ABSTRACT Objective: This study aimed to investigate the association between 25OHD (total, bioavailable and free) with bone mass and microarchitecture among primary hyperparathyroidism (PHPT) patients and controls. Subjects and methods: Sixty-four patients in the preoperative period of PHPT and 63 matched controls, who had not taken vitamin D in the last three months. To calculate the bioavailable and free 25OHD, the genetic variants of the vitamin D-binding protein (DBP) were determined. Bone mineral density (BMD) was determined by dual-energy X-ray absorptiometry (DXA). The distributions of total, bioavailable and free 25OHD and their correlation with TBS and DXA were evaluated. Results: PHPT showed BMD and TBS values lower than CTRL in all locations (p < 0.05). There were no statistical differences in the levels of free, bioavailable and total 25OHD between the PHPT and CTRL groups [mean, min-max: 3.4 (1.4-8.6) vs. 3.1 (1.0-9.8) pg/mL, 1.51 (0.43-3.58) vs. 1.41 (0.38-3.48) ng/mL, 22.6 (11.0-39.9) vs. 20.6 (8.9-35.3) ng/dL, respectively; (p > 0.05). The distribution of DBP haplotypes was similar between groups. DXA showed no correlation with any form of 25OHD in both groups. TBS presented a weak correlation with the total 25OHD in PHPT (r = 0.28; p = 0.02) and a moderate correlation with the total, free and bioavailable 25OHD in CTRL (r = 0.42; r = 0.42; r = 0.43; respectively, p < 0.01). Conclusion: The concentrations of total, free and bioavailable 25OHD were similar in both the PHPT and control groups. 25OHD concentrations correlated positively with TBS and not with DXA, especially in controls, suggesting that this method may be more sensitive to assessing the consequences of vitamin D deficiency on bone quality in individuals without PHPT.

ABSTRACT Objective To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. Subjects and methods 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. Results One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. Conclusion PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.

ABSTRACT Objective: Initial diagnosis of medullary thyroid carcinoma (MTC) is frequently associated with advanced stages and a poor prognosis. Thus, the need for earlier diagnoses and detection in relatives at risk for the disease has led to increased use of RET genetic screening. Subjects and methods: We performed RET screening in 247 subjects who were referred to the Brazilian Research Consortium for Multiple Endocrine Neoplasia (BRASMEN) Center in the State of Ceará. Direct genetic sequencing was used to analyze exons 8, 10, 11, and 13-16 in MTC index cases and specific exons in at risk relatives. Afterward, clinical follow-up was offered to all the patients with MTC and their affected relatives. Results: RET screening was performed in 60 MTC index patients and 187 at-risk family members. At the initial clinical assessment of the index patients, 54 (90%) were diagnosed with apparently sporadic disease and 6 (10%) diagnosed with hereditary disease. After RET screening, we found that 31 (52%) index patients had sporadic disease, and 29 (48%) had hereditary disease. Regarding at-risk relatives, 73/187 were mutation carriers. Mutations in RET codon 804 and the rare p.M918V mutation were the most prevalent. Conclusions: Performing RET screening in Ceará allowed us to identify a different mutation profile in this region compared with other areas. RET screening also enabled the diagnosis of a significant number of hereditary MTC patients who were initially classified as sporadic disease patients and benefited their relatives, who were unaware of the risks and the consequences of bearing a RET mutation.

Resumo Introdução: O hiperparatireoidismo é uma complicação frequente da doença renal crônica (DRC). A paratireoidectomia (PTX) total com autotransplante (AT) de tecido paratireoideano é uma opção terapêutica para os indivíduos que não respondem ao manejo clínico. Objetivo: Avaliar a resposta do tecido paratireoideano enxertado durante hipocalcemia induzida em pacientes portadores de DRC submetidos à PTX total com AT. Métodos: Dezoito pacientes portadores de hiperparatiroidismo associado à DRC foram submetidos à PTX total com AT de tecido paratireoideano selecionado por estereomicroscopia entre Abril e Outubro de 2008 em nosso serviço. Onze indivíduos (oito com transplante renal funcionante, 2 em diálise peritoneal e 1 em hemodiálise) apresentavam boa condição clínica e foram elegíveis para o teste. Induziu-se hipocalcemia por infusão de bicarbonato de sódio em 5 controles normais e nos pacientes 6-12 meses após a PTX. Resultados: A hipocalcemia determinou um aumento importante dos níveis de PTH intacto (iPTH) no grupo controle 4 minutos após a infusão de bicarbonato. Nos pacientes, houve uma redução significativa do cálcio ionizado [de 1,17 ± 0,12 para 1,09 ± 0,11 (media ± EP) mmol/L] no 4º minuto (p < 0,001) ilustrando o nadir do teste. No 10º minuto não houve elevação do cálcio ionizado comparado ao 4º minuto (p = 0,451). Os níveis de iPTH foram de 34,8 ± 18,6 para 34,1 ± 18,8 pg/mL (valor basal semelhante ao 4º minuto p = 0,087) e se mantiveram no 10º minuto (33,3 ± 19,6 pg/mL p = 0,693). Conclusão: Em pacientes portadores de DRC testados 6-12 meses depois da cirurgia, o enxerto de tecido paratireoideano revelou incapacidade de resposta à hipocalcemia induzida por bicarbonato sem mudança dos níveis de iPTH.

Abstract 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

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.

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.

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.

Avaliamos medida de PTH intraoperatório (IO-PTH) no intuito de melhorar índices de sucesso no tratamento cirúrgico do hiperparatiroidismo associado à doença renal. MÉTODO: Oitenta e seis pacientes realizaram paratiroidectomia total com autoimplante em musculatura pré-esternal entre abril de 2000 e outubro de 2009 com 26,5 meses de seguimento em média, prospectivo. Foram divididos em dois grupos: hiperparatiroidismo secundário (HPS) - pacientes em diálise e hiperparatiroidismo terciário (HPT) - transplantados renais. Medido IO-PTH (Elecsys-PTH-Immunoassay/Roche) na indução anestésica (IOPTH-0') e 20 minutos (IOPTH-20') após a retirada das paratireoides. RESULTADOS: 80,2% (69/86) do total de pacientes apresentaram queda de 80% ou mais do IOPTH-20' e todos se curaram. Em 11/86 (12,7%) pacientes, foi observada queda entre 70-79%, sendo que dois (18,1%) deles evoluíram com falha cirúrgica. 6/86 (6,9%) pacientes apresentaram redução de IOPTH-20' menor do que 70%: dois foram curados; três apresentaram paratireoide supranumerária/ectópica que foi localizada e removida; um paciente evoluiu com persistência da doença após término da cirurgia com a retirada de quatro paratireoides. CONCLUSÃO: Queda do IOPTH-20' de 80% ou mais foi preditor de cura em todos os pacientes renais durante o período avaliado. Redução menor que 70% sugere paratireoide hiperfuncionante não reconhecida/supranumerária, sendo preditor de falha cirúrgica em 66.6%. A queda marginal de 70%-79% delega ao cirurgião experiente a decisão de continuar ou não o procedimento cirúrgico.

In order to improve success rates in surgery of renal hyperparathyroidism, we evaluated intraoperative PTH (IOPTH) measurement utility. METHOD: 86 patients underwent total parathyroidectomy with intramuscular presternal autotransplantation from 04/2000 to 10/2009 and were followed for 26.5 months on average (prospective cohort). Patients were divided in secondary (SHPT) and tertiary hyperparathyroidism (THPT). SHPT group was composed by patients under dialysis treatment, THPT group included renal grafted ones. IOPTH (Elecsys-PTH-Immunoassay/Roche) was measured at anesthesia induction (IOPTH-0') and 20 minutes (IOPTH-20') after parathyroidectomy. RESULTS: 80.2% (69/86) presented with 80% decrease or more in the IOPTH-20' and all were cured. In 11/86 patients (12.7%), a lower IOPTH-20' drop (70-79%) was observed, and 2 of them (18.1%) failed to cure. 6/86 (6.9%) patients presented IO-PTH-20' decrease of less than 70%: two were cured, in three a supernumerary/ectopic parathyroid was found and removed, and in one of these six patients, surgery was finished after 4-gland excision and the patient failure to cure. CONCLUSION: IOPTH-20' decrease of 80% or more compared to IOPTH-0' predicts cure in all renal patients throughout follow-up. A decay of less than 70% points to missed or hyperfunctioning supernumerary gland and is predictive of surgical failure in 66.6%. A marginal IOPTH drop of 70-79% leaves the decision whether or not surgery should be continued up to the experienced surgeon.

O presente artigo descreve o relato de dois pacientes com carcinoma de paratiroide que apresentavam valores intensamente elevados de cálcio sérico e de PTH, associado a doença óssea e presença de nódulo cervical palpável ao diagnóstico. Ambos foram submetidos à paratiroidectomia, sendo que um evoluiu com metástases pulmonares. Hipocalcemia importante foi observada após a paratiroidectomia em um paciente e somente após remoção cirúrgica das metástases pulmonares em outro. Ambos necessitaram de reposição endovenosa de cálcio, revelando, assim, o estado de fome óssea (FO). A presença da FO usualmente reflete rápida mineralização óssea após correção do hiperparatiroidismo; assim, quanto mais severa a doença óssea previa à cirurgia, maior será a FO observada no pós-operatório desses pacientes. Embora inicialmente considerada um evento indesejável, a FO representa a bem-sucedida remoção cirúrgica do tecido paratiroideano hipersecretor. Fome óssea deve ser esperada no pós-operatório do tratamento cirúrgico bem-sucedido do carcinoma de paratiroide.

We hereby report two patients with parathyroid carcinoma presenting extremely high calcium and PTH levels, severe bone disease, and palpable neck mass at diagnosis. They both underwent parathyroidectomy, and one of them evolved to lung metastasis. Important hypocalcemia was observed after surgery in both: after parathyroidectomy in one patient, and only after surgical removal of the metastasis in the other. Both required intravenous calcium replacement, thus revealing hungry bone syndrome (HBS). HBS usually reflects rapid mineralization after correction of hyperparathyroidism. The more severe the bone disease before surgery, the more prone the patient is to HBS after surgery. Despite being an unfavorable outcome, HBS state suggests that surgical removal of hypersecretory parathyroid tissue was accomplished. In this study, HBS was observed in both patients, who presented severe bone disease prior to surgery. HBS would be expected post-operatively in successful parathyroid carcinoma removal.

OBJETIVO: O isolamento adequado de ácidos nucleicos a partir de sangue periférico, lâmina corada de punção aspirativa por agulha fina, tecido fixado em formalina e emblocado em parafina e tecido fresco é fundamental para assegurar o sucesso de técnicas aplicadas em endocrinologia molecular, principalmente quando lidamos com amostras estocadas por longos períodos ou quando há impossibilidade de nova coleta de amostra de pacientes que perderam o seguimento. Neste trabalho, objetivamos otimizar as metodologias clássicas para a extração de DNA (salting-out) e RNA. MATERIAIS E MÉTODOS: Utilizamos proteinase K, choque térmico, dentre outras modificações, com o objetivo de aumentar a quantidade e a qualidade do material recuperado a partir das amostras descritas acima. RESULTADOS: Isolamos com sucesso DNA e RNA de tais amostras e o material obtido foi adequado para a realização de PCR, perfil de metilação, PCR em tempo real e sequenciamento de DNA. CONCLUSÃO: As técnicas aplicadas neste estudo para isolar ácidos nucleicos permitiram a realização posterior de análises moleculares consistentes e confiáveis. Arq Bras Endocrinol Metab. 2012;56(9):618-26

OBJECTIVE: Adequate isolation of nucleic acids from peripheral blood, fine-needle aspiration cells in stained slides, and fresh and formalin-fixed/paraffin-embedded tissues is crucial to ensure the success of molecular endocrinology techniques, especially when samples are stored for long periods, or when no other samples can be collected from patients who are lost to follow-up. Here, we evaluate several procedures to improve current methodologies for DNA (salting-out) and RNA isolation. MATERIALS AND METHODS: We used proteinase K treatment, heat shock, and other adaptations to increase the amount and quality of the material retrieved from the samples. RESULTS: We successfully isolated DNA and RNA from the samples described above, and this material was suitable for PCR, methylation profiling, real-time PCR and DNA sequencing. CONCLUSION: The techniques herein applied to isolate nucleic acids allowed further reliable molecular analyses. Arq Bras Endocrinol Metab. 2012;56(9):618-26

Mutações no gene da glicoquinase (GCK) são determinantes de uma forma de diabetes monogênico denominada de MODY2 (maturity-onset diabetes of the young, tipo 2). O padrão clínico dessa forma de distúrbio glicêmico é bastante estável, com hiperglicemia leve, geralmente não progressiva. Intervenções farmacológicas raramente são necessárias e complicações crônicas secundárias ao diabetes são infrequentes. Descrevemos o acompanhamento clínico de dois casos de MODY2 com duas mutações diferentes, uma no éxon 7, p.Glu265Lys (c.793 G>A) já descrita anteriormente, e outra inédita no éxon 2 p.Ser69Stop (c. 206C>G). A evolução clínica de ambos os casos demonstra uma semelhança no padrão metabólico dessa forma de diabetes ao longo dos anos. Arq Bras Endocrinol Metab. 2012;56(8):490-5

Mutations in the glucokinase gene (GCK) account for many cases of monogenic diabetes featuring maturity-onset diabetes of the young type 2 (MODY2). The clinical pattern of this form of hyperglycemia is rather stable, with a slight elevation in blood glucose, which is usually not progressive. Patients rarely require pharmacological interventions and microvascular complications related to diabetes are unusual. We describe the clinical follow-up of two cases of MODY2 with two different mutations in GCK gene, one in exon 7, p.Glu265Lys (c.793 G> A), which has been previously described, and a novel one, in exon 2, p.Ser69Stop (c. 206C> G). The clinical course of both cases shows similarity in metabolic control of this form of diabetes over the years. Arq Bras Endocrinol Metab. 2012;56(8):490-5

OBJETIVO: O objetivo deste estudo é avaliar se a medida perioperatória do hormônio da paratireoide (PTH) pode identificar os pacientes com maior risco de desenvolver sintomas de hipocalcemia. SUJEITOS E MÉTODOS: Foram estudados quarenta pacientes submetidos à tireodiectomia total. A medida do cálcio sérico e do PTH foi feita após a indução anestésica, uma hora (PTH1) e um dia após a cirurgia. Os pacientes foram avaliados quanto à presença de sintomas de hipocalcemia e tratados com suplementação de cálcio e vitamina D quando necessário. RESULTADOS: Dezesseis pacientes apresentaram sintomas de hipocalcemia. Os pacientes sintomáticos apresentaram PTH1 significantemente menor e queda no PTH significativamente maior. Usando o valor de 12,1 ng/L como corte, conseguimos distinguir pacientes com e sem sintomas de hipocalcemia com sensibilidade de 93,7% e especificidade de 91,6%. Utilizando como corte a queda de 73,5% no valor do PTH, temos sensibilidade de 91,6% e especificidade de 87,5%. CONCLUSÃO: O PTH1 e a queda no PTH são bons preditores de hipocalcemia no pós-operatório de tireoidectomia total

OBJECTIVE: The purpose of this study was to evaluate if the measurement of peri-operative parathyroid hormone (PTH) is able to identify patients with increased risk of developing symptoms of hypocalcemia. SUBJECTS AND METHODS: Forty patients who underwent total thyroidectomy were studied prospectively. Ionized serum calcium and PTH were measured after induction of anesthesia, one hour (PTH1) and one day after surgery (PTH24). Patients were evaluated for symptoms of hypocalcemia and treated with calcium and vitamin D supplementation as necessary. RESULTS: Symptomatic hypocalcemia developed in 16 patients. Symptomatic patients had significant lower PTH1 and greater drops in PTH levels. The selection of 12.1 ng/L as PTH1 level cutoff level divided patients with and without symptoms with 93.7% sensitivity and 91.6% specificity. The selection of 73.5% as the cutoff value for PTH decrease resulted in 91.6% sensitivity and 87.5% specificity. CONCLUSION: PTH1 levels and the drop in PTH levels are reliable predictors of developing symptomatic hypocalcemia after total thyroidectomy.

OBJETIVO: Avaliar a evolução dos marcadores de metabolismo ósseo (MMO) e da densidade mineral óssea (DMO) após cinco anos de uso de alendronato em mulheres osteoporóticas na pós-menopausa. SUJEITOS E MÉTODOS: 40 pacientes (pct) osteoporóticas, na pós-menopausa, em uso de alendronato (10 mg/dia) por pelo menos 5 anos (Grupo 1 − G1) tiveram o uso do bisfosfonato suspenso. O grupo 2 (G2): 25 mulheres na pós-menopausa, em uso de alendronato (10 mg/dia) há pelo menos 1 ano. Grupo 3 (G3): 23 pct osteoporóticas, controles ainda sem tratamento. G1 e G2 submeteram-se à avaliação da DMO por DXA (basal e após 12 meses de seguimento). Todas as pct colheram amostras basais de CTX e P1NP, e G1 e G2 submeteram-se a coletas trimestrais de CTX e P1NP durante 1 ano. Resultados foram analisados por ANOVA on ranks e Mann-Whitney. RESULTADOS: Níveis médios de DMO não variaram em G1 ou G2 durante o estudo; no entanto, 16 pct (45,7%) no G1 e 1 pct (5,2%) no G2 apresentaram redução clinicamente significativa de DMO (P < 0,001). Níveis basais de CTX e P1NP não diferiram entre G1 e G2, com ambos inferiores aos níveis de G3. Em G1, observou-se elevação significativa de CTX e P1NP após 3 meses. Os níveis de CTX e P1NP em G2 permaneceram estáveis durante todo o seguimento. CONCLUSÃO: Não parece haver supressão excessiva do metabolismo ósseo na prática clínica. A suspensão temporária do alendronato após seu uso prolongado pode não ser segura.

OBJECTIVE: To assess bone turnover markers (BTM) and bone mineral density (BMD) after discontinuation of alendronate treatment used for five or more years. SUBJECTS AND METHODS: 40 patients (pt) with post-menopausal osteoporosis treated with alendronate (10 mg/d) for at least five years (Group 1, G1) had their medication discontinued. Group 2 (G2): 25 pt treated with alendronate for at least one year. Group 3 (G3): 23 treatment-naïve osteoporotic pt. BMD was evaluated in G1 and G2 at baseline and after 12 months. Collagen type I cross-linked C-telopeptide (CTX) and procollagen type 1 N-terminal propeptide (P1NP) levels were measured in all pt at baseline, and in G1 and G2 every three months for 12 months. Data were analyzed using ANOVA on ranks and Mann-Whitney tests. RESULTS: Mean BMD values in G1 and G2 did not differ during follow-up. However, 16 pt (45.7%) in G1 and one (5.2%) in G2 lost BMD (P < 0.001). BTM at baseline was not different between G1 and G2, and both were lower than G3. A significant increase in BTM levels was detected in G1 pt after three months, but not in G2. CONCLUSION: Observed BMD loss and BTM rise after alendronate withdrawal imply that bone turnover was not over suppressed, and alendronate discontinuation may not be safe.

Canais iônicos auxiliam diferentes funções celulares, principalmente na transdução de sinal. Nas células endócrinas, esses canais têm funções importantes na secreção hormonal, sinalização do Ca2+, transporte transepitelial, regulação da motilidade, volume e conteúdo iônico celular e da acidificação do compartimento lisossomal (pH). Como esperado, as alterações nos canais iônicos podem causar distúrbios endocrinológicos, como pseudo-hipoaldosteronismo tipo 1, síndrome de Liddle, síndrome de Bartter, hipoglicemia hiperinsulinêmica da infância, diabetes melito neonatal, fibrose cística, doença de Dent, hipomagnesemia com hipocalcemia secundária, diabetes insípido nefrogênico e paralisia periódica tirotóxica hipocalêmica. Este artigo propõe uma breve revisão das canalopatias endócrinas conhecidas, com foco particular nos recentes progressos no conhecimento dos mecanismos fisiopatológicos adquirido a partir das alterações funcionais encontradas.

Ion channels serve diverse cellular functions, mainly in cell signal transduction. In endocrine cells, these channels play a major role in hormonal secretion, Ca2+-mediated cell signaling, transepithelial transport, cell motility and growth, volume regulation and cellular ionic content and acidification of lysosomal compartments. Ion channel dysfunction can cause endocrine disorders or endocrine-related manifestations, such as pseudohypoaldosteronism type 1, Liddle syndrome, Bartter syndrome, persistent hyperinsulinemic hypoglycemia of infancy, neonatal diabetes mellitus, cystic fibrosis, Dent's disease, hypomagnesemia with secondary hipocalcemia, nephrogenic diabetes insipidus and, the most recently genetically identified channelopathy, thyrotoxic hypokalemic periodic paralysis. This review briefly recapitulates the membrane action potential in endocrine cells and offers a short overview of known endocrine channelopathies with focus on recent progress regarding the pathophysiological mechanisms and functional genetic defects.

OBJETIVO: Estudar as formas carboxi-terminal (COOH) circulantes de paratormônio (PTH) em pacientes com hiperparatiroidismo devido à insuficiência renal crônica (IRC) terminal. MÉTODOS: Foi desenvolvido um ensaio imunométrico que reconhece formas intactas e COOH longas de PTH. Esse ensaio foi utilizado, em conjunto com um ensaio para molécula intacta de PTH, em amostras de 25 pacientes com hiperparatiroidismo devido à IRC. As amostras também foram submetidas à cromatografia de gel filtração em coluna de Superdex® 30 de 1,6 x 60 cm, e o conteúdo de PTH nos tubos de eluato foi medido, empregando-se os dois ensaios. RESULTADOS: Valores entre 39.000 e 232.300 ng/mL (média ± dp = 101,680 ± 45,330 ng/mL) foram obtidos usando-se o ensaio COOH (PTH 39-84 foi utilizado como padrão). Com o ensaio para PTH intacto, os valores distribuíram-se entre 318 e 3,307 ng/mL (1,769 ± 693 ng/mL) com correlação entre ambos de 0,462 (p = 0,02). O perfil cromatográfico obtido com o ensaio COOH mostrou predomínio de formas com PM entre 8.500 e 4.500 daltons. Os perfis cromatográficos dos 25 pacientes foram bastante semelhantes. CONCLUSÕES: Em pacientes com hiperparatiroidismo devido à IRC, os níveis circulantes de PTH contêm um espectro de formas moleculares que incluem formas carboxi-terminais, com PM entre 8.500 e 4.500 daltons. Essas formas não são reconhecidas pelos ensaios de rotina utilizados para a medida de PTH intacto. A correlação entre esses achados e os aspectos clínicos da doença óssea em pacientes com IRC necessita de maiores estudos.

OBJECTIVE: To study carboxyl-terminal (COOH) parathyroid hormone (PTH) circulating forms in patients with hyperparathyroidism due to end stage renal disease (ESRD). METHODS: An immunometric assay that recognizes both intact and COOH PTH forms was developed. The assay, in conjunction with an intact assay, was used to measure PTH in serum samples obtained from 25 patients with hyperparathyroidism due to ESRD. Samples were also submitted to gel filtration chromatography in a Superdex® 30 1.6 x 60 cm column, and the PTH content in the elution tubes, measured using both assays. RESULTS: Values from 39.000 to 232.300 ng/mL (mean ± sd = 101.680 ± 45.330 ng/mL) were found using the COOH assay (PTH 39-84 was used as standard). Values obtained by the intact PTH assay ranged from 318 to 3.307 ng/mL (1.769 ± 693 ng/mL) with a correlation between assays of 0.462 (p = 0.02). The elution profile obtained using the COOH assay showed a preponderance of forms with MW ranging from 8.500 to 4.500 daltons. The profiles obtained from the 25 patients were very similar. CONCLUSIONS: In patients with hyperparathyroidism due to ESRD circulating PTH levels contain a broad range of molecular forms including COOH with MW ranging from 8.500 to 4.500 daltons. These forms are not recognized by the standard intact PTH assays. The correlation of these findings to the clinical aspects of bone disease in ESRD patients remains to be studied.

A forma hereditária do carcinoma medular da tiróide pode ocorrer de modo isolado, o carcinoma medular da tiróide familiar (FMTC), ou como parte das neoplasias endócrinas múltiplas tipo 2A (MEN2A) e 2B (MEN2B). MEN2B é uma síndrome rara e seu fenótipo é usualmente, mas nem sempre, notado pelo médico. Na infância, nenhuma das características de MEN2B estão presentes, exceto pela disfunção gastrintestinal precoce, causada pelos neuromas intestinais. Quando disponível, a análise genética confirma o diagnóstico e orienta a avaliação pré-operatória e extensão da cirurgia. Neste artigo, apresentamos quatro casos de MEN2B, nos quais o diagnóstico tardio teve impacto significativo na evolução clínica e, potencialmente, na mortalidade em geral. APRESENTAÇÃO DOS CASOS: Apresentamos quatro casos, dois homens e duas mulheres, com diferenças em seus fenotipos e com diagnóstico tardio. O primeiro caso tem história de obstrução gastrintestinal importante em que foi necessária cirurgia dois dias após o nascimento. O segundo paciente apresentava nódulos na mucosa oral e constipação desde a infância. O terceiro referia história de constipação desde o nascimento até 5 meses de idade. O quarto tinha história de constipação intestinal desde a infância. DISCUSSÃO: Novos conceitos emergiram desde que o oncogene RET foi identificado, em 1993, como o gene responsável pelo carcinoma medular da tiróide hereditário. A maioria dos indivíduos apresenta a mutação M918T no éxon 16 do RET, enquanto poucos casos apresentam a mutação A883F ou a associação de V804M com E805K, Y806C ou S904C. O consenso recomenda a tiroidectomia total com dissecção dos linfonodos no compartimento central até os 6 meses após o nascimento. O diagnóstico rápido e preciso é essencial para o atingir os objetivos. CONCLUSÃO: O diagnóstico precoce de MEN2B é muito importante para propiciar a investigação apropriada de doenças associadas e para permitir aconselhamento e rastreamento dos parentes para uma mutação do RET. Pacientes com MEN2B, que apresentam frequentemente achados típicos ao exame físico, podem não ser reconhecidos e seguidos como casos esporádicos. Por causa disso, todos os casos de neoplasia endócrina múltipla devem ser avaliados pelo teste genético para mutações do RET.

BACKGROUND: The hereditary form of medullary thyroid carcinoma may occur isolated as a familial medullary thyroid carcinoma (FMTC) or as part of Multiple Endocrine Neoplasia 2A (MEN2A) and 2B (MEN2B). MEN2B is a rare syndrome, its phenotype may usually, but not always, be noted by the physician. In the infant none of the MEN2B characteristics are present, except by early gastrointestinal dysfunction caused by intestinal neuromas. When available, genetic analysis confirms the diagnosis and guides pre-operative evaluation and extent of surgery. Here we report four cases of MEN2B in which the late diagnosis had a significant impact in clinical evolution and, potentially, in overall survival. CASE REPORT: We report four cases, 2 men and 2 women, with differences in their phenotypes and with a late diagnosis. The first case has a history of severe gastrointestinal obstruction requiring a surgery intervention two days after his birth. The second told had nodules in the oral mucosa and constipation since childhood. The third case referred a history of constipation from birth until 5 months of life. The fourth has had a history of chronic constipation since childhood. DISCUSSION: New concepts have emerged since the RET oncogene was identified in 1993 as the responsible gene for hereditary medullary thyroid carcinoma. The majority of MEN2B individuals have M918T mutation in the exon 16 of RET, with a few cases having a mutation A883F or the association of V804M with E805K, Y806C or S904C mutations. The consensus classifies the RET mutation in codon 918 as of highest risk and recommends total thyroidectomy and central lymph node dissection until 6 months after birth. A fast and precise diagnosis is essential to reach these goals. The identification of early manifestations such as intestinal ganglioneuromatosis and oral mucosal neuromas should prompt the physician to initiate an investigation for multiple endocrine neoplasia type 2B. CONCLUSION: The diagnosis of MEN2B is very important to allow appropriate investigation of associated diseases and to allow counseling and appropriate screening of relatives for a RET mutation. Even patients with MEN2B, which often have typical physical features, may not be properly recognized and be followed as a sporadic case. Based on this, all suspicious cases of multiple endocrine neoplasia should undergo a molecular genetic test.