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.

Prevalence of chronic postsurgical hypoparathyroidism not adequately controlled: an analysis of a nationwide cohort of 337 patients.

Purpose: The identification of patients with chronic hypoparathyroidism who are adequately (AC) or not adequately controlled (NAC) has clinical interest, since poor disease control is related to complications and mortality. We aimed to assess the prevalence of NAC patients in a cohort of subjects with postsurgical hypoparathyroidism. Methods: We performed a multicenter, retrospective, cohort study including patients from 16 Spanish hospitals with chronic hypoparathyroidism lasting ≥3 years. We analyzed disease control including biochemical profile and clinical wellness. For biochemical assessment we considered three criteria: criterion 1, normal serum calcium, phosphorus and calcium x phosphorus product; criterion 2, the above plus estimated glomerular filtration rate ≥60 ml/min/1.73 m2; and criterion 3, the above plus normal 24-hour urinary calcium excretion. A patient was considered AC if he or she met the biochemical criteria and was clinically well. Results: We included 337 patients with postsurgical hypoparathyroidism (84.3% women, median age 45[36-56] years, median time of follow-up 8.9[6.0-13.0] years). The proportions of NAC patients with criteria 1, 2 and 3 were, respectively, 45.9%, 49.2% and 63.1%. Patients who had dyslipidemia at the time of diagnosis presented a significantly higher risk of NAC disease (criterion 3; OR 7.05[1.44-34.45]; P=0.016). NAC patients (criterion 2) had a higher proportion of subjects with incident chronic kidney disease and eye disorders, and NAC patients (criterion 3) had a higher proportion of incident chronic kidney disease, nephrolithiasis and dyslipidemia than AC patients. Conclusion: The present study shows a strikingly high prevalence of NAC patients in the clinical practice of Spanish endocrinologists. Results suggest that NAC disease might be associated with some prevalent and incident comorbidities.

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.

Differentiated thyroid carcinoma in the elderly: influence of age on disease-free and overall survival.

PURPOSE: We investigated whether age at diagnosis of differentiated thyroid carcinoma (DTC) may be a risk factor for structural disease and mortality after primary treatment in aging patients. METHODS: A multicenter, retrospective analysis including patients older than 60 years at DCT diagnosis was designed. All subjects were treated by surgery with or without radioiodine adjuvant therapy and had a minimum follow-up of one year. We compared elderly patients (group 1, 60-74 years) with very old patients (group 2, ≥75 years). RESULTS: The study involved 1668 patients (74.3% women, median age 67 years, 87.6% papillary thyroid cancer, 73.3% treated with radioiodine), including 1397 in group 1 and 271 in group 2. Patients in group 2 had larger tumor size (1.8 [0.8-3.0] vs 1.5 [0.7-2.8] cm; P = 0.005), higher proportions of tumors with vascular invasion (23.8 vs 16.4%; P = 0.006), and lower proportion of lymphocytic thyroiditis (18.6 vs 24.9%; P = 0.013) than subjects in group 1. Kaplan-Meier survival analysis showed that patients in group 2 had significantly lower structural disease-free survival (DFS) and overall survival (OS) than patients in group 1 (P = 0.035 and <0.001, respectively). In multivariate Cox regression analysis, age was a risk factor significantly associated with OS. However, age was significantly associated with DFS in unadjusted analysis and in analysis adjusted by gender and risk classification variables, but not when pathological and therapy-related variables were introduced in the model. On the other hand, patients who received radioiodine had worse DFS (P < 0.001) compared to those who did not. CONCLUSION: Although age is a conditioning factor for OS, very old patients do not have a greater risk of developing structural disease throughout the follow-up than elderly patients with DTC.

Efficacy in size and symptom reduction of radiofrequency ablation of benign non-functioning thyroid nodules.

INTRODUCTION: Radiofrequency ablation (RFA) plays an increasing role in the management of thyroid nodules. The purpose of this study was to evaluate the safety and efficacy of RFA of benign thyroid nodules in terms of volume reduction and symptom relief. METHODS: We reviewed the medical records of patients with a solitary thyroid nodule who received RFA at our centre from April 2016 to January 2020. Ultrasound-guided RFA was performed by the moving-shot technique. Patients were followed up with ultrasound examinations and thyroid function tests. We evaluated changes in volume and in compressive (0-10 scale) and cosmetic (4-point scale) symptoms to analyse efficacy and complications, and in thyroid function to evaluate safety. RESULTS: A total of 72 patients were included in the study. The mean follow-up was 11.1±0.7 months. There was a statistically significant reduction in size of the nodules at Month 1, 3, 6 and 12 after RFA (expressed as volume reduction rate: 34%±2.1, 50.8%±2.2, 60.3%±2.6, 58.87%±3.5, p<0.0001). We found statistically significant improvement in compressive symptoms (from 7.1±0.26 to 1.76±0.33, p<0.0001) and in cosmetic alteration (from 3.66±0.09 to 2.14±0.14, p<0.0001). No major complications were observed. DISCUSSION: RFA achieved significant volume reduction and improved compressive symptoms as well as cosmetic complaints, with minimum side effects. Our results are in line with recent available evidence and further support the use of RFA as a safe and effective therapeutic option in the management of benign thyroid nodules.

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.

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.

Mortality risk in adults according to categories of impaired glucose metabolism after 18 years of follow-up in the North of Spain: The Asturias Study.

People who develop type 2 diabetes (T2D) are known to have a higher mortality risk. We estimated all-cause, cardiovascular, and cancer mortality-risks in our patient cohort according to categories of impaired glucose metabolism. This 18-year retrospective analysis included a region-wide, representative sample of a population aged 30-75 years. Age- and sex-stratified hazard ratios (HRs) were calculated for 48 participants with diagnosed T2D, 83 with undiagnosed T2D (HbA1c ≥6.5%, fasting glycemia ≥126 mg/dL, or glycemia after 75 g glucose load ≥200 mg/dL); 296 with prediabetes (HbA1c 5.7%-6.4%, fasting glycemia 100-125 mg/dL, or glycemia after 75 g glucose load 140-199 mg/dL), and 607 with normoglycemia. Over 18,612 person-years, 32 individuals with undiagnosed T2D, 30 with diagnosed T2D, 62 with prediabetes, and 80 with normoglycemia died. Total sample crude mortality rate (MR) was 10.96 deaths per 1,000 person-years of follow-up. MR of the diagnosed T2D group was more than 3-times higher and that of newly diagnosed T2D was 2-times higher (34.72 and 21.42, respectively) than total sample MR. Adjusted HR for all-cause mortality was 2.02 (95% confidence interval 1.29-3.16) and 1.57 (95% CI 1.00-2.28) in the diagnosed T2D group and the newly diagnosed T2D group, respectively. Adjusted HR for cardiovascular mortality in the T2D group was 2.79 (95% CI 1.35-5.75); this risk was greatly increased in women with T2D: 6.72 (95% CI 2.50-18.07). In Asturias, age- and sex-standardized all-cause mortality is more than 2-times higher for adults with T2D than for adults without T2D. The HR for cardiovascular mortality is considerably higher in T2D women than in normoglycemic women.

Correction: Mortality risk in adults according to categories of impaired glucose metabolism after 18 years of follow-up in the North of Spain: The Asturias Study.

[This corrects the article DOI: 10.1371/journal.pone.0211070.].

Estimation of body fat mass using the CUN-BAE index and mortality risk by sex in the Asturias Study cohort. / Estimación de grasa corporal según ecuación CUN-BAE e IMC y riesgo de mortalidad por sexos en la cohorte del Estudio Asturias.

INTRODUCTION AND OBJECTIVES: In epidemiological studies, excess body fat (BF) has been associated with cardiometabolic risk factors, some types of cancer, and other causes of death. A new anthropometric method has been defined: The CUN-BAE index (University of Navarra Clinic-Body Fat Estimator), which is based on BMI, sex, and age. BMI and CUN-BAE index were used to assess their contribution to mortality risk from any cause in the Asturias Study cohort. MATERIAL AND METHODS: The Asturias study is a cohort study including 1.034 individuals aged 30-75years who participated in the first study phase (1998-1999). The study included a clinical survey, physical examination, and an oral glucose tolerance test. Vital status was determined in the cohort after 18years of follow-up. RESULTS: Two hundred and four subjects died: 93 females and 111 males (16.6% and 23.5% respectively men). Baseline values of both BMI and %BF suggesting obesity (BMI>30kg/m2 and CUN-BAE >25% in males and >35% in females) were found in most subjects. After adjusting for T2DM, HBP, CVD, and tobacco, the risk of all-cause and cardiovascular mortality was significantly higher as CUN-BAE increased, especially in females. CONCLUSIONS: The CUN-BAE equation is a useful tool, especially in females, to detect those who will have a greater risk of mortality, regardless of cardiovascular risk factors.

Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: a multicentric and nation-wide retrospective analysis.

PURPOSE: The prevalence of postoperative hypoparathyroidism has been studied in registries and in surgical series with highly variable and imprecise results. However, the frequency of this hormonal deficiency in the clinical practice of endocrinologists is not known with accuracy. We aimed to assess the prevalence and risk factors of hypoparathyroidism in patients undergoing total thyroidectomy in Spain. METHODS: We designed a retrospective, multicentre and nation-wide protocol including all patients with total thyroidectomy who were seen in the endocrinology clinic of the participant centers from January to March 2018. Prevalence of hypoparathyroidism was evaluated at discharge of surgery, 3-6 months after surgery, 12 months after surgery and at last visit. Twenty hospitals participated in the study. RESULTS: Of 1792 patients undergoing total thyroidectomy, 866 (48.3%) developed postoperative hypoparathyroidism at discharge of surgery. Most of them recover parathyroid function over time. Prevalence of hypoparathyroidism at 3-6 months, 12 months and at last visit was 22.9%, 16.7% and 14.5%, respectively. The risk of developing definitive hypoparathyroidism was related to the presence of parathyroid tissue at histology, lymph node dissection, and two-stage thyroidectomy. Patients with thyroid cancer, with higher postoperative calcium levels and treated by expert surgical teams exhibited lower risk of developing permanent hypoparathyroidism. CONCLUSIONS: Although most patients with postsurgical hypoparathyroidism recover parathyroid function, the prevalence of permanent disease in clinical practice is non negligible (14.5%). Postoperative calcium, extent and timing of surgery, the presence of cancer, expert surgical team, and parathyroid tissue at histology are predictors of permanent hypoparathyroidism.

Correction to: Prevalence and risk factors for hypoparathyroidism following total thyroidectomy in Spain: a multicentric and nation-wide retrospective analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Circulating irisin levels are positively associated with metabolic risk factors in sedentary subjects.

INTRODUCTION: A physically active life-style plays an independent role in the protection against type 2 diabetes and cardiovascular diseases. Irisin, a novel exercise-induced myokine, activates thermogenesis in rodents through increasing beige fat cells abundance within white fat. We aimed to investigate circulating irisin levels in association with the degree of physical activity and various metabolic parameters in humans. METHODS: Circulating irisin levels (ELISA) and metabolic parameters were analyzed in 428 subjects (195 men/233 women). Participants were classified according to their self-reported physical activity and to their area of residence. RESULTS: Circulating irisin levels were higher in active than in sedentary subjects (p = 0.006). Rural inhabitants showed higher circulating irisin levels than urban subjects (p < 0.0001). The increase in irisin levels related to an active lifestyle was only observed in rural citizens (p = 0.014). Among sedentary participants, irisin levels were positively associated with metabolic risk factors (BMI, fasting insulin, HOMA and fasting triglycerides). The area of residence (ß = - 0.592, p = < 0.0001) contributed independently to circulating irisin levels variance after controlling for age, gender, BMI, HOMAIR, triglycerides and physical activity. CONCLUSIONS: In sedentary participants, circulating irisin levels were positively associated with parameters related to an increased cardiometabolic risk. The present study confirmed that an active lifestyle increases circulating irisin levels, but only among subjects living in a rural environment. Area of residence might be a determinant of irisin levels.

Efectividad del tratamiento con sulfonilureas en paciente con mutación en el gen ABCC8 (MODY12) / Effectiveness of sulfonylurea treatment in a patient with a mutation in ABCC8 (MODY12)

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Estimación de grasa corporal según ecuación CUN-BAE e IMC y riesgo de mortalidad por sexos en la cohorte del Estudio Asturias / Estimation of body fat mass using the CUN-BAE index and mortality risk by sex in the Asturias Study cohort

Introducción y objetivos: Conocemos que el exceso de grasa corporal (GC) se asocia con factores de riesgo cardiovascular, algunos tipos de cáncer y otras causas principales de muerte. Se ha definido un nuevo método antropométrico: el índice CUN-BAE (Clínica Universidad de Navarra-Estimador de Adiposidad Corporal), que se basa en el IMC, el sexo y la edad. Hemos utilizado IMC y CUN-BAE para evaluar su contribución en la asociación con mortalidad en la cohorte del Estudio Asturias. Material y métodos: El Estudio Asturias se trata de un estudio de cohortes que incluyó a 1.034 individuos de 30-75 años de edad que participaron en la primera fase del estudio (1998-1999), realizando encuesta, exploración física y sobrecarga oral de glucosa. Se registraron los fallecimientos en la cohorte tras 18 años de seguimiento. Resultados: 204 personas fallecieron: 93 mujeres y 111 varones (16,6% de las mujeres y 23,5% de los varones). Valores basales tanto de IMC como de %GC determinantes de obesidad (> 30 kg/m2 para IMC; > 25% en hombres y > 35% en mujeres para CUN-BAE) fueron mayoritarios en los datos de individuos fallecidos. Tras ajuste por DM2, HTA, ECV y tabaco, el riesgo de mortalidad por todas las causas y cardiovascular es significativamente mayor según se incrementa el CUN-BAE, sobre todo en mujeres. Conclusiones: La ecuación CUN-BAE es una herramienta útil en mujeres para detectar las que van a presentar un mayor riesgo de mortalidad, independientemente de factores de riesgo

Introduction and objectives: In epidemiological studies, excess body fat (BF) has been associated with cardiometabolic risk factors, some types of cancer, and other causes of death. A new anthropometric method has been defined: The CUN-BAE index (University of Navarra Clinic-Body Fat Estimator), which is based on BMI, sex, and age. BMI and CUN-BAE index were used to assess their contribution to mortality risk from any cause in the Asturias Study cohort. Material and methods: The Asturias study is a cohort study including 1.034 individuals aged 30-75 years who participated in the first study phase (1998-1999). The study included a clinical survey, physical examination, and an oral glucose tolerance test. Vital status was determined in the cohort after 18years of follow-up. Results: Two hundred and four subjects died: 93 females and 111 males (16.6% and 23.5% respectively men). Baseline values of both BMI and %BF suggesting obesity (BMI > 30 kg/m2 and CUN-BAE > 25% in males and >35% in females) were found in most subjects. After adjusting for T2DM, HBP, CVD, and tobacco, the risk of all-cause and cardiovascular mortality was significantly higher as CUN-BAE increased, especially in females. Conclusions: The CUN-BAE equation is a useful tool, especially in females, to detect those who will have a greater risk of mortality, regardless of cardiovascular risk factors