Observational Study

. 2025 Apr 22;110(5):e1377-e1384.

doi: 10.1210/clinem/dgae559.

Data-driven Thyroglobulin Cutoffs for Low- and Intermediate-risk Thyroid Cancer Follow-up: ITCO Real-world Analysis

Giorgio Grani¹, Silvia D'Elia², Efisio Puxeddu³, Silvia Morelli³, Emanuela Arvat⁴, Alice Nervo⁴, Giovanna Spiazzi⁵, Nicoletta Rolli⁵, Maria Chiara Zatelli⁶, Maria Rosaria Ambrosio⁶, Graziano Ceresini⁷, Michela Marina⁷, Chiara Mele⁸, Gianluca Aimaretti⁸, Maria Giulia Santaguida⁹, Camilla Virili⁹, Anna Crescenzi^{10

11}, Andrea Palermo¹², Ruth Rossetto Giaccherino¹³, Letizia Meomartino¹³, Maria Grazia Castagna¹⁴, Fabio Maino¹⁴, Matteo Trevisan¹⁵, Simone De Leo¹⁵, Maria Grazia Chiofalo¹⁶, Luciano Pezzullo¹⁶, Clotilde Sparano¹⁷, Luisa Petrone¹⁷, Giulia Di Dalmazi¹⁸, Giorgio Napolitano¹⁸, Dario Tumino¹⁹, Umberto Crocetti²⁰, Francesco Bertagna²¹, Maurilio Deandrea²², Alessandro Antonelli²³, Caterina Mian²⁴, Antonella Carbone²⁵, Salvatore Monti²⁶, Tommaso Porcelli²⁷, Giulia Brigante^{28

29}, Daniele Barbaro³⁰, Marco Alfò², Umberto Ferraro Petrillo², Sebastiano Filetti¹, Cosimo Durante¹

Affiliations

¹ Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy.
² Department of Statistical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
³ Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy.
⁴ Oncological Endocrinology Unit, Department of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, 10126 Turin, Italy.
⁵ Endocrinology and Diabetology Unit, Department of Medicine, Azienda Ospedaliera-Universitaria di Verona, 37126 Verona, Italy.
⁶ Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
⁷ Unit of Internal Medicine and Oncological Endocrinology, University Hospital of Parma, 43126 Parma, Italy.
⁸ Endocrinology, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
⁹ Endocrinology Unit, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
¹⁰ Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy.
¹¹ Unit of Endocrine Organs and Neuromuscolar Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.
¹² Unit of Metabolic Bone and Thyroid Diseases, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.
¹³ Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
¹⁴ Department of Medicine, Surgery and Neuroscience, Section of Endocrinology, University of Siena, 53100 Siena, Italy.
¹⁵ Endocrine Oncology Unit, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, 20095 Milan, Italy.
¹⁶ IRCCS Fondazione G. Pascale, National Cancer Institute, 80131 Naples, Italy.
¹⁷ Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.
¹⁸ Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.
¹⁹ Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy.
²⁰ Department of Medical Sciences, Hospital "Casa Sollievo della Sofferenza", IRCCS, 71013 San Giovanni Rotondo, Italy.
²¹ Nuclear Medicine, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Spedali Civili di Brescia, 25123 Brescia, Italy.
²² UO Endocrinologia, Diabetologia e Malattie del metabolismo, AO Ordine Mauriziano Torino, 10128 Torino, Italy.
²³ Department of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, 56100 Pisa, Italy.
²⁴ Operative Unit of Endocrinology Department of Medicine-DIMED University of Padua, 35128 Padua, Italy.
²⁵ Endocrine Unit, Tinchi Hospital, Asm Matera, 75015 Matera, Italy.
²⁶ Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, Sapienza University of Rome, 00189 Rome, Italy.
²⁷ Department of Public Health, University of Naples "Federico II", 80131 Naples, Italy.
²⁸ Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
²⁹ Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41124 Modena, Italy.
³⁰ Unit of Endocrinology ASL North West Tuscany, Ospedali Riuniti, 57124 Livorno, Italy.

PMID: 39150986
PMCID: PMC12012673
DOI: 10.1210/clinem/dgae559

Observational Study

Data-driven Thyroglobulin Cutoffs for Low- and Intermediate-risk Thyroid Cancer Follow-up: ITCO Real-world Analysis

Giorgio Grani et al. J Clin Endocrinol Metab. 2025.

. 2025 Apr 22;110(5):e1377-e1384.

doi: 10.1210/clinem/dgae559.

Authors

Affiliations

¹ Department of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, Italy.
² Department of Statistical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
³ Department of Medicine and Surgery, University of Perugia, 06129 Perugia, Italy.
⁴ Oncological Endocrinology Unit, Department of Medical Sciences, Città della Salute e della Scienza Hospital, University of Turin, 10126 Turin, Italy.
⁵ Endocrinology and Diabetology Unit, Department of Medicine, Azienda Ospedaliera-Universitaria di Verona, 37126 Verona, Italy.
⁶ Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy.
⁷ Unit of Internal Medicine and Oncological Endocrinology, University Hospital of Parma, 43126 Parma, Italy.
⁸ Endocrinology, Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy.
⁹ Endocrinology Unit, Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy.
¹⁰ Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, 00161 Rome, Italy.
¹¹ Unit of Endocrine Organs and Neuromuscolar Pathology, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.
¹² Unit of Metabolic Bone and Thyroid Diseases, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy.
¹³ Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
¹⁴ Department of Medicine, Surgery and Neuroscience, Section of Endocrinology, University of Siena, 53100 Siena, Italy.
¹⁵ Endocrine Oncology Unit, Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, 20095 Milan, Italy.
¹⁶ IRCCS Fondazione G. Pascale, National Cancer Institute, 80131 Naples, Italy.
¹⁷ Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.
¹⁸ Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.
¹⁹ Department of Clinical and Experimental Medicine, University of Catania, 95122 Catania, Italy.
²⁰ Department of Medical Sciences, Hospital "Casa Sollievo della Sofferenza", IRCCS, 71013 San Giovanni Rotondo, Italy.
²¹ Nuclear Medicine, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia and Spedali Civili di Brescia, 25123 Brescia, Italy.
²² UO Endocrinologia, Diabetologia e Malattie del metabolismo, AO Ordine Mauriziano Torino, 10128 Torino, Italy.
²³ Department of Surgery, Medical and Molecular Pathology and Critical Area, University of Pisa, 56100 Pisa, Italy.
²⁴ Operative Unit of Endocrinology Department of Medicine-DIMED University of Padua, 35128 Padua, Italy.
²⁵ Endocrine Unit, Tinchi Hospital, Asm Matera, 75015 Matera, Italy.
²⁶ Endocrinology and Diabetes Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, Sapienza University of Rome, 00189 Rome, Italy.
²⁷ Department of Public Health, University of Naples "Federico II", 80131 Naples, Italy.
²⁸ Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
²⁹ Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, 41124 Modena, Italy.
³⁰ Unit of Endocrinology ASL North West Tuscany, Ospedali Riuniti, 57124 Livorno, Italy.

PMID: 39150986
PMCID: PMC12012673
DOI: 10.1210/clinem/dgae559

Abstract

Context: The utility of thyroglobulin (Tg) in the follow-up of patients with differentiated thyroid cancer has been well-documented. Although third-generation immunoassays have improved accuracy, limitations persist (interfering anti-Tg antibodies and measurement variability). Evolving treatment strategies require a reevaluation of Tg thresholds for optimal patient management.

Objective: To assess the performance of serum Tg testing in 2 populations: patients receiving total thyroidectomy and radioiodine remnant ablation (RRA) or treated with thyroidectomy alone.

Design: Prospective observational study.

Setting: Centers contributing to the Italian Thyroid Cancer Observatory database.

Patients: We included 540 patients with 5 years of follow-up and negative anti-Tg antibodies.

Interventions: Serum Tg levels assessed at 1-year follow-up visit.

Main outcome measure: Detection of structural disease within 5 years of follow-up.

Results: After excluding 26 patients with structural disease detected at any time point, the median Tg did not differ between patients treated with or without radioiodine. Data-driven Tg thresholds were established based on the 97th percentile of Tg levels in disease-free individuals: 1.97 ng/mL for patients undergoing thyroidectomy alone (lower than proposed by the Memorial Sloan Kettering Cancer Center protocol and ESMO Guidelines, yet demonstrating good predictive ability, with a negative predictive value of 98% and 0.84 ng/mL for patients receiving postsurgical RRA. High sensitivity and negative predictive value supported the potential of these thresholds in excluding structural disease.

Conclusion: This real-world study provides evidence for the continued reliability of 1-year serum Tg levels. The data-driven Tg thresholds proposed offer valuable insights for clinical decision-making in patients undergoing total thyroidectomy with or without RRA.

Keywords: predictor; radioiodine; threshold; thyroglobulin; treatment response.

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Figures

**Figure 2.**
Distribution of 1-year serum thyroglobulin value in patients who underwent total thyroidectomy with or without radioiodine treatment.

See this image and copyright information in PMC

References

1. Spencer CA, LoPresti JS, Fatemi S, Nicoloff JT. Detection of residual and recurrent differentiated thyroid carcinoma by serum thyroglobulin measurement. Thyroid. 1999;9(5):435‐441. - PubMed
1. Haugen BR, Alexander EK, Bible KC, et al. . 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1‐133. - PMC - PubMed
1. Filetti S, Durante C, Hartl D, et al. . Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019;30(12):1856‐1883. - PubMed
1. Spencer CA, Bergoglio LM, Kazarosyan M, Fatemi S, LoPresti JS. Clinical impact of thyroglobulin (tg) and tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2005;90(10):5566‐5575. - PubMed
1. Spencer CA, Lopresti JS. Measuring thyroglobulin and thyroglobulin autoantibody in patients with differentiated thyroid cancer. Nat Clin Pract Endocrinol Metab. 2008;4(4):223‐233. - PubMed

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Data-driven Thyroglobulin Cutoffs for Low- and Intermediate-risk Thyroid Cancer Follow-up: ITCO Real-world Analysis

Affiliations

Data-driven Thyroglobulin Cutoffs for Low- and Intermediate-risk Thyroid Cancer Follow-up: ITCO Real-world Analysis

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

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LinkOut - more resources

Full Text Sources

Medical

Miscellaneous