus at the gene level by RT-PCR, viral RNA transcripts localization by in situ hybridization, and by detecting viral proteins by immunohistochemistry for the nucleocapsid and the spike proteins. Furthermore, we also described the immunoexpression of key host factors for virus entry in the COVID-19 thyroid samples.

Results

We performed RT-PCR for SARS-CoV-2 in all autopsy specimens and detected viral genome positivity in 13 of 15 thyroid tissues and in a lung specimen. In 9 of the 14 positive samples, we were also able to confirm SARS-CoV-2 signal by in situ hybridization. Immunohistochemistry for the viral nucleocapsid and spike protein was also positive for ten and nine of the RT-PCR-positive cases, respectively, but revealed a lower sensitivity. We also described, for the first time in a COVID-19 series, the immunohistochemical expression of ACE-2, TMPRSS2, and furin in the thyroid.

Conclusions

Our results obtained in thyroid specimens from deceased COVID-19 patients indicate that thyrocytes can be directly infected by SARS-CoV-2 since we detected the presence of SARS-CoV-2 genome in follicular cells. Nevertheless, we did not find a clear correlation between the presence of viral genome and the expression of the host factors for virus entry, namely ACE-2, TMPRSS2, and furin.

Open access

Giulia Brigante, Clara Lazzaretti, Elia Paradiso, Federico Nuzzo, Martina Sitti, Frank Tüttelmann, Gabriele Moretti, Roberto Silvestri, Federica Gemignani, Asta Försti, Kari Hemminki, Rossella Elisei, Cristina Romei, Eric Adriano Zizzi, Marco Agostino Deriu, Manuela Simoni, Stefano Landi, and Livio Casarini

To identify a peculiar genetic combination predisposing to differentiated thyroid carcinoma (DTC), we selected a set of single-nucleotide polymorphisms (SNPs) associated with DTC risk, considering polygenic risk score (PRS), Bayesian statistics, and a machine learning (ML) classifier to describe cases and controls in 3 different datasets. Dataset 1 (649 DTC, 431 controls) has been previously genotyped in a genome-wide association study (GWAS) on Italian DTC. Dataset 2 (234 DTC, 101 controls) and dataset 3 (404 DTC, 392 controls) were genotyped. Associations of 171 SNPs reported to predispose to DTC in candidate studies were extracted from the GWAS of dataset 1, followed by replication of SNPs associated with DTC risk (P<0.05) in dataset 2. The reliability of the identified SNPs was confirmed by PRS and Bayesian statistics after merging the three datasets. SNPs were used to describe the case/control state of individuals by ML classifier. Starting from 171 SNPs associated with DTC, 15 were positive in both the datasets 1 and 2. Using these markers, PRS revealed that individuals in the fifth quintile had a 7-fold increased risk of DTC than those in the first. Bayesian inference confirmed that the selected 15 SNPs differentiate cases from controls. Results were corroborated by ML, finding a maximum AUC of about 0.7. A restricted selection of only 15 DTC-associated SNPs is able to describe the inner genetic structure of Italian individuals and ML allows a fair prediction of case or control status based solely on the individual genetic background.

Open access

Temesgen Muche Ewunie, Robel Hussen Kabthymer, Samrawit Hailu, Moges Mareg, Tesfa Mengie, Daniel Sisay, and Getachew Arage

Background

Iodine deficiency disorder (IDD) is a major public health problem in Ethiopia. The availability of adequate iodized dietary salt at the household level is immensely important. Hence, this review aimed to estimate the pooled prevalence of adequate iodine concentration level of iodized dietary salt at the household level and its associated factors in Ethiopia.

Methods

We searched the literature using electronic databases (PubMed/Medline, Google Scholar, Science Direct, and Embase) and gray literature from January 9, 2022, to February 25, 2022. The rapid test kit was used to measure the adequacy of iodine level of dietary salt. The quality of studies was assessed using Joanna Briggs Institute critical appraisal tool. Heterogeneity between studies was checked using I2 test statistics and publication bias was checked using funnel plot and Egger’s statistical test at a 5% significance level. A random-effects model was employed to estimate the pooled prevalence of the outcome variable and its determinants in Ethiopia.

Results

The search identified 149 studies of which 18 studies were included with a total of 10,556 participants. The pooled prevalence of adequate iodine levels of iodized salt in Ethiopia was 44.37% (95% CI: 35.85-52.88). Women who had formal education (adjusted odds ratio (AOR) = 1.99 (95% CI: 1.47–2.48)), good knowledge of women (AOR = 2.14, 95% CI: 1.36–3.36), packed iodized salt (AOR = 3.85 (95% CI: 1.88–7.87)) and storage of iodized salt at home for less than 2 months (AOR = 2.66 (95% CI: 2.11–3.35) were the significant factors.

Conclusion

This review suggests that the pooled prevalence of adequate iodine levels was low. Our finding highlights the need for considering the educational status, knowledge, and duration of salt storage to enhance the prevalence of adequate levels of iodized salt at the national level.

Open access

M Grussendorf, I Ruschenburg, and G Brabant

Objectives

Ultrasound diagnosis of thyroid nodules has greatly increased their detection rate. Their risk for malignancy is estimated between 7 and 15% in data from specialized centers which are used for guidelines recommendations. This high rate causes considerable anxiety to patients upon first diagnosis. Here, we retrospectively analyzed the malignancy rate of sonographically diagnosed nodules larger than 1 cm from a primary/secondary care center when long-term longitudinal follow-up was included.

Patients/methods

In the study, 17,592 patients were diagnosed with a thyroid nodule larger than 1 cm, of whom 7776 were assessed by fine-needle aspiration cytology (FNAC) and 9816 by sonography alone. 9568 patients were initially discharged due to innocent results of FNAC and/or ultrasound. In 1904 patients, definitive histology was obtained, and 6731 cases were included in the long-term follow-up (up to 23 years, median 5 years).

Results

Malignancy was histologically confirmed in 189 patients (1.1% of all) when excluding accidentally diagnosed papillary microcarcinomas. 155 were diagnosed during the first year of management, 25 in years 2–5 of follow-up, 9 in years 6–10 and nil in 1165 patients followed beyond 10 years.

Conclusions

The malignancy rate of thyroid nodules from primary/secondary care was much lower than that previously reported. During follow-up for more than 5 years, their rate rapidly dropped to less than 1/1000 cases. This low malignancy rate may help to reassure patients first confronted with the diagnosis of a thyroid nodule, substantially reduce their anxiety and avoid unwarranted diagnostic and therapeutic procedures.

Open access

Ringo Manta, Charlotte Martin, Vinciane Muls, and Kris G Poppe

A 22-year-old male with a history of ulcerative colitis and nephrotic syndrome treated with immunomodulatory agents including vedolizumab and mycophenolic acid developed hyperthyroidism 2 weeks following the first administration of BNT162b2 vaccine (Pfizer-BioNTech COVID-19 vaccine). Graves’ disease (GD) was diagnosed based on the elevated thyrotropin-receptor antibody, thyroid scintigraphy and ultrasound. To this day, four cases of new-onset GD following SARS-CoV-2 vaccine were reported in patients with no previous history of thyroid disease. Two cases of recurrence of GD following SARS-CoV-2 vaccine were also reported. Although the underlying mechanisms of vaccine-induced autoimmunity remain to be clarified, there is a rationale for the association between SARS-CoV-2 vaccination and the development of Th1-mediated diseases, at least in predisposed individuals. The BNT162b2 vaccine could be a trigger for GD in some patients. However, the benefit/risk ratio remains by far in favour of SARS-CoV-2 vaccination considering the potentially higher risk of severe infection in these patients.

Open access

Diana Borges Duarte, Vânia Benido Silva, Guilherme Assunção, André Couto Carvalho, and Cláudia Freitas

Introduction

The occurrence of non-thyroidal second primary malignancy (NTSPM) in patients with papillary thyroid cancer (PTC) is well documented, but epidemiological data are conflicting.

Objective

The aim of this study was to evaluate the incidence of NTSPM in a large series of patients with PTC and to assess its potential risk factors.

Methods

Single-center cohort study with retrospective data collection conducted on consecutive PTC patients diagnosed from 1988 to 2018 with a minimum follow-up time of 2 years. NTSPM was defined as any primary malignancy with histological confirmation occurring in an anatomical site other than the thyroid. According to the timing of occurrence, NTSPM were subdivided into anachronous, synchronous or metachronous (diagnosed >6 months before, within 6 months and >6 months after PTC diagnosis, respectively).

Results

We included 773 individuals (83.3% females), median age at PTC diagnosis was 47.0 (IQR: 37.0–58.0) years and median follow-up time was 9.9 (6.2–16.3) years. Incidence of NTSPM was 15.5% (n  = 120) and its standard incidence ratio (SIR) was higher when compared to the general population (SIR: 2.70). Family history of malignancy and younger age at diagnosis were associated respectively with 206 and 4% increased risk of developing metachronous neoplasia (HR: 2.06 (95% CI: 1.10–3.86) and 1.04 (95% CI: 1.02–1.05), respectively).

Conclusion

In our series, the occurrence of NTSPM was not uncommon and its incidence was higher compared to the general population. First-degree family history of malignancy was a strong risk factor for multiple primary malignancies.