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.

Interobserver variability in thyroid ultrasound.

PURPOSE: Ultrasound evaluation of thyroid nodules is the preferred technique, but it is dependent on operator interpretation, leading to inter-observer variability. The current study aimed to determine the inter-physician consensus on nodular characteristics, risk categorization in the classification systems, and the need for fine needle aspiration puncture. METHODS: Four endocrinologists from the same center blindly evaluated 100 ultrasound images of thyroid nodules from 100 different patients. The following ultrasound features were evaluated: composition, echogenicity, margins, calcifications, and microcalcifications. Nodules were also classified according to ATA, EU-TIRADS, K-TIRADS, and ACR-TIRADS classifications. Krippendorff's alpha test was used to assess interobserver agreement. RESULTS: The interobserver agreement for ultrasound features was: Krippendorff's coefficient 0.80 (0.71-0.89) for composition, 0.59 (0.47-0.72) for echogenicity, 0.73 (0.57-0.88) for margins, 0.55 (0.40-0.69) for calcifications, and 0.50 (0.34-0.67) for microcalcifications. The concordance for the classification systems was 0.7 (0.61-0.80) for ATA, 0.63 (0.54-0.73) for EU-TIRADS, 0.64 (0.55-0.73) for K-TIRADS, and 0.68 (0.60-0.77) for K-TIRADS. The concordance in the indication of fine needle aspiration puncture (FNA) was 0.86 (0.71-1), 0.80 (0.71-0.88), 0.77 0.67-0.87), and 0.73 (0.64-0.83) for systems previously described respectively. CONCLUSIONS: Interobserver agreement was acceptable for the identification of nodules requiring cytologic study using various classification systems. However, limited concordance was observed in risk stratification and many ultrasonographic characteristics of the nodules.

Therapeutic Management and Long-Term Outcome of Hyperthyroidism in Patients with Antithyroid-Induced Agranulocytosis: A Retrospective, Multicenter Study.

BACKGROUND: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. METHODOLOGY: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. RESULTS: The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA. CONCLUSIONS: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.

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.

Cribriform morular thyroid carcinoma: a case report with pathological, immunohistochemical, and molecular findings suggesting an origin from follicular cells (or their endodermal precursors).

Cribriform morular thyroid carcinoma (CMTC) is a rare malignant thyroid tumor with a peculiar growth pattern secondary to permanent activation of the WNT/ß-catenin pathway. CMTC may be associated with familial adenomatous polyposis or sporadic; it shares morphological features with papillary thyroid carcinoma (PTC) and was considered a variant of PTC in the 2017 WHO classification of tumors of endocrine organs. The new 5th edition of the WHO classification of endocrine and neuroendocrine tumors considered CMTC an independent thyroid neoplasm of uncertain histogenesis. A thymic/ultimobranchial pouch-related differentiation in CMTC has been recently postulated. We, however, have used the pathological and immunohistochemical features of this case of CMTC with 2 novel oncogenic somatic variants (c.3428_3429insA, p.(Tyr1143Ter) and c.3565del, p. (Ser1189Hisfs*76) of the APC gene to propose an origin from follicular cells (or their endodermal precursors). As usual in CMTC, the morular component of this tumor was positive for CDX2. Given the fact that WNT/ß-catenin signaling, through CDX2, activates large intestine and small intestine gene expression, we postulate that in CMTC, the tumor cells have their terminal differentiation blocked, thus showing a peculiar primitive endodermal (intestinal-like) phenotype negative for sodium-iodide symporter, thyroperoxidase, and thyroglobulin. Establishing the histogenesis of CMTC is very relevant for the development of appropriate therapies of redifferentiation, particularly in patients where the tumor cannot be controlled by surgery.

Incidentally discovered papillary thyroid microcarcinoma in patients undergoing thyroid surgery for benign disease.

INTRODUCTION: The incidence of thyroid carcinoma has grown significantly over the last few decades. A possible explanation is the increased diagnosis of small thyroid microcarcinoma (TMc). TMc reach a maximum diameter of ≤1 cm, identified during histopathology examination following a thyroidectomy performed for reasons not pertaining to malignancy. This study aims to investigate the prevalence of papillary thyroid microcarcinoma (PTMc) according to the benign pathology that refers patients to surgery and its trend evolution. METHODS: Retrospective cohort analysis of 1815 patients who underwent total thyroidectomy for non-malignant diseases in the 2005-2020 period. RESULTS: The mean age of the subjects was 53.5 years, with a higher proportion of women (1481, 82.1%). A total of 167 PTMc (9.3%) were incidentally discovered. A multivariate logistic regression analysis was performed, showing no differences in prevalence according to sex or age in patients with PTMc compared to final benign histology. Multinodular goiter increases the risk of PTMc with an odds ratio of 2.2 (p = 0.001) compared to Hashimoto's thyroiditis and Graves' disease (GD). There is a statistically significant increase in the incidence of PTMc in the group operated in the 2017-2020 vs. 2005-2008 period (p = 0.005). CONCLUSION: The overall prevalence of PTMc in patients who underwent thyroid surgery for the benign disease was 9.3%. Thyroid nodular hyperplasia was the most frequent benign pathology associated with PTMc compared to Hashimoto's or GD. Gender and age were not correlated with the prevalence of TMc. Over the years, surgical findings of PTMc have grown, particularly in the 2017-2020 period.

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.

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.

Late Recovery of Parathyroid Function After Total Thyroidectomy: A Case-Control Study.

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

Rate of non-invasive follicular thyroid neoplasms with papillary-like nuclear features depends on pathologist's criteria: a multicentre retrospective Southern European study with prolonged follow-up.

PURPOSE: To determine the rate of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in a multi-institutional series from the Iberian Peninsula and describing this NIFTP cohort. METHODS: Retrospective study of papillary thyroid carcinoma (PTC) or well-differentiated tumours of uncertain malignant potential (WDT-UMP) diagnosed between 2005 and 2015 and measuring ≥5 mm in adult patients from 17 hospitals. Pathological reports were reviewed to determine the cases that fulfil the original criteria of NIFTP and histology was reassessed. Rates were correlated with the number of PTC and its follicular variant (FVPTC) of each institution. Demographic data, histology, management, and follow-up of the reclassified NIFTP cohort were recorded. RESULTS: A total of 182 cases with NIFTP criteria were identified: 174/3372 PTC (rate: 5.2%; range: 0-12.1%) and 8/19 WDT-UMP (42.1%). NIFTP rate showed linear correlation with total PTC (p: 0.03) and FVPTC (p: 0.007) identified at each centre. Ultrasound findings were non-suspicious in 60.1%. Fine-needle cytology or core biopsy diagnoses were undetermined in 49.7%. Most patients were treated with total thyroidectomy. No case had nodal disease. Among patients with total thyroidectomy, 89.7% had an excellent response evaluated 1 year after surgery. There were no structural persistence or relapses. Five patients showed residual thyroglobulin after 90 months of mean follow-up. CONCLUSIONS: NIFTP rate is low but highly variable in neighbouring institutions of the Iberian Peninsula. This study suggests pathologist's interpretation of nuclear alterations as the main cause of these differences. Patients disclosed an excellent outcome, even without using the strictest criteria.

Evolución del estado de nutrición de yodo en gestantes del area sanitaria de Pamplona / Change over time in the iodine nutritional status of pregnant women from the Pamplona healthcare region

INTRODUCCIÓN: La ingesta adecuada de yodo es esencial durante el embarazo. Sin embargo, una parte de la población gestante de nuestro país persiste en una situación de yododeficiencia. Un estudio previo realizado en embarazadas del área sanitaria de Pamplona mostró una yoduria insuficiente (125 mcg/l) y un bajo consumo de sal yodada. El objetivo del presente trabajo es conocer la ingesta de yodo y analizar la evolución del estado de yodación en gestantes de nuestro medio en los últimos años. MÉTODOS: Estudio observacional de 400 gestantes de primer trimestre sin antecedentes conocidos de enfermedad tiroidea. Se cumplimentó un cuestionario de consumo de yodo. Como marcadores del estado de yodación se analizaron la yoduria en una muestra simple de orina y la tiroglobulina sérica, y se calculó el volumen tiroideo mediante ecografía cervical. RESULTADOS: El 70,5% de las participantes consumía sal yodada (55,3% pregestacional) y el 98,5% suplementos farmacológicos con yodo (dosis 202,6±30,1 mcg/día). La mediana de la yoduria fue 242 mcg/l (138,5-415,5 mcg/l) y de la tiroglobulina 12,3 mcg/l (8,39 mcg/l). El consumo de sal yodada se asoció a mayor yoduria y a un menor volumen tiroideo. No se encontraron diferencias en los parámetros estudiados en función del consumo de lácteos, pescado o huevos. CONCLUSIONES: La ingesta de yodo en gestantes de Pamplona ha aumentado, tanto a expensas del empleo de sal yodada como de la dosis de la suplementación farmacológica. Esto ha permitido alcanzar un estado de yodación adecuado

INTRODUCTION: Adequate iodine intake is essential during pregnancy. A previous study of pregnant women from the Pamplona healthcare region showed mild iodine deficiency (mean urinary iodine level, 125 mcg/L). This study was intended to ascertain the iodine intake of pregnant women in our region and to analyze the change over time in their iodine nutritional status. METHODS: An observational study of 400 women in their first trimester of pregnancy. An iodine intake questionnaire was administered. To assess iodine status, urinary iodine concentration (UIC) was measured in a simple urine sample, and serum thyroglobulin levels were determined. In addition, thyroid volume was measured by cervical ultrasound examination. RESULTS: Iodized salt was used by 70.5% of all participants (55.3% since the pre-gestational period) and 98.5% of them received iodine-containing supplements (mean dose, 202.6±30.1 mcg/day). Mean urinary iodine concentration was 242 mcg/L (138.5-415.5 mcg/L) and the mean serum thyroglobulin level was 12.3 mcg/L (8.3-9 mcg/L). Iodized salt intake was associated with higher UICs and lower thyroid volume. No differences were found in any of the tested parameters regarding the intake of dairy products, fish, or eggs. CONCLUSIONS: Iodine intake by pregnant women in Pamplona has increased due to a greater use of iodized salt and to higher doses of iodine supplements. As a result of this, an adequate iodine status has been achieved in the last decade

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.

Change over time in the iodine nutritional status of pregnant women from the Pamplona healthcare region. / Evolución del estado de nutrición de yodo en gestantes del area sanitaria de Pamplona.

INTRODUCTION: Adequate iodine intake is essential during pregnancy. A previous study of pregnant women from the Pamplona healthcare region showed mild iodine deficiency (mean urinary iodine level, 125 mcg/L). This study was intended to ascertain the iodine intake of pregnant women in our region and to analyze the change over time in their iodine nutritional status. METHODS: An observational study of 400 women in their first trimester of pregnancy. An iodine intake questionnaire was administered. To assess iodine status, urinary iodine concentration (UIC) was measured in a simple urine sample, and serum thyroglobulin levels were determined. In addition, thyroid volume was measured by cervical ultrasound examination. RESULTS: Iodized salt was used by 70.5% of all participants (55.3% since the pre-gestational period) and 98.5% of them received iodine-containing supplements (mean dose, 202.6±30.1 mcg/day). Mean urinary iodine concentration was 242 mcg/L (138.5-415.5 mcg/L) and the mean serum thyroglobulin level was 12.3 mcg/L (8.3-9 mcg/L). Iodized salt intake was associated with higher UICs and lower thyroid volume. No differences were found in any of the tested parameters regarding the intake of dairy products, fish, or eggs. CONCLUSIONS: Iodine intake by pregnant women in Pamplona has increased due to a greater use of iodized salt and to higher doses of iodine supplements. As a result of this, an adequate iodine status has been achieved in the last decade.

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.

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.

Optimización del seguimiento de gestantes con enfermedad tiroidea autoinmune / Optimization of the follow-up of pregnant women with autoimmune thyroid disease

Objetivo: Determinar el riesgo de hipotiroidismo en gestantes con enfermedad tiroidea autoinmune y tirotropina (TSH) < 2,5 mUI/l al inicio del embarazo. Métodos: Estudio prospectivo longitudinal en gestantes de primer trimestre sin antecedentes de patología tiroidea y con TSH en primer trimestre < 2,5 mUI/l. Se determinaron TSH, tiroxina libre (T4l) y anticuerpos antiperoxidasa (TPO) y antitiroglobulina en los 3 trimestres. Se comparó la evolución de la función tiroidea y la aparición de hipotiroidismo gestacional (TSH > 4 mUI/l), entre las gestantes con autoinmunidad positiva y autoinmunidad negativa. Resultados: Se incluyeron 300 gestantes con TSH basal 1,3 ± 0,6 mUI/l (semana gestacional 9). El 17,7% (n = 53) tenían autoinmunidad positiva en el primer trimestre. Los títulos de anticuerpos TPO y antitiroglobulina disminuyeron entre el primer y el tercer trimestre un 76,8% y un 80,7% respectivamente. La evolución de la función tiroidea fue similar en el grupo con autoinmunidad positiva y el grupo con autoinmunidad negativa, y la aparición de hipotiroidismo fue del 1,9% (1/53) y del 2% (5/247) respectivamente. Las gestantes en las que la TSH aumentó por encima de 4 mUI/l (n = 6) tenían cifras superiores de TSH basal en comparación con las que mantuvieron TSH≤4 mUI/l a lo largo del embarazo (1,8 vs. 1,3 mUI/l; p = 0,047). Conclusión: En nuestra población, las mujeres con TSH < 2,5 mUI/l al inicio del embarazo tienen un riesgo mínimo de desarrollar hipotiroidismo durante la gestación, independientemente de la autoinmunidad tiroidea

Objective: To determine the risk of hypothyroidism in pregnant women with autoimmune thyroid disease and thyrotropin (TSH) < 2,5 mIU/l at the beginning of pregnancy. Methods: Prospective longitudinal study of pregnant women with no personal history of thyroid disease, and with TSH < 2.5 mIU/l in the first trimester. TSH, free thyroxine (FT4), anti peroxidase (TPO) and anti thyroglobulin antibodies were measured in the 3 trimesters of pregnancy. We compared thyroid function throughout pregnancy, and the development of gestational hypothyroidism (TSH >4 mIU/l) among pregnant women with positive thyroid autoimmunity and those with negative autoimmunity. Results: We included 300 pregnant women with mean baseline TSH 1.3 ± 0.6 mIU/l (9th gestational week). Positive thyroid autoinmunity was detected in 17.7% of women (n = 53) at the first trimester. Between the first and the third trimesters, TPO and anti thyroglobulin antibodies titers decreased 76.8% and 80.7% respectively. Thyroid function during pregnancy was similar among the group with positive autoimmunity and the group with negative autoimmunity, and the development of hypothyroidism was 1.9% (1/53) and 2% (5/247) respectively. Pregnant women in whom TSH increased above 4 mIU/l (n = 6), had higher baseline TSH levels compared to those who maintained TSH ≤4 mIU/l during pregnancy (1.8 vs. 1.3 mIU/l; p=.047). Conclusion: In our population, women with TSH levels <2.5 mIU/l at the beginning of pregnancy have a minimal risk of developing gestational hypothyroidism regardless of thyroid autoimmunity

Thyroid Function Reference Values in Healthy Iodine-Sufficient Pregnant Women and Influence of Thyroid Nodules on Thyrotropin and Free Thyroxine Values.

BACKGROUND: Thyroid function assessment in pregnancy requires specific reference intervals stratified by gestational age and according to each laboratory method. Thyroid nodules may influence thyroid function in pregnant women. The aims of this study were to define the reference values of thyrotropin (TSH) and free thyroxine (fT4) in the three pregnancy trimesters in iodine-sufficient pregnant women, and to analyze the influence of thyroid nodules on thyroid function during pregnancy. METHODS: This was a prospective, longitudinal study comprising 400 pregnant women with no history of thyroid disease and no medication influencing thyroid function. TSH, fT4, antithyroglobulin, and antithyroid peroxidase antibodies were measured each trimester by chemiluminescent immunoassays. Urinary iodine concentration was measured in the first trimester when a thyroid echography was also performed. Women with multiple gestation pregnancies, positive thyroid autoimmunity, TSH values >5 or <0.1 mIU/L with a simultaneous fT4 level above the general population reference value in the first trimester, or clinically significant thyroid nodules (nodules ≥1 cm and/or multiple nodules) were excluded to establish TSH and fT4 reference values. RESULTS: Reference intervals in the first, second, and third trimesters were 0.13-4.16, 0.31-3.73, and 0.58-4.36 mIU/L, respectively, for TSH, and 0.85-1.24, 0.82-1.20, and 0.67-1.06 ng/dL, respectively, for fT4. The total prevalence of thyroid nodules was 28.8% [95% confidence interval (CI) 24.4-33.5%], and 6.0% of the participants showed clinically significant nodules. Pregnant women with thyroid nodules (n = 115) showed consistently lower TSH values during all pregnancy stages (first trimester: median 1.14 mIU/L [interquartile range (IQR) 0.53-1.75 mIU/L] vs. 1.48 mIU/L [IQR 0.94-2.19 mIU/L], p < 0.001; second trimester: 1.22 mIU/L [IQR 0.66-1.77 mIU/L] vs. 1.45 mIU/L [1.04-2.05 mIU/L], p = 0.001; third trimester: 1.74 mIU/L [IQR 1.08-2.36 mIU/L] vs. 1.93 mIU/L [IQR 1.37-2.58 mIU/L], p = 0.041) and higher fT4 values in the first trimester (M ± SD = 1.08 ± 0.14 ng/dL vs. 1.03 ± 0.12, p < 0.001) compared to those without nodules (n = 285). Both pregnant women with clinically significant thyroid nodules and those with nonsignificant ones had lower TSH values than women without nodules. CONCLUSIONS: TSH/fT4 reference intervals in pregnant women from the authors' geographical area will thyroid dysfunction in pregnancy to be appropriately diagnosed. The prevalence of thyroid nodules is high in iodine-sufficient pregnant women, and is associated with low TSH values across pregnancy.

Optimization of the follow-up of pregnant women with autoimmune thyroid disease. / Optimización del seguimiento de gestantes con enfermedad tiroidea autoinmune.

OBJECTIVE: To determine the risk of hypothyroidism in pregnant women with autoimmune thyroid disease and thyrotropin (TSH) < 2,5 mIU/l at the beginning of pregnancy. METHODS: Prospective longitudinal study of pregnant women with no personal history of thyroid disease, and with TSH < 2.5 mIU/l in the first trimester. TSH, free thyroxine (FT4), anti peroxidase (TPO) and anti thyroglobulin antibodies were measured in the 3 trimesters of pregnancy. We compared thyroid function throughout pregnancy, and the development of gestational hypothyroidism (TSH >4 mIU/l) among pregnant women with positive thyroid autoimmunity and those with negative autoimmunity. RESULTS: We included 300 pregnant women with mean baseline TSH 1.3 ± 0.6 mIU/l (9th gestational week). Positive thyroid autoinmunity was detected in 17.7% of women (n = 53) at the first trimester. Between the first and the third trimesters, TPO and anti thyroglobulin antibodies titers decreased 76.8% and 80.7% respectively. Thyroid function during pregnancy was similar among the group with positive autoimmunity and the group with negative autoimmunity, and the development of hypothyroidism was 1.9% (1/53) and 2% (5/247) respectively. Pregnant women in whom TSH increased above 4 mIU/l (n = 6), had higher baseline TSH levels compared to those who maintained TSH ≤4 mIU/l during pregnancy (1.8 vs. 1.3 mIU/l; p=.047). CONCLUSION: In our population, women with TSH levels <2.5 mIU/l at the beginning of pregnancy have a minimal risk of developing gestational hypothyroidism regardless of thyroid autoimmunity.

Incidence and Risk Factors Involved in the Development of Nephropathy in Patients with Type 1 Diabetes Mellitus: Follow Up Since Onset.

OBJECTIVES: Estimation of the incidence of nephropathy as well as potential risk factors involved in its onset in a cohort of patients with type 1 diabetes who were followed from diagnosis. METHODS: We studied 716 patients, who were followed for a mean (standard deviation [SD]) of 10.1 (SD: 5.3) years. We analyzed the influence of demographic characteristics and levels of glycated hemoglobin (A1C), lipids and blood pressure during the course of the disease by univariate and multivariate survival methods. RESULTS: The cumulative incidence of nephropathy was 2.6%, 6.3% and 11.9% at 5, 10 and 15 years of evolution, respectively. The factors associated with increased risk for nephropathy were systolic blood pressure and A1C levels. An increment of 10 mm Hg in systolic blood pressure increases the risk by 36%, and an increment of 1% in A1C levels raises the risk by 13% at 5 years since onset and 68% at 10 years, and it doubles the risk at 15 years. Women have higher risk than men (hazard ratio 1.79; p=0.024). CONCLUSIONS: Our study suggests that female gender and high levels of A1C and systolic blood pressure throughout the course of the disease are the main factors associated with an increased risk for development of nephropathy in patients with type 1 diabetes mellitus.