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Primary Hyperparathyroidism (PHPT) often leads to bone loss, even in its asymptomatic presentations. Trabecular Bone Score (TBS) is a method to assess the trabecular bone structure of the spine. This study aimed to evaluate TBS measurements combined with Dual X-ray Absorptiometry (DXA) values in the search for more accurate bone fragility risk assessment among PHPT patients. From 2017 to 2019, patients diagnosed with PHPT (n = 64), before surgery, were invited to participate in this study. Bone mineral density (BMD) by DXA at the lumbar spine, total hip, femoral neck, distal third radius, and TBS were determined in patients and controls (n = 63). The vertebral fracture was defined using the Genant method in vertebral images by DXA and vertebral fracture assessment (VFA). Patients and controls did not differ in age, sex, menopausal status, or body mass index (BMI). The PHPT patients presented significantly lower BMD values than the controls in all sites evaluated. The TBS measurements were also statistically lower in PHPT patients than controls (mean TBS PHPT = 1.233 vs TBS controls = 1.280, p = 0.044). Osteoporosis was observed in 50% of PHPT patients and 26.6% of controls (p = 0.02). However, lumbar spine T-Score-2.5 was observed only in 21.8% of PHPT patients. Vertebral fractures were detected in nine individuals (14%) from the PHPT group and four (6.3%) in the controls (p = 0.24). The TBS area under the curve (AUC) was higher than DXA AUC in all sites, for vertebral fracture assessment. The TBS AUC was significant in the PHPT group (0.75, 95% CI 0.62 - 0.88, p = 0.02) and not significant in the DXA analysis. The ROC curve showed that TBS values1.187 are associated with a significantly higher risk of vertebral fracture among PHPT patients (p = 0.02). The TBS used as a complement to DXA measurements is a useful tool which may better assess fragility risk among PHPT patients.

Introduction Heterozygotes (HZs) for 21-hydroxylase deficiency (21OHD) are highly prevalent, ranging from 1:60 to 1:11 for classic and nonclassic (NC) forms, respectively. Detection of HZ and asymptomatic NC by CYP21A2 genotyping is valuable for genetic counselling, but costly, complex and narrowly available. Adrenocorticotropic hormone (ACTH)-stimulated serum 17-hydroxyprogesterone (17P) and 21-deoxycortisol (21DF) discriminate 21OHD phenotypes effectively, notably if measured simultaneously by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Objective This study was performed to reassess former LC-MS/MS-defined post-ACTH 21DF, 17P and cortisol (F) cutoffs in family members at risk for 21OHD. Design and patients Prospective study in which we screened 58 asymptomatic relatives from families with 21OHD patients and compared post-ACTH steroid phenotypes with subsequent genotypes. Results Post-ACTH 21DF, 17P, F and (21DF + 17P)/F ratio segregate NC, HZ and wild-type (WT) phenotypes (subsequently genotyped) with some overlap. New receiver operating characteristic curve-defined cutoffs for post-ACTH 21DF, 17P and (21DF + 17P)/F ratio are 60 ng/dl, 310 ng/dl and 12 (unitless). Twenty-six of 33 HZ and all 6 NC (82.1%) had post-ACTH 21DF > 60 and 17P > 310 ng/dl, whereas 17/19 WT (89.5%) had values below cutoffs. Post-ACTH 21DF and 17P had a strong positive correlation (r = .9558; p 12 correctly identified 36 of 39 HZ plus NC (92.3% sensitivity) with 84.2% specificity (16 of 19 WT). Given the high frequency of 21OHD HZ, the negative prediction of ratio values below 12 excludes heterozygosity in 99.8% and 99.1% for classic and NC mutations, respectively. Conclusions Reassessed ACTH-stimulated 21DF and 17P cutoffs by LC-MS/MS (60 and 310 ng/dl, respectively) correctly recognised 82.5% HZ plus NC, but combined precursor-to-product ratio ([21DF + 17P]/F) cutoff of 12 was superior, identifying 92.3% HZ plus NC. Since one WT subject is an outlier (potential HZ), these values would be somewhat better reinforcing their utility for screening asymptomatic relatives at risk for 21OHD.

In recent years the immunomodulatory actions of vitamin D, a steroid hormone, have been extensively studied. In 2020, due to the COVID-19 pandemic, the question arose as to 25(OH)D status would be related to susceptibility to SARS-CoV-2 infection, since several studies pointed out a higher prevalence and severity of the disease in populations with low levels of 25(OH)D. Thus, we investigated the 25(OH)D levels in adults “Detected” positive for SARS CoV-2 by RT-PCR (reverse transcriptase polymerase chain reaction) test, and in negative controls, “not Detected”, using the Fleury Group's examination database, in Sao Paulo, Brazil. Of a total of 14.692 people with recent assessments of 25(OH)D and RT-PCR tests for COVID-19, 2.345 were positive and 11.585 were negative for the infection. The groups did not differ in the percentage of men and women, or in the age distribution. There were no differences in the distribution of 25(OH)D between the two groups (p = 0.08); mean 25(OH)D of 28.8 ± 21.4 ng/mL and 29.6 ± 18.1 ng/mL, respectively. In the specific population studied, clinical, environmental, socioeconomic and cultural factors should have greater relevance than 25(OH)D in determining the susceptibility to COVID-19.

Estuarine regions are strategically important from an environmental, economic, and social point of view. To reduce vulnerability and increase resilience, it is crucial to know their dynamics that usually are poorly understood. Numerical models have proven to be an appropriate tool to improve this knowledge and simulate scenarios for future conditions. However, as the modelling results may be inaccurate, the application of the ensembles technique can be very useful in reducing possible uncertainties. In the EsCo-Ensembles project, this technique is proposed to improve hydrodynamic predictions for two Portuguese estuaries: Douro and Minho.Two already validated numerical models (openTELEMAC-MASCARET and Delft3D), which have demonstrated their ability to accurately describe estuarine hydrodynamic patterns and water elevation for river flow in normal and extreme conditions, were applied. Several scenarios for climate change effects were defined including river flood peak flows for the 100 and 1000 year return periods and sea level extreme values for RCPs 4.5 and 8.5 in 2100.The results demonstrated a clear difference between the hydrodynamic behaviour of the two estuaries. Model outcomes for the Minho estuary, which is dominated by the tide and therefore by oceanographic conditions, show a pronounced effect of rising sea levels on estuarine hydrodynamics. Whereas, for the Douro estuary, which is heavily dominated by the river flow, the effect of the sea level rise is hardly noticeable during flood events.These and further results of this ongoing project are expected to (i) provide a complete hydrodynamic characterization of the two estuaries; (ii) evaluate future trends; (iii) estimate the flood risks associated with extreme events and (iv) demonstrate that the combined use of different models reduces their uncertainty and increases the confidence and consistency of the forecasts.Acknowledgements: To the Strategic Funding UIDB/04423/2020 and UIDP/04423/2020 (FCT and ERDF) and to the project EsCo-Ensembles (PTDC/ECI-EGC/30877/2017, NORTE 2020, Portugal 2020, ERDF and FCT). The authors also want to acknowledge the data provided by EDP, IH and Confederación Hidrográfica Miño-Sil.

Spits are landforms that present a complex morphology, which depends on currents, waves, sediment transport, tidal range and anthropic-induced changes. Their position and shape is subject to extreme events like flood river discharges and storms. They can also respond to processes that take place at larger time scales, as plate tectonics, sea level rise or even climatological patterns with teleconnections all over the world, as the well know North Atlantic Oscillation (NAO) or El Niño-Southern Oscillation (ENSO). This is the case of the Douro river mouth sand spit located on the northern coast of Portugal. This naturally dynamic sand spit, which has moved landwards over the past decades, has caused frequent nuisance to navigation, affecting width and depth of the navigation channel. Therefore, a breakwater was constructed in an attempt to stabilise the sand spit and the estuary inlet.Validated hydrodynamic numerical models (openTELEMAC-MASCARET and Delft3D) of the Douro river estuary have demonstrated ability to accurately describe the estuarine hydrodynamic patterns and water elevation under extreme flood conditions. Model results showed that for higher river flow discharges the sand spit is partially inundated.In this work a morphodynamic model (Delft3D) of the estuary was implemented to assess both the morphodynamics of the sand spit under extreme events, including the effect of sea level rise due to climate change, and the variation of extreme water levels along the estuary due to spit erosional processes that can occur during flood events.Preliminary results show that the sand spit will be locally eroded for the higher river flood discharges, forming a two-secondary-channels system, with one channel located near the breakwater’s southern extremity and the other, narrower, near the south bank. Associated with these two channels, two depositional bars will be formed in front of the channels at the coastal platform. However, the inner immersed sand spit will be suffering a sedimentation process for all of the simulated scenarios. This way, neither the river mouth discharge conditions nor the water levels inside the estuary will suffer significant changes according to the simulated scenarios.These results will be complemented with further analyses considering the sediment size influence, tidal level, storm surge, sea level rise and river flood discharges.Acknowledgements: To the Strategic Funding UIDB/04423/2020 and UIDP/04423/2020 (FCT and ERDF) and to the project EsCo-Ensembles (PTDC/ECI-EGC/30877/2017, NORTE 2020, Portugal 2020, ERDF and FCT). The authors also want to acknowledge the data provided by EDP and IH.

Objectives Results can vary between different free thyroxine (FT4) assays; global standardization would improve comparability of results between laboratories, allowing development of common clinical decision limits in evidence-based guidelines. Content We summarize the path to standardization of FT4 assays, and challenges associated with FT4 testing in special populations, including the need for collaborative efforts toward establishing population-specific reference intervals. The International Federation of Clinical Chemistry and Laboratory Medicine Committee for Standardization of Thyroid Function Tests has undertaken FT4 immunoassay method comparison and recalibration studies and developed a reference measurement procedure that is currently being validated. Further studies are needed to establish common reference intervals/clinical decision limits. Standardization of FT4 assays will change test results substantially; therefore, a major education program will be required to ensure stakeholders are aware of the benefits of FT4 standardization, planned transition procedure, and potential clinical impact of the changes. Assay recalibration by manufacturers and approval process simplification by regulatory authorities will help minimize the clinical impact of standardization. Summary Significant progress has been made toward standardization of FT4 testing, but technical and logistical challenges remain. Outlook Collaborative efforts by manufacturers, laboratories, and clinicians are required to achieve successful global standardization of the FT4 assays.

A gestão costeira enfrenta grandes desafios relacionados com a crescente vulnerabilidade resultante do impacto de atividades antrópicas como o turismo, urbanização crescente e instalação de infraestruturas, ao que se associa um crescente risco decorrente dos impactos de alterações climáticas. Uma gestão costeira integrada requer, assim, a avaliação da vulnerabilidade e dos riscos costeiros em cenários de alterações climáticas, relacionados com a subida do nível médio do mar ou o aumento de frequência e intensidade de eventos extremos. Neste trabalho apresenta-se a metodologia seguida no âmbito do projeto MarRisk, para a determinação e quantificação de diversos indicadores morfométricos e morfodinâmicos de vulnerabilidade, baseada na classificação de praias e em modelos digitais de terreno e superfície, obtidos a partir de levantamentos de LiDAR e de fotografia aérea, de 2011, 2017 e 2018. Os resultados obtidos para a costa norte de Portugal, entre Espinho e Caminha são apresentados e discutidos. As metodologias aplicadas permitiram obter imagens de elevada resolução (ortofotos) e indicadores morfométricos (posição da linha de praia, largura e volume de praias e dunas, declive da face da praia) e morfodinâmicos (variações da posição da linha de praia e do volume observadas entre levantamentos) para a área de estudo. Observou-se, em média para toda a área de estudo, estabilidade da linha de praia entre 2011 e 2017, mas uma regressão de mais de 17 m entre 2017 e 2018, o que pode, em parte, dever-se a efeitos sazonais. Quanto ao volume do sistema praia/ dunas, observou-se uma (aparente) acentuada acreção de 10% entre 2011 e 2017, e erosão de 2% entre 2017 e 2018. Contudo, demonstramos que o modelo digital de terreno obtido a partir do levantamento com LiDAR não é diretamente comparável com os modelos digitais de superfície produzidos no âmbito do projeto, e que o aumento de volume observado é, pelo menos em parte, devido à diferença de metodologias e não a uma real acreção. Sugere-se a implementação de um plano de monitorização preventivo, baseado em métodos normalizados definidos a partir do conhecimento adquirido relativo às dinâmicas instaladas nesta região., Coastal management is challenging given the increasing vulnerability due to impacts of human activities, like tourism, growing settlements and development of infrastructures, associated with the growing risk of climate change impacts. Integrated Coastal Zone Management thus requires an evaluation of coastal vulnerability and risks for climate change scenarios, which predict sea-level rise and an increase in the frequency and intensity of extreme events. In this work, the methodology used to quantify several morphometric and morphodynamic vulnerability indicators, in the scope of the MarRisk project, is presented. Indicators are determined based on beach classification and on digital terrain and surface models, derived from LiDAR and aerial photography survey data, collected in 2011, 2017 and 2018. Results obtained for the Northern-Portuguese coast are presented and discussed. The applied methodology resulted in high-resolution imagery (orthophotos) and in morphometric (shoreline position, beach and dune width and volume, shoreface slope) and morphodynamic (changes of shoreline position and beach/dune volume between surveys) indicators for the study area. On average, and for the whole area studied, the coastline was stable between 2011 and 2017, but retreated more than 17 m between 2017 and 2018, which can be partly attributed to seasonal effects. The beach/dune volume (apparently) increased by 10% between 2011 and 2017 and decreased by 2% between 2017 and 2018. However, we found that the digital terrain model (DTM) based on the LiDAR data cannot be directly compared to the digital surface models (DSM) obtained during the project, as at least part of the observed increase in volume is due to differences in the method and not to real accretion. The implementation of a preventive monitoring plan is suggested, which should use normalized methods, defined according to the knowledge acquired about the dynamics established in the region., 0262_MarRISK - Programa Interreg V-A Espanha-Portugal (POCTEP)

Background: Vitamin D deficiency is common among PHP patients. While data are limited, some studies suggest that vitamin D deficiency may exacerbates skeletal disease in PHP. TBS is a software-based method for assessment of trabecular bone structure of the spine, based on analysis of pixels obtained in dual energy x-ray absorptiometry (DXA) images. The aim of this study was to evaluate TBS, vitamin D status, clinical and laboratorial measurements in a PHP group of patients in a search for a more accurate bone fragility test for risk assessment in this group of patients. Methods: From June/2017 to January/2019, patients who met the criteria for PHP diagnosis were included in this study. Control group was composed by age and sex-matched healthy individuals. Overall, 64 PHP and 63 controls were enrolled. Bone mineral density (BMD) measured by DXA (Hologic QDR 4500) at the lumbar spine, total hip, femoral neck, and TBS values (InSight™) were determined in both groups. Total and ionized calcium, PTH, 25-hydroxyvitamin D (25(OH)D), creatinine, alkaline phosphatase, P1NP and CTX were measured. None were in use of Vitamin D supplementation. Results: As expected, PHP patients had lower BMD values than controls in all sites (p Conclusion: Serum total calcium presents negative correlation and phosphorus a positive one with TBS in PHP patients. We also found a correlation between TBS and 25(OH)D, both in PHP and in controls. 25(OH)D

Recently, the use of Vitamin D in high doses for treatment of several conditions, mainly autoimmune in nature, has been advocated with dubious results. Hypercalcemia is an important side effect of this intervention. Here we describe our findings in samples that presented 25(OH)D in excess of 150 ng/mL (375 nmol/L) and had 1,25(OH)2D also measured. Material and Methods: we used serum samples from our diagnostic routine, received for measurement of 25(OH)D and 1,25(OH)2D according to medical requisition. A first group (group A) included 213 samples collected up to November 2018, used Diasorin’s chemiluminescent assays for 25OHD and 1,25(OH)2D, and a second group (group B), comprising 88 samples, used the same 25(OH)D assay and LC-MS/MS method for 1,25(OH)2D. 1,25(OH)2D measurement in the group A used a chemiluminescent competitive assay (Liason XL, Diasorin). The 1,25(OH)2D LC-MS/MS assay includes a previous sample prep, extraction, derivatization and chromatrography. APCI+ is followed by SRM (Selected Reaction Monitoring) and CAD (Collision Activated Dissociation) fragmentation. Precision studies showed, between run CVs of 6.8% to 7.4% and within run of 2.9% to 5.5%. In vitro investigations testing standards and spiked samples with 25(OH)D3, 25(OH)D2, 3-epimer-25(OH)D3 and 24R,25(OH)2D3 were also used to verify possible analytical interferences in the 1,25(OH)2D LC-MS/MS. Results: in group A, 25(OH)D median was 371 ng/mL (928 nmol/L), range 154 ng/mL to 856 ng/mL; 1,25(OH)2D median of 350 pg/mL (875 pmol/L), range 41 pg/mL to 1280 pg/mL. Correlation (Spearman) between 25(OH)D and 1,25(OH)2 was r= 0.8649 (P In group A 189 samples had calcium measurement (median 9.7 mg/dL, range of 8.7 to 13.6 mg/dL), 182 creatinine (median of 0.8 mg/dL range of 0.3 to 1.8 mg/dL) and 179 PTH (median 19 pg/mL, range 5 to 68 pg/mL). In group B 75 cases had measurements of calcium (median 9.7, range 8.6 to 16.6 mg/dL), 75 of creatinine (median 0.8, range 0.3 to 2.5 mg/dL) and 75 of PTH (median 20, range 9 to 49 pg/mL). The in vitro tests showed a slight interference from 25(OH)D3, 3-epimer-25(OH)D3 and 24R,25(OH)2D3 molecules in the LC-MS/MS method. Conclusion: our results confirm data already published showing interference of high levels of 25(OH)D in 1,25(OH)2D measured by immunoassay and, in a milder way, by LC-MS/MS (1). V. Care should be taken in the interpretation of 1,25(OH)2D values in samples with high 25(OH)D values. 1. Hawkes CP, Schnellbacher S, Singh RJ, Levine MA. 25-Hydroxyvitamin D can interfere with a common assay for 1,25-dihydroxyvitamin D in vitamin D intoxication. J Clin Endocrinol Metab. 2015; 100:2883-2889.

Background: PHP is a common disorder, and regardless of being an asymptomatic entity, often leads to bone loss and osteoporosis. TBS is a software-based assessment method of trabecular bone structure of the spine based on the analysis of pixels in dual energy x-ray absorptiometry (DXA) images. The aim of this study was to evaluate TBS measurements in combination with DXA values by searching for more accurate bone fragility risk assessment among PHP patients. Methods: From June/2017 to January/2019, all patients who met the criteria for PHP diagnosis prior to surgery were selected to take part in this study. Control group was composed by non-family related healthy volunteers. Bone mineral density (BMD) by DXA (DXA; Hologic QDR 4500) at the lumbar spine, total hip, femoral neck, distal third of the non-dominant radius and TBS values by InSight were determined in 64 PHP patients and 63 controls. Total and ionized calcium, PTH, 25-hydroxyvitamin D (25(OH)D), creatinine, alkaline phosphatase, P1NP and CTX were measured in all patients and control group. Results: Primary hyperparathyroidism patients presented significant lower BMD values in all evaluated sites compared to controls. TBS measurements were also statistically different among PHP patients and controls (mean TBS PHP=1233 vs TBS controls= 1280, p=0.044). Patients and controls didn’t differ in age, sex, menopausal state or BMI (body mass index). Osteoporosis diagnosis by DXA analysis was observed in 50% of PHP patients and in 26.6% of controls. Self-reported or image-diagnosed fracture occurred in 15 PHP (23.4%) patients and in 11 (17.5%) controls. Among these fractures, vertebral fracture account for 9 (14%) in PHP group and 4 (6.3%) in controls. ROC curve analysis showed that the TBS value < 1187 is associated to significant high risk of vertebral fracture (sensibility 87.5%, specificity 67.3%) among PHP patients. Conclusion: TBS, used as a complement to DXA measurements, is a useful tool to better assess fragility risk among PHP patients.

The aims of this study were to assess the role of an in-house competitive thyroglobulin assay (Tg-c) in the follow-up of metastatic differentiated thyroid carcinoma (DTC) patients who presented underestimated Tg measurements by immunometric assays (Tg-IMA) and to compare the results with IMA and LC-MS/MS Tg methods.This prospective study included 40 patients. Twenty-one with metastatic disease: 14 had Tg-IMA levels inappropriately low or undetectable (eight patients with positive and six with borderline TgAb) and seven had high Tg-IMA levels. Nineteen had an excellent response to therapy. The competitive assay employs a polyclonal antibody produced in rabbits immunized with human Tg, Tg labeled with biotin, and for the solid phase separation, a monoclonal anti-rabbit IgG antibody adsorbed to microtiter plates.All 14 patients with structural disease and underestimated levels of Tg-IMA presented detectable Tg-c levels. The median Tg-c level in the group with positive TgAb was 183 µg/L (range: 22-710 µg/L), and 58 µg/L (range 23-148 µg/L) in the borderline TgAb group. The levels of Tg-LC-MS/MS were detectable in some patients (range 0.5-18 µg/L). All seven patients with high Tg-IMA presented also high levels of Tg-c. Only 2/19 patients with excellent response had Tg-c levels above the functional sensitivity.The competitive assay was able to detect Tg in all patients, even in the presence of serum TgAb, and may be an option in patients with underestimated Tg-IMA and relevant structural disease.

Fractures are common in individuals with COPD and occur at higher bone mass values than expected. COPD appears to be an important risk factor for bone fragility. Patients with chronic obstructive pulmonary disease (COPD) have an increased risk of osteoporosis and fractures, but screening and prophylactic measures to prevent both disorders are often neglected in this population. This case-control study assessed the prevalence of osteopenia, osteoporosis, and fractures in patients with COPD, and identified potential risk factors for fractures in this population. Overall, 91 patients with COPD (COPD group; COPDG) and 81 age- and sex-matched controls (control group; CG) were assessed with bone mineral density (BMD), thoracic/lumbar spine radiographs, and serum PTH and 25-hydroxyvitamin D (25[OH]D) levels. The occurrence of prior fractures was retrieved from clinical history. The prevalence of total fractures in the COPDG was 57.1% (odds of fracture 4.7 times greater compared with the CG), and the femoral neck T-score emerged as the best predictor of fractures. Compared with the CG, the COPDG had lower spine and femoral BMD (p ≤ 0.01) and 25(OH)D levels (p = 0.01) and 2.6 times greater odds of osteoporosis. Among men, vertebral fractures were more prevalent in the COPDG versus CG (25.9% vs. 6.5%, respectively, p = 0.01). The odds of fracture increased with femoral neck T-scores ≤ − 2.7 in the CG and ≤ − 0.6 in the COPDG. These results add robust evidence to an increased odds of osteoporosis and fractures in COPD. Fractures in the COPDG occurred at higher BMD values than expected, suggesting that COPD may be an independent marker of fracture risk, reinforcing a need for regular osteoporosis screening with BMD measurement and prophylaxis of fractures in patients with this disorder.

Introduction: Determination of reference ranges for thyroid function tests, such as TSH, are not a simple task. There are several biological and individual aspects to be considered, one of the most important is age, particularly for the extremes, children and the elderly population. Several studies demonstrated a progressive increase in age-related TSH in older adults. Therefore, the aim of this study is to establish specific reference values for Brazilian population over 60 years old using Big Data strategy. Methods: Data from 10.43 million TSH tests performed in the same method were retrospectively analyzed. All the samples are from the same clinical laboratory, with samples from several regions of Brazil. The samples were selected using the following filters: free T4 concentration within the reference values (RV), absence of anti-thyroid antibodies and of medication use. Groups were divided by age from 18 to 59 years old (under-60), and over 60 up to 107 years old (over-60). Statistical analyzes were performed using R software and EP Evaluator. Both R package ‘boot’ and EP Evaluator nonparametric (CLSI C28-A) were used to estimate the 97.5% confidence interval (IC). Results: After filtering the samples, 306,289 were selected. Mean TSH was similar in both sex. However, there were differences between the two age-groups, in under-60 group, the lower RV was 0.59 mUI/L (95% IC = 0.57, 0.59) and the upper RV was 6.00 mUI/L (95% IC = 5.94, 6.08). Interestingly, in over-60 group the lower RV was 0.36 mUI/L (95% IC = 0.34, 0.38) and the upper RV was 9.38 mUI/L (95% IC = 8.86, 9.44). Furthermore, this upper limit of reference range increases within the older group with TSH of 7.4 mUI/L from 60 to 69, 9.60 mUI/L from 70 to 79 and 12.30 mUI/L above 80 years old. Conclusion: Big data strategy could be a useful tool to reach agreeable population reference values. In particular, for TSH, the higher upper reference limits for adults over 60 years old would be important to avoid overdiagnosis and over-treatment of subclinical hypothyroidism in this population.

Background: Low levels of vitamin D 25OHD are frequently described in PHP patients. The aim of this study was to evaluate bone parameters and vitamin D status in PHP patients and controls. Methods: Prior to surgery, 64 PHP patients and 63 healthy matched control subjects regarding age, gender and body mass index were enrolled in this study along 18 months. 25OHD and PTH were measured using Roche® Immunoassays. Bone mineral density (BMD) by dual X-ray absorptiometry (DXA) (Hologic QDR 4500) and TBS (InSight™) were determined in all patients and controls. Distribution of total, bioavailable and free (calculated) 25OH and its correlation with TBS and DXA in both groups was evaluated. DBP (vitamin D binding protein) SNPs genetic analysis was performed by ABI 7500 real time PCR System. None of the patients and controls were taking vitamin D supplements before the study. Results: PHP patients had lower BMD values than controls in all sites (p

Wastewater treatment facilities of the Ave River basin (located in NW Portugal) are especially vulnerable to infiltration since they present considerable extensions of sewers installed in streams and rivers and collect wastewaters from longstanding sewer networks of five municipalities. The operational management of this complex system involves decision variables such as the selection of the treatment plant where collected wastewater will be treated, with implications for pumped volumes and consequent energy consumption. Aiming to reduce these inflows and increase the management performance of TRATAVE, the company responsible for operating the system, a monitoring network that includes the entire drainage network and treatment facilities operated by the company was designed and implemented. Several flow measurement devices were installed at strategic locations within the sewer network and integrated with a SCADA system responsible for its operation. All measured data was organized in databases. This monitoring platform will support the implementation of a decision support system (DSS) based on a hydrological model of the basin, a hydrodynamic model of the river network and the sewer network. The DSS is being implemented using the Delft-FEWS platform, integrating monitoring data and models. The DSS conceptual framework and the first results of the estimated infiltration volumes are presented, info:eu-repo/semantics/publishedVersion

INTRODUCTION: Several methods have been proposed to improve operative success in renal hyperparathyroidism. OBJECTIVE: To evaluate stereomicroscopy in parathyroid tissue selection for total parathyroidectomy with autotransplantation in secondary (SHPT)/tertiary (THPT) hyperparathyroidism. METHODS: 118 renal patients underwent surgery from April of 2000 to October 2009. They were divided into two groups: G1, 66 patients operated from April of 2000 to May of 2005, with tissue selection based on macroscopic observation; G2, 52 patients operated from March of 2008 to October 2009 with stereomicroscopy for tissue selection searching for the presence of adipose cells. All surgeries were performed by the same surgeon. Patients presented SHPT (dialysis treatment) or THPT (renal-grafted). Follow-up was 12-36 months. Intra-operative parathyroid hormone (PTH) was measured in 100/118 (84.7%) patients. RESULTS: Data are presented as means. G1 included 66 patients (38 SHPT, 24 females/14 males; 40.0 years of age; 28 THPT, 14 females/14 males; 44 years of age). G2 included 52 patients (29 SHPT, 11 females/18 males; 50.7 years of age; 23 THPT, 13 females/10 males, 44.4 years of age). SHPT patients from G2 presented preoperative serum calcium higher than those of SHPT patients in G1 (p < 0.05), suggesting a more severe disease. Definitive hypoparathyroidism was found in seven of 118 patients (5.9%). Graft-dependent recurrence occurred in four patients, two in each group. All occurred in dialysis patients. CONCLUSION: Stereomicroscopy in SHPT/THPT surgical treatment may be a useful tool to standardize parathyroid tissue selection. INTRODUÇÃO: Diversos métodos têm sido propostos com intuito de melhorar índices de sucesso cirúrgico no tratamento do hiperparatiroidismo associado à doença renal crônica (DRC). OBJETIVOS: Avaliar uso do estereomicroscópio na seleção de tecido paratiroideano na paratiroidectomia total com autoimplante em pacientes com DRC. MÉTODOS: 118 pacientes DRC operados entre 04/2000-10/2009 foram divididos em: G1-66 pacientes operados entre 04/2000-05/2005 cuja seleção de tecido foi realizada por método convencional (macroscopia); G2-52 pacientes operados entre 03/2008-10/2009, cuja seleção de tecido foi realizada com uso da estereomicroscopia: Leica-Stereomicroscope (amplificação: 10×-80×). Pacientes foram ainda categorizados em hiperparatiroidismo secundário (HPS) ou terciário (HPT) (HPS-diálise/HPT-transplantados renais). Seguimento pós-operatório: 12-36 meses. PTH intraoperatório medido 100/118 pacientes (84.7%). Todos pacientes foram operados pelo mesmo cirurgião. RESULTADOS: Dados em média. G1, 66 pacientes (38 HPS, 24f/14m; 40 anos; 28 HPT, 14f/14m; 44 anos). G2, 52 pacientes (29 HPS, 11f/18m; 50,7 anos; 23 HPT, 13f/10m; 44,4 anos). Pacientes dialíticos do G2 apresentaram cálcio pré-operatório maior que G1 (p < 0,05), sugerindo doença mais severa. Hipoparatiroidismo definitivo: 7/118 (5,9%) pacientes: G1, 4/66 (6%); G2, 3/52 (5,7%). Recorrência do hiperparatiroidismo no autoimplante: 4 pacientes, 2 em cada grupo. Todas foram em pacientes em diálise. CONCLUSÃO: Estereomicroscopia no tratamento do hiperparatiroidismo associado à DRC é útil na padronização da técnica de seleção de tecido para o autoimplante.

Guidelines for the follow-up of differentiated thyroid cancer (DTC) recommend the measurement of TSH-stimulated thyroglobulin (s-Tg) instead of basal Tg on T4 therapy (b-Tg). However, these guidelines were established using first-generation Tg assays with a functional sensitivity (FS) of 0.5-1.0 ng/ml. Current more sensitive second-generation Tg assays (Tg2G; FS 0.05-0.10 ng/ml) have shown that low-risk DTC patients with undetectable b-Tg rarely have recurrences.This study was undertaken to compare b-Tg using a chemiluminescent Tg2G assay (Tg2GICMA; FS 0.1 ng/ml) with s-Tg in DTC patients with an intermediate risk of recurrence.We evaluated 168 DTC patients with a low (n = 101) and intermediate (n = 67) risk of recurrence treated by total thyroidectomy (147 also treated with radioiodine), with a mean follow-up of 5 years.b-Tg was undetectable with the Tg2GICMA in 142 of 168 patients. s-Tg was2 ng/ml in 138 of these 142 patients, and only 3 of these 138 (2%) presented metastases on cervical ultrasound (US). Of the 4 of 142 patients with s-Tg2 ng/ml, 1 had cervical metastases seen after radioiodine. Furthermore, 26 of 168 patients presented detectable b-Tg with the Tg2GICMA; 17 of these 26 patients also presented s-Tg2 ng/ml. In 10 of these 17 patients, metastases were detected. Cervical US or b-Tg were positive in 14 of 15 patients with recurrent disease. Globally, the sensitivity and negative predictive value of the Tg2GICMA plus US were 93 and 99%, respectively.b-Tg measured with a Tg2GICMA and cervical US, used together, are equivalent to s-Tg in identifying metastases in patients with DTC with a low or intermediate risk of recurrence.

Background: Serum calcitonin (sCT) is a useful biomarker for medullary thyroid cancer (MTC). Consensus has not been reached concerning sCT measurements in the evaluation of nodular thyroid disease (NTD). Objective and Methods: We developed a new immunofluorometric assay for sCT and have validated it in samples from 794 patients [203 with MTC, 205 with autoimmune thyroid disease (ATD), 248 with NTD, 80 with differentiated thyroid cancer (DTC) ‘free of disease', 58 with chronic renal failure (CRF)] and 178 normal individuals, including samples after pentagastrin tests and samples from the washout of 92 FNA procedures in patients with NTD or MTC. We also compared some samples from patients with low or high calcitonin levels using both this assay and the Nichols Institute Diagnostics (NID) assay. Results: The assay's analytical sensitivity was 1.0 pg/ml. Considering MTC patients prior to surgery, the cut-off values for the 95% reference range were 11.1 pg/ml for males and 5.5 pg/ml for females and employing the ROC curve were 18.4 pg/ml for males and 7.8 pg/ml for females. sCT in patients with MTC was strongly correlated with disease status. Patients with NTD and ATD did not present false-positive results. sCT measurements were significantly correlated with age (excluding MTC and CRF). The NID test had a strong correlation with our assay. A hook effect was observed only with concentrations >200,000 pg/ml. Conclusions: We developed a novel sCT assay and validated it in healthy subjects, as well as in a large cohort of patients with MTC, NTD, ATD, DTC, and CRF.

Serum calcitonin (sCT) is the main tumor marker for medullary thyroid cancer (MTC), but it has certain limitations. Various sCT assays may have important intra-assay or interassay variation and may yield different and sometimes conflicting results. A pentagastrin- or calcium-stimulation calcitonin (CT) test may be desirable in some situations. Alternatively, or in the absence of the stimulation test, mRNA detection offers the advantages of being more comfortable and less invasive; it only requires blood collection and has no side effects. The objective of this study was to investigate the applicability of measuring calcitonin-related polypeptide alpha (CALCA) gene transcripts (CT-CALCA and calcitonin gene-related peptide [CGRP]-CALCA) in patients with MTC and in relatives diagnosed with a RET mutation and to test mRNA as an alternative diagnostic tool for the calcitonin-stimulation test.Twenty-three healthy controls and 26 individuals evaluated for MTC were selected, including patients with sporadic or hereditary MTC and RET mutation-carrying relatives. For molecular analysis, RNA was extracted from peripheral blood, followed by cDNA synthesis using 3.5 μg of total RNA. Quantitative real-time polymerase chain reaction (RT-qPCR) was performed with SYBR Green and 200 nM of each primer for the two specific mRNA targets (CT-CALCA or CGRP-CALCA) and normalized with the ribosomal protein S8 as the reference gene.We detected CALCA transcripts in the blood samples and observed a positive correlation between them (r=0.946, p0.0001). Both mRNAs also correlated with sCT (CT-CALCA, r=0.713, p0.0001; CGRP-CALCA, r=0.714, p0.0001). The relative expression of CT-CALCA and CGRP-CALCA presented higher clinical sensitivity (86.67 and 100, respectively), specificity (97.06 and 97.06), positive predictive value (92.86 and 93.75), and negative predictive value (94.29 and 100), than did sCT (73.33, 82.35, 64.71, and 87.50, respectively). In addition, the CALCA transcript measurement mirrored the response to the pentagastrin test.We demonstrate that the measurement of CALCA gene transcripts in the bloodstream is feasible and may refine the management of patients with MTC and RET mutation-carrying relatives. We propose considering the application of this diagnostic tool as an alternative to the calcitonin-stimulation test.

High homology of GH with placental GH (pGH) and hPL frequently resulted in falsely high GH levels in competitive immunoassays during pregnancy. However, in immunometric assays, falsely high or low GH levels can result from GH-like molecules binding to both or only one monoclonal antibody. Since our GH-IFMA assay detected GH suppression in both normal and acromegalic pregnancies, we evaluated potential negative interference of pregnancy serum in the assay.GH was measured in samples from acromegalic patients with and without the addition of normal pregnancy serum using a sensitive in-house two-step GH-IFMA (no crossreactivity with pGH, Prolactin or hPL). Standard GH assay curves were run with and without pGH (20 and 22 K). Pegvisomant, a GH-antagonist with high homology to GH, was also tested for cross-reactivity.Addition of pregnancy serum to acromegaly serum resulted in marked decrease in GH, but addition of pGH did not change GH measurements. Redesign of the routine assay by switching the positions of the antibodies ("inverted" assay) completely abrogated the interference of pregnancy serum. GH by both routine and inverted assays declined progressively throughout pregnancy in controls, with higher nadir levels in the "inverted" assay (median 0.03 μg/L vs 0.50 μg/L, P0.05). GH suppression during acromegalic pregnancy previously found with the routine assay was not observed in the "inverted" assay. Pegvisomant does not cross-react with GH in the "inverted" assay.GH measurements in pregnancy by immunometric assays must be made after exclusion of pregnancy serum interference by dilutional tests. Redesigning a two-step immunometric GH assay by switching the positions of the antibodies can be a successful strategy to abrogate such interference.

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Measuring thyroid hormones is an important aspect for the study of metabolism and for monitoring diseases in both human and animal models. The traditional method for hormone measurement in rats is the radioimmunoassay (RIA). However, the RIA is associated with some practical disadvantages, including the use of radioactive material, the need for specialized equipment and expert staff, the short shelf-life of kits according to the half-life of the radioisotope and high costs. The objective of this study was to develop a new cost-effective method for measuring TSH levels in rats that avoids the use of radioactive material. We developed an in-house competitive immunoassay using a reference standard, polyclonal antibody produced in rabbits and biotinylated antigen. This method was tested in 64 Wistar rats that were divided into a control group (n = 41) and a group with hypothyroidism (n = 23). Our assay demonstrated an analytical sensitivity of 0.24 ng/mL (n = 12) and an intra-assay coefficient of variation (CV) of 8.9% for sera with TSH levels of 1.5 ng/mL and 13.2% for sera with TSH levels of 17.5 ng/mL (n = 14). The inter-assay CV was 13.5% for sera with TSH levels of 1.4 ng/mL and 14.5% for TSH levels of 18.2 ng/mL (n = 5). The analysis of mean TSH levels in control rats (5.06 +/- 0.5701) and hypothyroid rats (51.09 +/- 5.136) revealed a statistically significant difference (p < 0.001) between the groups. This method showed good sensitivity, can be automated and is low-cost compared with RIA. Our method offers a viable alternative for TSH measurement in rats. Univ Fed São Paulo Unifesp, Lab Endocrinol Mol & Translac, Div Endocrinol, Dept Med, São Paulo, SP, Brazil Univ Fed São Paulo, Escola Paulista Med, Dept Bioquim, Div Biol Mol, São Paulo, SP, Brazil Grp Fleury, São Paulo, SP, Brazil Unifesp, Dept Ciencias Biol, Diadema, SP, Brazil Univ Fed São Paulo Unifesp, Lab Endocrinol Mol & Translac, Div Endocrinol, Dept Med, São Paulo, SP, Brazil Univ Fed São Paulo, Escola Paulista Med, Dept Bioquim, Div Biol Mol, São Paulo, SP, Brazil Unifesp, Dept Ciencias Biol, Diadema, SP, Brazil FAPESP: 2013/26851-7 Web of Science

Objective To evaluate the usefulness of a third-generation PTH assay in the diagnosis of primary hyperparathyroidism (PHPT). Subjects and methods Forty-one PHPT patients (4 men and 37 women) with 61.2 ± 10.9 (mean ± SD) years, were studied and had PTH levels measured with two different methods using the same immunochemiluminescent assay plataform (Elecsys 2010 System, Roche). We compared a second-generation assay (I-PTH) with a third-generation PTH assay (Bio-PTH). Two populations of 423 and 120 healthy adults with serum 25OHD levels above 25 ng/mL were used to define normal values in the I-PTH and Bio-PTH assays respectively. Results Normal PTH values based in the healthy adults population were 24.2-78.0 pg/mL for the I-PTH assay and 19.9-58.5 pg/mL for Bio-PTH assay. In PHPT patients, PTH values ranged from 67 to 553 pg/mL (median: 168 pg/mL) using the I-PTH assay and from 55 to 328 pg/mL (median: 111 pg/mL) using the Bio-PTH assay. Results obtained with the Bio-PTH assay were significantly lower (p < 0.0001, Wilcoxon). In general I-PTH and Bio-PTH showed highly significant correlation (r = 0.952, p < 0.0001). Passing–Bablok analysis gave a regression equation of Bio PTH = 13.44 + 0.59 x intact PTH. PHPT patients had 25OHD levels ranging from 4 to 36 ng/mL (mean 16.2 ng/mL); 35 subjects (85.3%) had values bellow 25 ng/mL. Conclusion Our results demonstrate that both second and third generation PTH methods are strongly correlated in PHPT patients and control subjects. Lower results with Bio-PTH tests are expected in function of the assay specificity determined by the amino-terminal antibody used.

Purpose: Magnesium is an important electrolyte for very many cell functions and its deficiency may lead to a wide spectrum of diseases. We report a clinical case of hypomagnesemia resulting from the chronic use of a proton pump inhibitor (PPI). PPIs are drugs widely used in medical practice, and a growing number of cases of PPIs causing hypomagnesemia have been described. Our aim was to monitor the clinical and electrolyte findings during recovery from hypomagnesemia caused by long-term PPI use. Results: A 65-year old female who had been using omeprazole for 10 years, presented with arrhythmia and paresthesia of the lower and upper limbs that had been attributed to severe hypomagnesemia, hypocalcemia, and hypoparathyroidism. Her laboratory tests revealed the following results: magnesium 0.6 mg/dL (NR: 1.5 to 2.5 mg/dL), calcium 7.3 mg/dL (NR: 8.5 to 10.2 mg/dL), parathyroid hormone (PTH) 13.3 pg/mL (NR: 15 to 65 pg/mL), and low urinary calcium and magnesium excretion. Her electrocardiogram disclosed typical, prolonged QT interval, ST depression, and U waves. We discuss the differential diagnoses, pathophysiology, and reversibility of symptoms after effective treatment of the hypomagnesemia. Conclusion: this report emphasizes that even if long-term PPI users appear largely asymptomatic, life-threatening arrhythmias can present very suddenly. Long-term PPI users should be monitored for otherwise unexplained hypomagnesemia, hypocalcemia, functional hypoparathyroidism and associated symptoms.

INTRODUÇÃO: O teste de supressão com 1 mg de dexametasona (TSDx) é amplamente empregado no rastreamento da síndrome de Cushing (SC) dada sua elevada acurácia diagnóstica. A SC é um distúrbio endocrinometabólico resultante do hipercortisolismo crônico com característica de ausência de supressão do cortisol no TSDx. OBJETIVO: Desenvolver um radioimunoensaio (RIE) para a dosagem de dexametasona (Dx) no soro para complementar o TSDx. MÉTODOS: Foram imunizados três coelhos com o conjugado dexametasona-21-hemissuccinato-BSA para escolha do melhor anticorpo e o RIE foi desenvolvido de acordo com as recomendações da RE 899/2003 da Agência Nacional de Vigilância Sanitária (ANVISA). Analisamos 96 voluntários, sendo 67 submetidos ao TSDx e 29 não, e 12 pacientes com SC, estudados na Universidade Federal de São Paulo (UNIFESP) e na Santa Casa de Misericórdia de São Paulo. RESULTADOS: O anticorpo contra Dx selecionado mostrou boa especificidade, coeficiente de variação (CV%) intra e interensaio < 20%, exatidão de 93,8% e dose mínima detectada de 19,5 ng/dl. A concentração de Dx no soro foi semelhante nos voluntários e pacientes com SC (ausência/supressão do cortisol): 205 a 703 ng/dl e 174 a 661 ng/dl (intervalo de confiança [IC] 95%), respectivamente; os valores foram indetectáveis naqueles que não se submeteram ao teste. DISCUSSÃO: O anticorpo empregado apresenta boa afinidade e especificidade para quantificar a Dx no soro. O RIE mostrou reprodutibilidade e eficiência na determinação dos níveis séricos de Dx durante o TSDx. CONCLUSÃO: O presente RIE para a dosagem de Dx no soro é acurado e confiável, permitindo estabelecer uma faixa de referência de valores para subsidiar a interpretação do TSDx. INTRODUCTION: The 1 mg dexamethasone suppression test (DxST) is widely used to screen Cushing's syndrome (CS) due to its high diagnostic accuracy. CS is an endocrine-metabolic disorder caused by hypercorticism, which is characterized by the absence of cortisol suppression in DxST. OBJECTIVE: To develop a radioimmunoassay (RIA) for the measurement of serum dexamethasone (Dx) to complement DxST. METHODS: Three rabbits were inoculated with dexamethasone-21-hemisuccinate-BSA in order to choose the best antibody. Serum Dx RIA was performed according to RE 899/2003 (Agência Nacional de Vigilância Sanitária [ANVISA]) regulations. Serum samples from 96 volunteers from Universidade Federal de São Paulo (UNIFESP) and Santa Casa de Misericórdia de São Paulo were analyzed, 67 of which were submitted to DxST and 29 were not. There were 12 patients with CS. RESULTS: The Dx antibody chosen showed good specificity. Intra- and interassay CV were < 20% with 93.8% accuracy and the lowest detection limit was 19.5 ng/dl. Serum Dx concentration was similar among both volunteers and CS patients (absence of cortisol suppression): 205 to 703 ng/dl and 174 to 661 ng/dl (95% CI), respectively. Values were undetectable among those that were not submitted to the test. Discussion: The anti-Dx antibody shows high specificity and reliability to quantify serum Dx in DxST. The Dx RIA presented reproducibility and reliability in the determination of serum Dx levels during DxST. CONCLUSION: The current RIA for serum Dx is accurate and reliable, which permits to establish a reference value range to substantiate DxST interpretation.

Summary Background Congenital adrenal hyperplasia caused by classic 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder with a high prevalence of asymptomatic heterozygote carriers (HTZ) in the general population, making case detection desirable by routine methodology. HTZ for classic and nonclassic (NC) forms have basal and ACTH-stimulated values of 17-hydroxyprogesterone (17OHP) that fail to discriminate them from the general population. 21-Deoxycortisol (21DF), an 11-hydroxylated derivative of 17OHP, is an alternative approach to identify 21OHD HTZ. Objective To determine the discriminating value of basal and ACTH-stimulated serum levels of 21DF in comparison with 17OHP in a population of HTZ for 21OHD (n = 60), as well as in NC patients (n = 16) and in genotypically normal control subjects (CS, n = 30), using fourth generation tandem mass spectrometry after HPLC separation (LC-MS/MS). Results Basal 21DF levels were not different between HTZ and CS, but stimulated values were increased in the former and virtually nonresponsive in CS. Only 17·7% of the ACTH-stimulated 21DF levels overlapped with CS, when compared to 46·8% for 17OHP. For 100% specificity, the sensitivities achieved for ACTH-stimulated 21DF, 17OHP and the quotient [(21DF + 17OHP)/F] were 82·3%, 53·2% and 87%, using cut-offs of 40, 300 ng/dl and 46 (unitless), respectively. Similar to 17OHP, ACTH-stimulated 21DF levels did not overlap between HTZ and NC patients. A positive and highly significant correlation (r = 0·846; P

In type 1 diabetes mellitus (T1DM), growth hormone (GH) responses to provocative stimuli are normal or exaggerated, whereas the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH secretagogue that also increases adrenocorticotropic hormone (ACTH) and cortisol levels, similarly to GH-releasing peptide-6 (GHRP-6). Ghrelin's effects in patients with T1DM have not been evaluated. We therefore studied GH, ACTH, and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1DM and 9 control subjects. The GH-releasing hormone (GHRH)-induced GH release was also evaluated. Mean fasting GH levels (micrograms per liter) were higher in T1DM (3.5 ± 1.2) than in controls (0.6 ± 0.3). In both groups, ghrelin-induced GH release was higher than that after GHRP-6 and GHRH. When analyzing Δ area under the curve (ΔAUC) GH values after ghrelin, GHRP-6, and GHRH, no significant differences were observed in T1DM compared with controls. There was a trend (P = .055) to higher mean basal cortisol values (micrograms per deciliter) in T1DM (11.7 ± 1.5) compared with controls (8.2 ± 0.8). No significant differences were seen in ΔAUC cortisol values in both groups after ghrelin and GHRP-6. Mean fasting ACTH values were similar in T1DM and controls. No differences were seen in ΔAUC ACTH levels in both groups after ghrelin and GHRP-6. In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6, and GHRH. The ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH-, ACTH-, and cortisol-releasing mechanisms stimulated by these peptides.

In thyrotoxicosis GH responses to stimuli are diminished and the hypothalamic-pituitary-adrenal axis is hyperactive. There are no data on ghrelin or GHRP-6-induced GH, ACTH and cortisol release in treated hyperthyroidism. We, therefore, evaluated these responses in 10 thyrotoxic patients before treatment and in 7 of them after treatment. GHRH-induced GH release was also studied. Peak GH (μg/L; mean ± SE) values after ghrelin (22.6 ± 3.9), GHRP-6 (13.8 ± 2.3) and GHRH (4.9 ± 0.9) were lower in hyperthyroidism before treatment compared to controls (ghrelin: 67.6 ± 19.3; GHRP-6: 25.4 ± 2.7; GHRH: 12.2 ± 2.8) and did not change after 6 months of euthyroidism (ghrelin: 32.7 ± 4.7; GHRP-6: 15.6 ± 3.6; GHRH: 7.4 ± 2.3), although GH responses to all peptides increased in ~50% of the patients. In thyrotoxicosis before treatment ACTH response to ghrelin was two fold higher (107.4 ± 26.3) than those of controls (54.9 ± 10.3), although not significantly. ACTH response to GHRP-6 was similar in both groups (hyperthyroid: 44.7 ± 9.0; controls: 31.3 ± 7.9). There was a trend to a decreased ACTH response to ghrelin after 3 months of euthyroidism (35.6 ± 5.3; P = 0.052), but after 6 months this decrease was non-significant (50.7 ± 14.0). After 3 months ACTH response to GHRP-6 decreased significantly (20.4 ± 4.2), with no further changes. In hyperthyroidism before treatment, peak cortisol (μg/dL) responses to ghrelin (18.2 ± 1.2) and GHRP-6 (15.9 ± 1.4) were comparable to controls (ghrelin: 16.4 ± 1.6; GHRP-6: 13.5 ± 0.9) and no changes were seen after treatment. Our results suggest that the pathways of GH release after ghrelin/GHRP-6 and GHRH are similarly affected by thyroid hormone excess and hypothalamic mechanisms of ACTH release modulated by ghrelin/GHSs may be activated in this situation.

OBJETIVO: Diante de um paciente portador de hiperparatiroidismo primário com indicação de tratamento cirúrgico, a localização pré-operatória da paratiroide é de fundamental importância para definir a melhor abordagem cirúrgica. MATERIAIS E MÉTODOS: A realização adicional de imagens SPECT e da cintilografia com 99mTc durante a cintilografia das paratiroides com Setamibi não é rotina em nosso meio, sendo comum a aquisição apenas das imagens planas − precoce (15 minutos) e tardia (2 horas). RESULTADOS: Na nossa experiência, tem-se percebido que a realização do protocolo completo contribui de maneira decisiva na sensibilidade da localização pré-operatória da paratiroide. CONCLUSÃO: A aplicação completa de todos os métodos cintilográficos disponíveis (SPECT e 99mTc) e a análise cuidadosa das imagens em um contexto multidisciplinar podem aumentar a acurácia da cintilografia das paratiroides.

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective: in Cushing's disease (CD), GH responsiveness to several stimuli, including ghrelin, GHRP-6, and GHRH. is blunted. Recovery of GH secretion after remission of hypercortisolism after transsphenoidal surgery. radiotherapy or adrenalectomy is controversial. There are no studies evaluating the effect of primary clinical treatment with ketoconazole on GH secretion in CD. the aim of this study is to compare ghrelin-, GHRP-6-, and GHRH-induced GH release before and after ketoconazole in MDesign: GH responses to ghrelin. GHRP-6, and GHRH of eight untreated patients with CD (mean age: 33.8 +/- 3.1 years; body mass index: 28.5 +/- 0.8 kg/m(2)) were evaluated before and after 3 and 6 months of ketoconazole treatment. and compared with I I controls (32.1 +/-.2.5: 25.0 +/- 0.8).Methods: Serum GH was measured by an immunofluorometric assay and urinary free cortisol (UFC) by liquid chromatography and tandem mass spectrometry.Results: After ketoconazole use, mean UFC decreased significantly (before: 222.4 +/- 35.0 mu g/24 h: third month: 61.6 +/-+10.1: sixth month: 39.1 +/- 10.9). Ghrelin-induced GH secretion increased significantly after 6 months (peak before: 6.8 +/- 2.3 mu g/l: sixth month: 16.0 +/- 3.6). but remained lower than that of controls (54.1 +/- 11.2). GH release after GHRP-6 increased, although not significantly. while GH responsiveness to GHRH Was unchanged.Conclusions: Ghrelin-induced GH release increases significantly after 6 months of ketoconazole treatment in CD. This could suggest that, it decrease in cortisol levels during this time period can partially restore glucocorticoid-induced GH suppression in CD. GH-releasing mechanisms stimulated by ghrelin/GHS could be more sensitive, as no changes in GHRH-induced GH release were observed. Universidade Federal de São Paulo, Div Endocrinol, BR-04039002 São Paulo, Brazil Inst Fleury, BR-04344903 São Paulo, Brazil Universidade Federal de São Paulo, Div Endocrinol, BR-04039002 São Paulo, Brazil FAPESP: 02/14118-9 Web of Science

Objective: Verifying the association between glycemic fluctuation and GH response in the glucagon stimulation test. Basal evaluation of growth hormone (GH) has poor diagnostic accuracy due to its pulsatile secretion. GH-stimulation tests are used for an adequate evaluation of somatotrophic axis. Various stimuli can be employed, among them glucagon, which has an elusive mechanism of action. Since hypoglycemia reportedly occurs during the test, investigation of its role as a stimulus to GH release is granted. Design: Retrospective analysis of glucagon-stimulated GH tests performed in 128 children (36.7% female; age 12.4+3.3 years), at Fleury Functional Tests Facility from July 2000 to 2006. GH and blood glucose (BG) curves, IGF-1, and IGFBP-3 have been assessed. Positive GH response was defined by a peak GH value ⩾3.3μg/L. Normal IGF-1 levels were defined as those between 2.5th and 97.5th percentiles for age and gender. Results: Hypoglycemia under 2.2mmol/L did not occur during the test. BG decrease occurred with lower magnitude and was not associated to GH response. Comparison between patients with negative and positive GH response showed, respectively, BG nadir 3.74 vs. 3.62mmol/L, glucose AUC 23.3 vs. 22.4, and glycemic decrease (below 3.3mmol/L) 19% vs. 35.5% (with P non-significant for all comparisons). Conclusion: Hypoglycemia was not seen after glucagon stimulation and decrease in BG occurred above levels physiologically expected to stimulate GH release, being apparently not associated to GH response.

Fapesp CNPq Capes Thyroglobulin (Tg) is the major glycoprotein produced by the thyroid gland, where it serves as a template for thyroid hormone synthesis and as an intraglandular store of iodine. Measurement of Tg levels in serum is of great practical importance in the follow-up of differentiated thyroid carcinoma (DTC), a setting in which elevated levels after total thyroidectomy are indicative of residual or recurrent disease. The most recent methods for serum Tg measurement are monoclonal antibody-based and are highly sensitive. However, major challenges remain regarding the interpretation of the results obtained with these immunometric methods, particularly in patients with endogenous antithyroglobulin antibodies or in the presence of heterophile antibodies, which may produce falsely low or high Tg values, respectively. The increased prevalence of antithyroglobulin antibodies in patients with DTC, as compared with the general population, raises the very pertinent possibility that tumor Tg may be more immunogenic. This inference makes sense, as the tumor microenvironment (tumor cells plus normal host cells) is characterized by several changes that could induce posttranslational modification of many proteins, including Tg. Attempts to understand the structure of Tg have been made for several decades, but findings have generally been incomplete due to technical hindrances to analysis of such a large protein (660 kDa). This review article will explore the complex structure of Tg and the potential role of its marked heterogeneity in our understanding of normal thyroid biology and neoplastic processes. Univ Fed Sao Paulo EPM Unifesp, Escola Paulista Med, Lab Endocrinol Mol & Translac, Div Endocrinol & Metab,Dept Med, Sao Paulo, SP, Brazil Univ Fed Mato Grosso do Sul UFMS, Fac Med Famed, Dept Med, Clin Integrada 5,Endocrinol & Metab, Campo Grande, MS, Brazil Univ Fed Sao Paulo, EPM, Dept Bioquim, Div Mol Biol, Sao Paulo, SP, Brazil Univ Fed Sao Paulo EPM Unifesp, Escola Paulista Med, Lab Endocrinol Mol & Translac, Div Endocrinol & Metab,Dept Med, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, EPM, Dept Bioquim, Div Mol Biol, Sao Paulo, SP, Brazil Web of Science

Sao Paulo State Research Foundation-FAPESP FAPESP Federal Agency of Support and Evaluation of Postgraduate Education (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior) National Council for Scientific and Technological Development Context: Calcitonin (CT) is a sensitive marker of medullary thyroid carcinoma (MTC) and is used for primary diagnosis and follow-up after thyroidectomy. However, persistently elevated CT is observed even after complete surgical removal without evidence of a recurrent or persistent tumor. Objective: To investigate the presence of assay interference in the serum CT of MTC patients who are apparently without a structural disease. Patients and Methods: We studied three index MTC cases for CT assay interference and 14 patients with metastatic MTC. The CT level was measured using an immunofluorometric assay. Screening for assay interference was performed by determination of CT levels before and after serum treatment with polyethylene glycol. Additionally, samples were analyzed by chromatography on ultra-performance liquid chromatography and protein A-Sepharose. Results: Patients with biochemical and structural disease showed CT mean recovery of 84.1% after polyethylene glycol treatment, whereas patients suspected of interference showed recovery from 2-7%. The elution profile on UPLC showed that the immunometric CT from these three patients behaved like a high molecular mass aggregate (>300 kDa). Additionally, when these samples were applied to the protein A-Sepharose, CT immunoreactivity was retained on the column and was only released after lowering the pH. Conclusions: For the first time, our results show the presence of a novel pitfall in the CT immunoassay: "macrocalcitonin." Its etiology, frequency, and meaning remain to be defined, but its recognition is of interest and can help clinicians avoid unnecessary diagnostic investigations and treatment during the follow-up of MTC. Univ Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Dept Med,Thyroid Dis Ctr, BR-04039032 Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Dept Med,Lab Mol & Translat Endocrinol, BR-04039032 Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Escola Paulista Med, Dept Biochem, Div Mol Biol, BR-04044020 Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Dept Med,Thyroid Dis Ctr, BR-04039032 Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Escola Paulista Med, Div Endocrinol, Dept Med,Lab Mol & Translat Endocrinol, BR-04039032 Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Escola Paulista Med, Dept Biochem, Div Mol Biol, BR-04044020 Sao Paulo, SP, Brazil FAPESP: 2006/60402-1 FAPESP: 2010/51547-1 FAPESP: 2010/19478 Web of Science

Desenvolvemos método semi-automatizado em placa para a determinação de iodo urinário; utilizamos, primeiramente, a digestão das amostras de urina com persulfato de amônio e, a seguir, estimamos a quantidade de iodo pela redução do sulfato cérico amoniacal. O método foi validado no inquérito nacional de monitoração da deficiência de iodo, realizado em 1994, que empregou um sistema de amostragem mista da população brasileira e analisou a iodúria em 16.803 amostras de urina de escolares obtidas por coleta casual. Em 401 municípios estudados encontramos 4 com deficiência de iodo de grau moderado (Almas, Arraias e Paraná, em Tocantins, e Cocos, na Bahia) e 116 de grau leve. Desta forma, este estudo mostrou a presença de regiões com deficiência de iodo em 1994, a despeito do programa de iodação do sal. Dados recentes de outros autores, com número menor de municípios, indicam excesso de ingestão de iodo. Assim, num país de dimensões continentais e heterogêneo como o Brasil, é necessária a realização de avaliações periódicas de amplitude nacional para a verificação da ingestão de iodo da população. O método apresentado neste estudo apresenta as características de simplicidade e eficiência necessários para este tipo de estudo populacional. In this study we developed a semi-automated method for the measurement of urinary iodine using firstly ammonium persulfate for digestion of urine followed by estimation of iodine content in the Sandell-Kolthoff reaction, in which iodine acts as a catalyst for the reduction of cerium. This method was validated in the 3rd Brazilian National Survey of iodine deficiency in 1994. We studied 16,803 casual urine samples from schoolchildren of 401 cities and found 4 moderately-deficient towns (Almas, Arraias, and Parana, in the State of Tocantins, and Cocos, in the State of Bahia), and 116 mildly-deficient. This work suggests that despite the salt iodization program, there was some iodine-deficient areas in Brazil in 1994. Recent surveys, involving less cities, are indicating an excess of iodine ingestion. Therefore, in a country of continental dimensions and very heterogeneous in terms of public health, periodical evaluations are necessary to monitor the real situation of iodine nutrition in Brazil. The method developed in this paper is suitable for these surveys.

Objective Consuming a low-iodine diet (LID) is a widely accepted practice before administering radioiodine (131I) to evaluate and to treat thyroid disease. Although this procedure is well established for the management of patients with differentiated thyroid cancer, its use in patients with benign disease is unclear. So, we aimed to evaluate the influence of a LID on the outcome in patients with Graves’ disease (GD) treated with131I. Subjects and methods We evaluated 67 patients with GD who were divided into 2 groups: one group (n = 31) consumed a LID for 1-2 weeks, and the second group (n = 36) was instructed to maintain a regular diet (RD). Results The LID group experienced a 23% decrease in urinary iodine after 1 week on the diet and a significant 42% decrease after 2 weeks on the diet. The majority (53%) of the patients in the LID group had urinary iodine levels that were consistent with deficient iodine intake. However, there was no difference in the rate of hyperthyroidism’s cure between the LID and the RD groups 6 months after 131I therapy. Furthermore, the therapeutic efficacy did not differ in patients with varying degrees of sufficient iodine intake (corresponding urinary iodine levels: < 10 μg/dL is deficient; 10-29.9 μg/dL is sufficient; and > 30 μg/dL is excessive). Conclusion In the present study, we demonstrated that although a LID decreased urinary iodine levels, those levels corresponding with sufficient or a mild excess in iodine intake did not compromise the therapeutic efficacy of131I for the treatment of GD.

Introduction: Hyperparathyroidism is a frequent complication of chronic kidney disease (CKD). Total parathyroidectomy (PTX) with parathyroid tissue autotransplantation (AT) is a treatment option in those individuals that do not respond to clinical management. Objective: To evaluate grafted parathyroid tissue response during induced hypocalcemia among CKD patients who underwent total PTX with AT. Methods: Eighteen patients with renal hyperparathyroidism were submitted to total PTX with parathyroid AT selected by stereomicroscopy between April and October 2008. Eleven (eight with successful kidney transplantation, 2 in peritoneal dialysis and 1 in hemodialysis) were clinically stable and eligible for testing. Hypocalcemia was induced using sodium bicarbonate infusion in 5 healthy controls and in patients 6-12 months after surgery. Results: Among controls, hypocalcemia elicited a major rise in intact PTH (iPTH) levels 4 minutes after bicarbonate infusion. In patients, a significant decrease in ionized calcium concentration was observed [from 1.17 ± 0.12 to 1.09 ± 0.11 mean (± SE) mmol/L] in the 4th minute (p < 0.001) illustrating the nadir point. In the 10thminute, ionized calcium did not show a statistical increase compared to the 4th minute (p = 0.451). The iPTH levels ranged from 34.8 ± 18.6 to 34.1 ± 18.8 pg/mL (similar values between base line and 4thminute p = 0.087) and did not change in the 10th minute (33.3 ± 19,6 pg/ mL p = 0.693). Conclusion: Among CKD patients tested 6-12 months after surgery, grafted parathyroid tissue revealed a blunted secretory capacity during bicarbonate induced hypocalcemia with no changes in iPTH levels

Com o objetivo de correlacionar os níveis séricos de cálcio e PTH com a porcentagem de resultados positivos na cintilografia das paratiróides (CP), analisamos retrospectivamente 194 pacientes submetidos à CP. Avaliou-se visualmente a distribuição dos resultados das CP em um diagrama de dispersão cujos eixos eram os níveis de cálcio (eixo Y) e PTH (eixo X) séricos. Foram definidos 6 grupos de pacientes: 1) cálcio > 12mg/dL; 2) 11mg/dL < cálcio < 12mg/dL; 3) 9,9mg/dL < cálcio < 11mg/dL com PTH > 120pg/mL; 4) 9,9mg/dL < cálcio < 11mg/dL com 65pg/mL < PTH < 120pg/mL; 5) 9,9mg/dL < cálcio < 11mg/dL com PTH < 65pg/mL; e 6) cálcio < 9,9mg/dL. A porcentagem de exames positivos nestes 6 grupos foram respectivamente: 10/10 (100%), 18/29 (62%), 7/9 (78%), 18/45 (40%), 2/21 (10%) e 1/80 (1%). Em conclusão, nos pacientes com suspeita de hiperparatiroidismo primário, as CPs realizadas antes da cirurgia de paratiroidectomia naqueles com níveis de cálcio acima de 11mg/dL são, na maioria das vezes, positivas. Para pacientes com níveis de cálcio sérico entre 9,9mg/dL e 11mg/dL, a pertinência da realização da cintilografia vai depender dos níveis de PTH sérico, sendo esta pertinência alta para pacientes com níveis de PTH acima de 120pg/mL e muito baixa para pacientes com PTH abaixo de 65pg/mL. Pacientes com cálcio sérico abaixo de 9,9mg/dL raramente apresentam cintilografia das paratiróides positivas. To correlate PTH and calcium serum levels with the percentages of positive results on the parathyroid scintigraphy, we retrospectively analyzed 194 patients who performed parathyroid scintigraphy. The distribution of the parathyroid scintigraphy results was visually analyzed in a scatter plot, being calcium (Y axis) and PTH (X axis) serum levels the axes. Six groups of patients were defined: 1) calcium > 12mg/dL; 2) 11mg/dL ¾ calcium < 12mg/dL; 3) 9.9mg/dL < calcium < 11mg/dL with PTH > 120pg/mL; 4) 9.9mg/dL < calcium < 11mg/dL with 65pg/mL < PTH < 120pg/mL; 5) 9.9mg/dL < calcium < 11mg/dL with PTH < 65pg/mL; and 6) calcium < 9.9mg/dL. The percentage of positive scintigraphy in these groups were respectively: 10/10 (100%), 18/29 (62%), 7/9 (78%), 18/45 (40%), 2/21 (10%) and 1/80 (1%). We conclude that in patients with suspected primary hyperparathyroidism, parathyroid scintigraphies performed before surgery on those with calcium level above 11mg/dL are frequently positive. In patients with calcium levels between 9.9mg/dL and 11mg/dL the pertinence of performing the scintigraphy will depend on the PTH levels, and it will be high for patients with PTH serum level above 120pg/mL and very low for patients with PTH level below 65pg/mL. Patients with calcium level below 9.9mg/dL rarely present positive results on parathyroid scintigraphies.

The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P< 0.0001). Insulin gene −2221 C/T polymorphism was also associated with diabetes risk: CC genotype was found among 83.1% of patients compared to 69.3% of healthy controls (P= 0.0369, OR 1.98) but CTLA-4 gene +49 A/G polymorphism did not significantly differ between patients and controls. Despite the diversity of the Brazilian population the screening sensitivity and specificity of the used method for T1D risk was similar to that obtained in Europe.

In contrast to most developed countries, most patients with primary hyperparathyroidism in Brazil are still symptomatic at diagnosis. However, we have been observing a change in this pattern, especially in the last few years. We evaluated 104 patients, 77 females and 27 males aged 11-79 years (mean: 54.4 years), diagnosed between 1985 and 2002 at a University Hospital. Diagnosis was made on the basis of clinical findings and of high total and/or ionized calcium levels, high or inappropriate levels of intact parathyroid hormone and of surgical findings in 80 patients. Patients were divided into three groups, i.e., patients diagnosed from 1985 to 1989, patients diagnosed from 1990 to 1994, and patients diagnosed from 1995 to 2002. The number of new cases diagnosed/year increased from 1.8/year in the first group to 6.0/year in the second group and 8.1/year in the third group. The first group comprised 9 patients (mean serum calcium ± SD, 13.6 ± 1.6 mg/dl), 8 of them (88.8%) defined as symptomatic. The second group comprised 30 patients (mean calcium ± SD, 12.2 ± 1.63 mg/dl), 22 of them defined as symptomatic (73.3%). The third group contained 65 patients (mean calcium 11.7 ± 1.1 mg/dl), 34 of them symptomatic (52.3%). Patients from the first group tended to be younger (mean ± SD, 43.0 ± 15 vs 55.1 ± 14.4 and 55.7 ± 17.3 years, respectively) and their mean serum calcium was significantly higher (P < 0.05). All of symptomatic patients independent of group had higher serum calcium levels (12.4 ± 1.53 mg/dl, N = 64) than asymptomatic patients (11.4 ± 1.0 mg/dl, N = 40). Our data showed an increase in the percentage of asymptomatic patients over the years in the number of primary hyperparathyroidism cases diagnosed. This finding may be due to an increased availability of diagnostic methods and/or to an increased awareness about the disease. Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Medicina Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço UNIFESP, EPM, Depto. de Medicina UNIFESP, EPM, Depto. de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço SciELO

This cross-sectional study covered 301 individuals over 70 years of age--207 women (W) and 94 men (M)--living in the city of São Paulo, Brazil. Our aims were to evaluate the prevalence of low bone mineral density (BMD) in this population and the possible factors that influence BMD. The subjects were submitted to a bone densitometry scan (DXA) to evaluate the BMD at lumbar spine (LS), femoral neck (FN), trochanter (T), total femur (TF) and total body composition. At the time, the participants filled in a questionnaire about lifestyle habits, diet and medical history, as well as having blood samples taken to check hormone and biochemical levels. Anthropometric parameters were measured. Osteopenia and osteoporosis were defined in accordance with the criteria suggested by the World Health Organization. In the different sites studied, the prevalence of osteopenia and osteoporosis varied, in men ranging 33.3-57.4% and 6.4-16.1%, respectively, and in women ranging 36.6-56.5% and 22.2-33.2%, respectively. Weight was the variable that most strongly correlated with BMD at the proximal femur in both sexes (men, r =0.44-0.52; women, r =0.48-0.52) and with BMD at LS in women (r =0.44). Height was the parameter that best correlated with BMD at LS in men (r =0.34). In men follicle-stimulating hormone, growth hormone and glycemia correlated with BMD at T and TF, while plasma albumin only correlated with BMD at T. In women glycemia correlated with BMD at LS, and follicle-stimulating hormone correlated with BMD at FN, T and TF. In conclusion, we found a high prevalence of osteopenia and osteoporosis in this population, with weight being the best predictor of BMD. The prevalence of osteoporosis and osteopenia at FN was as high in men as that observed in women.

UNLABELLED Chronic kidney disease (CKD) leads to reduced bone mineral density (BMD) in pre-dialysis and dialysis patients. A few studies have used dual-energy x-ray absorptiometry (DEXA) to assess BMD in pre-dialysis CKD patients and have shown low BMD to be highly prevalent. Until now there have been no studies reporting the histological features of low BMD in pre-dialysis CKD patients. AIM To determine the prevalence and histological features of low BMD in pre-dialysis CKD patients. METHOD Pre-dialysis CKD patients (n = 103, 46 females/57 males), median creatinine clearance of 29 (10 - 78) ml/min/ 1.73 m2, were evaluated using biochemical analysis and DEXA. Bone biopsies were obtained from those with low BMD. RESULTS Fifty (48.5%) out of the 103 patients had low BMD (LBD group) and 53 (51.5%) had normal BMD (NBD group). The risk for low BMD was increased in those patients with alkaline phosphatase levels above 190 U/l and intact-PTH (iPTH) below 70 pg/ml (p < 0.05). Demographic and biochemical parameters from both groups were comparable, except for lower body mass index (BMI) in LBD subjects (p = 0.04). Women who had been post-menopausal for at least 1 year comprised 65% (13/20) and 50% (13/26) of the LBD and NBD groups, respectively (p = NS). In 40 LBD patients, bone histomorphometry revealed adynamic bone disease (ABD, 52.5%), osteomalacia (OM, 42.5%) and mixed bone disease (MBD, 5%). Trabecular bone volume (BV/TV) was lower in ABD and OM patients. A nearly significant association was found between ABD and iPTH < or = 150 pg/ml (p = 0.056), whereas higher values of iPTH were associated with OM. Total alkaline phosphatase < or = 190 U/l was significantly associated with ABD, whereas higher values were associated with OM. No correlation was observed between BV/TV and BMD. CONCLUSION Low BMD is frequent in pre-dialysis CKD patients, and low turnover bone disease, manifesting as ABD and OM, was the hallmark of this bone loss.

The response to an oral calcium load test was assessed in 17 hypercalciuric nephrolithiasis patients who presented elevated parathyroid hormone (PTH) irrespective of the ionized calcium (sCa2+) levels. Blood samples were collected at baseline (0 min) and at 60 and 180 min after 1 g calcium load for serum PTH, total calcium, sCa2+, and 1.25(OH)2D3 determinations. According to the sCa2+ level at baseline, patients were classified as normocalcemic (N = 9) or hypercalcemic (N = 8). Six healthy subjects were also evaluated as controls. Bone mineral density was reduced in 14/17 patients. In the normocalcemic group, mean PTH levels at 0, 60 and 180 min (95 +/- 76, 56 +/- 40, 57 +/- 45 pg/ml, respectively) did not differ from the hypercalcemic group (130 +/- 75, 68 +/- 35, 80 +/- 33 pg/ml) but were significantly higher compared to healthy subjects despite a similar elevation in sCa2+ after 60 and 180 min vs baseline in all 3 groups. Mean total calcium and 1.25(OH)2D3 were similar in the 3 groups. Additionally, we observed that 5 of 9 normocalcemic patients presented a significantly higher concentration-time curve for serum PTH (AUC0',60',180') than the other 4 patients and the healthy subjects, suggesting a primary parathyroid dysfunction. These data suggest that the individual response to an oral calcium load test may be a valuable dynamic tool to disclose a subtle primary hyperparathyroidism in patients with high PTH and fluctuating sCa2+ levels, avoiding repeated measurements of both parameters.

A gravidez é acompanhada por uma série de modificações fisiológicas que incluem uma elevação significativa da globulina ligadora de tiroxina (Thyroxine-Binding Globulin, TBG). Tal elevação interfere nos níveis séricos totais da tiroxina (T4) e corrobora a utilização da medida de tiroxina livre (T4L), em conjunto com a dosagem de TSH, como métodos de primeira linha para a avaliação de função tiroidiana na gravidez. Uma definição cuidadosa dos valores normais de T4L durante a gestação é fundamental para o estudo de alterações da função tiroidiana, desde que disfunções mínimas podem resultar em anormalidades fetais significativas. Estudamos 132 grávidas normais, entre 6 e 38 semanas de gestação, e os resultados da medida de T4L por método indireto em duas etapas (valores normais de 0,7 a 1,5ng/dL em não grávidas, n= 797) mostraram valores entre 0,5 e 1,3ng/dL, com média±DP de 0,78±0,16ng/dL, significativamente mais baixos que os observados em não grávidas (0,98±0,14ng/dL, P

A calcitonina é um hormônio secretado pelas células parafoliculares tiroideanas. O diagnóstico de carcinoma medular de tiróide (CMT) pode ser suspeitado a partir do encontro de níveis aumentados de calcitonina basal ou após testes de estímulos específicos. Neste sentido, a calcitonina caracteriza-se como um importante marcador tumoral para o diagnóstico e seguimento de pacientes portadores de CMT. Neste artigo, revisamos alguns tópicos referentes à utilidade da dosagem de calcitonina basal em pacientes portadores de nódulos de tiróide para rastreamento de CMT. Comentamos a respeito dos principais testes de estímulo para secreção de calcitonina disponíveis e finalizamos com algumas observações sobre os ensaios para dosagem de calcitonina. Calcitonin is a hormone secreted by the parafollicular thyroid cells. Diagnosis of medullary thyroid carcinoma (MTC) should be considered when high basal calcitonin levels or high calcitonin levels after specific provocative test are found. In this context, calcitonin is considered a relevant tumor marker for diagnosis and follow-up of MTC. In this manuscript, we review some issues related to the usefulness of measuring basal calcitonin in patients with thyroid nodules. The current available provocative tests for calcitonin are discussed. Finally, we comment on some aspects related to the assays for calcitonin measurement.

Summary objective Abnormal corticosteroid-binding globulin (CBG) is an extremely rare condition and only three mutations have been described in four families. The molecular basis of an abnormal CBG in a Brazilian family was studied and correlations between genotype and serum cortisol, cortisol binding capacity (CBC) and CBG levels were determined. subjects All 10 family members, comprising three generations, and nine healthy volunteers were studied. measurements Genomic DNA was extracted from white blood cells from all family members. The human cbg exons 2–5 were amplified by PCR, submitted to automatic sequencing. Cortisol and CBG levels in serum were measured by radioimmunoassay (RIA). CBC in serum was determined using tritiated cortisol and other cortisol binding parameters were calculated through Scatchard analysis. results A missense mutation in exon 5 of cbg (1254G → A; Asp367Asn), recently described as CBG Lyon, was found in all family members. The proband and one sister were homozygous whereas all other family members, including parents, were heterozygous for this mutation. Cortisol levels in the only two homozygotes were lower than in heterozygotes and both were significantly lower as compared to controls (69 and 182 nmol/l vs. 267 ± 129 nmol/l vs. 459 ± 195 nmol/l, respectively, P