Background: Comprehensive molecular studies on tumours are needed to delineate immortalization process steps and identify sensitive prognostic biomarkers in thyroid cancer. Methods and results: In this study, we extensively characterize telomere-related alterations in a series of 106 thyroid tumours with heterogeneous clinical outcomes. Using a custom-designed RNA-seq panel, we identified five telomerase holoenzyme-complex genes upregulated in clinically aggressive tumours compared to tumours from long-term disease-free patients, being TERT and TERC denoted as independent prognostic markers by multivariate regression model analysis. Characterization of alterations related to TERT re-expression revealed that promoter mutations, methylation and/or copy gains exclusively co-occurred in clinically aggressive tumours. Quantitative-FISH (fluorescence in situ hybridization) analysis of telomere lengths showed a significant shortening in these carcinomas, which matched with a high proliferative rate measured by Ki-67 immunohistochemistry. RNA-seq data analysis indicated that short-telomere tumours exhibit an increased transcriptional activity in the 5-Mb-subtelomeric regions, site of several telomerase-complex genes. Gene upregulation enrichment was significant for specific chromosome-ends such as the 5p, where TERT is located. Co-FISH analysis of 5p-end and TERT loci showed a more relaxed chromatin configuration in short telomere-length tumours compared to normal telomere-length tumours. Conclusions: Overall, our findings support that telomere shortening leads to a 5p subtelomeric region reorganization, facilitating the transcription and accumulation of alterations at TERT-locus.

Background: Hypothyroidism is one of the leading conditions in endocrinology. Despite that fact, clinical indications for treatment still vary among Spanish specialists. Aims: To identify attitudes of Spanish specialists relating to the use of levothyroxine (LT4) and the management of hypothyroidism. Methods: The members of the Sociedad Espanola de Endocrinologia y Nutricion (Spanish Society of Endocrinology and Nutrition) were invited to participate in a web-based survey. The survey, initially in English, was modified to reflect in accordance with the availability of thyroid hormone formulations in Spain. Results: A total of 505 of 1956 (25.8%) members (66% female) completed the survey; 97.4% declared that LT4 is the first-line therapy for hypothyroidism. The indications for LT4 therapy in euthyroidism were infertility in thyroid antibody-positive women (48.5%) and simple goitre (21.2%). However, 44.2% of specialists reported that there was no indication for LT4 therapy in such patients. Only a minority of respondents (2.6%) considered combining LT4 with liothyronine as the treatment of choice from inception, whereas 49% stated that it should never be used. Conclusions: The standard of treatment of hypothyroidism in Spain is almost exclusively with LT4 tablets. Availability of other formulations of LT4 or combination therapy for hypothyroidism management remains to be explored, especially in patients with persistent symptoms. Notably, non-evidence-based use of LT4 is widely practiced in Spain for euthyroid women with autoimmune thyroiditis and fertility issues. (c) 2021 SEEN y SED. Published by Elsevier Espana, S.L.U. All rights reserved.

Objective: A differential diagnosis of thyrotoxicosis is crucial as the treatment of the main causes of this condition can vary significantly. Recently published diagnostic guidelines on thyrotoxicosis embrace the presence of thyrotropin receptor (TSH-R) antibodies (TRAb) as the primary and most important diagnostic step. The application of diagnostic algorithms to aid in the treatment of hyperthyroidism supports using thyroid radionuclide scintigraphy (TRSt) in baffling clinical scenarios, when TRAb are absent or when third-generation TRAb are not available. First-generation TRAb measurement may have limitations. Consequently, patients with thyrotoxicosis and first-generation TRAb results may be misdiagnosed and consequently improperly treated. Our purpose was to compare first-generation TRAb values to TRSt in the differential diagnosis of hyperthyroidism. Methods: We conducted a retrospective study of 201 untreated outpatients with overt or subclinical hyperthyroidism on whom first-generation TRAb and TRSt had been performed at the time of diagnosis. Histological specimens were analysed in patients who had previously undergone thyroid surgery at our centre. SPSS 20.0 was used in statistical analysis. Results: Seventy-three out of 201 (36.3%) patients had positive TRAb. A diffuse uptake was present in 83.5% (61/73), whereas 13.7% (10/73) had a heterogeneous uptake and 2.7% (2/73) had an absent uptake. Thirty out of 91 (33%) patients with diffuse uptake were negative for positive TRAb and were diagnosed with Graves' disease. Analysis of 37 histological specimens indicated that TRSt had greater accuracy (81% vs 75.7%) and specificity (79.2% vs 57.1%) when compared to TRAb in the differential diagnosis of thyrotoxicosis. However, TRSt sensitivity was inferior to TRAb (84.6% vs 92.3%). Conclusions: Our study endorses that initial differential diagnosis of thyrotoxicosis should not be based solely on first-generation TRAb as this approach may leave nearly 20% of the patients misdiagnosed and, consequently, improperly treated. Our results underscore that thyroid scintigraphy should also be performed when only first-generation TRAb assays are available during the initial differential diagnosis of thyrotoxicosis.

The clinical characteristics of patients with postoperative hypoparathyroidism who recover parathyroid function more than 12 months after surgery have not been studied. We aimed to evaluate whether the intensity of replacement therapy with calcium and calcitriol is related to the late recovery of parathyroid function. We compared the demographic, surgical, pathological, and analytical features of two groups of patients: cases, i.e., late recovery patients (those who recover parathyroid function>1 year after thyroidectomy, n=40), and controls, i.e., patients with permanent hypoparathyroidism (n=260). Replacement therapy with calcium and calcitriol was evaluated at discharge of surgery, 3-6 months, 12 months, and last visit. No significant differences were found in clinical, surgical, pathological, or analytical characteristics between cases and controls. The proportion of cases who required treatment with calcium plus calcitriol at 12 months was significantly lower than that found in controls (p<0.001). Furthermore, daily calcium and calcitriol doses in controls were significantly higher than those in cases at 3-6 months (p=0.014 and p=0.004, respectively) and at 12 months (p<0.001 and p=0.043, respectively). In several models of logistic regression analysis therapy with calcium and calcitriol at 12 months was negatively related to late recovery of parathyroid function. Although delayed recuperation of parathyroid function after total thyroidectomy is uncommon (13%), follow-up beyond 12 months is necessary in patients with postoperative hypoparathyroidism, especially in those whose needs of treatment with Ca and calcitriol are reducing over time.

Objective: We aimed to study the predictive factors for recovery of parathyroid function in hypoparathyroid patients after total thyroidectomy for thyroid cancer. Methods: We designed a retrospective, multicentre and nation-wide analysis of patients with total thyroidectomy who were seen in twenty endocrinology departments from January to March 2018. We selected patients with histologically proven thyroid cancer and retrieved information related to surgical procedure and thyroid cancer features. Survival analysis and Cox regression analysis were used to study the relationship between these variables and the recovery of parathyroid function. Results: From 685 patients with hypoparathyroidism at discharge of surgery, 495 (72.3%) recovered parathyroid function over time. Kaplan-Meier analysis showed that this recovery was significantly related to the presence of specialized surgical team (P<0.001), identification of parathyroid glands at surgery (P<0.001), papillary histopathology (P=0.040), and higher levels of postoperative calcium (Ca) (P<0.001) and parathyroid hormone (PTH) (P<0.001). Subjects with gross extrathyroidal extension (P=0.040), lymph node metastases (P=0.004), and surgical re-intervention after initial surgery (P=0.024) exhibited a significant risk of persistence of hypoparathyroidism. Multivariate Cox regression analysis showed that the significant and independent factors for recovery of parathyroid function were postoperative concentrations of Ca (P=0.038) and PTH (P=0.049). The presence of lymph node metastases was a negative predictor of recuperation of parathyroid function (P=0.042) in this analysis. Conclusion: In patients with thyroid cancer, recovery of parathyroid function after total thyroidectomy was directly related to postoperative Ca and PTH concentrations, and inversely related to lymph node metastases.

BackgroundWe aimed to measure satisfaction of patients with thyroid cancer concerning different aspects of healthcare.MethodsWe developed a web-based survey. Questions focused on patient satisfaction with specialists, the health centers and departments, and the information received about their disease. Level of satisfaction was quantified using a scale of 1 to 5. Values >= 4 were considered a high degree of satisfaction.ResultsFour hundred eighty-five patients (aged 43.49.9yrs., 88% females) completed the survey. A high overall satisfaction with the specialists was reported by 52.5% of patients. The most highly valued specialists were surgeons, oncologists, and endocrinologists. 56.5% of respondents reported a high overall satisfaction with the health centers and departments. Lastly, the proportion of patients who were highly satisfied with the information received was only 42.5%. The presence of complications was indirectly related with satisfaction with specialists and information. Satisfaction with health centers and services was directly related with the level of education and inversely related to the time of evolution of the disease.Conclusion Our results show a high degree of overall satisfaction of thyroid cancer patients. However, satisfaction can be improved in some areas, such with regards to the information provided to patients.

Objective: The objective of this study was to query thyroid cancer patients about 1) both the characteristics of the healthcare facilities where they were treated and the healthcare professionals that provided that treatment, as well as 2) the multidisciplinary approach used in the treatment process. Methods: Using a web-based survey, patients were asked to give their opinion of the healthcare centers, the professionalism of their team of specialists, and the thyroid cancer multidisciplinary teams (MDT). Results: For the 485 patients that responded, the most highly rated aspect of healthcare centers was the reduced waiting time between diagnosis and surgical intervention, an opinion expressed by 62.7% of patients. The most appreciated aspect of professionalism was the kindness shown toward patients by healthcare staff (66.6%). About 44.3% of patients were aware of the existence of thyroid cancer MDT. Most of respondents (82.7%) agreed that patients' opinions should be considered by their physicians when making treatment decisions. Conclusion: We conclude that most patients with thyroid cancer appreciate therapeutic efficacy and kindness, and almost all are clearly in favor of using a multidisciplinary approach to their disease. Since such patients often demand to participate in the decision-making process, multidisciplinary teams should make every effort to share information with, and to integrate the opinion of, patients in the management of their thyroid disease.

Background: Total thyroidectomy is the standard initial surgery for differentiated thyroid carcinoma (DTC), but the extent of the thyroidectomy remains controversial. Thyroid lobectomy (TL) has been widely used in eastern countries; however, its use has not been generalized in western countries, including Spain. Our aims were to analyse the clinical outcome of a multicentre nation-wide cohort of DTC patients treated by TL and to assess the proportion of patients who required completion of the thyroidectomy and who presented disease recurrence. Methods: We retrospectively analyzed patients who underwent TL for DTC and were followed-up for >= 12 months. We collected demographic, clinical, and histopathological data. Dynamic risk stratification (DRS) was performed at 12 months and at last visit. Results: One hundred and sixty-four patients (128 women, mean age 50.8 years, median follow-up 45.4 months) from 9 hospitals were included. There were 158 cases of papillary and 6 of follicular thyroid carcinoma ( FTC). Remission of the disease (excellent response) was shown in 71.6% of the patients at 12 months and in 74.4% at the end of follow-up. At that time, there were 34 patients (20.7%) with indeterminate response, 6 (3.7%) with biochemical incomplete response, and 2 ( 1.2%) with structural incomplete response. Completion of the thyroidectomy was necessary in 8 patients (4.9%), but only 3 of them (1.8%) had disease recurrence. Conclusions: These results, obtained in real clinical practice, suggest that TL is a safe operative option for selected patients with DTC and that the intensity of the treatment must be tailored according to the presurgical tumor-associated risk, in line with a personalized medicine.