Low glomerular filtration rate values are associated with higher TSH in an elderly population at high cardiovascular disease risk.

Background: Hypothyroidism is associated with impaired glomerular filtration rate (GFR), a recognized cardiovascular disease (CVD), and mortality risk factor. In older adults, this association remains unexplored. We aimed to determine the relationship of elevated TSH with GFR in an elderly population at high CVD risk. Methods: Older adults (age>65ys) with high CVD risk defined by two or more CVD risk factors: smoking (S), high blood pressure (HBP), high total cholesterol, low HDL cholesterol, diabetes (DM), metabolic syndrome or previous cardiovascular event, were prospectively included at our ambulatory Endocrine Clinic. Patients under levothyroxine or thyroid disease were excluded. TSH> 6mU/l defined subclinical hypothyroidism (ScH) with normal free T4 levels. Estimated GFR was calculated by the Berlin-Initiative Study (BIS)-1 formula for elderly population. Urinary albumin to creatinine ratio (uACR), IL-6 and TNF-α, and Carotid intima-media thickness (CIMT) were also determined. The U Mann-Whitney test, the Spearman test, and multiple linear regression were used as statistical tests. Results: Finally 246 patients (68% females) were included and 20 (8%) had ScH. This group, was older (median, Q1-Q3: 77,72-78; 72,68-77 years, p=0.01) and DM was less frequent than in the euthyroid group (35 vs 58%, p=0.039). Lower fasting glucose (-20%,p=0.01), GFR (-14%,p=0.01) and freeT4 (-10%,p<0.001) were found compared to euthyroid patients. A higher prevalence of Kidney failure was found in ScH (80 vs. 46%, p=0.003) vs. euthyroid individuals. Significant correlations with GFR were detected: age (r-0.482,p<0.001), TSH (r-0.172,p=0.004), IL-6 (r-0.150,p=0.047), TNF-α (r-0.274,p<0.001), uACR (r-0.170,p=0.009) and CIMT(r-0.189,p=0.004). By multiple linear regression, in a model adjusted by age, sex, BMI, uACR, S, DM, TNF-α and HBP, TSH (Bst -0.14, p=0.023, R2 = 0.25) was found an independent predictor of GFR. Conclusion: In older adults with high CVD risk, ScH is associated with lower renal function, and this relationship is present regardless of other cardiometabolic risk factors. These results suggest that ScH could contribute to low GFR and excess CVD risk, although this hypothesis should be addressed in longitudinal studies.

Opiniones y recomendaciones de la Sociedad Argentina de Diabetes. Glucemia en ayunas alterada: ¿es oportuno utilizar el punto de corte en 100 mg/dl en Argentina? / Opinions and recommendations of the Argentine Diabetes Society. Impaired fasting blood glucose: is it appropriate to use a cut-off point of 100 mg/dl in Argentina?

Establecer el punto de corte entre la glucemia en ayunas normal y la alterada resulta de suma importancia a los efectos de considerar a un paciente en riesgo, tanto de progresar a estdos más avanzados de la enfermedad como de sufrir complicaciones micro y macroangiopáticas. Desde 2006 la Sociedad Argentina de Diabetes (SAD), sobre la base de la evidencia considerada en ese momento, estableció el límite inferior de la glucemia alterada en ayunas (GAA) en 110 mg/dl; posteriormente, durante 2022, la Comisión Directiva de la SAD convocó a un grupo de expertos con el objeto de evaluar si esta recomendación debía mantenerse o, al igual que otras sociedades científicas de prestigio, adoptar a tal efecto 100 mg/dl. En este documento de Opiniones y Recomendaciones se encuentran los fundamentos por los cuales la SAD adoptará, de ahora en más, 100 mg/dl como límite inferior de la GAA, en base a las nuevas evidencias científicas que muestran que desde este punto de corte se produce un aumento en la progresión a la diabetes mellitus y de las complicaciones tanto macro como microangiopáticas.

To establish the cut-off point between normal and impaired fasting glycemia (IFG) is extremely important for the purposes of considering a patient at risk both of progressing to more advanced stages of the disease and of suffering micro- and macroangiopathic complications. Since 2006, the Argentine Diabetes Society (ADS), based on the evidence considered at that time, established the lower limit of IFG at 110 mg/d, laterduring the year 2022, The Board of Directors of the ADS vened a group of experts in order to assess whether this recommendation should be maintained or, like other prestigious scientific societies, adopt 100 mg/dl for this purpose. This Opinions and Recommendations document contains therationale for which the SAD will adopt, from now on, 100 mg/dlas the lower limit of the IFG, based on the new scientific edence that shows that from this cut-off point it produces increase in progression to diabetes and both macro and microangiopathic complications.

Incidence and predictive factors of postoperative hypocalcaemia according to type of thyroid surgery in older adults.

PURPOSE: Transient hypocalcaemia after thyroid surgery and its possible predictors have not been extensively described in the elderly. This study aimed to establish the frequency of postsurgical transient hypocalcaemia according to the extent of thyroid surgery in older adults and to assess mineral metabolism biochemical parameters as its predictors. METHODS: All patients ≥60 years undergoing thyroid surgery were prospectively included. Type of surgery (hemithyroidectomy(HT) or total thyroidectomy(TT)); and preoperative 25OH Vitamin D (25OHD) and pre and 6 (only TT), 24 h and 6 months postsurgical serum levels of calcium, magnesium, phosphate and parathormone (PTH) were considered. Postsurgical hypoparathyroidism (hPTpost) was defined at PTH levels ≤11 pg/mL. RESULTS: Out of 46 patients (87% female), age (mean ± SD) 70.1 ± 6.2 years, 24 h postsurgical hypocalcaemia was found in ten patients (22%). In 25 (54%) TT patients, 36% and 16% had postsurgical hypocalcaemia at 6 and 24 h respectively; 28% hPTpost but no definitive hPT was recorded and 44% had 25OHD deficiency. Lower 24 h magnesium levels were found in those TT patients with 24 h hypocalcaemia (1.6 ± 0.1 vs 1.9 ± 0.1 mg/dL (p = 0.005)). Among 21 (46%) HT patients, 28.6% had 24 h postsurgical hypocalcaemia; 9.5% had hPTpost. A positive correlation was observed between preoperative 25OHD and 24 h calcaemia (r:0.51,p = 0.02). 43% of the patients were 25OHD deficient, in whom 55% had 24 h hypocalcaemia vs only 9% in the 25OHD sufficient group (p = 0.049). CONCLUSION: Postsurgical hypocalcaemia was common in elderly thyroidectomized patients. After TT, lower magnesium levels were found in those patients with 24 h hypocalcaemia. In the HT group, preoperative 25OHD deficiency predicted lower postsurgical calcium levels.

A study to assess the unmet medical needs associated with the use of basal insulin in patients with type 2 diabetes.

Aim: To describe in a real-world setting, the proportion of patients with a symptomatic hypoglycaemic event and the proportion of individuals with type 2 diabetes, who newly or recently initiated with basal insulin, achieving individual or general HbA1c target. Materials and Method: DINAS-AR was a national prospective observational study to assess the unmet needs in patients with type 2 diabetes treated with basal insulin with or without oral antihyperglycaemic drugs and/or GLP-1 receptor agonist. The study was conducted at 19 hospitals. Results: A total of 385 uncontrolled patients (≥18 years) who recently initiated basal insulin or who initiated treatment within a year prior to study enrolment entered the study. Outcomes were follow-up incidence of hypoglycaemic events, change of HbA1C and achievement of HBA1c <7% or individual target. A total of 44 patients (11.9%) reported the occurrence of ≥1 symptomatic hypoglycaemia event(s). HbA1c reductions were greater in patients who had recently initiated treatment with basal insulin (between 15 and 90 days prior to study entry) vs patients who initiated treatment within 1 year. A total of 80 patients (31.6%) achieved individual HbA1c target (or target <7.0%) at Week 24. Furthermore, the proportion of patients achieving this target without symptomatic hypoglycaemia was 26.1% (n = 66). A lower percentage of glycemia target achievement was observed in patients reporting hypoglycaemia (n = 14), 20.6% of all patients reporting hypoglycaemia event(s) vs (n = 66) 35.7% of all patients without hypoglycaemia event reported. Conclusion: In this real-world study, although the hypoglycaemia rate was not high in adults with type 2 diabetes treated with insulin, there was a lower percentage of patients that achieved glycemic target among those reporting hypoglycaemia events vs patients who did not report them.

Prevalence of gestational diabetes mellitus in Argentina according to the Latin American Diabetes Association (ALAD) and International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria and the associated maternal-neonatal complications.

In Argentina, gestational diabetes mellitus (GDM) is diagnosed by the Latin American Diabetes Association (ALAD) diagnostic criterion. In this work, we investigated GDM prevalence according to the ALAD and IADPSG diagnostic criteria, evaluated maternal and fetal outcomes and assessed whether fasting glycemia between 92-99 mg/dL was associated with increased risk of macrosomia and maternal obesity/overweight in an Argentine cohort of pregnant women. GDM prevalence was 9.8% with the ALAD diagnostic criterion and 25% considering the IADPSG criterion. Increased prevalence of maternal obesity/overweight was observed in patients with fasting glycemia over 99 mg/dL. A population of high metabolic risk is identified by the ALAD criterion.

Comparison of different systems of ultrasound (US) risk stratification for malignancy in elderly patients with thyroid nodules. Real world experience.

PURPOSE: To comparatively assess the performance of three sonographic classification systems, American Thyroid Association (ATA), the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS), and American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE)/Associazione Medici Endocrinologi (AME) in identifying malignant nodules in an elderly population. METHODS: Cross-sectional study of patients referred for fine needle aspiration biopsy in an academic center for the elderly. One nodule/patient was considered. Nodules classified Bethesda V/VI were considered malignant. Receiver operating characteristics (ROC) curves were established and compared to evaluate diagnostic performance. Malignancy among biopsies below the size cutoff for each ultrasound classification was also compared. RESULTS: One thousand, eight hundred sixty-seven patients (92% females); median (Q1-Q3), age 71 (67-76) years, were studied showing 82.8% benign (Bethesda II) and 2.6% malignant cytology. The three classifications correctly identified malignancy (P < 0.01). Nonetheless, in the ATA and AACE/ACE/AME 16 and 2 malignant nodules, respectively, were unclassifiable. Including unclassified malignant nodules (n = 1234, malignant = 50), comparison of the ROC curves showed lower performance of ATA [area under the curve (AUC) = ATA (0.49) vs. ACR TI-RADS (0.62), p = 0.008 and ATA vs. AACE/ACE/AME (0.59), p = 0.022]. Proportion of below size cutoff biopsies for ATA, ACR TI-RADS, and AACE/ACE/AME was different [16, 42, and 29% (all p < 0.001)], but no differences in malignancy rate were observed in these nodules. CONCLUSION: The present study is the first to validate in elderly patients these classifications showing that AACE/ACE/AME and ACR TI-RADS can predict thyroid malignancy more accurately than the ATA when unclassifiable malignant nodules are considered. Moreover, in this aged segment of the population, the use of ACR TI-RADS avoided more invasive procedures.

[Insulin therapy in special conditions]. / Insulinoterapia en situaciones especiales.

Hyperglycemia during hospitalization is a common condition associated with poor prognosis. To date, insulin is the best strategy to treat hyperglycemia in these patients. An adequate glycemic control is associated with better clinical results. Nevertheless, glycemic goals are still controversial due to the increase of hypoglycemia and other adverse events. Diabetes mellitus is still the main cause of chronic renal failure in our country and its treatment deserves a special analysis considering that insulin pharmacokinetics is altered. Recommendations in this setting are based in expert panel opinions, focusing mainly in intermediate or long acting insulins combined with regular insulin and/or rapid acting analogues. During pregnancy, NPH and regular insulin are safe and effective. It is worth mentioning that the development of new long and rapid acting molecules yielded lower glycemic variability, better post-prandial control and less hypoglycemia. The aim of this study is to provide a review of the proper use of insulin in these special conditions.

Insulinoterapia en situaciones especiales / Insulin therapy in special conditions

La hiperglucemia durante la internación es una condición frecuente que se asocia al aumento de complicaciones y resulta en un mal pronóstico para quienes la padecen. La estrategia para su tratamiento es la insulinoterapia. Un adecuado control glucémico se asocia a mejor evolución y pronóstico. Sin embargo, el nivel adecuado de glucemia se encuentra aún en debate, ya que aquellos ensayos en los cuales se fijaron metas estrictas demostraron incrementar las tasas de hipoglucemia y eventos clínicos adversos. La diabetes mellitus es la principal causa de enfermedad renal crónica en nuestro país. El tratamiento en ese contexto merece un análisis especial, ya que la vida media de la insulina puede resultar prolongada. Las opciones de insulinización en pacientes con enfermedad renal crónica e insuficiencia asociada provienen de recomendaciones de expertos en las cuales se jerarquizan esquemas que utilizan insulina de acción intermedia o prolongada asociadas a insulina regular o análogos de acción rápida. Durante el embarazo, las insulinas NPH y regular han demostrado seguridad y eficacia. Sin embargo, el desarrollo de nuevas moléculas de acción lenta y rápida permitió reducir la variabilidad glucémica, mejorar el control de la glucemia postprandial y reducir la tasa de hipoglucemias. El objetivo del presente trabajo es proporcionar una revisión sobre el adecuado uso de insulina en estas tres situaciones especiales.

Hyperglycemia during hospitalization is a common condition associated with poor prognosis. To date, insulin is the best strategy to treat hyperglycemia in these patients. An adequate glycemic control is associated with better clinical results. Nevertheless, glycemic goals are still controversial due to the increase of hypoglycemia and other adverse events. Diabetes mellitus is still the main cause of chronic renal failure in our country and its treatment deserves a special analysis considering that insulin pharmacokinetics is altered. Recommendations in this setting are based in expert panel opinions, focusing mainly in intermediate or long acting insulins combined with regular insulin and/or rapid acting analogues. During pregnancy, NPH and regular insulin are safe and effective. It is worth mentioning that the development of new long and rapid acting molecules yielded lower glycemic variability, better post-prandial control and less hypoglycemia. The aim of this study is to provide a review of the proper use of insulin in these special conditions.

Dynamic prediction of the risk of recurrence in patients over 60 years of age with differentiated thyroid carcinoma

ABSTRACT Objective The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age. Subjects and methods Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis. Results The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01). Conclusions The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

Atherogenic Lipoproteins in Subclinical Hypothyroidism and Their Relationship with Hepatic Lipase Activity: Response to Replacement Treatment with Levothyroxine.

BACKGROUND: Qualitative lipoprotein changes, such as an increase in fasting remnants, are reported in subclinical hypothyroidism (SCH). It was hypothesized that such changes are due to reduced hepatic lipase (HL) activity in SCH: HL is an enzyme regulated by thyroid hormones, and is involved in the degradation of triglyceride (TG)-rich remnants. This study aimed to quantify remnant-like lipoproteins (RLP), small dense LDL (sdLDL), and HL activity in women with SCH, and to assess these parameters after levothyroxine replacement therapy. METHODS: This was an observational cross-sectional study with a subsequent longitudinal follow-up. Findings in women with thyrotropin levels >4.5 mIU/L (SH group) were compared with age- and body mass index (BMI)-matched euthyroid women (control group). In addition, a subgroup analysis was undertaken in SCH women who chose to receive levothyroxine treatment (0.9 µg/kg/day) for 6 months. RLP was quantified by measuring cholesterol (RLP-C) and triglycerides (RLP-TG) after immunoaffinity chromatography, and sdLDL by automated standardized methods; HL activity was measured in post-heparin plasma. RESULTS: The SCH group included 37 women; 29 women were included in the control group. In addition, 22 women with SCH were included in the subgroup analysis (levothyroxine treatment). Significantly higher RLP values were observed in the SCH group than in the control group: RLP-C (median [range], mg/dL): 20.3 (5.8-66.8) versus 10.2 (2.7-36.3), p = 0.005; RLP-TG (mg/dL): 26.3 (3.2-123.3) versus 12.1 (2.5-61.6), p = 0.033. HL activity (mean ± standard deviation [SD], µmol free fatty acid/mL post-heparin plasma.h)-9.83 ± 4.25 versus 9.92 ± 5.20, p = 0.707-and sdLDL levels (mg/dL)-23.1 ± 10.7 versus 22.6 ± 8.4, p = 0.83-were similar. After levothyroxine, RLP-C decreased-21.5 (5.8-66.8) versus 17.2 (4.1-45.6), p = 0.023-and HL increased-9.75 ± 4.04 versus 11.86 ± 4.58, p = 0.012-in the subgroup of SCH women. No changes in sdLDL were observed. CONCLUSIONS: Women with SCH have higher RLP levels than matched controls do, but their RLP-C levels decrease significantly following levothyroxine therapy. Furthermore, HL activity also increases after levothyroxine therapy and can be interpreted as a possible explanation for the decrease in RLP-C.

Dynamic prediction of the risk of recurrence in patients over 60 years of age with differentiated thyroid carcinoma.

OBJECTIVE: The reclassification of the risk according to the response to the initial treatment makes the treatment of differentiated thyroid cancer (DTC) vary in each individual. As the influence of age on this diagnostic strategy is unknown, we have decided to assess it in adults who are over 60 years of age. SUBJECTS AND METHODS: Ninety patients with DTC above 60 years old were enrolled, with total thyroidectomy plus radioiodine ablation, negative anti-thyroglobulin antibodies, follow-up ≥ 2 years and with clinical and pathological information to classify the risk of recurrence according to ATA (American Thyroid Association) and reclassify based on the response to initial therapy according to MSKCC (Memorial Sloan Kettering Cancer Center). The structural persistence at the end of the follow-up was the gold standard of our analysis. RESULTS: The structural persistence in ATA low, intermediate and high risk categories was 0, 38, and 100%, respectively. In the intermediate group, none of those with an excellent response to the initial treatment showed structural persistence, whereas 39% of those with an incomplete/indeterminate response showed structural persistence (p < 0.01). CONCLUSIONS: The re-stratification according to the response to the initial treatment in patients over 60 years of age with an ATA intermediate risk of recurrence allowed for the distinction of disease-free patients at the end of the follow-up from those with structural persistence and a worse clinical progression.

Association between worse metabolic control and increased thyroid volume and nodular disease in elderly adults with metabolic syndrome.

BACKGROUND: Metabolic syndrome has been associated with nodular goiter. Our aim was to evaluate which metabolic parameters in elderly patients with metabolic syndrome are associated with thyroid enlargement or increased prevalence of thyroid nodules. METHODS: In this cross-sectional study, 77 patients >65 years of age with metabolic syndrome were included. We evaluated the presence of thyroid nodules and thyroid volume by ultrasonography and several biochemical, metabolic and anthropometric parameters. Only patients with thyrotropin (thyroid-stimulating hormone, TSH) levels between 0.3 and 6 mU/L were included. We further divided subjects into two groups-type 2 diabetes mellitus (T2DM) and non-T2DM and established comparisons between them. RESULTS: Among all parameters analyzed we found a significant correlation between glycated hemoglobin (HbA1c) and volume (r=0.261, P=0.027) or number of nodules (r=0.266, P=0.023). Neither sex, age, body mass index (BMI), metformin, nor levothyroxine use were associated with thyroid volume or nodularity. Within the whole cohort, those patients with T2DM had larger thyroid volumes compared to non-T2DM [median (confidence interval, CI) 6.976 (5.220-10.789) vs. 5.034 (3.796-6.034) mL, P<0.008). Furthermore, a larger proportion of T2DM patients presented thyroid volumes >5.8 mL [69 vs. 23%, P<0.001; odds ratio=7.25 (CI 2.04-25.56)]. CONCLUSIONS: In elderly patients with metabolic syndrome, worse metabolic control, represented by higher HbA1c levels, was found associated to increased prevalence of thyroid nodules and larger thyroid volume. Moreover, within the whole metabolic syndrome group, patients with T2DM had the largest thyroid volumes.

High TSH and low T4 as prognostic markers in older patients.

OBJECTIVE: To examine the association between thyroid profile and morbidity/mortality (MM) in hospitalized older patients. DESIGN: This is a retrospective study of patients over the age of 60 yr admitted to the Dr. Cesar Milstein Hospital between 2009 and 2010 and who had thyroid function tests (TFT). The patients were grouped as per their thyroid tests and their clinical characteristics and MM was associated with their TFT. High MM was defined as mortality, intensive care unit (ICU) requirement or prolonged hospital stay (>18 days, 75th percentile), and mortality assessed during an 18-month follow-up period after their hospital discharge. RESULTS: Out of 2599 older patients admitted to our hospital, 7% had TFT performed for various reasons. The patients who had TFT were mostly women and presented in a more serious clinical condition compared to the rest of the patients. The patients were grouped as per their thyroid values as follows: 61% of them had a non-thyroidal illness, 25% were euthyroid,7% had overt hyperthyroidism, 5% overt hypothyroidism and 1% had subclinical hyper- or hypothyroidism. The hypothyroid patients had a worse clinical outcome compared to the others. Patients with increased MM exhibited higher TSH and lower TT4 (p<0.005). Short-term MM (OR=2.0,95%CI=1.1-3.6, p<0.01) was associated with the decrease of TT4 adjusted by age, sex, T3 and TSH, while for long-term MM the increase in TSH (OR=1.6,95%CI 1.1-2.3, p<0.05) was also significant. CONCLUSION: Among hospitalized older patients who had TFT tests, low TT4 and high TSH were associated with a worse prognosis. We propose that TFT be used as an additional tool in assessing MM in elderly hospitalized patients.