A comprehensive pan-cancer analysis revealing SPAG6 as a novel diagnostic, prognostic and immunological biomarker in tumor.

Background: There have been studies on the role of sperm-associated antigen 6 (SPAG6) in cytoskeleton formation and growth cone stability, but it is also unknown how spag6 affect tumor growth and development. The aim of this study was to clarify the role of SPAG6 in pan-cancer, with some findings about thyroid carcinoma (THCA) validated through experiments. Methods: We examined the role of SPAG6 in pan-cancer, with the data being collected from databases. Further analysis was conducted to assess its correlations with prognosis, gene heterogeneity, stemness, and tumor immunity. The interacting proteins of SPAG6 were also identified, and gene ontology enrichment analysis was performed to determine its biological function. We preliminarily confirmed the role of SPAG6 via in vitro experiments and immunofluorescence staining. Results: This study found that SPAG6 expression was differentially expressed in cancers and at various tumor stages and grades. In stomach and esophageal carcinoma (STES), stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC), lung squamous cell carcinoma (LUSC), and adrenocortical carcinoma (ACC), SPAG6 expression was correlated with gender. SPAG6 expression was also found to be correlated with prognostic value, with low expression being associated with poor prognosis. Furthermore, SPAG6 expression was positively linked with immune-related cells in HNSC, chemokine receptors in LUSC, and immune checkpoint genes in THCA. Furthermore, SPAG6 overexpression suppressed the malignant phenotypes of THCA cells, manifested by slower proliferation and decreased migration. The different SPAG6 expression in THCA led to different malignant phenotypes, which are involved in the upregulation of DNA repair, MYC targets, peroxisome, and G2M checkpoint. Conclusions: SPAG6 plays a significant role as an oncogene and can be used as a marker to predict the prognosis of cancer. SPAG6 influences both the tumor immune infiltration and microenvironment, making it a promising immunotherapeutic target for tumor therapy.

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.

Incident comorbidities in patients with chronic hypoparathyroidism after thyroidectomy: a multicenter nationwide study.

Purpose: Population-based and registry studies have shown that chronic hypoparathyroidism is accompanied by long-term complications. We aimed to evaluate the risk of incident comorbidity among patients with chronic postsurgical hypoparathyroidism in real-life clinical practice in Spain. Methods: We performed a multicenter, retrospective cohort study including patients with chronic postsurgical hypoparathyroidism lasting ≥3 years with at least a follow-up visit between January 1, 2022 and September 15, 2023 (group H). The prevalence and incidence of chronic complications including chronic kidney disease, nephrolithiasis/nephrocalcinosis, hypertension, dyslipidemia, diabetes, cardiovascular disease, central nervous system disease, mental health disorders, eye disorders, bone mineral density alterations, fracture and cancer were evaluated. Patient data were compared with a group of patients who did not develop hypoparathyroidism, matched by gender, age, and follow-up time after thyroidectomy (group NH). Results: We included 337 patients in group H (median [IQR] age, 45 [36-56] years; median time of follow-up, 8.9 [6.0-13.0] years; women, 84.3%) and 669 in group NH (median age, 47 [37-55] years; median time of follow-up, 8.0 [5.3-12.0] years; women, 84.9%). No significant differences were found in the prevalence of comorbidities at the time of thyroidectomy between both groups. In multivariable adjusted analysis, patients with chronic hypoparathyroidism had significantly higher risk of incident chronic kidney disease (OR, 3.45; 95% CI, 1.72-6.91; P<0.001), nephrolithiasis (OR, 3.34; 95% CI, 1.55-7.22; P=0.002), and cardiovascular disease (OR, 2.03; 95% CI, 1.14-3.60; P=0.016), compared with patients without hypoparathyroidism. On the contrary, the risk of fracture was decreased in patients with hypoparathyroidism (OR, 0.09; 95% CI, 0.01-0.70; P=0.021). Conclusion: This study demonstrates that, in the clinical practice of Spanish endocrinologists, a significant increase in the risk of chronic kidney disease, nephrolithiasis and cardiovascular disease, as well as a reduction in the risk of fractures is detected. These results are of interest for the development of new clinical guidelines and monitoring protocols for patients with hypoparathyroidism.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Surgical management of low-risk papillary thyroid cancer in real life in Spain: a nationwide survey of endocrine neck surgeons and endocrinologists.

BACKGROUND: The extent of surgery in patients with papillary thyroid cancer (PTC) is a subject of ongoing debate. We aimed to explore the attitude of Spanish specialists (endocrinologists, surgeons, and otolaryngologists) in real life on the surgical management of low-risk PTC. METHODS: We designed an anonymous, web-based survey to inquire information regarding the preferences of interviewees for hemithyroidectomy (Hem), total thyroidectomy (TT) and prophylactic central neck dissection (pCND) in one standard patient with PTC and six clinical variants. We differentiated between small (1.1-2.5 cm) and large (2.6-4.0 cm) tumors. RESULTS: A total of 278 valid responses were received and divided into two groups: group END (n = 135) and group SUR (n = 143, 101 general surgeons and 42 otolaryngologists). The preference for Hem was low in the standard patient and similar between both groups (40.6 vs 49.0%, NS). This preference decreased for tumors measuring 2.6-4.0 cm, multifocal, with risk location, family history of thyroid cancer, or history of irradiation, and increased in patients older than 65 years or with comorbidity. Preference for pCND ranged from 12.6-71.1% in the group END and from 22.4-65.0% in the group SUR, with few differences between the two. In multivariate analysis, being a high-volume specialist was associated with a lower preference for Hem, while having private practice was associated with a more favorable opinion of Hem. CONCLUSION: The real clinical practice of Spanish specialists is far from what is recommended by the clinical guidelines in patients with low-risk PTC, especially among high-volume professionals.

Hyperthyroidism and cardiovascular disease: an association study using big data analytics.

BACKGROUND: The cardiovascular (CV) system is profoundly affected by thyroid hormones. Both hypo- and hyperthyroidism can increase the risk of severe CV complications. OBJECTIVE: To assess the association of hyperthyroidism with major CV risk factors (CVRFs) and CV diseases (CVDs) using a big data methodology with the Savana Manager platform. MATERIAL AND METHODS: This was an observational and retrospective study. The data were obtained from the electronic medical records of the University Hospital Puerta de Hierro Majadahonda (Spain). Artificial intelligence techniques were used to extract the information from the electronic health records and Savana Manager 3.0 software was used for analysis. RESULTS: Of a total of 540,939 patients studied (53.62% females; mean age 42.2 ± 8.7 years), 5504 patients (1.02%; 69.9% women) had a diagnosis of hyperthyroidism. Patients with this diagnosis had a significantly (p < 0.0001) higher frequency of CVRFs than that found in non-hyperthyroid subjects. The higher frequency of CVRFs in patients with hyperthyroidism was observed in both women and men and in patients younger and older than 65 years of age. The total frequency of CVDs was also significantly (p < 0.0001) higher in patients diagnosed with hyperthyroidism than that found in patients without this diagnosis. The highest odds ratio values obtained were 6.40 (4.27-9.61) for embolic stroke followed by 5.99 (5.62-6.38) for atrial fibrillation. The frequency of all CVDs evaluated in patients with a diagnosis of hyperthyroidism was significantly higher in both women and men, as well as in those younger and older than 65 years, compared to subjects without this diagnosis. A multivariate regression analysis showed that hyperthyroidism was significantly and independently associated with all the CVDs evaluated except for embolic stroke. CONCLUSION: The data from this hospital cohort suggest that there is a significant association between the diagnosis of hyperthyroidism and the main CVRFs and CVDs in our population, regardless of the age and gender of the patients. Our study, in addition to confirming this association, provides useful information for understanding the applicability of artificial intelligence techniques to "real-world data and information".

Clinical Significance of T2-Weighted Sequence Intensity on Magnetic Resonance Imaging in Clinically Non-Functioning Pituitary Adenomas.

BACKGROUND: Little is known about the relationship between signal intensity patterns on T2-weighted magnetic resonance imaging (MRI) in non-functioning pituitary adenomas (NFPAs). OBJECTIVE: In this study, the clinical, hormonal, histological features, and therapeutic responses were evaluated according to the T2 signal intensity in NFPAs. METHODS: This retrospective and multicenter study included a group of 166 NFPA patients (93 men, 56%, mean age 58.5 ±14.8 yr). RESULTS: Approximately half of the tumors (n=84, 50.6%) were hyperintense, while 34.3% (n=57) and 15.1% (n=25) were iso- and hypointense, respectively. The median maximum tumor diameter of the isointense group [16 (13-25) mm] was significantly lower than that of the hyperintense [23 (16.6-29.7) mm] group (p=0.003). Similarly, the tumor volume of the isointense group [1,523 (618-5,226) mm3] was significantly lower than that of the hyperintense [4,012 (2,506-8,320) mm3] group (p=0.002). Chiasmatic compression occurred less frequently in tumors with isointense signal characteristics (38.6%) compared to tumors with hypointense (68%) and hyperintense (65.5%) signal characteristics (p=0.003). Invasive adenomas (p=0.001) and the degree of cavernous sinus invasion (p<0.001) were more frequent in the hyperintense adenoma group compared to the remaining groups. Plurihormonal tumors and silent lactotroph adenomas were more frequent in the isointense tumor group. CONCLUSION: In conclusion, hyperintensity on T2-weighted MRI in NFPAs is associated with larger and more invasive tumors compared to isointense NFPAs.

Primary Hyperparathyroidism and Cardiovascular Disease: An Association Study Using Clinical Natural Language Processing Systems and Big Data Analytics.

Primary hyperparathyroidism (PHPT) seems to be associated with different cardiovascular diseases (CVDs). We evaluated the association of PHPT with major CV risk factors (CVRFs) and CVDs by using artificial intelligence (AI) tools. An observational and retrospective study was conducted using data from the electronic health records (EHRs) of the Hospital Universitario Puerta de Hierro Majadahonda (Spain). Of a total of 699,157 patients over 18 years of age studied (54.7% females), 6515 patients (0.9%; 65.4% women; mean age 67.6 ± 15.9 years) had a diagnosis of PHPT. The overall frequencies of hypertension, dyslipidemia, diabetes mellitus, and smoking habit in the cohort of patients with PTHP were all significantly (p < 0.001) higher than those found in patients without a diagnosis of PTHP. The total frequency of stroke, ischemic heart disease, atrial fibrillation, deep vein thrombosis, and pulmonary embolism in the cohort of PHPT patients were significantly (p < 0.001) higher than that found in patients without the diagnosis of PHPT. A multivariate regression analysis showed that PHPT was significantly (p < 0.001) and independently associated with all the CVDs evaluated. Our data show that there is a significant association between the diagnosis of PHPT and the main CVRFs and CVDs in our hospital population.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Prevalence of cancer in patients with hypothyroidism: Analysis using big data tools.

OBJECTIVE: To evaluate the frequency of different types of cancer in patients diagnosed with hypothyroidism using big data methodology on the Savana Manager platform. METHODS: An observational, retrospective study was carried out using electronic medical record (EMR) data from the Hospital Universitario Puerta de Hierro Majadahonda (Madrid). Information from the EMRs was extracted using artificial intelligence techniques and analysed using the Savana Manager v3.0 software. Searches were performed using the term "hypothyroidism" and the terms corresponding to the tumours analysed. RESULTS: Of a total population of 506,749 patients, 23,570 (4.7%) were diagnosed with hypothyroidism. Patients with this diagnosis had a significantly higher frequency of cancer than that found in non-hypothyroid subjects (OR 2.09, 95% confidence interval [CI] 2.01-2.17). This higher frequency was found both in women (OR 1.99, 95% CI 1.90-2.08) and in men (OR 2.83, 95% CI 2.63-3.05). However, this higher frequency of cancer was not observed in hypothyroid patients older than 60 years (OR 0.97, 95% CI 0.92-1.02). Although the frequency of most of the neoplasms studied individually was higher in the population with hypothyroidism, we observed that hypothyroid patients over 60 years of age had a significant decrease in the frequency of prostate, lung, colorectal, and liver cancer. CONCLUSION: Data from this hospital cohort suggest that there is a significant association between the diagnosis of hypothyroidism and cancer. However, this association is less evident in hypothyroid patients older than 60 years.

Identification and validation of subclusters of papillary thyroid carcinoma based on Human Phenotype Ontology.

Background: The increase in the diagnosis of papillary thyroid carcinoma (PTC) has prompted researchers to establish a diagnostic model and identify functional subclusters. The Human Phenotype Ontology (HPO) platform is widely available for differential diagnostics and phenotype-driven investigations based on next-generation sequence-variation data. However, a systematic and comprehensive study to identify and validate PTC subclusters based on HPO is lacking. Methods: We first used the HPO platform to identify the PTC subclusters. An enrichment analysis was then conducted to examine the key biological processes and pathways associated with the subclusters, and a gene mutation analysis of the subclusters was conducted. For each subcluster, the differentially expressed genes (DEGs) were selected and validated. Finally, a single-cell RNA-sequencing data set was used to verify the DEGs. Results: In our study, 489 PTC patients from The Cancer Genome Atlas (TCGA) were included. Our analysis demonstrated that distinct subclusters of PTC are associated with different survival times and have different functional enrichment, and that C-C motif chemokine ligand 21 (CCL21) and zinc finger CCHC-type containing 12 (ZCCHC12) were the common down- and upregulated genes, respectively, in the 4 subclusters. Additionally, 20 characteristic genes were identified in the 4 subclusters, some of which have previously been reported to have roles in PTC. Further, we found that these characteristic genes were mainly expressed in thyrocytes, endothelial cells, and fibroblasts, and were rarely expressed in immune cells. Conclusions: We first identified subclusters in PTC based on HPO and found that patients with distinct subclusters have different prognoses. We then identified and validated the characteristic genes in the 4 subclusters. These findings are expected to serve as a crucial reference that will improve our understanding of PTC heterogeneity and the use of novel targets.

Growth differentiation factor 15 (GDF-15) in endocrinology.

Human growth differentiation factor 15 (GDF-15) is a widely distributed protein that has shown to play multiple roles in both physiological and pathological conditions. In healthy individuals, GDF-15 is mainly expressed in the placenta, followed by the prostate, although low levels of expression have also been detected in different organs. GDF-15 acts through a recently identified receptor called glial-derived neurotrophic factor (GDNF) receptor alpha-like (GFRAL) which signals through the rearranged during transfection (RET) tyrosine kinase receptor. The effects of GDF-15 are pleiotropic and include appetite regulation, and actions on metabolism, pregnancy, cell survival, immune response, and inflammation. GDF-15 also plays different roles in the pathophysiology of cardiovascular disease, autoimmunity, cancer-associated anorexia/cachexia, and diabetes. In recent years, several studies have reported a link between GDF-15 and the endocrine system. In this review, we up-date and summarize the relevant investigations of the relationships between GDF-15 and different endocrine conditions. We also assess the potential pathogenic role and potential therapeutic applications of GDF-15 in the field of endocrinology.

Hyperthyroidism and cardiovascular risk factors: A nationwide study.

BACKGROUND: Thyroid hormones (THs) have important effects on cardiovascular (CV) physiology. Thyroid disorders are accompanied by serious effects on the CV system. OBJECTIVE: To study the association between hyperthyroidism and the main CV risk factors (CVRFs), such as hypertension, dyslipidemia, diabetes and smoking in the Spanish population. MATERIAL AND METHODS: An observational, retrospective, non-interventional study was performed using the statistical portal of the Spanish Ministry of Health associated with the Base de Datos Clínicos de Atención Primaria (BDCA) database. RESULTS: In 2019, 384,182 people [300,243 women (78.1%)] were diagnosed with hyperthyroidism, which represents 1.0% of the population with health problems registered in the BDCAP database (38,365,258 people). The prevalence of hyperthyroidism was more frequent in women (2.48 times) than in men and increased with age. When the whole population was considered, the prevalence of hypertension (34.90% vs. 19.90%; odds ratio, OR 2.16, 95% CI 2.14-2.17), dyslipidemia (34.47% vs. 21.57%; OR 1.90, 95% CI 1.88-1.91), diabetes (12.88% vs. 8.12%; OR 1.66, 95% CI 1.65-1.68) and smoking (10.89% vs. 7.61%; OR 1.48, 95% CI 1.46-1.49) was significantly (p<0.0001) higher in the population diagnosed with hyperthyroidism compared to those without this diagnosis. These significant differences were maintained in both women and men. A separate analysis of the age group 65 years or older showed statistically significant (p<0.0001) differences in the prevalence of hypertension (66.26% vs. 59.43%; OR 1.34, 95% CI 1.33-1.36), dyslipidemia (52.61% vs. 49.05%; OR 1.15, 95% CI 1.14-1.17) and smoking (6.29% vs. 5.93%; OR 1.06, 95% CI 1.04-1.09) between patients with and without a diagnosis of hyperthyroidism, but not in the prevalence of diabetes, which was similar (24.63% vs. 24.63%; OR 1.00, 95% CI 0.99-1.01; p=0.89). CONCLUSION: Our study shows that the diagnosis of hyperthyroidism is significantly associated with the main CVRFs in Spanish population attended by primary care regardless of the gender of the patients. This association disappears in those patients aged 65 years or older diagnosed with diabetes.

Consumption of health resources in older people with differentiated thyroid carcinoma: a multicenter analysis.

OBJECTIVE: There is hardly any information on the consumption of healthcare resources by older people with differentiated thyroid cancer (DTC). We analyzed these consumptions in older patients with DTC and compared patients 75 years and older with subjects aged 60-74 years. METHODS: A multicenter, retrospective analysis was designed. We recorded three groups of health resources consumption (visits, diagnostic procedures, and therapeutic procedures) and identified a subgroup of patients with high consumption of resources. We compared patients aged between 60-74 years (group 1) with patients aged 75 and over (group 2). RESULTS: We included 1654 patients (women, 74.4%), of whom 1388 (83.9%) belonged to group 1 and 266 (16.1%) to group 2. In group 2, we found a higher proportion of patients requiring emergency department visits (7.9 vs. 4.3%, P = 0.019) and imaging studies (24.1 vs. 17.3%; P = 0.012) compared to group 1. However, we did not find any significant difference between both groups in the consumption of other visits, diagnostic procedures, or therapeutic procedures. Overall, 340 patients (20.6%) were identified as high consumers of health resources, 270 (19.5%) in group 1 and 70 (26.3%) in group 2 (P = 0.013). Multivariate logistic regression analysis showed that the risk of recurrence and mortality, radioiodine treatment, tumor size, and vascular invasion were significantly related to the high global consumption of resources. However, the age was not significantly related to it. CONCLUSION: In patients with DTC over 60 years of age, advanced age is not an independent determining factor in the consumption of health resources.

Prevalencia de diabetes en personas con disfunción tiroidea / Prevalence of diabetes in people with thyroid dysfunction

Objetivo: Describir la prevalencia y el riesgo relativo de diabetes en personas con hipotiroidismo e hipertiroidismo.MétodosSe realizó un estudio retrospectivo utilizando la Base de Datos Clínicos de Atención Primaria (BDCAP) del Ministerio de Sanidad. Se calcularon los riesgos relativos (OR) y sus intervalos de confianza (IC) al 95% para diabetes tipo1 (DM1) y tipo2 (DM2).ResultadosEn el grupo de 2.596.041 pacientes hipotiroideos se encontró un OR de 1,77 (IC95%: 1,75-1,80) para DM1 y de 1,77 (IC95%: 1,76-1,78) para DM2. Este elevado riesgo se observó tanto en hombres como en mujeres. Las personas hipotiroideas de más de 65años presentaron un riesgo prácticamente neutro de DM1 (0,96 [IC95%: 0,94-0,99]) y DM2 (0,99 [IC95%: 0,98-0,99]). Los hipotiroideos en tratamiento sustitutivo mostraron un mayor riesgo de DM1 (1,32 [IC95%: 1,28-1,36]) y DM2 (1,23 [IC95%: 1,22-1,24]) en comparación con hipotiroideos no tratados. En el grupo de 418.772 personas con hipertiroidismo se observó también un riesgo incrementado de DM1 (1,66 [IC95%: 1,60-1,72]) y DM2 (1,71 [IC95%: 1,70-1,73]). Este riesgo se observó en ambos sexos. Los mayores de 65años no presentaron riesgo elevado de DM1 (0,89 [IC95%: 0,83-0,95]) y su riesgo de DM2 fue cercano a la neutralidad (1,03 [IC95%: 1,02-1,05]). Los hipertiroideos tratados con medicación antitiroidea presentaron un mayor riesgo de DM1 (1,26 [IC95%: 1,14-1,40]) y DM2 (1,32 [IC95%: 1,28-1,36]) que los no tratados. (AU)

Objective: To describe the prevalence and relative risk of diabetes in the population with hypothyroidism and hyperthyroidism.MethodsA retrospective study was carried out using the Primary Care Clinical Database (BDCAP) of the Ministry of Health. Relative risks (OR) and their 95% confidence intervals (CI) were calculated for type1 (T1D) and type2 (T2D) diabetes.ResultsIn the group of 2,596,041 hypothyroid patients, we found an OR of 1.77 (95%CI: 1.75-1.80) for T1D, and 1.77 (95%CI: 1.76-1.78) for T2D. This elevated risk was observed in both men and women. Hypothyroid people over 65years of age had a near neutral risk of T1D (0.96 [95%CI: 0.94-0.99]) and T2D (0.99 [95%CI: 0.98-0.99]). Hypothyroid patients receiving replacement therapy showed a higher risk of T1D (1.32 [95%CI: 1.28-1.36]) and T2D (1.23 [95%CI: 1.22-1.24]) compared to untreated hypothyroid patients. In the group of 418,772 people with hyperthyroidism, an increased risk of T1D (1.66 [95%CI: 1.60-1.72]) and T2D (1.71 [95%CI: 1.70-1.73]) was also noticed. This risk was observed in both sexes. Those over 65years of age did not present a high risk of T1D (0.89 [95%CI: 0.83-0.95]) and their risk of T2D was close to neutrality (1.03 [95%CI: 1.02-1.05]). Hyperthyroid patients treated with antithyroid agents had a higher risk of T1D (1.26 [95%CI: 1.14-1.40]) and T2D (1.32 [95%CI: 1.28-1.36]) than those without therapy.ConclusionPeople registered in BDCAP of both sexes, under 65years of age, with thyroid dysfunction have an increased risk of suffering from diabetes, especially those on thyroid medication. (AU)

Thyroid carcinoma in elderly people: Characterization using big data tools.

OBJECTIVE: To determine the clinical-histological data associated comorbidities and the use of health resources of elderly patients with thyroid cancer. METHODS: An observational, retrospective study was carried out using data from the electronic medical record (EMR) of the Hospital Universitario Puerta de Hierro Majadahonda (Madrid, Spain). The information was extracted using artificial intelligence techniques and analysed using the Savana Manager 3.0 software. We differentiated between younger people (0-59 years) and older people (60 or more years) and, within this latter group, between people of advanced age (60-74 years) and elderly people (75 or more years). RESULTS: Of a total of 509,517 patients, 1781 (0.35%) were diagnosed with thyroid cancer. Compared to younger patients, older patients presented a lower proportion of papillary carcinoma (64.2% vs. 75.3%) as well as a higher proportion of follicular carcinoma (9.3% vs. 5.0%) and other histological types (26.5% vs. 19.7%; p < 0.001). Young people with thyroid cancer exhibited prevalences of risk factors and most of the cardiovascular diseases studied significantly higher than those found in the general population. Elderly patients, compared with those of advanced age, showed greater comorbidity. However, a trend towards a lower consumption of healthcare resources was observed when elderly patients were compared with those of advanced age. CONCLUSION: The clinical characteristics, comorbidities and consumption of health resources of patients with thyroid cancer vary markedly with age. Elderly patients are characterized by a high burden of comorbidities that is not accompanied by a notable increase in their consumption of health resources.

Executive summary of the consensus document on hypophysitis of the Neuroendocrinology Area of Knowledge of the Spanish Society of Endocrinology and Nutrition.

The term hypophysitis is used to designate a heterogeneous group of pituitary conditions characterized by the presence of inflammatory infiltration of the adenohypophysis, neurohypophysis, or both. Although hypophysitis are rare disorders, the most common in clinical practice is lymphocytic hypophysitis, a primary hypophysitis characterized by lymphocytic infiltration, which predominantly affects women. Other forms of primary hypophysitis are associated with different autoimmune diseases. Hypophysitis can also be secondary to other disorders such as sellar and parasellar diseases, systemic diseases, paraneoplastic syndromes, infections, and drugs, including immune checkpoint inhibitors. The diagnostic evaluation should always include pituitary function tests and other analytical tests based on the suspected diagnosis. Pituitary magnetic resonance imaging is the investigation of choice for the morphological assessment of hypophysitis. Glucocorticoids are the mainstay of treatment for most symptomatic hypophysitis.

Mortality in Acromegaly Diagnosed in Older Individuals in Spain Is Higher in Women Compared to the General Spanish Population.

CONTEXT: There are no data on mortality of acromegaly diagnosed in older individuals. OBJECTIVE: This work aimed to compare clinical characteristics, growth hormone-related comorbidities, therapeutic approaches, and mortality rate of patients diagnosed before or after 2010 and to assess overall mortality rate compared with the general Spanish population. METHODS: A retrospective evaluation was conducted among Spanish tertiary care centers of 118 patients diagnosed with acromegaly at age 65 or older. Kaplan-Meier curves were constructed to trace survival, and Cox proportional hazard models were used to assess the risk factors associated with mortality. We also compared mortality with that of the Spanish population by using age- and sex-adjusted standardized mortality ratios (SMRs). RESULTS: No differences were found in first-line treatment or biochemical control, between both periods except for faster biochemical control after 2010. Twenty-nine (24.6%) patients died, without differences between groups, and had a median of follow-up 8.6 years (103, [72.3] months). Overall SMR was 1.02 (95% CI, 0.57-1.54), (0.60; 95% CI, 0.35-1.06) for men and (1.80; 95% CI, 1.07-2.94) for women. The most common cause of death was cardiovascular disease (CVD). CONCLUSION: The mortality in patients with acromegaly diagnosed in older individuals was no different between both periods, and there was no overall SMR difference compared with the general Spanish population. However, the SMR was higher in women. As CVD is the leading cause of mortality, it seems advisable to initiate an intense CVD protective treatment as soon as acromegaly is diagnosed, particularly in women, in addition to tight acromegaly control to prevent excess mortality.

Control of Thyroid Dysfunction in Spanish Population Registered in the Primary Care Clinical Database: An Analysis of the Proportion of Patients with Thyrotropin Values Outside the Reference Range.

Inadequate control of thyroid dysfunction is common and has deleterious health consequences. Our objective was to determine the prevalence of TSH values outside the reference range, as an indicator of inadequate control of hypothyroidism and hyperthyroidism in patients undergoing treatment for thyroid dysfunction in Spain. An observational, retrospective, non-interventional study was conducted using the Primary Care Clinical Database (BDCAP). Patients treated with thyroid hormone for hypothyroidism and with antithyroid drugs for hyperthyroidism were identified. We assessed serum TSH concentration, considering values from 0.4 to 4.0 mU/l as the reference interval. We found 360 313 people with hypothyroidism on thyroid hormone replacement and 9239 with hyperthyroidism on antithyroid drugs therapy. TSH values outside the reference range in hypothyroid subject were detected in 126 866 (35.20%) people, of whom 107 205 (29.75%) had TSH>4.0 mU/l, suggesting inappropriately low doses of levothyroxine, and 19 661 (5.46%) had TSH<0.4 mU/l, suggesting inappropriate over replacement. In the hyperthyroid group, TSH values outside the reference range were observed in 4252 (46.02%) patients. There were 2833 (30.66%) patients with TSH<0.4 mU/l, suggesting undertreatment, and 1419 (15.36%) with TSH>4.0 mU/l, suggesting overtreatment with antithyroid medication. People over 65 years of age had a lower frequency of undertreatment of hypothyroidism and a lower frequency of overtreatment and undertreatment of hyperthyroidism. In conclusion, our results suggest that inadequate control of thyroid dysfunction, due to its high frequency and its consequences for health, is a public health problem that should be addressed by clinicians and health authorities.