Tracking dynamic evolution of low- and intermediate-risk differentiated thyroid cancer: Identification of individuals at risk of recurrence.

OBJECTIVE: The generally good prognosis of low- and intermediate-risk differentiated thyroid cancer (DTC) underscored the need to identify those few patients who relapse. DESIGN: Records of 299 low- or intermediate-risk DTC patients (mean follow-up 8.2 ± 6.2 years) were retrospectively reviewed. The sample was classified following the American Thyroid Association (ATA) dynamic risk stratification (DRS) system. PATIENTS AND MEASUREMENT: After classifying patients according to DRS at the first visit following initial therapy (FU1), structural recurrence occurred in 2/181 (1.1%), 5/81 (6.2%) and 13/26 (50.0%) with excellent, indeterminate and biochemical incomplete response to treatment, respectively. All relapses but one happened within 5 years from FU1. Univariate analysis comparing excellent, indeterminate and biochemical incomplete with structural incomplete responses at the end of the follow-up, identified tumour size (p < .001), T status (<0.001), positive lymph nodes (N) (p < .01), multifocality (p < .004), need of additional radioactive iodine (RAI) (p < .0001) and first DRS status (p < .0003) as risk factors of recurrence. In the multivariate analysis, only RAI remained statistically significant (p < .02). Comparison between excellent and indeterminate with biochemical and structural incomplete responses, identified tumour size (p < .0004), T (p < .01), N (p < .0001), bilaterality (p < .03), first DRS status (p < .0001) and RAI (p < .001) as recurrence risk factors. T (p < .01) and first DRS (p < .0006) were confirmed in the multivariate analysis. CONCLUSIONS: Patients with DTC classified as low- or intermediate-risk of recurrence with excellent response to treatment at FU1 rarely develop structural disease and this occurs almost exclusively in the first 5 years. Initial DRS status is an accurate tool for determining the risk of recurrence.

Use of levothyroxine for euthyroid, thyroid antibody positive women with infertility: Analyses of aggregate data from a survey of European thyroid specialists (Treatment of Hypothyroidism in Europe by Specialists: An International Survey).

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.

Evaluation of the role of thyroid scintigraphy in the differential diagnosis of thyrotoxicosis.

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.

Thyroid cancer patients satisfaction at the management outcome: an analysis of the results of a nationwide survey in 485 subjects.

BACKGROUND: We aimed to measure satisfaction of patients with thyroid cancer concerning different aspects of healthcare. METHODS: We 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. RESULTS: Four hundred eighty-five patients (aged 43.4 ± 9.9 yrs., 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.

Prevalence of thyroid dysfunction in a Large Southern European Population. Analysis of modulatory factors. The APNA study.

CONTEXT: To study the prevalence of thyroid dysfunction in a very large unselected population. OBJECTIVE: To determine the prevalence of abnormal thyroid function and evaluate potential modulatory factors. DESIGN AND SETTING: The Estudio de Atención Primaria de Navarra, The APNA Study, is a cross-sectional study conducted in northern Spain. It involved 303 883 people, of 20 years of age and older, who live in the Navarra region. Participants are covered by the public healthcare system and medical records are digitalized. MAIN OUTCOME MEASURES: The information was gathered from e-registered data regarding serum thyrotropin (TSH), thyroid hormones, thyroid antibody concentration and clinical context. Measurements were logged (demographic information and potential thyroid function modulatory factors). RESULTS: Serum TSH (mU/L) normal range was established at 0.7-4.28. At the time of the study, 87% of the Navarra population had a TSH level within the normal range. Mean serum TSH in euthyroid individuals was higher in women (2.15) than in men (1.96) (P < .001) and higher in the obese with body mass index (BMI) ≥30 kg/m2 (2.12) as compared to the non-obese BMI <30 kg/m2 (2.06) (P < .001). Mean TSH for the entire population was 1.9. The native Spanish population had statistically significantly lower TSH (1.87) than non-native Spanish (2.15) (P < .001). Additionally, we observed that serum TSH levels decreased with age and an increase in the prevalence of hypothyroidism in the elderly and among people with low-income levels. The prevalence of thyroid dysfunction in Navarra was 12.3%. The prevalence of hypothyroidism (or high TSH) in the population was 8.8% (13.3% in women, 4.2% in men), and the prevalence of hyperthyroidism (or low TSH) was 4.3% (5.6% in women, 3.0% in men). CONCLUSIONS: Nearly 15% of the general population suffers from biochemical thyroid dysfunction. The serum TSH level appears to be influenced by sex, BMI, age, ethnic origin and socio-economic status.

Management of a pregnant woman with thyrotropinoma: a case report and review of the literature.

INTRODUCTION: Pituitary disorders during pregnancy are uncommon. The approach should include a close follow-up in order to reduce maternal and fetal risks associated with physiological changes during pregnancy or treatment side effects. MATERIALS AND METHODS: We report a 21-year-old woman with a thyroid-stimulating hormone-secreting pituitary macroadenoma and positive antithyroid antibodies. She was initially treated using transsphenoidal pituitary surgery. The patient relapsed 17-month post-surgery. Somatostatin analog therapy was started which rapidly controlled the hyperthyroidism. Eleven months later, while receiving octreotide, the patient reported to be pregnant and the medication was stopped. Gestation and delivery went well with a healthy full-term newborn. The patient developed a postpartum thyroiditis 15 weeks after giving birth. Twenty-eight months postpartum the patient remains euthyroid without medication. CONCLUSIONS: The overall positive outcomes of the four cases reported in literature, including this new case, suggest that pregnancy should not be absolutely contraindicated in women with thyrotropinomas. We emphasize the effectiveness of octreotide to control hyperthyroidism, as well as stopping medication when a patient is found to be pregnant. In our case, close observation following octreotide cessation had a positive outcome.

Thyroid dysfunction caused by immune checkpoint inhibitors improves cancer outcomes.

A common immune-related adverse event (irAE) with immune checkpoint inhibitors (ICIs) is thyroid dysfunction (TD-irAEs). The clinical presentation can be varied, and its association with prognosis remains unclear. We investigated the characteristics of TD-irAEs and their association with clinical outcomes among cancer patients treated with ICIs in a real-life setting. Response to treatment was assessed using RECIST v1.1. We calculated the probability of recurrence and survival associated with TD-irAEs using multivariable-adjusted regression and Cox proportional hazards models. In this single-center retrospective analysis, we included 238 patients (72% male) with a median age of 69.5 years. Primary tumors were melanoma (23.1%), lung (60.5%), or urothelial cancer (16.4%), treated with atezolizumab (23.1%), pembrolizumab (44.5%), ipilimumab (0.4%), and/or nivolumab (25.6%). Seventy (29%) patients developed TD-irAEs in a median time of 69 days (41-181). The incidence of TD-irAEs with combination therapy was higher than with monotherapy (67% vs 6.3%, P = 0.011). TD-irAE patients showed a higher objective response rate (ORR) than those without TD-irAEs (60% vs 42.3%, P = 0.013) and longer overall survival (OS) 45 vs 16 months, P < 0.006. Patients who developed TD-irAEs had a relative reduction of 77% (OR 0.23, 95% CI 0.11-0.47) in the risk of progression and of 47% in the risk of mortality (HR 0.53, 95% CI 0.36-0.80), independent of age, sex, primary tumor, or ICI regimen. TD-irAEs occur in nearly 30% of our patients receiving ICIs. In our analysis, TD-irAEs appeared to be associated with higher ORR and longer OS and showed a reduction in the risk of progression and mortality.

A cross-sectional study of the association between circulating TSH level and lipid profile in a large Spanish population.

OBJECTIVE: Some evidence suggests that high serum TSH levels are associated with an adverse lipid profile, but this association is not clear when plasma TSH is within the reference range. Nevertheless, these studies have never been conducted in Spain, a country with a strong adherence to the Mediterranean diet. The study aim was to analyse the association between blood TSH levels and circulating lipids in a large Spanish population and set up a TSH reference range in different age, gender and Body Mass Index (BMI) subpopulations from our cohort. DESIGN: Cross-sectional study on 20 783 subjects. PATIENTS: We analysed circulating levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc) and triglycerides (TG) and compared them with TSH serum levels. Discriminant function analysis was used to determine the TSH cut-off level from where hyperlipidaemia developed. RESULTS: In individuals free of thyroid dysfunction, the mean and the 95% TSH (mU/l) reference limits were 2·20 and 0·72-4·43, respectively. We observed a sex-related difference in TSH concentration (men, 2·07 and 0·72-4·29; women, 2·29 and 0·72-4·49; P < 0·01). We also observed a weight-related difference in TSH concentration (BMI < 30 kg/m(2) , 2·16 and 0·72-4·39; BMI ≥ 30 kg/m(2) , 2·28 and 0·71-4·47; P < 0·01). TSH was positively associated with TC, TG and LDLc levels and negatively with HDLc. CONCLUSION: We found an association between TSH and lipids in that as TSH increased, the lipid profile became less favourable, even within the normal range. Additionally, TSH reference ranges varied according to gender, age and BMI.

Clinical implications of changing thyroglobulin and antithyroglobulin antibodies analytical methods in the follow-up of patients with differentiated thyroid carcinoma.

BACKGROUND AND AIMS: Patients' response to treatment in differentiated thyroid cancer (DTC) is classified according to serum thyroglobulin concentrations (Tg), usually using the American Thyroid Association guidelines and considering potential interfering anti-thyroglobulin antibodies (Ab-Tg). We aim to evaluate the clinical implications of changing Tg and Ab-Tg quantification method. MATERIAL AND METHODS: Tg and Ab-Tg were quantified in 82 serum samples (60 from DTC patients) by Elecsys and Access immunoassays. RESULTS: Elecsys immunoassay rendered higher values of Tg than Access: mean bias 5.03 ng/mL (95%CI:-14.14-24.21). In DTC patients, there was an almost perfect agreement for response classification (kappa index = 0.833). Discrepancies appeared in patients with undetermined response, with a more tendency to subclassification with Access. Ab-Tg showed a poor correlation (r = 0.5394). When Elecsys cut-off was reduced to 43 IU/mL, agreement for positive/negative classification improved from a kappa index of 0.607 to 0.650. Prospective study with personalized follow-up showed that only 6.3% of Tg results required an analytical confirmation, being confirmed 93% of them. CONCLUSIONS: Despite the biases observed, clinical impact of an analytical change is minimal in patients' management. However, cautious and personalized follow-up period after the change is still mandatory, especially in patients with Tg levels between 0.2 and 1 ng/mL.

Use of thyroid hormone in hypothyroid patients and euthyroid subjects in Spain: A THESIS* questionnaire survey.

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 Española de Endocrinología y Nutrición (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.

Validation of dynamic risk stratification and impact of BRAF in risk assessment of thyroid cancer, a nation-wide multicenter study.

Introduction: The dynamic risk stratification (DRS) is a relatively new system in thyroid cancer that considers the response to primary treatment to improve the initial risk of recurrence. We wanted to validate DRS system in a nationwide multicenter study and explore if the incorporation of BRAFV600E into DRS helps to better categorize and predict outcomes. Materials and methods: Retrospective study of 685 patients from seven centers between 1991 and 2016, with a mean age of 48 years and a median follow-up time of 45 months (range 23-77). The overall BRAFV600E prevalence was 53.4%. We classified patients into four categories based on DRS ('excellent', 'indeterminate', 'biochemical incomplete', and 'structural incomplete' response). Cox regression was used to calculate adjusted hazard ratios (AHR) and proportions of variance explained (PVEs). Results: We found 21.6% recurrences and 2.3% cancer-related deaths. The proportion of patients that developed recurrence in excellent, indeterminate, biochemical incomplete and structural incomplete response to therapy was 1.8%, 54%, 91.7% and 96.2% respectively. Considering the outcome at the end of the follow up, patients showed no evidence of disease (NED) in 98.2, 52, 33.3 and 25.6% respectively. Patients in the structural incomplete category were the only who died (17.7%). Because they have similar outcomes in terms of NED and survival, we integrated the indeterminate and biochemical incomplete response into one unique category creating the 3-tiered DRS system. The PVEs of the AJCC/TNM staging, ATA risk classification, 4-tiered DRS, and 3-tiered DRS to predict recurrence at five years were 21%, 25%, 57% and 59% respectively. BRAFV600E was significantly associated with biochemical incomplete response (71.1 vs 28.9%) (HR 2.43; 95% CI, 1.21 to 5.23; p=0.016), but not with structural incomplete response or distant metastases. BRAF status slightly changes the AHR values of the DRS categories but is not useful for different risk grouping. Conclusions: This is the first multicenter study to validate the 4-tiered DRS system. Our results also show that the 3-tiered DRS system, by integrating indeterminate and biochemical incomplete response into one unique category, may simplify response to therapy keeping the system accurate. BRAF status does not provide any additional benefit to DRS.

Co-occurrence of mutations in NF1 and other susceptibility genes in pheochromocytoma and paraganglioma.

Introduction: The percentage of patients diagnosed with pheochromocytoma and paraganglioma (altogether PPGL) carrying known germline mutations in one of the over fifteen susceptibility genes identified to date has dramatically increased during the last two decades, accounting for up to 35-40% of PPGL patients. Moreover, the application of NGS to the diagnosis of PPGL detects unexpected co-occurrences of pathogenic allelic variants in different susceptibility genes. Methods: Herein we uncover several cases with dual mutations in NF1 and other PPGL genes by targeted sequencing. We studied the molecular characteristics of the tumours with co-occurrent mutations, using omic tools to gain insight into the role of these events in tumour development. Results: Amongst 23 patients carrying germline NF1 mutations, targeted sequencing revealed additional pathogenic germline variants in DLST (n=1) and MDH2 (n=2), and two somatic mutations in H3-3A and PRKAR1A. Three additional patients, with somatic mutations in NF1 were found carrying germline pathogenic mutations in SDHB or DLST, and a somatic truncating mutation in ATRX. Two of the cases with dual germline mutations showed multiple pheochromocytomas or extra-adrenal paragangliomas - an extremely rare clinical finding in NF1 patients. Transcriptional and methylation profiling and metabolite assessment showed an "intermediate signature" to suggest that both variants had a pathological role in tumour development. Discussion: In conclusion, mutations affecting genes involved in different pathways (pseudohypoxic and receptor tyrosine kinase signalling) co-occurring in the same patient could provide a selective advantage for the development of PPGL, and explain the variable expressivity and incomplete penetrance observed in some patients.

[Who is in the Hospital Emergency Department? Descriptive study of the variability of specialties in the Emergency Department.] / ¿Quién está en los servicios de urgencias hospitalarias? Estudio descriptivo de la variabilidad de especialidades en urgencias.

OBJECTIVE: Giving the absence of specialized training to work as a physician in the Emergency Department in Spain, the aim of the study was to describe the variability of specialties in these departments nationally, by regions and hospital complexity. METHODS: A descriptive cross-sectional study was carried out through a survey addressed to Emergency Chiefs of Spanish public hospitals, 65 of whom answered between January 2018 and September 2019. Descriptive and correlative analyzes of the variables were performed, assuming those with p<0.05 as statistically significant. RESULTS: 1,706 emergency physicians of 29 different specialties were described, of which 1,336 (78.31%) were Family and Community Medicine specialists. Different number of specialties among regions and hospitals of different complexities were described. 98.46% of surveyed chiefs demanded specialized formation on Emergency Medicine. Direct correlations were found between the complexity of the hospital and the number of specialties in the Emergency Department (r=0.2921, CI: 0.04445-0.5059; p<0.05); the complexity of the hospital and the number of emergency physicians (r=0.69, CI: 0.5310-0.8020; p<0.0001), as well as between the number of emergency physicians and the number of different specialties in the Emergency Department (r=0.3901, CI: 0.1543-0.5838; p<0.005). CONCLUSIONS: Physicians of 29 different specialties were described working in the Emergency Departments. The variability of specialties changed among regions and hospitals of different complexities. Heads of Emergency Departments agreed on the need for specialized formation on Emergency Medicine.

OBJETIVO: Ante la ausencia de una formación especializada para trabajar de médico adjunto en los Servicios de Urgencias Hospitalarios españoles, se buscó describir la variabilidad de especialidades de los médicos adjuntos en estos servicios a nivel nacional, por Comunidades Autónomas y complejidad del hospital. METODOS: Se realizó un estudio descriptivo transversal a través de una encuesta estructurada dirigida a los responsables de Servicios de Urgencias Hospitalarias públicos españoles, de los que contestaron 65 entre enero del 2018 y septiembre del 2019. Se elaboró un análisis descriptivo y correlacional de las variables, asumiendo valores estadísticamente significativos aquellos con una p<0,05. RESULTADOS: Se describieron 1.706 médicos de urgencias, distribuidos en 29 especialidades diferentes, de los cuales 1.336 (78,31%) eran especialistas en Medicina de Familia y Comunitaria. Se encontraron diferente número de especialidades entre Comunidades Autónomas y hospitales de distintas complejidades, y el 98,46% de los encuestados solicitaron una formación especializada en Medicina de Urgencias y Emergencias. Se hallaron correlaciones directas entre la complejidad del hospital y el número de especialidades en urgencias (r=0,2921, IC: 0,04445-0,5059) p<0,05; entre la complejidad del hospital y el número de adjuntos en urgencias (r=0,69, IC: 0,5310-0,8020) p<0,0001; y entre el número de adjuntos por servicio y su número de especialidades diferentes (r=0,3901, IC: 0,1543-0,5838) p<0,005. CONCLUSIONES: Se describieron médicos de 29 especialidades diferentes trabajando en urgencias. La variabilidad de especialidades difería entre Comunidades Autónomas y hospitales de distinta complejidad. Los responsables de urgencias coincidían en la necesidad de una formación especializada en Medicina de Urgencias y Emergencias.

Thyroid Cancer Patients' View of Clinician Professionalism and Multidisciplinary Approach to Their Management.

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.

Use of thyroid hormone in hypothyroid patients and euthyroid subjects in Spain: A THESIS* questionnaire survey.

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 Española de Endocrinología y Nutrición (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.

Recovery of parathyroid function in patients with thyroid cancer treated by total thyroidectomy: An analysis of 685 patients with hypoparathyroidism at discharge of surgery.

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.

The extent of surgery for low-risk 1-4 cm papillary thyroid carcinoma: a catch-22 situation. A retrospective analysis of 497 patients based on the 2015 ATA Guidelines recommendation 35.

PURPOSE: The adequate extent of surgery for 1-4 cm low-risk papillary thyroid carcinoma (PTC) is unclear. Our objective was to analyze the applicability of the 2015 ATA Guidelines recommendation 35B (R35) for the management low-risk PTC. METHODS: This multicentre study included patients with low-risk PTC who had undergone total thyroidectomy (TT). Retrospectively we selected those who met the R35 criteria for the performance of a thyroid lobectomy (TL). The aim was to identify the proportion of low-risk PTC patients treated using TT who would have required reintervention had they had a TL in accordance with R35. RESULTS: We identified 497 patients (400 female; 80.5%). Median tumor size (mm): 21.2 (11-40). A tumor size ≥2 cm was found in 252 (50.7%). Most of them, 320 (64.4%), were in Stage I (AJCC 7th Edition). Following R35, 286 (57.5%) would have needed TT. Thus, they would have required a second surgery had they undergone TL. The indications for reintervention would have included lymph node involvement (35%), extrathyroidal extension (22.9%), aggressive subtype (8%), or vascular invasion (22.5%). No presurgical clinical data predict TT. CONCLUSIONS: The appropriate management of low-risk PTC is unclear. Adherence to ATA R35 could lead to a huge increase in reinterventions when a TL is performed, though the need for them would be questionable. In our sample, more than half of patients (57.5%) who may undergo a TL for a seemingly low-risk PTC would have required a second operation to satisfy international guidelines, until better preoperative diagnostic tools become available.

Permanent postoperative hypoparathyroidism: an analysis of prevalence and predictive factors for adequacy of control in a cohort of 260 patients.

BACKGROUND: Recent guidelines for the treatment of hypoparathyroidism emphasize the need for long-term disease control, avoiding symptoms and hypocalcaemia. Our aim has been to analyze the prevalence of poor disease control in a national cohort of patients with hypoparathyroidism, as well as to evaluate predictive variables of inadequate disease control. METHODS: From a nation-wide observational study including a cohort of 1792 patients undergoing total thyroidectomy, we selected 260 subjects [207 women and 53 men, aged (mean ± SD) 47.2±14.8 years] diagnosed with permanent hypoparathyroidism. In every patient demographic data and details on surgical procedure, histopathology, calcium (Ca) metabolism, and therapy with Ca and calcitriol were retrospectively collected. A patient was considered not adequately controlled (NAC) if presented symptoms of hypocalcemia or biochemical data showing low serum Ca levels or high urinary Ca excretion. RESULTS: Two hundred and twenty-one (85.0%) patients were adequately controlled (AC) and 39 (15.0%) were NAC. Comparison between AC and NAC patients did not show any significant difference in demographic, surgical, and pathological features. Rate of hospitalization during follow-up was significantly higher among NAC patients in comparison with AC patients (35.9% vs. 10.9%, P<0.001). Dose of oral Ca and calcitriol were also significantly higher in NAC subjects. In a subgroup of 129 patients with serum parathyroid hormone (PTH) levels available, we found that NAC patients exhibited significantly lower postoperative PTH concentrations than AC patients [median (interquartile range) 3 (1.9-7.8) vs. 6.9 (3.0-11) pg/mL; P=0.009]. CONCLUSIONS: In a nation-wide cohort of 260 subjects with definitive hypoparathyroidism, 15% of them had poor disease control. These patients required higher doses of oral Ca and calcitriol, had higher rate of hospitalization during follow-up and showed lower PTH concentrations in the postoperative period.