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Features and outcome of differentiated thyroid carcinoma associated with Graves’ disease: results of a large, retrospective, multicenter study

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Abstract

Background

Whether differentiated thyroid cancer (DTC) occurring concomitantly with Graves’ disease (GD) is more aggressive and bound to a less favorable outcome is controversial.

Objective

Aim of this multicenter retrospective study was to compare baseline features and outcome of DTC patients with GD (DTC/GD+) or without GD (DTC/GD−).

Patients

Enrolled in this study were 579 patients referred to five endocrine units (Cagliari, Pavia, Pisa, Siena, and Varese) between 2005 and 2014: 193 patients had DTC/GD+ , 386 DTC/GD−. Patients were matched for age, gender and tumor size. They underwent surgery because of malignancy, large goiter size, or relapse of hyperthyroidism in GD.

Results

Baseline DTC features (histology, lymph node metastases, extrathyroidal extension) did not differ in the two groups, except for multifocality which was significantly more frequent in DTC/GD+ (27.5% vs. 7.5%, p < 0.0001). At the end of follow-up (median 7.5 years), 86% of DTC/GD+ and 89.6% DTC/GD− patients were free of disease. Patients with persistent or recurrent disease (PRD) had “biochemical disease” in the majority of cases. Microcarcinomas were more frequent in the DTC/GD+ group (60% vs. 37%, p < 0.0001) and had an excellent outcome, with no difference in PRD between groups. However, in carcinomas ≥ 1 cm, PRD was significantly more common in DTC/GD+ (24.4% vs. 11.5%; p = 0.005). In the whole group, univariate and multivariate analyses showed that GD+ , lymph node involvement, extrathyroidal invasion, multifocality and tall cell histotype were associated with a worse outcome. Female gender and microcarcinomas were favorable features. No association was found between baseline TSH-receptor antibody levels and outcome. Graves’ orbitopathy (GO) seemed to be associated with a better outcome of DTC, possibly because patients with GO may early undergo surgery for hyperthyroidism.

Conclusions

GD may be associated with a worse outcome of coexisting DTC only if cancer is ≥ 1 cm, whereas clinical outcome of microcarcinomas is not related to the presence/absence of GD.

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Acknowledgements

This study was supported by grants from the Ministry of Education, University and Research (MIUR, Rome) to Luigi Bartalena, Luca Chiovato, Rossella Elisei, Stefano Mariotti, Furio Pacini, and Paolo Vitti. Giovanni Veronesi carried out the statistical analyses.

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Author notes

  1. P. Premoli and M. L. Tanda equally contributed to this study.

Authors and Affiliations

  1. Department of Medicine and Surgery, University of Insubria, Endocrine Unit, Ospedale di Circolo, ASST dei Sette Laghi, Viale Borri, 57, 21100, Varese, Italy

    P. Premoli, M. L. Tanda, E. Piantanida, D. Gallo, E. Masiello, S. Rosetti, C. Cusini & L. Bartalena

  2. Research Centre in Epidemiology and Preventive Medicine, University of Insubria, Varese, Italy

    G. Veronesi

  3. Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy

    F. Boi, J. Bulla, R. Rodia & S. Mariotti

  4. Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

    V. Capelli, M. Rotondi, F. Magri & L. Chiovato

  5. Endocrinology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    R. Rocchi, M. C. Campopiano, R. Elisei & P. Vitti

  6. Endocrinology Unit, University of Siena, Siena, Italy

    F. Barbato, T. Pilli, M. G. Castagna & F. Pacini

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  1. P. Premoli
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Corresponding author

Correspondence to L. Bartalena.

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Conflict of interest

All authors state that they have no conflict of interest.

Ethical approval

All procedures performed in human participants during this retrospective study were in accordance with the ethical standards of institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The ethical committee approval is not required for retrospective studies.

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For this type of retrospective study, formal consent is not required. Data were anonymized.

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Premoli, P., Tanda, M.L., Piantanida, E. et al. Features and outcome of differentiated thyroid carcinoma associated with Graves’ disease: results of a large, retrospective, multicenter study. J Endocrinol Invest 43, 109–116 (2020). https://doi.org/10.1007/s40618-019-01088-5

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  • DOI: https://doi.org/10.1007/s40618-019-01088-5

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