Interleukin-6 response to insulin-induced hypoglycemia is associated with hypothalamic-pituitary-adrenal axis activation.

Increased plasma levels of interleukin-6 (IL-6) in response to acute hypoglycemia have been well documented. Aiming to study the interaction between IL-6 and counter-regulatory hormones during hypoglycemic stress we conducted an exploratory single center study involving 26 adult patients undergoing insulin tolerance test. Insulin-induced hypoglycemia elicited a significant dynamic response of IL-6, adrenaline, noradrenaline, GH, prolactin, ACTH and serum and salivary cortisol (P < 0.001 for all variables). Patients with insufficient HPA axis response had lower hypoglycemia-induced IL-6 increase (median: 0.88 pg/mL) compared with individuals with intact HPA axis response (2.03 pg/mL, P = 0.007). IL-6 maximal increase correlated with the maximal increase of serum cortisol (rs = 0.48; P = 0.013), salivary cortisol (rs = 0.66; P = 0.012), plasma ACTH (rs = 0.48; P = 0.013) and with the increase in procedure-related symptoms of anxiety and hypoglycemia (rs = 0.57; P = 0.003). In conclusion, hypoglycemic stress-induced IL-6 increase is associated with activation of the HPA axis, suggesting that IL-6 response to hypoglycemic stress may be regarded as part of the counter-regulatory response, possibly contributing to the maintenance of glucose homeostasis.

Copeptin response to hypoglycemic stress is linked to prolactin activation in children.

PURPOSE: The physiological role of arginine vasopressin (AVP) in the acute stress response in humans and especially in children is unclear. The aim of this study was to explore the interaction between copeptin, a well-established surrogate marker of AVP release, and anterior pituitary hormone activation in response to acute hypoglycemic stress in children and adolescents. METHODS: We conducted an exploratory single center study involving 77 children and adolescents undergoing insulin-induced hypoglycemia. Blood levels of copeptin, ACTH, cortisol, GH, prolactin, interleukin-6 (IL-6), adrenaline and noradrenaline were determined at baseline and after insulin-induced hypoglycemia. RESULTS: Basal plasma levels of copeptin (median: 5.2 pmol/L) increased significantly after hypoglycemia (median 9.7 pmol/L; P < 0.0001). Subjects with insufficient HPA axis response or severe GH deficiency had lower hypoglycemia-induced copeptin increase (median: 2.3 pmol/L) compared with individuals with intact pituitary response (median: 5.2 pmol/L, P = 0.02). Copeptin increase correlated significantly with the maximal increase of ACTH (rs = 0.30; P = 0.010), cortisol (rs = 0.33; P = 0.003), prolactin (rs = 0.25; P = 0.03), IL-6 (rs = 0.35; P = 0.008) and with BMI-SDS (rs = - 0.28, P = 0.01). In multivariate regression analysis, prolactin increase was the only independent variable associated with copeptin increase (P = 0.0004). CONCLUSION: Our data indicate that: (1) hypoglycemic stress elicits a marked copeptin response in children and adolescents, pointing out its role as an acute stress marker in this population; (2) stress-induced AVP/copeptin release is associated with anterior pituitary activation, mainly a prolactin response.

Establishing a blood fructosamine reference range for the Brazilian population based on data from ELSA - Brasil.

OBJECTIVES: The fructosamine test is used in the monitoring of diabetes mellitus, particularly in cases with restrictions on the use of glycated hemoglobin (mainly in the setting of altered red blood cell lifespan and interference by hemoglobin variants). It could also provide additional information on shorter-term glycemic control. The objective of the study is to establish the reference range of the fructosamine in the Brazilian population. DESIGN AND METHODS: The reference interval was defined as suggested by the Clinical and Laboratory Standards Institute (CLSI). The study participants were from a Brazilian cohort (The Longitudinal Study of Adult Health - ELSA-Brasil) with baseline data collected between 2008 and 2010. A total of 466 subjects were selected after exclusion of diabetic individuals, and those with altered glycemic markers and renal function tests. RESULTS: The reference interval was 186-248 µmol/L for women and 196-269 µmol/L for men. Fructosamine levels were higher in men than in women (p = 0.006) and in the non-white population (p = 0.034) and had a negative correlation with the body mass index (r = -0.117; p = 0.011). CONCLUSIONS: The reference intervals for fructosamine were affected by sex. Reference intervals stratified by sex would be more adequate in the interpretation of the fructosamine test.

A COMBINED OUTPATIENT AND INPATIENT OVERNIGHT WATER DEPRIVATION TEST IS EFFECTIVE AND SAFE IN DIAGNOSING PATIENTS WITH POLYURIA-POLYDIPSIA SYNDROME.

OBJECTIVE: The water deprivation test (WDT) is widely used for the differential diagnosis of the polyuria-polydipsia syndrome (PPS). However, it is inconvenient and may not always be precise in differentiating partial forms of diabetes insipidus (DI) from primary polydipsia (PP). The aim of this study was to evaluate the results of a combined outpatient and inpatient overnight WDT protocol that included an overnight unsupervised period concerning its feasibility and safety. METHODS: We performed a retrospective analysis of clinical data and laboratory results of 52 patients with PPS undergoing WDT at a single center. RESULTS: PP was the most frequent diagnosis, followed by complete central DI (cCDI), partial central DI (pCDI), and nephrogenic DI (NDI). Over 90% of the patients showed an expected increase in serum osmolality at the end of the dehydration period. There were no reports of complications during the overnight deprivation period. Post-dehydration urine osmolality and urine-to-serum osmolality ratio significantly differentiated all the groups ( P<.05), except for cCDI and NDI, which could be differentiated by basal and post-dehydration vasopressin (AVP) levels ( P<.05 for both). Although these measurements were useful for differentiating patients according to their allocation groups, results from WDT and direct AVP levels may often require a comprehensive diagnostic approach, particularly in the challenging groups of PP and pCDI. CONCLUSION: A combined outpatient and inpatient overnight WDT protocol is safe and feasible when the test is performed with special care at experienced centers. Newer diagnostic tools are expected to improve the accuracy of PPS diagnosis. ABBREVIATIONS: AQP2 = aquaporin-2; AVP = vasopressin; CDI = central diabetes insipidus; cCDI = complete central diabetes insipidus; DDAVP = desmopressin; DI = diabetes insipidus; IQR = interquartile range; MRI = magnetic resonance imaging; Na+ = sodium; NDI = nephrogenic diabetes insipidus; pCDI = partial central diabetes insipidus; PP = primary polydipsia; PPS = polyuria-polydipsia syndrome; S_osm = serum osmolality; U_osm = urine osmolality; WDT = water deprivation test.

Non-HDL-C goals based on the distribution of population percentiles in ELSA-Brasil: Is it time to change?

BACKGROUND AND AIMS: Non-high-density lipoprotein cholesterol (non-HDL-C) goals are defined as 30 mg/dL (0.78 mmol/L) higher than the respective low-density lipoprotein cholesterol (LDL-C) goals. This definition, however, do not consider the population distribution of non-HDL-C, which could represent a more appropriate individual goal when both markers are discordant. The aim of this study is to establish non-HDL-C goals at the same population percentiles of LDL-C. METHODS: Non-HDL-C values were assigned at the same percentiles correspondent to the LDL-C treatment goals for 14,837 participants from the Longitudinal Study of Adult Health (ELSA-Brasil) with triglycerides levels ≤ 400 mg/dL (4.52 mmol/L). We also assessed the frequency of reclassification, defined as the number of subjects with LDL-C levels in the recommended therapeutic category, but with non-HDL-C levels above or below the category. RESULTS: The non-HDL-C values, based on correspondent LDL-C population percentiles, were 92 (2.38), 122 (3.16), 156 (4.04), 191 (4.95), and 223 mg/dL (5.78 mmol/L). Among participants with LDL-C <70 mg/dL (1.81 mmol/L), 22.8% were reclassified in a higher category according to the guidelines-based non-HDL-C cut-off and 30.1% according to the population percentile-based cut-off; 25.6% and 64.1%, respectively, if triglycerides concurrently 150-199 mg/dL (1.69-2.25 mmol/L). CONCLUSIONS: Our results demonstrated that non-HDL-C percentiles-based goals were up to 8 mg/dL (0.21 mmol/L) lower than the guidelines recommended goal and had a profound impact on the reclassification of participants, notably when LDL-C was <100 mg/dL (2.56 mmol/L), the treatment goal for high risk patients. Therefore, non-HDL-C goals should be changed for reduction of residual risk.

Adverse effects during the oral glucose tolerance test in post-bariatric surgery patients

ABSTRACT Objective The oral glucose tolerance test (OGTT) is used in the screening of gestational diabetes, in diagnosis of type 2 diabetes in conjunction with fasting blood glucose and glycated hemoglobin. The aim of this study was to examine the incidence and risk factors of adverse effects of OGTT in patients who underwent bariatric surgery, in addition to proposing standardization for ordering the OGTT in these patients. Subjects and methods This study assessed the incidence of adverse effects in 128 post-bariatric surgery patients who underwent the OGTT. Descriptive and logistic regression analysis were performed, the dependent variables were defined as the presence of signs (tremor, profuse sweating, tachycardia), symptoms (nausea, diarrhea, dizziness, weakness), and hypoglycemia (blood glucose ≤ 50 mg/dL). Results One hundred and seventeen participants (91.4%) were female; 38 (29.7%) participants were pregnant. High incidence (64.8%) of adverse effects was observed: nausea (38.4%), dizziness (30.5%), weakness (25.8%), diarrhea (23.4%), hypoglycemia (14.8%), tachycardia (14.1%), tremor (13.3%), profuse sweating (12.5%) and one case of severe hypoglycemia (24 mg/dL). The presence of signs was associated with hypoglycemia (OR = 8.1, CI 95% 2.6-25.1). The arterial hypertension persisted as a risk factor for the incidence of signs (OR = 3.6, CI 95% 1.2-11.3). Fasting glucose below 75 mg/dL increased the risk of hypoglycemia during the test (OR = 9.5, CI 95% 2.6-35.1). Conclusion In this study, high incidence of adverse effects during the OGTT was observed in post-bariatric surgery patients. If these results are confirmed by further studies, the indication and regulation of the OGTT procedure must be reviewed for these patients.

Diagnostic Evaluation of ELISA and Chemiluminescent Assays as Alternative Screening Tests to Indirect Immunofluorescence for the Detection of Antibodies to Cellular Antigens.

OBJECTIVES: Detection of antinuclear antibodies (ANAs) plays an important role in the diagnosis of systemic autoimmune rheumatic disease (SARD). Our goal was to evaluate the diagnostic accuracy of three commercially available enzyme-linked immunosorbent assay (ELISA) kits and one chemiluminescent assay for ANA detection, using the clinical diagnostic as the reference standard. METHODS: We evaluated serum samples from 143 patients with an established diagnosis of SARD (group 1), 166 patients with infectious diseases and other rheumatic diseases for which the ANA test is not useful in diagnosis (group 2), and 89 outpatients with suspicion of SARD (group 3). RESULTS: The sensitivity for ANA HEp-2, calculated in group 1, was 87.4% and varied between 62.9% and 90.0% for other tests. The specificity for ANA HEp-2, calculated in group 2, was 72.3% and varied between 45.2% and 90.4% for other tests. In group 3, the negative predictive value for ANA Hep-2 was 92.5% and varied between 89.3% and 100% for other tests. CONCLUSIONS: Some ELISA kits have comparable or superior diagnostic sensitivity to ANA HEp-2 and could be used as an alternative method for ANA screening, therefore allowing the immediate report of the results with fewer false negatives than ANA HEp-2. Owing to the lower specificity, ELISA-positive samples should be submitted to ANA HEp-2 for confirmation of results.

Adverse effects during the oral glucose tolerance test in post-bariatric surgery patients.

OBJECTIVE: The oral glucose tolerance test (OGTT) is used in the screening of gestational diabetes, in diagnosis of type 2 diabetes in conjunction with fasting blood glucose and glycated hemoglobin. The aim of this study was to examine the incidence and risk factors of adverse effects of OGTT in patients who underwent bariatric surgery, in addition to proposing standardization for ordering the OGTT in these patients. SUBJECTS AND METHODS: This study assessed the incidence of adverse effects in 128 post-bariatric surgery patients who underwent the OGTT. Descriptive and logistic regression analysis were performed, the dependent variables were defined as the presence of signs (tremor, profuse sweating, tachycardia), symptoms (nausea, diarrhea, dizziness, weakness), and hypoglycemia (blood glucose ≤ 50 mg/dL). RESULTS: One hundred and seventeen participants (91.4%) were female; 38 (29.7%) participants were pregnant. High incidence (64.8%) of adverse effects was observed: nausea (38.4%), dizziness (30.5%), weakness (25.8%), diarrhea (23.4%), hypoglycemia (14.8%), tachycardia (14.1%), tremor (13.3%), profuse sweating (12.5%) and one case of severe hypoglycemia (24 mg/dL). The presence of signs was associated with hypoglycemia (OR = 8.1, CI 95% 2.6-25.1). The arterial hypertension persisted as a risk factor for the incidence of signs (OR = 3.6, CI 95% 1.2-11.3). Fasting glucose below 75 mg/dL increased the risk of hypoglycemia during the test (OR = 9.5, CI 95% 2.6-35.1). CONCLUSION: In this study, high incidence of adverse effects during the OGTT was observed in post-bariatric surgery patients. If these results are confirmed by further studies, the indication and regulation of the OGTT procedure must be reviewed for these patients.

Detection of anti-nuclear antibodies by indirect immunofluorescence on HEp-2 cells: setting the appropriate screening dilution for the diagnosis of autoimmune rheumatic diseases.

OBJECTIVE: To establish the abnormal title and the appropriate screening dilution for ANA (antinuclear antibodies) test by indirect immunofluorescence on HEp-2 cells (ANA HEp-2). METHODS: An analysis of ANA Hep-2 in serum samples from 126 healthy individuals was performed. The samples were screened at a dilution of 1:80, and those positive were diluted to the title of 1:5120. The abnormal title of ANA was defined as that corresponding to the 95th percentile of the test in this population. The sensitivity of the different titles of antinuclear antibodies was determined in a group of 136 patients with a diagnosis of autoimmune rheumatic disease, and the specificity was determined in a group of 118 patients with other rheumatic diseases. The optimal cutoff value of the test was determined by ROC curve analysis. RESULTS: The frequency of ANA positivity in healthy subjects was 13.2%. There was no difference in the frequency of positive results according to gender or age. The abnormal title of ANA was defined as the dilution of 1:160. The 1:80 dilution had sensitivity of 87.7% and specificity of 67.8%, while the 1:160 dilution had sensitivity of 82% and specificity of 73.7%. By ROC curve analysis, a dilution of 1:160 corresponded to the optimal cutoff value. CONCLUSION: The abnormal title and the optimal cutoff value of ANA HEp-2 in the population was 1:160. Therefore, the dilution of 1:160 is the optimal screening dilution, with better specificity but without significantly compromising the sensitivity of the diagnostic test.

Deteccao de anticorpos antinucleares por imunofluorescencia indireta em celulas HEp-2: definindo a diluicao de triagem adequada para o diagnostico das doencas reumaticas autoimunes / Detection of anti-nuclear antibodies by indirect immunofluorescence on HEp-2 cells: setting the appropriate screening dilution for the diagnosis of autoimmune rheumatic diseases

Objetivo: Definir o título anormal e a diluição de triagem adequada para o teste de FAN (fator antinúcleo) por imunofluorescência indireta em células HEp-2 (FAN HEp-2). Métodos: Realizamos a pesquisa do FAN HEp-2 em amostras de soro de 126 indivíduos saudáveis. As amostras foram triadas na diluição de 1:80, e aquelas positivas diluídas até o título de 1:5120. O título anormal de FAN foi definido como aquele correspondente ao percentil 95 do teste nesta população. A sensibilidade dos diferentes títulos do FAN foi determinada em um grupo de 136 pacientes com diagnóstico de doença reumática autoimune, e a especificidade em um grupo de 118 pacientes com diagnóstico de outras doenças reumáticas. O valor de corte ótimo do teste foi determinado pelo estudo da curva ROC. Resultados: A frequência de FAN positivo em indivíduos saudáveis foi de 13,2%. Não houve diferença na frequência de resultados positivos de acordo com o gênero ou a idade. O título anormal do FAN foi definido como a diluição de 1:160. A diluição dos soros de 1:80 apresentou sensibilidade de 87,7% e especificidade de 67,8%, enquanto a diluição de 1:160 apresentou sensibilidade de 82% e especificidade de 73,7%. Pela análise da curva ROC, a diluição de 1:160 correspondeu ao valor de corte ótimo. Conclusão: O título anormal e o valor de corte ótimo do FAN HEp-2 na população avaliada foram de 1:160. A diluição de 1:160 é, portanto, a diluição de triagem ideal, com melhor especificidade, porém sem comprometimento significativo da sensibilidade diagnóstica do teste. .

Objective: To establish the abnormal title and the appropriate screening dilution for ANA (antinuclear antibodies) test by indirect immunofluorescence on HEp-2 cells (ANA HEp-2). Methods: An analysis of ANA Hep-2 in serum samples from 126 healthy individuals was performed. The samples were screened at a dilution of 1:80, and those positive were diluted to the title of 1:5120. The abnormal title of ANA was defined as that corresponding to the 95th percentile of the test in this population. The sensitivity of the different titles of antinuclear antibodies was determined in a group of 136 patients with a diagnosis of autoimmune rheumatic disease, and the specificity was determined in a group of 118 patients with other rheumatic diseases. The optimal cutoff value of the test was determined by ROC curve analysis. Results: The frequency of ANA positivity in healthy subjects was 13.2%. There was no difference in the frequency of positive results according to gender or age. The abnormal title of ANA was defined as the dilution of 1:160. The 1:80 dilution had sensitivity of 87.7% and specificity of 67.8%, while the 1:160 dilution had sensitivity of 82% and specificity of 73.7%. By ROC curve analysis, a dilution of 1:160 corresponded to the optimal cutoff value. Conclusion: The abnormal title and the optimal cutoff value of ANA HEp-2 in the population was 1:160. Therefore, the dilution of 1:160 is the optimal screening dilution, with better specificity but without significantly compromising the sensitivity of the diagnostic test. .

Analytical validation of anti-toxoplasma IgG immunoassays.

There are often discrepancies when using different methods to measure anti-Toxoplasma gondii IgG levels in patient samples. The diagnostic performance of a chemiluminescent immunoassay (CLIA) and an enzyme-linked fluorescent assay (ELFA) used as confirmatory tests for samples identified as positive or equivocal by an electrochemiluminescent immunoassay (ECLIA) were examined. Cut-off values were those stated by the manufacturer, and Western blot was used to confirm the results of all methods. All samples identified as positive by ECLIA (n=93) were confirmed as positive by Western blot, as were 14 of the 28 samples identified as equivocal. When these 121 samples were retested, the sensitivities of CLIA and ELFA were 64.4% and 73.8%, respectively. Both methods exhibited a specificity of 100%. This study confirms that the results obtained from the different immunoassays are not comparable, and neither CLIA nor ELFA should be used to confirm ECLIA results, which should instead be confirmed by methods such as Western blot or Sabin-Feldman dye test.

[Pseudomalabsorption of levothyroxine: a case report]. / Pseudomalabsorção de levotiroxina: relato de um caso.

A 49-year-old woman who had been treated with sodium levothyroxine because of hypothyroidism after diagnosis of Hashimoto thyroiditis and total thyroidectomy for multinodular atoxic goiter was evaluated for persistent hypothyroidism despite the use of large doses of levothyroxine (600 microg/day). The patient showed signs and symptoms of hypothyroidism and her laboratory tests were: TSH of 351 microUI/mL, free thyroxine of 0.20 ng/dL, and total triiodothyronine of 27 ng/dL. She was submitted, under medical supervision, to a levothyroxine overload test with no evidence of malabsorption of the thyroid hormone. Diagnosis of factitious disorder and Munchausen syndrome leading to the pseudomalabsorption of levothyroxine was considered.

Pseudomalabsorcão de levotiroxina: relato de um caso / Pseudomalabsorption of levothyroxine: a case report

Uma mulher de 49 anos, em tratamento de hipotireoidismo com levotiroxina, após diagnóstico de tireoidite de Hashimoto e tireoidectomia total para bócio multinodular atóxico, foi avaliada devido a hipotireoidismo persistente apesar do uso de altas doses de levotiroxina (600æg/dia). Clinicamente, a paciente apresentava sinais e sintomas de hipotireoidismo, e os exames laboratoriais mostravam tiroxina livre de 0,20ng/dL; hormônio tireoestimulante de 351æUI/mL; triiodotironina total de 27ng/dL. Foi confirmada a não aderência ao tratamento e considerados os diagnósticos de sindrome de Munchausen e transtorno factício, levando ao quadro de pseudomalabsorcão de levotiroxina.