RESUMO
BACKGROUND: No randomised controlled trial has ever been done in patients with metastatic phaeochromocytomas and paragangliomas. Preclinical and first clinical evidence suggested beneficial effects of sunitinib. We aimed to evaluate the safety and efficacy of sunitinib in patients with metastatic phaeochromocytomas and paragangliomas. METHODS: FIRSTMAPPP is a multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial done at 14 academic centres across four European countries. Eligible participants were adults (aged ≥18 years) with sporadic or inherited progressive metastatic phaeochromocytomas and paragangliomas. Patients were randomly assigned (1:1) to receive either oral sunitinib (37·5 mg per day) or placebo. Randomisation was stratified according to SDHB status (mutation present vs wild type) and number of previous systemic therapies (0 vs ≥1). Primary endpoint was the rate of progression-free survival at 12 months according to real-time central review (Response Evaluation Criteria in Solid Tumours version 1.1). On the basis of a two-step Simon model, we aimed for the accrual of 78 patients, assuming a 20% improvement of the 12-month progression-free survival rate from 20% to 40%, to conclude that sunitinib is effective. Crossover from the placebo group was allowed. This trial is registered with ClinicalTrials.gov, number NCT01371201, and is closed for enrolment. FINDINGS: From Dec 1, 2011, to Jan 31, 2019, a total of 78 patients with progressive metastatic phaeochromocytomas and paragangliomas were enrolled (39 patients per group). 25 (32%) of 78 patients had germline SDHx variants and 54 (69%) had used previous therapies. The primary endpoint was met, with a 12-month progression-free survival in 14 of 39 patients (36% [90% CI 23-50]) in the sunitinib group. In the placebo group, the 12-month progression-free survival in seven of 39 patients was 19% (90% CI 11-31), validating the hypotheses of our study design. The most frequent grade 3 or 4 adverse events were asthenia (seven [18%] of 39 and one [3%] of 39), hypertension (five [13%] and four [10%]), and back or bone pain (one [3%] and three [8%]) in the sunitinib and placebo groups, respectively. Three deaths occurred in the sunitinib group: these deaths were due to respiratory insufficiency, amyotrophic lateral sclerosis, and rectal bleeding. Only the latter event was considered drug related. Two deaths occurred in the placebo group due to aspiration pneumonia and septic shock. INTERPRETATION: This first randomised trial supports the use of sunitinib as the medical option with the highest level of evidence for anti-tumour efficacy in progressive metastatic phaeochromocytomas and paragangliomas. FUNDING: French Ministry of Health, through the National Institute for Cancer, German Ministry of Education and Research, and the German Research Foundation within the CRC/Transregio 205/2, EU Seventh Framework Programme, and a private donator grant.
Assuntos
Neoplasias das Glândulas Suprarrenais , Hipertensão , Feocromocitoma , Adulto , Humanos , Adolescente , Sunitinibe/uso terapêutico , Feocromocitoma/tratamento farmacológico , Feocromocitoma/etiologia , Intervalo Livre de Progressão , Hipertensão/etiologia , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Neoplasias das Glândulas Suprarrenais/etiologia , Método Duplo-Cego , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND: Animal studies have demonstrated that fetal exposure to high maternal cholesterol levels during pregnancy predisposes to aortic atheroma in the offspring. In humans, little is known about the consequences of this exposure on the development of atherosclerotic cardiovascular disease later in life. We wanted to assess whether maternal/paternal inheritance of familial hypercholesterolemia (FH) gene mutation could be associated with subclinical coronary atherosclerosis. METHODS: We retrospectively included 1350 patients, followed in the French registry of FH, with a documented genetic diagnosis. We selected 556 age- and sex-matched pair of patients based on the sex of the parents who transmitted the FH gene mutation, free of coronary cardiovascular event, and with a subclinical coronary atherosclerosis evaluation assessed using coronary artery calcium (CAC) score. We performed univariate and multivariate analysis to assess the individual effect of parental inheritance of the FH gene mutation on the CAC score. RESULTS: In the whole population, patients with maternal inheritance of FH gene mutation (n=639) less frequently had a family history of premature cardiovascular events (27.7% versus 45%, P<0.0001) and were 2 years older (46.9±16.8 versus 44.7±15.9 years old, P=0.02) than those with paternal inheritance (n=711). There was no difference in the prevalence of cardiovascular events between the two groups. In the matched subgroup, maternal inheritance was significantly associated with an increase in CAC score value by 86% (95% CI, 23%-170%; P=0.003), a 1.81-fold risk of having a CAC score ≥100 Agatston units (95% CI, 1.06-3.11; P=0.03), and a 2.72-fold risk of having a CAC score ≥400 Agatston units (95% CI, 1.39-5.51; P=0.004) when compared with paternal inheritance in multivariate analysis. CONCLUSIONS: Maternal inheritance of FH gene mutation was associated with more severe subclinical coronary atherosclerosis assessed by CAC score and may be considered as a potential cardiovascular risk factor.
Assuntos
Aterosclerose , Doença da Artéria Coronariana , Hiperlipoproteinemia Tipo II , Humanos , Adulto , Pessoa de Meia-Idade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Cálcio , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Hiperlipoproteinemia Tipo II/genética , Estudos Retrospectivos , Herança Materna , Aterosclerose/epidemiologia , Aterosclerose/genética , Aterosclerose/complicações , Mutação , Fatores de RiscoRESUMO
Importance: Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes. Objective: To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes. Design, Settings, and Participants: The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation. Interventions: Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations. Main Outcomes and Measures: The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval. Results: Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, -∞ to 10.5%; P=.19). Conclusion and Relevance: This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment. Trial Registration: clinicaltrials.gov Identifier: NCT01731431.
Assuntos
Diabetes Gestacional/tratamento farmacológico , Macrossomia Fetal/prevenção & controle , Glibureto/uso terapêutico , Hiperbilirrubinemia/prevenção & controle , Hipoglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Administração Oral , Adulto , Glicemia/análise , Diabetes Gestacional/sangue , Feminino , Macrossomia Fetal/etiologia , Glibureto/efeitos adversos , Humanos , Hiperbilirrubinemia/etiologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/etiologia , Hipoglicemiantes/efeitos adversos , Recém-Nascido , Doenças do Recém-Nascido/epidemiologia , Injeções Subcutâneas , Insulina/efeitos adversos , Gravidez , Resultado da GravidezRESUMO
Neuroendocrine carcinomas (NEC) are aggressive malignant diseases. Etoposide-based rechallenge (EBR) and the prognostic role of RB transcriptional corepressor 1 (RB1) status in second-line chemotherapy (2L) have not been studied. The objectives of this study were to report the results of 2L including EBR as well as prognostic factors in a national retrospective multicentre study. NEC patients treated with 2L and further, with tissue samples available, were included. RB1 status and morphological classification were reviewed centrally. Among the 121 NEC patients (40% female, median age 61 years) included, there were 73 small-cell NEC (60%), 34 large-cell NEC (28%) and 14 NEC (not otherwise specified, 12%). Primary sites were lung (39%), gastroenteropancreatic (36%), other (13%) and unknown (12%). Median Ki-67 index was 80%. Median progression-free survival (PFS) and overall survival (OS) under 2L were 2.1 and 6.2 months, respectively. No difference was observed between patients who received an 'adenocarcinoma-like' or a 'neuroendocrine-like' 2L or according to the RB1 status. Thoracic NEC primary was the only adverse prognostic factor for OS. EBR, administered to 31 patients, resulted in a 62% disease control rate with a median PFS and OS of 3.2 and 11.7 months, respectively. In the 94 patients with a relapse-free interval of ≥3 months after first-line platinum-etoposide chemotherapy, the median OS was 12 months in patients who received EBR as compared to 5.9 months in patients who did not (P = 0.043). EBR could be the best 2L option for patient with initial response to first-line platinum-etoposide lasting at least 3 months. RB1 status does not provide prognostic information in this setting.
Assuntos
Carcinoma Neuroendócrino , Etoposídeo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Etoposídeo/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Platina/uso terapêutico , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION AND AIM: Neuroendocrine carcinomas (NECs) are aggressive malignant diseases. Platinum-etoposide (PE) combination is the standard first-line treatment, whatever the primary location. The NEC score and also retinoblastoma protein (Rb) status have been suggested to be predictive/prognostic factors in NEC. The primary objective of our multicentric retrospective study was to evaluate the prognostic relevance of the NEC score and Rb status, assessed by immunohistochemistry in PE-treated patients with metastatic NEC. METHODS: Seven centres participated. The inclusion criteria were NEC, whatever the primary site, metastatic stage, first-line treatment with PE and tissue samples available. Rb status was determined centrally. RESULTS: We report multicentric data from 185 metastatic patients (37% women, median age 63). There were 108 small-cell NECs (SCNECs, 58.4%), 50 large-cell NECs (LCNECs, 27%) and 27 not otherwise specified NECs (nosNECs, 14.6%). The primary sites were the thorax (37%), gastroenteropancreatic sites (38%), unknown (15%) and other (9%). The mean Ki-67 index was 76% (range 20-100). Rb status was interpretable in 122 cases. Rb expression was lost in 74% of the cases: 84% of SCNEC vs. 60% and 63% of LCNEC and nosNEC, respectively (p = 0.016). Objective response was seen in 70% of SCNEC, 45% of LCNEC and 48% of nosNEC (p < 0.001) and in 62% of Rb-negative tumours vs. 46% of Rb-positive tumours (p = 0.3). There was no difference in median progression-free survival or overall survival (OS) as per Rb status. Age, NEC score and response to chemotherapy were the main factors associated with OS in our cohort. CONCLUSION: In our series, Rb status had no prognostic impact in PE-treated metastatic patients with NEC, whereas age, NEC score and response to chemotherapy were the main factors associated with OS.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/análise , Carcinoma Neuroendócrino/mortalidade , Etoposídeo/administração & dosagem , Proteínas de Ligação a Retinoblastoma/análise , Ubiquitina-Proteína Ligases/análise , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carboplatina/administração & dosagem , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Cisplatino/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Proteínas de Ligação a Retinoblastoma/metabolismo , Estudos Retrospectivos , Medição de Risco , Ubiquitina-Proteína Ligases/metabolismo , Adulto JovemRESUMO
CONTEXT: The behavior of locally advanced pheochromocytoma (LAP) remains unknown. OBJECTIVE: We characterized the population with LAP and recurrence-free survival (RFS). METHODS: This retrospective multicentric study was run within the ENDOCAN-COMETE network and French Group of Endocrine Tumors (GTE) from 2003 to 2018, including patients from 11 French referral centers with LAP as defined by capsular invasion, vascular invasion, adipose tissue invasion, and/or positive locoregional lymph nodes at diagnosis without evidence of distant metastasis. The main outcome measure was recurrence, defined as tumor reappearance, including local site and/or distant metastasis. The primary endpoint was RFS analysis; secondary endpoints were characterization, overall survival (OS), and prognostic factors of recurrence. RESULTS: Among 950 patients, 90 (9%) exhibited LAP criteria and 55 met inclusion criteria (median age, 53 years; 61% males; 14% with germline mutation; 84% with catecholamine excess). LAP was defined by 31 (56%) capsular invasions, 27 (49%) fat invasions, 6 (11%) positive lymph nodes, and 22 (40%) vascular invasions. After median follow-up of 54 months (range, 6-180), 12 patients (22%) had recurrences and 3 (5%) died of metastatic disease. Median RFS was 115 months (range, 6-168). Recurrences were local in 2 patients, distant in 2, and both local and distant in 8 patients. Median OS of patients was not reached. Size above 6.5 cm (P = 0.019) and Ki-67 > 2% (P = 0.028) were identified as independent significant prognostic factors in multivariate analysis. CONCLUSION: LAP represents 9% of pheochromocytoma's population and has a metastatic behavior. This study paves the way for future pathological TNM classification.
Assuntos
Neoplasias das Glândulas Suprarrenais/mortalidade , Recidiva Local de Neoplasia/mortalidade , Feocromocitoma/mortalidade , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Feocromocitoma/patologia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics. METHODS: In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology. RESULTS: Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies. CONCLUSIONS: The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.
Assuntos
Adenoma/genética , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Neoplasias Hepáticas/genética , Mutação , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adolescente , Adulto , Criança , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/patologia , Diagnóstico por Imagem/métodos , Saúde da Família , Feminino , França , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are characterized by a strong genetic component, with up to 40% of patients carrying a germline mutation in a PPGL susceptibility gene. International guidelines recommend that genetic screening be proposed to all patients with PPGL. OBJECTIVE: Our objective was to evaluate how a positive genetic test impacts the management and outcome of patients with SDHx or VHL-related PPGL. DESIGN: We performed a multicentric retrospective study involving 221 propositi carrying an SDHB, SDHD, SDHC, or VHL germline mutation. Patients were divided into two groups: genetic patients, who were informed of their genetic status within the year following the first PPGL diagnosis, and historic patients, who only benefited from the genetic test several years after initial PPGL diagnosis. RESULTS: Genetic patients had better follow-up than historic patients, with a greater number of examinations and a reduced number of patients lost to follow-up (9.6% vs 72%, respectively). During follow-up, smaller (18.7 vs 27.6 mm; P = 0.0128) new PPGLs and metastases as well as lower metastatic spread were observed in genetic patients. Of note, these differences were reversed in the historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival rate than historic patients (P = 0.0127). CONCLUSION: Altogether, our data suggest that early knowledge of genetic status had a positive impact on the management and clinical outcome of patients with a germline SDHx or VHL mutation.
Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Testes Genéticos , Neoplasias Primárias Múltiplas/diagnóstico , Paraganglioma/diagnóstico , Feocromocitoma/diagnóstico , Adolescente , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/mortalidade , Adulto , Assistência ao Convalescente/métodos , Assistência ao Convalescente/estatística & dados numéricos , Idoso , Criança , Feminino , Seguimentos , Mutação em Linhagem Germinativa , Humanos , Estimativa de Kaplan-Meier , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/mortalidade , Paraganglioma/genética , Paraganglioma/mortalidade , Feocromocitoma/genética , Feocromocitoma/mortalidade , Prognóstico , Estudos Retrospectivos , Succinato Desidrogenase/genética , Taxa de Sobrevida , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adulto JovemRESUMO
BACKGROUND: Malignant pheochromocytoma and paraganglioma (MPP) are characterized by prognostic heterogeneity. Our objective was to look for prognostic parameters of overall survival (OS) in MPP patients. PATIENTS AND METHODS: Retrospective multicenter study of MPP characterized by a neck-thoraco-abdomino-pelvic CT or MRI at the time of malignancy diagnosis in European centers between 1998 and 2010. RESULTS: One hundred sixty-nine patients from 18 European centers were included. Main characteristics of patients with MPP were: primary pheochromocytoma in 53% of patients; tumor- or hormone-related symptoms in 57% or 58% of cases; positive plasma or urine hormones in 81% of patients; identification of a mutation in SDHB in 42% of cases. Metastatic sites included bone (64%), lymph node (40%), lung (29%), and liver (26%); mean time between initial and malignancy diagnosis was 43 months (range, 0 to 614). Median follow-up was 68 months and median survival 6.7 years. Using univariate analysis, better survival was associated with head and neck paraganglioma, age <40 years, metanephrines less than fivefold the upper limits of the normal range, and low proliferative index. In multivariate analysis, hypersecretion [hazard ratio 3.02 (1.65 to 5.55); P = 0.0004] was identified as an independent significant prognostic factor of worst OS. CONCLUSIONS: Our results do not confirm SDHB mutations as a major prognostic parameter in MPP and suggest additional key molecular events involved in MPP tumor progression. Aside from SDHB mutation, the biology of aggressive MPP remains to be understood.
Assuntos
Neoplasias das Glândulas Suprarrenais/mortalidade , Paraganglioma/mortalidade , Feocromocitoma/mortalidade , Neoplasias das Glândulas Suprarrenais/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Paraganglioma/genética , Feocromocitoma/genética , Prognóstico , Estudos Retrospectivos , Succinato Desidrogenase/genéticaRESUMO
BACKGROUND: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. FINDINGS: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. INTERPRETATION: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. FUNDING: None.
Assuntos
Neoplasias das Glândulas Suprarrenais/mortalidade , Carcinoma Neuroendócrino/mortalidade , Neoplasia Endócrina Múltipla Tipo 2b/mortalidade , Feocromocitoma/mortalidade , Neoplasias da Glândula Tireoide/mortalidade , Tireoidectomia/mortalidade , Adolescente , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Agências Internacionais , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 2b/patologia , Neoplasia Endócrina Múltipla Tipo 2b/cirurgia , Feocromocitoma/patologia , Feocromocitoma/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Adulto JovemRESUMO
The pregnancy is a state of thyroid hyperstimulation, therefore of changes of thyroid hormone values. Results of thyroid hormone measurement have to be analysed in the context of gestation age. Hyperthyroidism, mostly represented by Graves' disease, requires a multidisciplinary management, owing to possible maternal, foetal and neonatal complications. Treatment with antithyroid drugs, is a compromise between the risk of uncontrolled maternal hyperthyroidism and the risk of iatrogenic foetal hypothyroidism. Evaluation of foetal thyroid function considers the titre of thyrotropin receptor antibodies in the mother's blood, the dose of antithyroid drugs to maintain euthyroidism in the mother, and the signs of foetal hyperthyroidism on ultrasound. Maternal hypothyroidism is associated with foetal and maternal morbidity. Untreated or inappropriately treated, it is associated with poorer performances of offspring in intelligence tests. Thyroid autoimmunity is associated with hypofertility, particularly with spontaneous abortion. Screening for thyroid dysfunction during pregnancy, although not systematic, should have broad indications.