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.

Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group.

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.

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.

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.

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.

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