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Francesco Latrofa

Bio: Francesco Latrofa is an academic researcher from University of Pisa. The author has contributed to research in topics: Thyroid & Thyroglobulin. The author has an hindex of 26, co-authored 67 publications receiving 2253 citations. Previous affiliations of Francesco Latrofa include World Health Organization & University of California, Los Angeles.


Papers
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Journal ArticleDOI
TL;DR: A large group of patients with differentiated thyroid carcinoma who had serum thyroid peroxidase, thyroglobulin, or TSH-receptor antibodies due to coexistent thyroid autoimmune disease were studied, finding gradual disappearance of antibodies gradually disappeared in most patients.
Abstract: Le malattie autoimmuni della tiroide sono caratterizzate dalla presenza di anticorpi diretti contro la tireoperossidasi (TPO), la tireoglobulina (Tg) e il recettore per l’ormone tireotropo (TSH-R). Questo studio ha valutato se la rimozione completa degli antigeni tiroidei fosse in grado di indurre la scomparsa dei segni di autoimmunita tiroidea circolante. Lo studio e basato su una revisione retrospettiva delle cartelle cliniche di pazienti che erano stati seguiti e trattati secondo un protocollo standard. Sono stati studiati 182 pazienti affetti da tumore differenziato della tiroide i quali, per la coesistenza di una tiroidite cronica autoimmune, di un morbo di Basedow o di una tiroidite focale autoimmune, risultavano positivi per anticorpi anti-TPO (TPOAb), anti-Tg (TgAb) o anti-TSH-R (TRAb). Dei 182 soggetti, 151 erano di sesso femminile e 31 di sesso maschile; l’eta media era di 39,7±13,7 anni, con un range da 6 a 81 anni. Tutti i pazienti sono stati sottoposti a tiroidectomia totale e a trattamento con iodio radioattivo allo scopo di ablare il tessuto tiroideo residuo o metastatico. Il follow-up e stato effettuato mediante scintigrafie corporee totali con radioiodio e dosaggio della Tg circolante. La media del follow-up era di 10,1±4,1 anni, con un range di 4–20 anni. A seguito del trattamento con tiroidectomia totale e iodio radioattivo, si e verificata la scomparsa dei TgAb, TPOAb e TRAb. La mediana di scomparsa e stata di 6,3 anni per iTPOAb e di 3,0 anni per i TgAb. La scomparsa del tessuto tiroideo e quella degli anticorpi antitiroide erano correlate in modo statisticamente significativo. La persistenza di TPOAb e TgAb non veniva influenzata dal sesso, dall’eta e dalla concomitanza della tiroidite autoimmune o del morbo di Basedow.

318 citations

Journal ArticleDOI
TL;DR: The first case of SAT related to SARS-CoV-2 infection is reported and clinicians are alerted to additional and unreported clinical manifestations associated with COVID-19.
Abstract: Context Subacute thyroiditis (SAT) is a thyroid disease of viral or postviral origin. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, has spread rapidly worldwide and Italy has been severely affected by this outbreak. Objectives The objective of this work is to report the first case of SAT related to SARS-CoV-2 infection. Methods We describe the clinical, laboratory, and imaging features of an 18-year-old woman who came to our attention for fever, neck pain radiated to the jaw, and palpitations occurring 15 days after a SARS-CoV-2-positive oropharyngeal swab. Coronavirus disease 2019 (COVID-19) had been mild and the patient had completely recovered in a few days. Results At physical examination the patient presented with a slightly increased heart rate and a painful and enlarged thyroid on palpation. At laboratory exams free thyroxine and free triiodothyronine were high, thyrotropin undetectable, and inflammatory markers and white blood cell count elevated. Bilateral and diffuse hypoechoic areas were detected at neck ultrasound. One month earlier, thyroid function and imaging both were normal. We diagnosed SAT and the patient started prednisone. Neck pain and fever recovered within 2 days and the remaining symptoms within 1 week. Thyroid function and inflammatory markers normalized in 40 days. Conclusions We report the first case of SAT after a SARS-CoV-2 infection. We alert clinicians to additional and unreported clinical manifestations associated with COVID-19.

271 citations

Journal ArticleDOI
TL;DR: Goiter and hyperthyroidism occur to a much greater extent when the adenovirus expresses the free A subunit as opposed to a genetically modified TSHR that cleaves minimally into subunits, and new insight is provided into the etiology of Graves disease.
Abstract: Graves disease, a common organ-specific autoimmune disease affecting humans, differs from all other autoimmune diseases in being associated with target organ hyperfunction rather than organ damage. Clinical thyrotoxicosis is directly caused by autoantibodies that activate the thyrotropin receptor (TSHR). The etiology of Graves disease is multifactorial, with nongenetic factors playing an important role. Of the latter, there is the intriguing possibility that the molecular structure of the target antigen contributes to the development of thyroid-stimulatory autoantibodies (TSAb's). Among the glycoprotein hormone receptors, only the TSHR undergoes intramolecular cleavage into disulfide-linked subunits with consequent shedding of some of the extracellular, autoantibody-binding A subunits. Functional autoantibodies do not arise to the noncleaving glycoprotein hormone receptors. Recently, TSAb's were found to preferentially recognize shed, rather than attached, A subunits. Here we use a new adenovirus-mediated animal model of Graves disease to show that goiter and hyperthyroidism occur to a much greater extent when the adenovirus expresses the free A subunit as opposed to a genetically modified TSHR that cleaves minimally into subunits. These data show that shed A subunits induce or amplify the immune response leading to hyperthyroidism and provide new insight into the etiology of Graves disease.

211 citations

Journal ArticleDOI
TL;DR: The results of the present study demonstrate that the mRNA encoding for the ACE-2 receptor is expressed in thyroid follicular cells, making them a potential target for SARS-COV-2 entry.
Abstract: SARS-COV-2 is a pathogenic agent belonging to the coronavirus family, responsible for the current global world pandemic. Angiotensin-converting enzyme 2 (ACE-2) is the receptor for cellular entry of SARS-CoV-2. ACE-2 is a type I transmembrane metallo-carboxypeptidase involved in the Renin-Angiotensin pathway. By analyzing two independent databases, ACE-2 was identified in several human tissues including the thyroid. Although some cases of COVID-19-related subacute thyroiditis were recently described, direct proof for the expression of the ACE-2 mRNA in thyroid cells is still lacking. Aim of the present study was to investigate by RT-PCR whether the mRNA encoding for ACE-2 is present in human thyroid cells. RT-PCR was performed on in vitro ex vivo study on thyroid tissue samples (15 patients undergoing thyroidectomy for benign thyroid nodules) and primary thyroid cell cultures. The ACE-2 mRNA was detected in all surgical thyroid tissue samples (n = 15). Compared with two reporter genes (GAPDH: 0.052 ± 0.0026 Cycles−1; β-actin: 0.044 ± 0.0025 Cycles−1; ACE-2: 0.035 ± 0.0024 Cycles−1), the mean level of transcript expression for ACE-2 mRNA was abundant. The expression of ACE-2 mRNA in follicular cells was confirmed by analyzing primary cultures of thyroid cells, which expressed the ACE-2 mRNA at levels similar to tissues. The results of the present study demonstrate that the mRNA encoding for the ACE-2 receptor is expressed in thyroid follicular cells, making them a potential target for SARS-COV-2 entry. Future clinical studies in patients with COVID-19 will be required for increase our understanding of the thyroid repercussions of SARS-CoV-2 infection.

157 citations

Journal ArticleDOI
TL;DR: Evidence supports the concept that A subunit shedding either initiates or amplifies the autoimmune response to the TSHR, thereby causing Graves disease in genetically susceptible individuals.
Abstract: Graves disease is directly caused by thyroid-stimulating autoantibodies (TSAb’s) that activate the thyrotropin receptor (TSHR). We observed upon flow cytometry using intact cells that a mouse mAb (3BD10) recognized the TSHR ectodomain with a glycosidylphosphatidylinositol (ECD-GPI) anchor approximately tenfold better than the same ectodomain on the wild-type TSHR, despite the far higher level of expression of the latter. The 3BD10 epitope contains the N-terminal cysteine cluster critical for TSAb action. Consequently, we hypothesized and confirmed that TSAb (but not thyrotropin-blocking autoantibodies [TBAb’s]) also poorly recognize the wild-type TSHR relative to the ECD-GPI. Despite poor recognition by TSAb of the holoreceptor, soluble TSHR A subunits (known to be shed from surface TSHR) fully neutralized autoantibody-binding activity. These data indicate that the epitope(s) for TSAb’s, but not for TBAb’s, are partially sterically hindered on the holoreceptor by the plasma membrane, the serpentine region of the TSHR, or by TSHR dimerization. However, the TSAb epitope on the soluble A subunit is freely accessible. This observation, as well as other evidence, supports the concept that A subunit shedding either initiates or amplifies the autoimmune response to the TSHR, thereby causing Graves disease in genetically susceptible individuals.

140 citations


Cited by
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Journal ArticleDOI
01 Nov 2009-Thyroid
TL;DR: Evidence-based recommendations are developed to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer and represent, in the authors' opinion, contemporary optimal care for patients with these disorders.
Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

10,501 citations

Journal ArticleDOI
04 Nov 2009-Thyroid
TL;DR: Evidence-based recommendations in response to the appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer represent, in the authors' opinion, contemporary optimal care for patients with these disorders.
Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. Methods: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, a...

7,525 citations

Journal ArticleDOI
TL;DR: A comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae is provided in this paper, where the authors discuss relevant considerations for the multidisciplinary care of COPD survivors and propose a framework for the identification of those at high risk for COPD and their coordinated management through dedicated COPD clinics.
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic, which has resulted in global healthcare crises and strained health resources. As the population of patients recovering from COVID-19 grows, it is paramount to establish an understanding of the healthcare issues surrounding them. COVID-19 is now recognized as a multi-organ disease with a broad spectrum of manifestations. Similarly to post-acute viral syndromes described in survivors of other virulent coronavirus epidemics, there are increasing reports of persistent and prolonged effects after acute COVID-19. Patient advocacy groups, many members of which identify themselves as long haulers, have helped contribute to the recognition of post-acute COVID-19, a syndrome characterized by persistent symptoms and/or delayed or long-term complications beyond 4 weeks from the onset of symptoms. Here, we provide a comprehensive review of the current literature on post-acute COVID-19, its pathophysiology and its organ-specific sequelae. Finally, we discuss relevant considerations for the multidisciplinary care of COVID-19 survivors and propose a framework for the identification of those at high risk for post-acute COVID-19 and their coordinated management through dedicated COVID-19 clinics.

2,307 citations

Journal ArticleDOI
TL;DR: European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium Furio Pacini, Martin Schlumberger, Henning Dralle, Rossella Elisei, Johannes W A Smit, Wilmar Wiersinga and the European Thyroid Cancer Taskforce Section of Endocrinology and Metabolism are presented.
Abstract: European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium Furio Pacini, Martin Schlumberger, Henning Dralle, Rossella Elisei, Johannes W A Smit, Wilmar Wiersinga and the European Thyroid Cancer Taskforce Section of Endocrinology and Metabolism, University of Siena, Via Bracci, 53100 Siena, Italy, Service de Medicine Nucleaire, Institut Gustave Roussy, Villejuif, France, Department of General, Visceral and Vascular Surgery, University of Halle, Germany, Department of Endocrinology, University of Pisa, Italy, Department of Endocrinology and Metabolic Disease, Leiden University Medical Center, The Netherlands and Department of Endocrinology and Metabolism, University of Amsterdam, The Netherlands

1,926 citations