Doege-Potter syndrome associated to metastatic solitary fibrous tumor

ABSTRACT Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal neoplasm with an estimated annual incidence of 0.35 per 100,000 individuals. Doege-Potter syndrome is a paraneoplastic syndrome related to solitary fibrous tumor clinically characterized by hypoglycemia, occurring in less than 5% of cases. Herein, we report a case of metastatic SFT associated with recurrent severe hypoglycemia. A 43-year-old male with a noncontributory medical history presented with a painless and progressive growing mass in the right thigh. The histological evaluation rendered the diagnosis of SFT, and tumor resection was performed. One year after the operation, on the oncological follow-up, he was admitted to the emergency unit, manifesting an early-morning seizure associated with a severe hypoglycemia. The laboratory findings of non-islet cell tumor hypoglycemia (NICTH) in the background of a relapsed metastatic solitary fibrous tumor were consistent with the diagnosis of Doege-Potter syndrome. Hepatic embolization associated with oral glucocorticoid was an efficient palliative treatment to control the hypoglycemic crisis and allow hospital discharge.

Less-than-subtotal parathyroidectomy as treatment for primary hyperparathyroidism in multiple endocrine neoplasiatype 1: a good option?

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is a genetic syndrome manifested initially as primary hyperparathyroidism (HPT/MEN 1). The treatment is classically surgical with total parathyroidectomy with autograft or subtotal parathyroidectomy. In order to maintain normal postoperative function, less than subtotal parathyroidectomy (LTSPTx) has been suggested as an alternative technique. Objective: Analyse critically LTSPTx as a treatment option for patients with HPT/MEN 1. Methods: A retrospective cohort study of patients submitted to LTSPTx from january 2011 to december 2018. Data from demographics, laboratory tests, 6 months postoperative clinical outcomes, intraoperative PTH values and localization studies were analized. Results: LTSPTx was performed non-intentionally in 13 patients and intentionally in 13 other cases; 17 females and 9 males. The mean age was 44 years, but in patients with identified mutation it was 37 years. Seventeen patients (65.4%) had normal parathyroid function, 5 (19.2%) had hypoparathyroidism, in all of them LTSPTx was performed non intentionally. Four patients (15.4%) had persistence, all submitted intentionally to LTSPTx. The mean intraoperative PTH drop was 85.5% (±10.4%), without difference intergroup. A patient with persistence had PTH intraoperative drop > 80%, which also occurred in another patient with postoperative hypoparathyroidism. No persistence was found in patients with concordant image exams, what happened in three cases with non-concordant studies. Conclusion: LTSPTx may be intentionally performed as treatment for HPT/MEN 1, however social aspects, technical expertise, image exams and patient expectations must be taken into account.

Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center

Most cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/ multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.

Transitory increase in creatinine levels after parathyroidectomy: evidence of another action of the parathyroid glands? / Alteração transitória da creatinina após paratireoidectomia: evidência de outra ação das glândulas paratireoides?

OBJECTIVE: Little information is available on glomerular function changes after surgical treatment of primary hyperparathyroidism. The acute effects of some head and neck operations on renal function were studied. MATERIAL AND MATHODS: Retrospective analysis of changes in creatinine levels and estimated glomerular filtration rate (eGFR) after surgery. Preoperative values were compared with values available until 72 hours after the operation. RESULTS: In tertiary hyperparathyroidism, mean preoperative and postoperative eGFR values were 57.7 mL/min and 40.8 mL/min (p < 0.0001), respectively. A similar decrease was observed after parathyroidectomy for primary hyperparathyroidism, from 85.4 mL/min to 64.3 mL/min (p < 0.0001). After major head and neck procedures, there was a slight increase in eGFR (from 94.3 mL/min to 105.4 mL/min, p = 0.002). CONCLUSION: Parathyroidectomy may be followed by a transient decrease in eGFR that is not often observed in other head and neck operations.

OBJETIVO: Há pouca informação sobre alterações da função glomerular após o tratamento cirúrgico do hiperparatireoidismo primário. O efeito agudo sobre a função renal foi estudado após algumas operações em cirurgia de cabeça e pescoço. MATERIAIS E MÉTODOS: Análise retrospectiva dos níveis de creatinina e da taxa de filtração glomerular estimada (eGFR). Os valores pré-operatórios foram comparados aos valores disponíveis até 72 horas após a operação. RESULTADOS: No hiperparatireoidismo terciário, os valores médios pré e pós-operatórios da eGFR foram 57,7 mL/min e 40,8 mL/min (p < 0,0001), respectivamente. O decréscimo após paratireoidectomia por hiperparatireoidismo primário foi de 85,4 mL/min para 64,3 mL/min (p < 0,0001). Após operações maiores de cabeça e pescoço, houve leve elevação da eGFR (de 94,3 mL/min para 105,4 mL/min, p = 0,002). CONCLUSÕES: A paratireoidectomia pode ser seguida de uma redução transitória na eGFR que não é frequentemente observada após outras operações em cabeça e pescoço.

Timectomia na abordagem cirúrgica do hiperparatireoidismo na neoplasia endócrina múltipla do tipo 1 / Thymectomy in the surgical approach to hyperparathyroidism in type 1 multiple endocrine neoplasia

Introdução: O hiperparatireoidismo (HPT) é comum na neoplasia endócrina múltipla do tipo I (NEM 1). O tratamento definitivo é cirúrgico. Objetivo: Analisar os resultados da timectomia no tratamento do HPT associado à NEM 1. Método: Estudo retrospectivo de 24 pacientes com NEM 1 submetidos a paratireoidectomia entre 1988 e 2003. Analisaram-se a ocorrência de recidivas e a necessidade de re-operações em pacientes com e sem a timectomia. Resultados: A média etária foi de 37,6 anos, com 12 homens e 12 mulheres. Vinte foram submetidos à primeira cirurgia já com o diagnóstico de NEM1 e quatro pacientes foram operados inicialmente sem esse diagnóstico no pré-operatório (dois em outros Serviços). Nos 20 casos com diagnóstico préoperatório, a calcemia média no pré-operatório que era de 11,5 mg/dL reduziu-se para 8,37 mg/dL nos primeiros dias após a cirurgia e medidas com 6 e 12 meses de pós-operatório; 9,2 e 9,4 mg/dL, respectivamente. Os 13 pacientes com exérese de 4 glândulas: 10 (76,9%) encontravam-se euparatireoideos; 1 paciente (7,7%) apresentou HPT recorrente (retirada de uma glândula intratímica após 10 anos e recidiva do enxerto após 14 anos); e 2 (15,4%) pacientes evoluíram com hipoparatireoidismo. Dos 20 pacientes com diagnóstico pré-operatório, em 17 foi realizada timectomia na primeira cirurgia. Nos 3 pacientes não submetidos a esse procedimento, um apresentou recidiva por glândula intratímica, outro evoluiu com tumor carcinoide tímico e o terceiro está euparatireoideo. Conclusão: O tratamento do HPT na NEM 1 é mais complexo. A realização de timectomia associou-se a melhores resultados no seguimento.

Introduction: Hyperparathyroidism (HPT) is common in type I Multiple Endocrine Neoplasia (MEN 1). Surgery is the definitive treatment. Objective: To analyze the results of thymectomy in the surgical treatment of MEN 1 HPT. Method: Retrospective study of 24 MEN 1 patients submitted to parathyroidectomy between 1988 and 2003. Recurrences and the need of re-operative intervention were evaluated according to the type of operation. Results: Mean age was 37.6 years. Twelve were men. Twenty patients were operated on with the preoperative diagnosis of MEN 1 and four, not (two of them at another facilities). In the 20 cases with preoperative diagnosis, mean preoperative calcemia was 11.5 mg/dL and it dropped to 8.37 mg/dL in the early moment. At six and 12 months means were 9.2 and 9.4 mg/dL, respectively. In 13 patients with four gland excision, 10 (76.9%) were normocalcemic; one patient (7.7%) recurred twice (an intratimic fifth parathyroid after 10 years and autograft recurrence after 14 years); and two (15.4%) presented hypoparathyroidism. Of 20 patients with MEN 1 preoperative diagnosis, thymectomy was performed at the first operation in 17. In the three cases without prophylatic thymectomy, one recurred in a fifht thymic parathyroid, one developed thymic carcinoid and one was normocalcemic. Conclusion: Treatment of HPT in MEN 1 is more complex. Concomitant thymectomy was associated with better results.

Alteração transitória da taxa de filtração glomerular após paratireoidectomia independe da funçao renal pré-operatória / Transient change of glomerular function rate after parathyroidectomy is not dependent on preoperative renal function

Introdução: Após paratireoidectomia por hiperparatireoidismo primário, alguns pacientes apresentam redução transitória da função renal. O mecanismo dessa alteração ainda é incerto. Objetivo: Analisar se a função renal pré-operatória está relacionada à alteração da taxa de filtração glomerular após paratireoidectomia. Casuística e Método: Em pacientes submetidos a tratamento cirúrgico por hiperparatireoidismo primário a taxa de filtração glomerular (eGFR) foi estimada a partir dos valores da creatinina antes e até 48 horas após a operação. As variações foram comparadas em doentes com doença renal pré-operatória severa/moderada, leve e função normal. Resultados: Em 52 casos havia valores passíveis de análise, sendo 43 mulheres. A média de idade foi 56,4 anos. A eGFR pré-operatória foi de 83 mL/min/1,73m2 e a média pós-operatória foi de 63 mL/min/1,73m2 (p<0,0001). Nos pacientes com Doença Renal Severa/Moderada a eGFR reduziu-se em 21,8%. A redução nos pacientes com Doença Renal Leve foi de 30,3% e nos casos com função renal pré-operatória normal houve decréscimo de 21,8%. (p=0,35) Não houve correlação significativa entre a função renal pré-operatória e queda da eGFR no pós-operatório (R2 =0,0038; p=0,66). Em 47 casos observou-se alguma redução da eGFR, que variou entre - 1 mL/min/1,73m2 a - 140 mL/min/1,73m2. Conclusão: Após paratireoidectomia há uma redução da eGFR. Não há relação do percentual de variação de acordo com a situação renal de base.

Introduction: After successful parathyroidectomy for primary hyperparathyroidism, some patients present a transient reduction of renal function. The mechanism for this change is uncertain. Objective: To evaluate if preoperative renal function correlates with the degree of estimated glomerular filtration rate (eGFR) change after parathyroidectomy. Patients and Method: In patients submitted to surgical treatment of primary hyperparathyroidism, the eGFR was determined from creatinine levels before and until 48 hours after the operation. Changes were compared according to a stratified renal function as follows: severe and moderate, mild and normal renal function. Results: In 52 cases there were available measures of creatinine to evaluate eGFR. Of these, 43 were women. Mean age was 56.4 years. The preoperative eGFR was 83 mL/min/1.73m2 and the postoperative mean was 63 mL/min/1.73m2 (p<0.0001). In patients with severe or moderate kidney disease, the EGFR reduction was of 21.8%. The reduction in patients with mild renal disease was of 30.3% and in patients with preoperative normal renal function a transient decrease of 21.8% was observed (p=0.35) There was not a significant correlation between preoperative renal function and the mean decrease of eGFR during postoperative period (R2 =0.0038; p=0.66). In 47 cases some reduction of eGFR was observed, ranging from - 140 mL/min/1.73m2 to -1 mL/min/1.73m2. Conclusion: After parathyroidectomy there is a significant reduction of eGFR. There is no correlation between the previous renal function and the relative change of renal function.

Isolated familial somatotropinoma: 11Q13-LOH and gene/protein expression analysis suggests a possible involvement of aip also in non-pituitary tumorigenesis

OBJECTIVE: Non-pituitary tumors have been reported in a subset of patients harboring germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. However, no detailed investigations of non-pituitary tumors of AIP-mutated patients have been reported so far. PATIENTS: We examined a MEN1- and p53-negative mother-daughter pair with acromegaly due to somatotropinoma. Subsequently, the mother developed a large virilizing adrenocortical carcinoma and a grade II B-cell non-Hodgkin's lymphoma. DESIGN: Mutational analysis was performed by automated sequencing. Loss-of-heterozygosity (LOH) analysis was carried out by sequencing and microsatellite analysis. AIP expression was assessed through quantitative PCR (qPCR) and immunohistochemistry. RESULTS: The functional inactivating mutation c.241C>T (R81X), which blocks the AIP protein from interacting with phosphodiesterase 4A (PDE4A), was identified in the heterozygous state in the leukocyte DNA of both patients. Analyzing the tumoral DNA revealed that the AIP wild-type allele was lost in the daughter's somatotropinoma and the mother's adrenocortical carcinoma. Both tumors displayed low AIP protein expression levels. Low AIP gene expression was confirmed by qPCR in the adrenocortical carcinoma. No evidence of LOH was observed in the DNA sample from the mother's B-cell lymphoma, and this tumor displayed normal AIP immunostaining. CONCLUSIONS: Our study presents the first molecular analysis of non-pituitary tumors in AIP-mutated patients. The finding of AIP inactivation in the adrenocortical tumor suggests that further investigation of the potential role of this recently identified tumor suppressor gene in non-pituitary tumors, mainly in those tumors in which the cAMP and the 11q13 locus are implicated, is likely to be worthwhile.

Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma: [revision]

Hypercalcitoninemia has frequently been reported as a marker for medullary thyroid carcinoma. Currently, calcitonin measurements are mostly useful in the evaluation of tumor size and progression, and as an index of biochemical improvement of medullary thyroid carcinomas. Although measurement of calcitonin is a highly sensitive method for the detection of medullary thyroid carcinoma, it presents a low specificity for this tumor. Several physiologic and pathologic conditions other than medullary thyroid carcinoma have been associated with increased levels of calcitonin. Several cases of thyroid nodules associated with increased values of calcitonin are not medullary thyroid carcinomas, but rather are related to other conditions, such as hypercalcemias, hypergastrinemias, neuroendocrine tumors, renal insufficiency, papillary and follicular thyroid carcinomas, and goiter. Furthermore, prolonged treatment with omeprazole (> 2-4 months), beta-blockers, glucocorticoids and potential secretagogues, have been associated with hypercalcitoninemia. An association between calcitonin levels and chronic auto-immune thyroiditis remains controversial. Patients with calcitonin levels >100 pg/mL have a high risk for medullary thyroid carcinoma (~90%-100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, < 5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary thyroid carcinoma. In multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventivethyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive calcitonin results within MEN2 families have led to incorrect indications of preventive total thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis...

Sporadic medullary thyroid carcinoma: clinical data from a university hospital

INTRODUCTION: Medullary thyroid carcinoma may occur in a sporadic (s-medullary thyroid carcinoma, 75 percent) or in a multiple endocrine neoplasia type 2 form (MEN2, 25 percent). These clinical forms differ in many ways, as s-medullary thyroid carcinoma cases are RET-negative in the germline and are typically diagnosed later than medullary thyroid carcinoma in MEN2 patients. In this study, a set of cases with s-medullary thyroid carcinoma are documented and explored. PURPOSE: To document the phenotypes observed in s-medullary thyroid carcinoma cases from a university group and to attempt to improve earlier diagnosis of s-medullary thyroid carcinoma. Some procedures for diagnostics are also recommended. METHOD: Patients (n=26) with apparent s-medullary thyroid carcinoma were studied. Their clinical data were reviewed and peripheral blood was collected and screened for RET germline mutations. RESULTS: The average age at diagnosis was 43.9 years (± 10.82 SD) and did not differ between males and females. Calcitonin levels were increased in all cases. Three patients presented values that were 100-fold greater than the normal upper limit. Most (61.54 percent) had values that were 20-fold below this limit. Carcinoembryonic antigen levels were high in 70.6 percent of cases. There was no significant association between age at diagnosis, basal calcitonin levels or time of disease onset with thyroid tumor size (0.6-15 cm). Routine thyroid cytology yielded disappointing diagnostic accuracy (46.7 percent) in this set of cases. After total thyroidectomy associated with extensive cervical lymph node resection, calcitonin values remained lower than 5 pg/mL for at least 12 months in eight of the cases (30.8 percent). Immunocyto- and histochemistry for calcitonin were positive in all analyzed cases. None of the 26 cases presented germline mutations in the classical hotspots of the RET proto-oncogene. CONCLUSION: Our cases were identified late. The basal ...

Screening of RET gene mutations in multiple endocrine neoplasia type-2 using Conformation Sensitive Gel Electrophoresis (CSGE)

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited tumor syndrome caused by RET proto-oncogene germline mutations (RET). Here we tested the Conformation Sensitive Gel Electrophoresis (CSGE) as a screening method for RET hot-spot mutations. Seven MEN2 families were studied by direct sequencing analysis, CSGE and Single Strand Conformational Polymorphism (SSCP). Using CSGE/SSCP, we were able to detect four out of five types of RET mutations verified by sequencing analysis: Cys620Arg, Cys634Arg, Cys634Tyr, and Met918Thr, furthermore a missense substitution at codon 648 (Val648Ile). RET polymorphisms 691 and 769 were also verified. Data obtained using CSGE/SSCP were fully concordant. We conclude that CSGE showed to be a sensitive, fast, low-cost, and simple procedure to detect RET mutations in codons which are reported as the most prevalent RET variants (~ 95 percent) in large MEN2 series. As to the Val804Met mutation, this method still needs to be optimized.

A neoplasia endócrina múltipla tipo 2 (NEM2) é uma síndrome tumoral herdada por mutações germinativas no proto-oncogene RET (RET). Analisamos a aplicação do método Eletroforese em Gel Sensível à Conformação (CSGE) no rastreamento de mutações hot spots do RET. Sete famílias com NEM2 foram rastreadas pelo seqüenciamento gênico, CSGE e análise do Polimorfismo Conformacional de Cadeia Simples (SSCP). Usando ambas as metodologias de rastreamento, identificamos quatro dos cinco tipos de mutações verificadas pelo seqüenciamento: Cys620Arg, Cys634Arg, Cys634Tyr e Met918Thr, além da variação gênica Val648Ile. Das análises englobando mutações hot spots do RET, 90,6 por cento concordaram com o seqüenciamento genético (incluindo a variação gênica Val648Ile). Polimorfismos nos códons 691 e 769 foram documentados. Os dados obtidos por CSGE/SSCP foram totalmente concordantes. Concluímos que o CSGE revelou ser metodologia sensível, rápida, de fácil execução e baixo custo no rastreamento de mutações nos códons associados à grande maioria (~ 95 por cento) dos pacientes com NEM2.

Decréscimo transitório da função renal no pós-operatório imediato de paratireoidectomia: uma observação clínica indicativa da ação hemodinâmica renal do hormônio da paratireóide? / Transitory decrease of renal function after parathyroidectomy: a clinical observation indicating the renal hemodynamic effect of parathyroid hormone?

Introdução: a hipocalcemia recebe grande atenção após paratireoidectomia no tratamento do hiperparatireoidismo (HPT). Há evidência de decréscimo da função renal após paratireoidectomia em transplantados renais. Essa alteração é pouco estudada após o tratamento do HPT primário. Objetivo: avaliar a variação da creatinina no pós-operatório de diferentes modalidades de operações em Cirurgia de Cabeça e Pescoço. Casuística e Método: estudo retrospectivo de 1997 a 2007 da variação da creatinina após operações em doentes com HPT primário, HPT após transplante renal bem sucedido, ressecção de tumores de cabeça e pescoço em transplantados renais, tireoidectomia e ressecção de neoplasias em cabeça e pescoço. Analisaram-se a creatinina pré-operatória e as medidas pós-operatórias próximas. Calculou-se a diferença percentual do valor pós-operatório em relação ao pré, pela diferença pós e pré, dividida pelo valor préoperatório. Resultados: Houve elevação da creatinina pósoperatória superior a 10% em 77 de 105 casos de HPT primário, em 32 de 38 doentes transplantados renais após paratireoidectomia, em um de sete transplantados renais operados por outros tumores, em 11 de 22 indivíduos submetidos à tireoidectomia total e em três casos de 18 portadores de câncer de mucosa ou pele de cabeça e pescoço. As médias de variação percentual foram de +30,8%, +39,5%, -2,7%, +18,7% e -6,4%, respectivamente, nos grupos citados. Não houve diferença significativa entre os transplantados renais com HPT, os tireoidectomizados e portadores de HPT primário. Houve diferença significativa entre os transplantados renais entre si (p<0,05, Kruskal-Wallis) e entre os portadores de HPT primário e os tratados por câncer de cabeça e pescoço (p<0,001, Kruskal-Wallis). Quando os tireoidectomizados foram estratificados de acordo com a ocorrência de hipocalcemia pósoperatória (possível hipoparatireoidismo), houve diferença significativa, com média de elevação da creatinina média 28,5% nos hipocalcêmicos e de 1,2% nos não hipocalcêmicos (p=0,02, Teste t não pareado). Conclusão: Em operações com redução aguda do nível de paratormônio há elevação do nível de creatinina também de modo agudo. Essa observação é compatível com estudos em animais que mostraram diminuição da função renal após paratireoidectomia em ratos.

Introduction: hypocalcemia is the major concern after parathyroid operations. Notwithstanding, there are some reports of decreased renal function after parathyroidectomy after renal transplantation. Little attention was given to creatinine levels after primary hyperparathyroidism operation. Objective: to evaluate the creatinine levels after the surgical treatment of different head and neck patients groups. Patients and methods: retrospective analysis of creatinine levels of patients operated on from 1997 to 2007 for primary hyperparathyroidism, hyperparathyroidism after successful renal transplantation, head and neck neoplasms in both renal transplant and non transplant patients and thyroid disorders. Creatinine values before and close after surgical treatment were evaluated. Percent creatinine variation was calculated by subtracting preoperative from postoperative value and dividing this result by the preoperative level. Results: More than 10% creatinine elevation occurred in 77 of 105 patients with primary hyperparathyroidism, in 32 of 38 cases of parathyroidectomy after renal transplantation, in 1 of 7 renal transplant patients with other head and tumors, in 11 of 22 individuals after thyroidectomy and in 3 of 18 submitted to major head and neck surgery for cancer. Mean percent variations of creatinine were +30.8%, +39.5%, -2.7%, +18.7% e - 6.4%, respectively for those groups. No significant differences were observed between hyperparathyroidism transplant renal cases, thyroid patients and primary hyperparathyroidism individuals. Significant difference occurred between transplant patients with and without hyperparathyroidism (p<0.05, Kruskal-Wallis), and among those with primary hyperparathyroidism and head and neck neoplasms (p<0.001, Kruskal-Wallis). When thyroidectomy patients were stratified according to the postoperative hypocalcemia and presumed hypoparathyroidism, a significant difference was observed. Mean creatinine increase was of 28.5% for those with hypocalcemia and only 1.2% on the other group (p=0.02, non paired t test). Conclusion: Acute elevation of creatinine was observed in operations with acute reduction of parathyroid hormone. This clinical observation is in accordance with previous animals studies showing renal function reduction after parathyroidectomy.

The impact of clinical and genetic screenings on the management of the multiple endocrine neoplasia type 1

PURPOSE: To perform clinical and genetic screening for multiple endocrine neoplasia type 1 (MEN1) in patients at the Academic Hospital of the University of São Paulo School of Medicine, and to analyze its impact on clinical management of patients with MEN1. METHODS: The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III). RESULTS: In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8 percent of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4 percent of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy. CONCLUSION: Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome.

OBJETIVOS: Realizar rastreamentos clínico e gênico para Neoplasia Endócrina Múltipla tipo 1 (NEM1) e analisar seu impacto no seguimento clínico desses pacientes no Hospital das Clínicas, SP. MÉTODOS: O diagnóstico clínico de NEM1 foi realizado de acordo com o Consenso sobre neoplasias endócrinas múltiplas. A análise genética para identificação de mutações foi realizada por sequenciamento automático de todas as regiões codificadoras e fronteiras exon/intron do gene MEN1. Os casos afetados foram sub-divididos em 3 grupos e analisados separadamente: casos-índices (grupo I), familiares diagnosticados clinicamente (grupo II) e genicamente (grupo III). RESULTADOS: Um total de 154 casos participou desse estudo, sendo 52 diagnosticados com NEM1: 13 do grupo I, 28 do grupo II e 11 do grupo III. A idade média ao diagnóstico no grupo III (27 anos) foi significativamente menor que a dos grupos I (39,5 anos; p = 0,03) e II (42,4 anos; p = 0,01). A maioria dos pacientes dos grupos I e II apresentou 2 ou 3 tumores, enquanto que 81,8 por cento dos casos do grupo III apresentavam 1 ou nenhum tumor relacionado à NEM1. Além disto, 45,4 por cento dos casos do grupo III eram assintomáticos, não sendo observados nenhuma metástase ou óbito. Os demais 102 familiares sob-risco estudados não herdaram mutação MEN1 e foram excluídos do rastreamento clínico. Um caso de fenocópia NEM1 foi também localizado. DISCUSSÃO: Nossos dados demonstraram importantes benefícios no seguimento dos pacientes NEM1, obtidos pela implementação dos rastreamentos clínico e gênico para essa doença.

Impact of RET proto-oncogene analysis on the clinical management of multiple endocrine neoplasia type 2

A neoplasia endócrina múltipla tipo 2 (NEM2) é caracterizada pela ocorrência do carcinoma medular de tireóide (CMT), hiperparatiroidismo primário (HPT) e feocromocitoma (FEO).1-12 Desde 1993, quando as primeiras mutações do tipo missense no proto-oncogene RET (RET), associadas a NEM2 foram identificadas, 46 diferentes mutações causadoras de doenças foram descritas.13-17 Como há uma forte correlação genótipo-fenótipo na NEM2, a detecção de mutações no RET adquiriu grande impacto no tratamento precoce do CMT e NEM2. A NEM2 persiste como uma doença subdiagnosticada e/ou tardiamente diagnosticada em várias áreas geográficas do globo. A análise de mutações do RET deve ser realizada em todas os casos de NEM2 e atualmente, a tireoidectomia total profilática é indicada para todos os indivíduos portadores de mutações no RET.1 Para a grande maioria dos portadores de mutações gaméticas ativadoras no RET este procedimento cirúrgico é indicado nos primeiros anos de vida, promovendo melhora na qualidade de vida, aumento da sobrevida ou mesmo levando à cura definitiva.1 Discutimos nesta revisão, o impacto da análise do proto-oncogene RET na conduta clínica da neoplasia endócrina múltipla tipo 2. Além disso, o diagnóstico molecular do RET fornece à clínicos e cirurgiões a mais valiosa das informações, permitindo indicação de tireoidectomia total profilática.

Rastreamento gênico da neoplasia endócrina múltipla tipo 2: experiência da Unidade de Endocrinologia Genética da USP / Genetic screening of multiple endocrine neoplasia type 2: experience of the USP Endocrine Genetics Unit

A neoplasia endócrina múltipla tipo 2 (NEM-2) é uma síndrome tumoral hereditária que compreende: carcinoma medular de tireóide, hiperparatiroidismo primário, feocromocitoma e outras doenças não-endócrinas. Desde a identificação das primeiras mutações missense no RET associadas ao NEM-2, a detecção de mutações no RET adquiriu grande impacto no tratamento clínico da NEM-2, tais como o pronto diagnóstico e tratamento do CMT. Atualmente a tireoidectomia total possibilita real cura dos casos de CMT nos quais os diagnósticos moleculares foram efetuados precocemente. Depois de identificadas as mutações no RET, os demais familiares devem ser rastreados para esta mutação utilizando-se métodos como DGGE, SSCP, enzima de restrição, seqüenciamento e mini-seqüenciamento gênico. Apresentamos uma breve revisão da nossa experiência com seqüenciamento gênico direto do RET e DGGE. Em 50 pacientes com NEM-2 analisados por ambas as técnicas, não encontramos falsos resultados, sugerindo que o DGGE é uma metodologia de rastreamento adequada para mutações no proto-oncogene RET.

Sistema nervoso autônomo intracardíaco em caso humano fatal de doença de Chagas aguda / Intracardial autonomous nervous system in a fatal case of acute Chagas' disease

Procedeu-se à análise do sistema nervoso autônomo intracardíaco (SNAIC) em 150 cortes histológicos obtidos a partir de fragmentos atriais de homem de 74 anos, falecido de insuficiência cardíaca consecutiva à doença de Chagas aguda (DCA), provavelmente adquirida por via digestiva. Em 10 lâminas havia discretos infiltrados de mononucleares em torno de gânglios e/ou filetes nervosos sem alteraçöes morfológicas significativas do neurônios; em um preparado constatou-se ganglionite e periganglionite, de moderada intensidade, associadas a alteraçöes neuronais. Epicardite focal, em geral discreta, foi observada em todas as lâminas. Os achados sugerem que a inflamaçäo dos gânglios e fibras do SNAIC na DCA ocorre, pelo menos em parte, da propagaçäo da epicardite adjacente e, que mesmo nos casos fatais da tripanosomose cruzi as lesöes morfológicas do SNAIC podem ser discretas