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Carles Zafon, Juan J. Díez, Juan C. Galofré, and David S. Cooper

The management of thyroid nodules, one of the main clinical challenges in endocrine clinical practice, is usually straightforward. Although the most important concern is ruling out malignancy, there are grey areas where uncertainty is frequently present: the nodules labelled as indeterminate by cytology and the extent of therapy when thyroid cancer is diagnosed pathologically. There is evidence that the current available precision medicine tools (from all the “-omics” to molecular analysis, fine-tuning imaging or artificial intelligence) may help to fill present gaps in the future. We present here a commentary on some of the current challenges faced by endocrinologists in the field of thyroid nodules and cancer, and illustrate how precision medicine may improve their diagnostic and therapeutic capabilities in the future.

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Giacomo Sturniolo, Carles Zafon, Mariacarla Moleti, Josep Castellví, Francesco Vermiglio, and Jordi Mesa

Background: Papillary thyroid cancer (PTC) prevalence is nearly 3 times higher in females than in males. This gender difference suggests that growth and progression of PTC might be influenced by female sex hormones. Objectives: To analyze the expression of both estrogen receptor (ER)-α and progesterone receptor (PR) by immunohistochemistry in 203 PTC patients. Methods: ER-α and PR expression was evaluated in paraffin-embedded tumor tissue samples of 45 males and 158 females followed up for 7.2 ± 3.7 years. Results: ER-α was expressed in 52 (25.6%) patients (41 females and 11 males) and PR in 94 (46.3%) patients (75 females and 19 males). ER-α and PR were coexpressed in 31 (15.3%) patients (27 females and 4 males). ER-α expression correlated significantly with tumor size in the whole sample (ER-α positive 22.8 ± 11.8 mm vs. ER-α negative 15.1 ± 12.4 mm; p = 0.02) and in the subgroup of women (ER-α positive 18.8 ± 12.8 mm vs. ER-α negative 14.9 ± 12.3 mm; p = 0.048). In addition, ER-α expression significantly correlated with remission of the disease. In fact, of the 192 patients followed up, 50/153 (32.7%) disease-free patients were ER-α positive, in contrast to only 3/39 (7.7%) with evidence of disease persistence/recurrence (χ<sup>2</sup> = 8.5, p = 0.0036). PR expression was not associated with any of the parameters analyzed. Conclusions: The present study confirmed recent data indicating that ER-α and PR expression is a common finding in thyroid tumor tissue. However, in contrast to previous reports, we observed an association between ER-α expression and a more favorable outcome in PTC patients.

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Carles Zafon, Juan Antonio Baena, Josep Castellví, Gabriel Obiols, Oscar Gonzalez, José Manuel Fort, Ramon Vilallonga, Enric Caubet, Manuel Armengol, and Jordi Mesa

Background: Numerous studies have shown an increase in the incidence of thyroid cancer (TC) in recent years. Objectives: In this paper, we reviewed the incidence of TC in a series of patients undergoing thyroid surgery at a single institution over a 10-year period. Patients and Methods: The cohorts were divided into two periods (2001-2005 and 2006-2010) with the purpose of comparing various clinicopathologic variables. Results: A total of 1,263 patients were included. A significant increase in the number of malignancies was shown in the second period, namely 90 cases in 2001-2005 (15.2% of all interventions) compared to 163 cases in 2006-2010 (24.3%) (p < 0.001). These differences were attributed to an increase in papillary thyroid carcinoma (PTC), as there were 66 PTC cases in the first period (11.13% of thyroidectomies performed) compared to 129 cases in the second period (19.25%). There were no clinicohistological differences among PTC cases in these two periods. Conclusions: Over the last decade, there has been an increase in the incidence of TC in patients undergoing thyroid surgery. This increase is exclusively due to increases in PTC. Our study verifies the existence of this trend in our geographical area, similar to that noted in other parts of the world.

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


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


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


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.


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).


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.