Archives of Endocrinology and Metabolism, Volume: 61, Issue: 5, Published: 2017
  • Is the 18F-FDG PET/CT the definite resource to detect the recurrence on high-risk thyroid cancer patients? editorial

    Buchpiguel, Carlos Alberto
  • Biochemical diagnosis of acromegaly without a typical clinical phenotype: what are the concerns? editorial

    Ribeiro-Oliveira, Antonio; Barkan, Ariel
  • Clinical utility of 18F-FDG PET/CT in the follow-up of a large cohort of patients with high-risk differentiated thyroid carcinoma Original Articles

    Yang, Ji H.; Maciel, Rui M. B.; Nakabashi, Claudia C. D.; Janovsky, Carolina C. P. S.; Padovani, Rosalia P.; Macellaro, Danielle; Camacho, Cléber P.; Osawa, Akemi; Wagner, Jairo; Biscolla, Rosa Paula M.

    Abstract in English:

    ABSTRACT Objective To evaluate the clinical utility of 18F-FDG PET/CT in patients with high-risk DTC. Subjects and methods Single-center retrospective study with 74 patients with high-risk differentiated thyroid cancer (DTC), classified in 4 groups. Group 1: patients with positive sTg or TgAb, subdivided in Group 1A: negative RxWBS and no foci of metastases identified at conventional image (n = 9); Group 1B: RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level (n = 13); Group 2: patients with histological findings of aggressive DTC variants (n = 21) and Group 3: patients with positive RxWBS (n = 31). Results 18F-FDG PET/CT identified undifferentiated lesions and helped restage the disease in groups 1B and 2. The scan helped guide clinical judgment in 9/13 (69%) patients of group 1B, 10/21 (48%) patients of group 2 and 2/31 (6%) patients of group 3. There was no clinical benefit associated with group 1A. 18F-FDG PET/CT was associated with progressive disease. Conclusion 18F-FDG PET/CT is a useful tool in the follow-up of patients with high-risk DTC, mainly in the group of RxWBS not compatible with suspicious foci at conventional image or not proportional to sTg level and in those with aggressive DTC variants. Additionally, this study showed that 18F-FDG PET/CT was associated with progression and helped display undifferentiated lesions guiding clinical assessments regarding surgeries or expectant treatments.
  • Long-term follow-up of patients with elevated IGF-1 and nadir GH > 0.4 µg/L but < 1 µg/L Original Articles

    Rosario, Pedro Weslley; Calsolari, Maria Regina

    Abstract in English:

    ABSTRACT Objective To report the results of initial investigation and after 5 years of patients with a suspicious clinical scenario for acromegaly, elevated IGF-1, and nadir GH during an oral glucose tolerance test (OGTT) > 0.4 µg/L but < 1 µg/L. Subjects and methods Seventeen patients who had elevated IGF-1 (outside puberty and pregnancy) in two measurements and GH between 0.4 and 1 µg/L during OGTT were selected. Results During initial assessment, only one patient had microadenoma on magnetic resonance imaging (MRI) of the pituitary. In this patient, IGF-1 returned to normal spontaneously after 5 years. In the remaining 16 patients, spontaneous normalization of IGF-1 was observed in four and IGF-1 continued to be elevated in 12 after 5 years. None of the latter patients developed a phenotype of acromegaly, changes in physiognomy or increase in IGF-1 and no tumor was detected by imaging methods. Two patients had nadir GH < 0.4 µg/L, while the nadir GH remained between 0.4 and 1 µg/L in 10 patients. Conclusion In patients (notably young adult or adult women) without a typical phenotype in whom IGF-1 is measured due to a suspicious clinical scenario and is found to be slightly elevated, even if confirmed and in the absence of other causes, a nadir GH cut-off value of 0.4 µg/L instead of 1 µg/L in the OGTT might be inadequate for the diagnosis.
  • Timing of thyroid ultrasonography in the etiological investigation of congenital hypothyroidism Original Articles

    Borges, Maria de Fátima; Sedassari, Nathalie de Almeida; Sedassari, Anelise de Almeida; Souza, Luis Ronan Marquez Ferreira de; Ferreira, Beatriz Pires; Lara, Beatriz Hallal Jorge; Palhares, Heloísa Marcelina Cunha

    Abstract in English:

    ABSTRACT Objectives To describe the findings of thyroid ultrasonography (T-US), its contribution to diagnose congenital hypothyroidism (CH) and the best time to perform it. Subjects and methods Forty-four patients with CH were invited to undergo T-US and 41 accepted. Age ranged from 2 months to 45 years; 23 patients were females. All were treated with L-thyroxine; 16 had previously undergone scintigraphy and 30 had previous T-US, which were compared to current ones. Results At the current T-US, the thyroid gland was not visualized in its normal topography in 10 patients (24.5%); 31 T-US showed topic thyroid, 17 with normal or increased volume due to probable dyshormonogenesis, 13 cases of hypoplasia and one case of left-lobe hemiagenesis. One patient had decreased volume due to central hypothyroidism. Scintigraphy scans performed 3-4 years earlier showed 100% agreement with current results. Comparisons with previous T-US showed concordant results regarding thyroid location, but a decrease in current volume was observed in eight due to the use of L-thyroxine, calling the diagnosis of hypoplasia into question. Conclusions The role of T-US goes beyond complementing scintigraphy results. It allows inferring the etiology of CH, but it must be performed in the first months of life. An accurate diagnosis of CH will be attained with molecular study and the T-US can guide this early assessment, without therapy withdrawal.
  • IL-6, TNF-α, and IL-10 levels/polymorphisms and their association with type 2 diabetes mellitus and obesity in Brazilian individuals Original Articles

    Rodrigues, Kathryna Fontana; Pietrani, Nathalia Teixeira; Bosco, Adriana Aparecida; Campos, Fernanda Magalhães Freire; Sandrim, Valéria Cristina; Gomes, Karina Braga

    Abstract in English:

    ABSTRACT Objective This study aimed to investigate the association of plasma TNF-α, IL-6, and lL-10 levels and cytokine gene polymorphisms [TNF-α (-308 G→A), IL-6 (-174 C→G) and IL-10 (-1082 A→G, -819 T→C and -592 A→C)] in type 2 diabetes mellitus (T2DM) and obese patients. Subjects and methods One hundred and two T2DM patients and 62 controls were included in this study. Cytokine plasma levels were measured by the Cytometric Bead Array method. Genotyping was carried out by the polymerase chain reaction. Results IL-6 levels were significantly different between T2DM patients and controls. Interestingly, IL-6 levels were higher in T2DM patients with BMI > 30 kg/m2 compared with other patients and obese controls. The genotype and allele frequencies were similar between patients and controls. In the T2DM group, the SNP IL-10 -819 T/C showed a difference between the cytokine level and genotypes: IL-10 level in the TT genotype was significantly higher when compared to CC genotype. Conclusions These results suggest an association between IL-6 levels and obesity, and IL-10 levels and the SNP -819 T/C in T2DM. Knowledge of these variants in T2DM might contribute to a better understanding of the role of inflammation in the etiology and progression of this disease.
  • Use of prophylactic oral calcium after total thyroidectomy: a prospective study Original Articles

    Langner, Erwin; Tincani, Alfio José; Negro, André del

    Abstract in English:

    ABSTRACT Objective The aim of this study was to evaluate the use of prophylactic oral calcium after total thyroidectomy in the prevention of symptomatic hypocalcemia, and to develop a rational strategy of oral calcium supplementation following this type of surgery. Subjects and methods Prospective study including 47 patients undergoing total thyroidectomy from January 2007 to February 2012. The patients were allocated to one of the following groups: I (no postoperative calcium) or II (oral calcium 3 g per day). Oral calcium was started at the first postoperative day and administered until the sixth postoperative day. The patients were followed up for a minimum of 6 months and evaluated with a minimum of five measurements of ionized calcium: preoperative, 16 hours after surgery, seventh postoperative day, and at postoperative days 90 (PO90) and 180 (PO180). The cohort included three men and 44 women, of whom 24 (51.9%) had benign thyroid disease, and 23 had suspected or confirmed malignant disease. Results When compared with Group II, Group I had significantly higher rates of postoperative biochemical hypocalcemia at PO1 and PO180, and of symptomatic hypocalcemia at PO1, PO7, and PO90. Other data were not significantly different between the groups. Conclusion We conclude that postoperative calcium supplementation effectively prevents symptomatic and biochemical hypocalcemia after total thyroidectomy, and can be safely used after this procedure. The presented strategy of oral calcium supplementation may be implemented in a viable manner.
  • Serum nesfatin-1 levels are decreased in pregnant women newly diagnosed with gestational diabetes Original Articles

    Ademoglu, Esra Nur; Gorar, Suheyla; Keskin, Muge; Carlioglu, Ayse; Ucler, Rifki; Erdamar, Husamettin; Culha, Cavit; Aral, Yalcin

    Abstract in English:

    ABSTRACT Objective To investigate serum nesfatin-1 levels at 24-28 weeks of pregnancy in women newly diagnosed with gestational diabetes and determine the association of nesfatin-1 with several metabolic parameters. Subjects and methods Forty women newly diagnosed with gestational diabetes at 24-28 weeks of pregnancy and 30 healthy pregnant women matched in age and gestational week were included in this cross-sectional study. Serum nesfatin-1 levels were analyzed using ELISA, and the relationship between nesfatin-1 and several metabolic parameters were assessed. Results Serum nesfatin-1 levels were found to be lower in women with gestational diabetes compared to the pregnant women in the control sample (p = 0.020). Multiple linear regression analysis revealed that nesfatin-1 was lower in participants with gestational diabetes independently from gestational age, BMI, HOMA-IR, fasting plasma glucose, and age. In correlation analysis, the only variable that was found to have a statistically significant correlation with nesfatin-1 was gestational age (p = 0.015, r = 0.30). Conclusion Lower nesfatin-1 levels in women with gestational diabetes compared to the control group at 24-28 weeks of gestation draws attention to nesfatin-1 levels in gestational diabetes and motivates further research in this area.
  • Novel immunoassay for TSH measurement in rats Original Articles

    Alves, Thalita G.; Melo, Maria Clara de C.; Kasamatsu, Teresa S.; Oliveira, Kelen C.; Souza, Janaina Sena de; Conceição, Rodrigo Rodrigues da; Giannocco, Gisele; Dias-da-Silva, Magnus R.; Chiamolera, Maria Izabel; Vieira, José Gilberto

    Abstract in English:

    ABSTRACT 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.
  • Serum ghrelin levels in papillary thyroid carcinoma Original Articles

    Ucan, Bekir; Sahin, Mustafa; Kizilgul, Muhammed; Ozbek, Mustafa; Ozdemir, Seyda; Calıskan, Mustafa; Cakal, Erman

    Abstract in English:

    ABSTRACT Objective Ghrelin plays a role in several processes of cancer progression, and numerous cancer types express ghrelin and its receptor. We aimed to investigate serum levels of ghrelin in patients with papillary thyroid carcinoma (PTC) and its association with the prognostic factors in PTC. Materials and methods We enrolled 54 patients with thyroid cancer (7 male, 47 female) and 24 healthy controls (6 male, 18 female) in the study. We compared demographic, anthropometric, and biochemical data, and serum ghrelin levels between the groups. Serum ghrelin levels were measured using as enzyme-linked immunosorbent assay. Results Ghrelin levels were similar between the groups, but plasma ghrelin levels were significantly higher in tumors larger than 1 cm diameter compared with papillary microcarcinomas. Serum ghrelin levels also correlated with tumor size (r = 0.499; p < 0.001). Body mass index, thyroid-stimulating hormone, and HOMA-IR levels were similar between the groups. There were no statistically significant differences regarding average age and other prognostic parameters including lymph node invasion, capsule invasion, multifocality and surgical border invasion between patients with microcarcinoma and tumors larger than 1 cm. Conclusion In our study, no significant difference in serum ghrelin levels was determined between patients with papillary thyroid cancer and healthy controls however, serum ghrelin levels were higher in tumors larger than 1 cm compared to in those with thyroid papillary microcarcinoma.
  • Screening tests for distal symmetrical polyneuropathy in Latin American patients with type 2 diabetes mellitus Original Articles

    Gómez-Banoy, Nicolás; Cuevas, Virginia; Soler, Fernando; Pineda, Maria Fernanda; Mockus, Ismena

    Abstract in English:

    ABSTRACT Objective This cross sectional study intended to evaluate two bedside tests (Neuropad and VibraTip) as screening tools for distal symmetrical polyneuropathy (DSPN) in Latin American patients with type 2 diabetes mellitus (T2D). Subjects and methods Ninety-three Colombian patients diagnosed with T2D were recruited. Anthropometric variables, glycemic control parameters, lipid profile and renal function were assessed for each patient. DSPN was defined by a Michigan Neuropathy Screening Instrument (MNSI) clinical score greater than 2. Both Neuropad and Vibratip tests were applied to each patient. Contingency analyses were performed to evaluate the diagnostic power of both tools. Results The prevalence of DSPN determined clinically by MNSI was 25.8%. DSPN in these patients was associated with age, worsening renal function, and insulin treatment. The sensitivity and specificity of the Neuropad test for DSPN was 66.6% and 63% respectively. Its negative predictive value (NPV) was 84.6%. The VibraTip test exhibited a sensitivity of 54.1% and specificity of 91.3%, with a NPV of 85.1%. Conclusion Neuropad and VibraTip are reliable screening tools for DSPN in Latin American population. VibraTip presents a considerable diagnostic power for DSPN in this population. Further studies regarding the cost-effectiveness of these tools in clinical practice are needed.
  • Endothelial dysfunction in children with type 1 diabetes mellitus Original Articles

    Nascimento, Antonella Márcia Mercadante de Albuquerque do; Sequeira, Inês Jorge; Vasconcelos, Daniel França; Gandolfi, Lenora; Pratesi, Riccardo; Nóbrega, Yanna Karla de Medeiros

    Abstract in English:

    ABSTRACT Objective The purpose of this study was to verify the presence of endothelial dysfunction and initial structural atherosclerotic changes in children with Type 1 diabetes mellitus (T1DM). Subjects and methods The study population comprised 31 diabetic children aged 6 to 12 years, divided into two subgroups according to the duration of the T1DM diagnosis: subgroup 1, with less than 5 years elapsed since diagnosis, and subgroup 2, with more than 5 years elapsed since diagnosis. The control group comprised 58 age-matched healthy children. Ultrasonographic techniques were used to measure the flow-mediated dilatation (FMD) of the brachial artery and the intima-media thickness (IMT) of the carotid arteries. Results Children with T1DM with longer disease duration showed significantly decreased mean values of FMD compared with those in the control group. No significant differences between the groups were found in relation to IMT. The FMD percentage presented a moderate negative correlation with glycated hemoglobin (HbA1c) and fasting glucose levels. Conclusion Our findings suggest that endothelial dysfunction may be already present in children with 5 years or more elapsed since diagnosis, even in the absence of atherosclerotic structural changes. The decreased vasodilation response correlated with hyperglycemia.
  • Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil – A longitudinal study Original Articles

    Santos, Willian dos; Tureck, Luciane Viater; Saliba, Louise Farah; Schenknecht, Caroline Schovanz; Scaraboto, Débora; Souza, Ricardo Lehtonen R.; Furtado-Alle, Lupe

    Abstract in English:

    Objective Butyrylcholinesterase (BChE) activity has been associated with obesity, lipid concentrations, and CHE2 locus phenotypes. This, the aim of this study was to evaluate the effects of an energetic restriction diet intervention on anthropometrical and biochemical variables and on absolute and relative BChE activity in CHE2 C5+ and CHE2 C5- individuals. Subjects and methods One hundred eleven premenopausal obese women from Southern Brazil participated in an energetic restriction diet intervention (deficit of 2500 kJ/day) for 8 weeks. Their anthropometric and biochemical parameters were evaluated before and after the intervention. Plasma BChE activity was measured, and BChE bands in plasma and CHE2 locus phenotypes were detected by electrophoresis. Results The dietetic intervention decreased anthropometric and biochemical parameters as well as absolute BChE activity and relative activity of the G4 band. The CHE2 C5+ phenotype presented a different effect when compared with the CHE2 C5- phenotype. The CHE2 C5+ phenotype showed an effect in absolute BChE activity and in the relative activity of the G4 form, maintaining higher BChE activity regardless of the metabolic changes. Conclusion In our study, 8 weeks was not sufficient time to lower the body mass index to normal, but it was enough to significantly reduce the absolute BChE activity, which became similar to the levels in nonobese individuals. CHE2 C5+ individuals were resistant to the decrease in BChE activity compared to CHE2 C5- individuals. This shows that the diet did not affect the CHE2 and G4 fraction complex and that the products of the CHE2 locus in association with BChE have a role in energy metabolism, maintaining high levels of enzymatic activity even after dietary intervention.
  • The clinical genetics of phaeochromocytoma and paraganglioma review

    Kavinga Gunawardane, P. T.; Grossman, Ashley

    Abstract in English:

    ABSTRACT Phaeochromocytoma and paraganglioma are rare catecholamine-producing tumours, recognised to have one of the richest hereditary backgrounds of all neoplasms, with germline mutations seen in approximately 30% of patients. They can be a part of genetic syndromes such as MEN 2 or Neurofibromatosis type 1, or can be found as apparently sporadic tumours. Germline mutations are almost always found in syndromic patients. Nonetheless, apparently sporadic phaeochromocytoma too show high germline mutation rates. Early detection of a genetic mutation can lead to early diagnosis of further tumours via surveillance, early treatment and better prognosis. Apart from this, the genetic profile has important relevance for tumour location and biochemical profile, and can be a useful predictor of future tumour behaviour. It also enables family screening and surveillance. Moreover, recent studies have demonstrated significant driver somatic mutations in up to 75% of all tumours. Arch Endocrinol Metab. 2017;61(5):490-500
  • Mechanisms involved in hearing disorders of thyroid ontogeny: a literature review review

    Andrade, Caio Leônidas Oliveira de; Machado, Gabriela Carvalho; Fernandes, Luciene da Cruz; Albuquerque, Jamile Morais de; Casais-e-Silva, Luciana Lyra; Ramos, Helton Estrela; Alves, Crésio de Aragão Dantas

    Abstract in English:

    ABSTRACT Endocochlear, retrocochlear and/or central origin hearing damage may be related to the absence of appropriate levels of thyroid hormone during morphogenesis and/or auditory system development. Hearing disorders related to the thyroid are not well studied, despite speculation on the pathophysiological mechanisms. The objective of this review was to characterize the main pathophysiological mechanisms of congenital hypothyroidism and to evaluate the relationship with central and peripheral hearing disorders. We conducted a literature review using the databases MedLine, LILACS, Cochrane Library, SciELO, Institute for Scientific Information (ISI), Embase, and Science Direct between July and September on 2016. We identified the studies that address hearing disorder mechanisms on the congenital hypothyroidism. Congenital hypothyroidism may have clinical and subclinical manifestations that affect the auditory system and may be a potential risk factor for hearing impairment. Hearing impairment can severely impact quality-of-life, which emphasizes the importance of monitoring and evaluating hearing during the clinical routine of these patients.
  • Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor Case Report

    Valdes-Socin, Hernan; Almanza, Matilde Rubio; Fernández-Ladreda, Mariana Tomé; Daele, Daniel Van; Polus, Marc; Chavez, Marcela; Beckers, Albert

    Abstract in English:

    SUMMARY Neuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia.
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