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Doença de Hashimoto , Humanos , Medicina Interna , Estudos Prospectivos , Projetos de PesquisaRESUMO
In the setting of differentiated thyroid cancer (DTC) management, < 0.1 mU/L TSH suppression has been proven to be beneficial for patients likely to have microscopic or macroscopic disease, as TSH has a direct trophic effect on thyroid cancer cells. However, the optimal degree of TSH reduction remains unclear for other categories of DTC patients with better prognosis. Excessive thyroid hormone replacement can lead to atrial fibrillation and osteoporosis. Therefore, levothyroxine dose should be carefully adjusted with respect to underlying individual health status, dynamically reassessed risk of relapse and medical monitoring. Future guidelines should give priority to a tailored approach to TSH suppression therapy in DTC patients.
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Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Tireotropina/antagonistas & inibidores , Tiroxina/uso terapêutico , Idoso , Fibrilação Atrial/induzido quimicamente , Doenças Ósseas/induzido quimicamente , Doenças Cardiovasculares/induzido quimicamente , Feminino , Humanos , Hipertireoidismo/complicações , Pessoa de Meia-Idade , Osteoporose/induzido quimicamente , Prognóstico , Qualidade de Vida , Medição de Risco , Tiroxina/administração & dosagem , Tiroxina/efeitos adversosRESUMO
Hyperthyroidism is mainly due to autoimmune thyroid disorders or toxic goiter, and very rarely to the presence of thyrotropin (TSH)-secreting pituitary adenomas (TSHomas). These tumors are characterized by high levels of circulating free thyroid hormones (FT4 and FT3) in the presence of nonsuppressed serum TSH concentrations. Failure to correctly diagnose TSHomas may result in inappropriate thyroid ablation, which results in a significant increase of pituitary tumor mass. The diagnosis is mainly achieved by measuring TSH after T3 suppression and TRH stimulation tests. These dynamic tests, together with pituitary imaging and genetic testing are useful in distinguishing TSHomas from the syndromes of resistance to thyroid hormone action. The treatment of choice is surgery. In cases of surgical failure, somatostatin analogs have been found to be effective in normalizing TSH secretion in more than 90% of patients.
Assuntos
Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/cirurgia , Cirurgia Assistida por Computador/normas , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/normas , Ultrassonografia de Intervenção/normas , Adenocarcinoma Folicular/química , Adenocarcinoma Folicular/secundário , Biomarcadores Tumorais/análise , Biópsia por Agulha Fina/métodos , Contraindicações , Diagnóstico Diferencial , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Ablação por Ultrassom Focalizado de Alta Intensidade/normas , Humanos , Metástase Linfática , Prontuários Médicos/normas , Esvaziamento Cervical/métodos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Risco , Cirurgia Assistida por Computador/métodos , Tireoglobulina/análise , Doenças da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/métodos , Ultrassonografia de Intervenção/métodosRESUMO
INTRODUCTION: Gitelman syndrome (GS) is a tubulopathy caused by SLC12A3 gene mutations, which lead to hypokalaemic alkalosis, secondary hyperaldosteronism, hypomagnesaemia and hypocalciuria. AIM: The aim of this study was to assess the prevalence of SLC12A3 gene mutations in adult hypokalaemic patients; to compare the phenotype of homozygous, heterozygous and non-mutated patients; and to determine the efficiency of treatment. METHODS: Clinical, biological and genetic data were recorded in 26 patients. RESULTS: Screening for the SLC12A3 gene detected two mutations in 15 patients (six homozygous and nine compound heterozygous), one mutation in six patients and no mutation in five patients. There was no statistical difference in clinical symptoms at diagnosis between the three groups. Systolic blood pressure tended to be lower in patients with two mutations (P=0.16). Hypertension was unexpectedly detected in four patients. Five patients with two mutated alleles and two with heterozygosity had severe manifestations of GS. Significant differences were observed between the three groups in blood potassium, chloride, magnesium, supine aldosterone, 24 h urine chloride and magnesium levels and in modification of the diet in renal disease. Mean blood potassium levels increased from 2.8 ± 0.3, 3.5 ± 0.5 and 3.2 ± 0.3 before treatment to 3.2 ± 0.5, 3.7 ± 0.6 and 3.7 ± 0.3 mmol/l with treatment in groups with two (P=0.003), one and no mutated alleles respectively. CONCLUSION: In adult patients referred for renal hypokalaemia, we confirmed the presence of mutations of the SLC12A3 gene in 80% of cases. GS was more severe in patients with two mutated alleles than in those with one or no mutated alleles. High blood pressure should not rule out the diagnosis, especially in older patients.
Assuntos
Síndrome de Gitelman/genética , Síndrome de Gitelman/metabolismo , Hipopotassemia/etiologia , Nefropatias/complicações , Receptores de Droga/genética , Simportadores/genética , Adolescente , Adulto , Idade de Início , Idoso , Aldosterona/sangue , Pressão Sanguínea/fisiologia , Peso Corporal/fisiologia , Pré-Escolar , Canais de Cloreto/genética , Doença Crônica , Análise Mutacional de DNA , Complicações do Diabetes/genética , Complicações do Diabetes/metabolismo , Feminino , Seguimentos , França , Genótipo , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Mutação/fisiologia , Fenótipo , Potássio/sangue , Membro 3 da Família 12 de Carreador de Soluto , Adulto JovemRESUMO
The present document is a follow-up of the clinical practice guidelines of the French Society of Endocrinology, which were established for the use of its members and made available to scientific communities and physicians. Based on a critical analysis of data from the literature, consensuses and guidelines that have already been published internationally, it constitutes an update of the report on the diagnostic management of thyroid nodules that was proposed in France, in 1995, under the auspices of the French National Agency for Medical Evaluation (l'Agence nationale d'évaluation médicale). The current guidelines were deliberated beforehand by a number of physicians that are recognised for their expertise on the subject, coming from the specialities of endocrinology (the French Thyroid Research Group) and surgery (the French Association for Endocrine Surgery), as well as representatives from the fields of biology, ultrasonography, cytology and nuclear medicine. The guidelines were presented and submitted for the opinion of the members of the Society at its annual conference, which was held in Nice from 7-10 October 2009. The amended document was posted on the website of the Society and benefited from additional remarks of its members. The final version that is presented here was not subjected to methodological validation. It does not claim to be universal in its scope and will need to be revised in concert with progress made in technical and developmental concepts. It constitutes a document that the Society deems useful for distribution concerning the management of thyroid nodules, which is current, efficient and cost effective.
Assuntos
Guias de Prática Clínica como Assunto , Nódulo da Glândula Tireoide/terapia , Biópsia , Criança , Diagnóstico Diferencial , Diagnóstico por Imagem , Endocrinologia , Feminino , França , Doença de Graves/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Complicações na Gravidez , Fatores de Risco , Sociedades Médicas , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/epidemiologia , UltrassonografiaRESUMO
Good practice guide for cervical ultrasound scan and echo-guided techniques in treating differentiated thyroid cancer of vesicular origin. American, European and French Recommendations for the treatment of differentiated vesicular thyroid cancer were recently published. Cervical ultrasound scanning is now considered a key examination in the follow-up of these cancers. This examination is noninvasive, easy to perform and to obtain, is not costly, but remains operator-dependent. To date, there are no recommendations published that assemble all the technical aspects, results, indications and the limits of this examination in the initial medical report and the follow-up of these cancers. In order to standardise the procedure and validate the quality of the examination, a workgroup made up of a panel of experts particularly involved in carrying out ultrasound scans was set up. The aim was to draw up a good practice guide for performing cervical ultrasound scans and echo-guided techniques in treating patients with differentiated thyroid cancer of vesicular origin. The main objectives are to: (a) standardise the procedure and reports, (b) define the criteria for establishing whether lesions identified during a cervical ultrasound scan are malignant or benign, (c) standardise the indications for carrying out cytological tests and an in situ assay of markers, (d) help doctors to select the patients who ought to receive a cervical ultrasound scan and or cytological tests, (e) discuss how frequently the examinations should be carried out depending on the risk of recurrence.
Assuntos
Adenoma/diagnóstico por imagem , Carcinoma/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Ultrassonografia/normas , Adenoma/mortalidade , Adenoma/cirurgia , Carcinoma/mortalidade , Carcinoma/cirurgia , Feminino , Humanos , Radioisótopos do Iodo , Masculino , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Ultrassonografia/métodosRESUMO
BACKGROUND: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). OBJECTIVE, DESIGN, AND SETTING: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. PATIENTS AND INTERVENTION: Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. MAIN OUTCOME MEASURES: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. RESULTS: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. CONCLUSION: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.
Assuntos
Bócio Nodular/terapia , Tireotropina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anatomia Transversal , Terapia Combinada , Preparações de Ação Retardada , Método Duplo-Cego , Feminino , Bócio Nodular/tratamento farmacológico , Bócio Nodular/radioterapia , Humanos , Radioisótopos do Iodo/farmacocinética , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Proteínas Recombinantes/uso terapêutico , Testes de Função Tireóidea , Hormônios Tireóideos/sangue , Tireoidectomia , Tireotropina/administração & dosagem , Tireotropina/efeitos adversos , Traqueia/anatomia & histologiaRESUMO
BACKGROUND: In hereditary medullary thyroid carcinoma (HMTC), prophylactic surgery is the only curative option, which should be properly defined both in time and extent. OBJECTIVES: To identify and characterize prognostic factors associated with disease-free survival (DFS) in children from HMTC families. DESIGN: We conducted a retrospective analysis of a multi-center cohort of 170 patients below age 21 at surgery. Demographic, clinical, genetic, biological data [basal and pentagastrine-stimulated calcitonin (CT and CT/Pg, respectively)], and tumor node metastasis (TNM) status were collected. DFS was assessed based on basal CT levels. Kaplan-Meier curves, Cox regression, and logistic regression models were used to determine factors associated with DFS and TNM staging. RESULTS: No patients with a preoperative basal CT <31 ng/ml had persistent or recurrent disease. Medullary thyroid carcinoma defined by a diameter ≥10 mm [hazard ratio (HR): 6.0; 95% confidence interval (95% CI): 1.8-19.8] and N1 status (HR: 20.8; 95% CI: 3.9-109.8) were independently associated with DFS. Class D genotype [odds ratio (OR): 48.5, 95% CI: 10.6-225.1], preoperative basal CT >30 ng/liter (OR: 43.4, 95% CI: 5.2-359.8), and age >10 (OR: 5.5, 95% CI: 1.4-21.8) were associated with medullary thyroid carcinoma ≥10 mm. No patient with a preoperative basal CT <31 ng/ml had a N1 status. Class D genotype (OR: 48.6, 95% CI: 8.6-274.1), and age >10 (OR: 4.6, 95% CI: 1.1-19.0) were associated with N1 status. CONCLUSION: In HMTC patients, DFS is best predicted by TNM staging and preoperative basal CT level below 30 pg/ml. Basal CT, class D genotype, and age constitute key determinants to decide preoperatively timely surgery.
Assuntos
Carcinoma Medular/genética , Carcinoma Medular/cirurgia , Mutação/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adolescente , Adulto , Calcitonina/sangue , Carcinoma Medular/patologia , Criança , Pré-Escolar , DNA/genética , Intervalo Livre de Doença , Feminino , Genótipo , Guias como Assunto , Humanos , Lactente , Estudos Longitudinais , Masculino , Micronúcleo Germinativo , Neoplasia Endócrina Múltipla Tipo 2a/genética , Prognóstico , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de Risco , Neoplasias da Glândula Tireoide/patologia , Resultado do Tratamento , Adulto JovemRESUMO
Somatostatinoma are rare well-differentiated endocrine tumors with malignant behavior arising from the pancreas and duodenum. They are defined by somatostatin positive immunostaining of the majority of tumor cells. The main clinical features are diabetes, diarrhea and biliary lithiasis related to somatostatin production. Somatostatinoma secreting both calcitonin and somatostatin may be unrecognized as a small number of such observations have been published. We report the case of a 57- year-old woman referred for weight loss, diarrhea and worsening diabetes. Computer tomography scan revealed multiple hypervascular liver lesions suggestive of metastases. High plasma calcitonin level was evidenced, with normal chromogranin-A value, and high plasma somatostatin results lately communicated. Calcitonin secretion of extra-thyroidal origin was suspected leading to the identification of a pancreatic mass by further multiphase CT. The patient underwent left pancreatectomy with surgical hepatic resection. Histological and immunostaining studies confirmed definitive diagnosis of somatostatinoma secreting both somatostatin and calcitonin. Plasma calcitonin should be measured in the assessment of duodeno-pancreatic endocrine neoplasm. Calcitonin determination is available, more reproducible than other specific pancreatic endocrine markers and could be effective for diagnosis and follow-up of such foregut-derived endocrine neoplasia.
Assuntos
Calcitonina/metabolismo , Neoplasias Duodenais/metabolismo , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/metabolismo , Somatostatinoma/metabolismo , Diabetes Mellitus Tipo 2/complicações , Neoplasias Duodenais/diagnóstico por imagem , Neoplasias Duodenais/cirurgia , Feminino , Humanos , Imuno-Histoquímica , Laparoscopia , Fígado/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Tomografia Computadorizada por Raios X , UltrassonografiaAssuntos
Poliendocrinopatias Autoimunes/diagnóstico , Anti-Inflamatórios/uso terapêutico , Antifúngicos/uso terapêutico , Criança , Terapia Combinada , Diagnóstico Diferencial , Humanos , Imunidade Celular/imunologia , Imunossupressores/uso terapêutico , Hormônio Paratireóideo/uso terapêutico , Poliendocrinopatias Autoimunes/tratamento farmacológico , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/imunologia , PrognósticoRESUMO
BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS1) has been poorly evaluated in France. We focused on the north-western part of the country to describe clinical phenotypes, especially severe forms of the disease, and AIRE gene mutations. METHODS: Clinical and immunological data were collected, and pathological mutations were identified by DNA sequencing. RESULTS: Nineteen patients were identified with APS1. Clinical manifestations varied greatly, showing 1-10 components. Mucocutaneous candidiasis, adrenal failure, hypoparathyroidism, alopecia and other severe infections were the most frequent components. Four patients had severe forms, needing immunosuppressive therapy: 2 for hepatitis; 1 for severe malabsorption, and 1 for a T cell large granular lymphocytic leukemia. These therapies were very effective but caused general discomfort. One patient died of septicemia. Four different AIRE gene mutations were identified, and a 13-bp deletion in exon 8 (c.967-979del13) was the most prevalent. There was at least one allele correlating with this mutation and alopecia occurrence (p = 0.003). No novel mutation was detected. CONCLUSION: APS1 appears to be rare in north-western France. We identified 4 cases with a severe form needing immunosuppressive therapy. The AIRE gene mutations are more like those found in north-western Europe than those found in Finland.
Assuntos
Terapia de Imunossupressão , Polimorfismo Genético , Fatores de Transcrição/genética , Adolescente , Adulto , Alopecia/epidemiologia , Alopecia/genética , Criança , Análise Mutacional de DNA , Feminino , França/epidemiologia , Genótipo , Humanos , Imunossupressores , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Poliendocrinopatias Autoimunes/epidemiologia , Poliendocrinopatias Autoimunes/genética , Poliendocrinopatias Autoimunes/fisiopatologia , Poliendocrinopatias Autoimunes/terapia , Índice de Gravidade de Doença , Adulto Jovem , Proteína AIRERESUMO
Primary hyperparathyroidism is frequent. Most new cases are diagnosed in post-menopausal women, and are mildly progressive. Surgery is imperative for patients under 50, for symptomatic patients, especially with osteoporosis. Familial hyperparathyroidism can be related to mutations of the menin (MEN1), Ret (MEN2), HRPT 1 and 2 genes or calcium sensor, and have different management, work-up and prognosis.
Assuntos
Hiperparatireoidismo Primário , Fatores Etários , Densitometria , Feminino , Humanos , Hipercalcemia/etiologia , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/genética , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 2a/genética , Mutação , Osteoporose/diagnóstico , Osteoporose/etiologia , PrognósticoRESUMO
Euthyroid Graves' disease is defined as an ophtalmopathy without any clinical or biological signs of thyroid dysfunction. It highlights the apparent dissociation between orbitopathy and thyroid disease. Diagnosis is often too late while early treatment could really improve functional prognosis. We report a 57-year-old woman who presented with this entity and that illustrates both the diagnostic difficulty and disease course after intravenous corticosteroid therapy.
Assuntos
Oftalmopatia de Graves , Feminino , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/tratamento farmacológico , Humanos , Pessoa de Meia-IdadeRESUMO
TSH-secreting adenomas are rare tumors, representing only 0.5 to 2.5% of pituitary adenomas. Their main clinical characteristics include signs of thyrotoxicosis, diffuse goiter and a compressive syndrome. Biologically, free T4 and T3 serum levels are elevated, contrasting with inadequate serum TSH levels and increased alpha chains. Magnetic resonance (MR) imaging shows a pituitary tumor, the main differential diagnosis being resistance to thyroid hormones. Treatment is based on surgery, possibly associated with somatostatin analogs and radiotherapy. Though the long-term evolution of this rare pathology seems to have improved, some clinical situations are still a challenge to treat. We report one such case that was resistant to both stereotactic radiotherapy and somatostatin analogs, but surprisingly improved with cabergoline. We suggest that cabergoline should be considered as an alternative treatment in cases of pituitary adenomas that resist traditional treatments.
Assuntos
Antineoplásicos/uso terapêutico , Ergolinas/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/metabolismo , Tireotropina/metabolismo , Adulto , Osso e Ossos/anormalidades , Osso e Ossos/patologia , Cabergolina , Humanos , Masculino , Neoplasias Hipofisárias/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Anaplastic thyroid carcinoma may represent the ultimate dedifferentiation step of thyroid tumorigenesis and is one of the poorest cancers in human. It accounts for less than 2% of thyroid cancers and affects older patients in their sixth to eighth decade. Usual clinical presentation is a rapidly growing thyroid mass invading surrounding structures with compressive symptoms. Cervical lymph nodes enlargement and distant metastases occur frequently. Though cytological results obtained by fine needle aspiration may be suggestive of diagnosis, tissue biopsy for immunohistochemical study can be necessary to exclude lymphoma and to validate aggressive therapies. Patients developing anaplastic thyroid cancer must be referred urgently in cancer centers to plan multimodality therapeutic approach depending on their performance status. The treatment regimen combines surgery when feasible, hyperfractionated and accelerated external beam radiotherapy and doxorubicin based chemotherapy. Such treatment can provide control of locoregional disease but does not impact on overall survival in patients with distant metastases. The prognosis is dismal with a mean survival of four to nine months after diagnosis. Long survivors are patients with emerging disease presenting a resectable tumor and receiving adjuvant radiotherapy and/or chemotherapy. Therapeutic researches investigate redifferenciation strategies and targeted therapies to inhibit EGF receptors and neoplastic angiogenesis. Primary prevention of this lethal disease may consist of adequate treatment of differentiated thyroid cancers and goiters in elderly.
Assuntos
Carcinoma/terapia , Neoplasias da Glândula Tireoide/terapia , Idoso , Antineoplásicos/uso terapêutico , Carcinoma/prevenção & controle , Carcinoma/cirurgia , Bócio/complicações , Bócio/terapia , Humanos , Pessoa de Meia-Idade , Doenças da Glândula Tireoide/complicações , Doenças da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/prevenção & controle , TireoidectomiaRESUMO
OBJECTIVE: Familial partial lipodystrophy due to LMNA (lamin A/C) mutations is a rare disorder characterized by a selective loss of adipose tissue and insulin resistance. Dyslipidemia and severe diabetes often occur during its evolution. Only isolated and contradictory case reports have been published on the obstetrical prognosis in lipodystrophy. The aim of our study was to compare the fertility and occurrence of obstetrical complications of women with familial partial lipodystrophy due to LMNA (lamin A/C) mutations with those of nonaffected relatives, women from the general population, and women with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: Data were obtained from clinical follow-up of seven families with patients exhibiting mutations in LMNA (five R482W, one R482Q, one R439C) (14 affected among 48 women). RESULTS: The mean number of live children per woman was 1.7 in affected patients vs. 2.8 in nonaffected relatives. Fifty-four percent of LMNA-mutated women exhibited a clinical phenotype of PCOS, 28% suffered from infertility, 50% experienced at least one miscarriage, 36% developed gestational diabetes, and 14% experienced eclampsia and fetal death. Mean blood leptin level was significantly lower in LMNA-mutated patients than in nonaffected relatives (5.0 +/- 3.8 ng/ml vs 14.3 +/- 3.6; P < 0.001) despite similar body mass index (21.0 +/- 4.2 vs 22.4 +/- 2.2; P = 0.49). CONCLUSION: In these LMNA-linked lipodystrophic patients, the prevalence of PCOS, infertility, and gestational diabetes was higher than in the general population. Moreover, the prevalence of gestational diabetes and miscarriages was higher in lipodystrophic LMNA-mutated women than previously reported in PCOS women with similar body mass index. Women with lipodystrophies due to LMNA mutations are at high risk of infertility, gestational diabetes, and obstetrical complications and require reinforced gynecological and obstetrical care.
Assuntos
Fertilidade/fisiologia , Infertilidade Feminina/epidemiologia , Lamina Tipo A/genética , Lipodistrofia Parcial Familiar/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Estudos de Casos e Controles , Estudos Transversais , Diabetes Gestacional/epidemiologia , Família , Feminino , Seguimentos , Humanos , Infertilidade Feminina/genética , Lipodistrofia Parcial Familiar/sangue , Lipodistrofia Parcial Familiar/complicações , Lipodistrofia Parcial Familiar/genética , Mutação , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/genética , Gravidez , Complicações na Gravidez/etiologia , Complicações na Gravidez/genética , Estudos RetrospectivosRESUMO
CONTEXT: Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a distinct X-linked phenotype of severe psychomotor retardation and consistently elevated T(3) levels. Lack of MCT8 transport of T(3) in neurons could explain the neurological phenotype. OBJECTIVE: Our objective was to determine whether the high T(3) levels could also contribute to some critical features observed in these patients. RESULTS: A 16-yr-old boy with severe psychomotor retardation and hypotonia was hospitalized for malnutrition (body weight = 25 kg) and delayed puberty. He had tachycardia (104 beats/min), high SHBG level (261 nmol/liter), and elevated serum free T(3) (FT(3)) level (11.3 pmol/liter), without FT(4) and TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral overfeeding was unsuccessful. The therapeutic effect of propylthiouracil (PTU) and then PTU plus levothyroxine (LT(4)) was tested. After PTU (200 mg/d), serum FT(4) was undetectable, FT(3) was reduced (3.1 pmol/liter) with high TSH levels (50.1 mU/liter). Serum SHBG levels were reduced (72 nmol/liter). While PTU prescription was continued, high LT(4) doses (100 microg/d) were needed to normalize serum TSH levels (3.18 mU/liter). At that time, serum FT(4) was normal (16.4 pmol/liter), and FT(3) was slightly high (6.6 pmol/liter). Tachycardia was abated (84 beats/min), weight gain was 3 kg in 1 yr, and SHBG was 102 nmol/liter. CONCLUSIONS: 1) When thyroid hormone production was reduced by PTU, high doses of LT(4) (3.7 microg/kg.d) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T(3) levels might exhibit some deleterious effects on adipose, hepatic, and cardiac levels. 3) PTU plus LT(4) could be an effective therapy to reduce general adverse features, unfortunately without benefit on the psychomotor retardation.
Assuntos
Deficiência Intelectual/tratamento farmacológico , Transportadores de Ácidos Monocarboxílicos/genética , Hipotonia Muscular/tratamento farmacológico , Propiltiouracila/administração & dosagem , Tiroxina/administração & dosagem , Adolescente , Antitireóideos/administração & dosagem , Humanos , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Masculino , Hipotonia Muscular/complicações , Hipotonia Muscular/genética , Mutação de Sentido Incorreto , Puberdade Tardia/complicações , Puberdade Tardia/tratamento farmacológico , Puberdade Tardia/genética , Simportadores , Síndrome , Taquicardia/complicações , Taquicardia/tratamento farmacológico , Taquicardia/genética , Síndrome da Resistência aos Hormônios Tireóideos/complicações , Síndrome da Resistência aos Hormônios Tireóideos/tratamento farmacológico , Síndrome da Resistência aos Hormônios Tireóideos/genética , Hormônios Tireóideos/sangue , Resultado do TratamentoRESUMO
OBJECTIVE: The RET (rearranged during transfection) proto-oncogene G691S variant is over-represented in the germline of patients with sporadic medullary thyroid carcinoma (sMTC) vs. normal controls but so far is not associated with any medical or pathological features of the tumour. The aim of our study was to assess the influence of this variant on the age of onset, clinical, biological and pathological features of sMTC. DESIGN AND PATIENTS: One hundred patients with histologically proven MTC, for whom the germline genetic analysis of RET was negative and medical records were available, were included in the study. RESULTS: Patients with the heterozygous GS variant or the homozygous SS variant (n = 36) were on average 8.0 years younger than patients with the wild-type GG variant (n = 64, mean age 43.9 vs. 51.9 years, P < 0.01). The former group did not differ from the wild-type group in terms of MTC size, prevalence of C-cell hyperplasia (CCH) or papillary thyroid carcinoma (PTC). However, the prevalence of an increased preoperative basal calcitonin (bCT) level (> 1000 pg/ml) was 2.75-fold higher in the patients with the GS or SS variant than in those with the wild-type variant (P < 0.001). The proportion of patients with lymph node metastases was also higher in the former group (P < 0.05). Multivariate analysis confirmed that the presence of the RET variant is independently associated with higher preoperative bCT values (P = 0.011). CONCLUSIONS: Our data demonstrate that the RET G691S variant could modulate the age of onset of sMTC as demonstrated previously for familial tumours. Moreover, this variant is an independent predictor of a higher basal calcitonin synthesis rate in patients with sMTC.