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1.
Clin Endocrinol (Oxf) ; 101(2): 180-190, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38856700

RESUMEN

OBJECTIVES: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. DESIGN: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. RESULTS: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%-83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7-0.9) and respondents >60 years (OR: 0.7; 0.6-0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients ("weekly" [OR: 1.4; CI: 1.0-1.9], "daily" [OR: 1.8; CI: 1.3-2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3-1.9) were most likely to consider LT4. CONCLUSIONS: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment.


Asunto(s)
Autoanticuerpos , Hipotiroidismo , Infertilidad Femenina , Tiroxina , Humanos , Tiroxina/uso terapéutico , Femenino , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/sangre , Europa (Continente) , Adulto , Autoanticuerpos/sangre , Infertilidad Femenina/tratamiento farmacológico , Persona de Mediana Edad , Masculino , Encuestas y Cuestionarios , Yoduro Peroxidasa/inmunología
2.
Clin Endocrinol (Oxf) ; 95(1): 217-223, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33682167

RESUMEN

CONTEXT: Anti-thyroglobulin antibodies (anti-Tg), present in 20%-25% of differentiated thyroid cancer (DTC) patients, interfere with thyroglobulin measurements posing a challenge in the follow-up. OBJECTIVES: The aim of this study was to identify clinical-histological factors that may affect anti-Tg persistence and disease outcome in DTC with positive anti-Tg. METHODS: We retrospectively studied 234 DTC patients, with positive anti-Tg at diagnosis (females: 82.1%, age at diagnosis: 46.0 ± 14.4 yrs, median follow-up: 5 yrs (1.5-32 yrs). 221/234 (94.4%) received radioiodine (RAI) ablation. Patients were divided into two subgroups: those whose anti-Tg became undetectable (anti-Tg-NEG) and those whose anti-Tg remained positive (anti-Tg-POS) at the end of the follow-up period. RESULTS: Anti-Tg-POS patients (n = 80, 34.2%) compared to anti-Tg-NEG (n = 154, 65.8%) had more frequently lymph node infiltration (36.3% vs 20.1%, P = .01), extrathyroidal extension (ETE, 35.0% vs 22.1%, P = .04), poorly differentiated DTC and increased tumour size (P ≤ .004). They received higher total RAI dose (P < .001). In most cases, additional RAI administration and/or additional surgeries did not lead to anti-Tg elimination. These had more frequently structural disease persistence/progression compared to anti-Tg-NEG (remission: 78.8% vs 95.5%, persistence: 13.8% vs 3.9%, progression: 7.5% vs 0.6%, P < .001). In Kaplan-Meier analysis, the probability of disease progression was higher in anti-Tg-POS. In Cox proportional hazard analysis, the predictors of disease progression were size (P = .002) and ETE (P = .006). CONCLUSIONS: Worse histological features are more frequent in patients with anti-Tg persistence during follow-up. Further additional RAI administration and/or surgeries do not affect anti-Tg elimination in most cases. Anti-Tg persistence correlates with structural persistence although tumour size and extrathyroidal extension are the main predictors of disease progression.


Asunto(s)
Radioisótopos de Yodo , Neoplasias de la Tiroides , Femenino , Humanos , Radioisótopos de Yodo/uso terapéutico , Estudios Retrospectivos , Tiroglobulina , Neoplasias de la Tiroides/cirugía , Tiroidectomía
3.
Neuropsychobiology ; 80(4): 342-351, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33508827

RESUMEN

INTRODUCTION: Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. Very few studies have assessed dehydroepiandrosterone sulphate (DHEA-S) in BD and its relation to cognitive functioning despite evidence showing its regulatory effects on glucocorticoid action. The aim of our study was to explore the association of cortisol, DHEA-S, and cortisol to DHEA-S ratio with visuospatial memory and executive functioning in BD. METHODS: Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using Cambridge Neuropsychological Test Automated Battery tasks targeting visuospatial memory (spatial recognition memory) and executive functions (planning [Stockings of Cambridge; SOC] and attentional set shifting [ID/ED]). Morning serum cortisol and DHEA-S levels were measured in patients. Main effects of cortisol, DHEA-S, and cortisol/DHEA-S ratio for each neurocognitive task were explored in multiple regression analyses correcting for demographic and clinical parameters as well as treatment-related factors (current use of antipsychotic and mood stabilizer medication). RESULTS: Bipolar patients showed poorer performance than healthy subjects in planning and attentional set shifting but not in visuospatial memory. Cortisol to DHEA-S ratio predicted worse performance in planning (SOC). CONCLUSIONS: This is the first study to assess memory and executive function in BD in relation to DHEA-S and cortisol to DHEA-S ratio. We report an association of cortisol to DHEA-S ratio with worse performance in planning in bipolar I patients, which warrants further investigation.


Asunto(s)
Trastorno Bipolar , Trastorno Bipolar/tratamiento farmacológico , Sulfato de Deshidroepiandrosterona , Función Ejecutiva , Humanos , Hidrocortisona , Pruebas Neuropsicológicas
4.
Clin Endocrinol (Oxf) ; 90(5): 737-743, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30740757

RESUMEN

BACKGROUND: Several ultrasound (US) risk stratification systems have been proposed for the assessment of thyroid nodules, and their performance was shown as good. However, the rate of nodules assessed at intermediate risk is not negligible and whether they should be submitted or not to further examination is still under debate. The present study aimed to evaluate the reliability of 18 F-FDG PET/CT in stratifying the risk of malignancy in these lesions. METHODS: Two institutions participated to this retrospective study in which a dedicated 18 F-FDG PET/CT was proposed to patients having a thyroid nodule with US assessment of EU-TIRADS 4 or 5. 18 F-FDG PET/CT did not influence the diagnostic and therapeutic decision. Histology was the gold standard for all patients. RESULTS: Ninety-three patients were included for the study with 48 EU-TIRADS 4 and 45 EU-TIRADS 5 nodules. Of these, 26 underwent thyroidectomy following FNAC suspicious for or consistent with malignancy, 38 for inconclusive cytology, 27 because of large goitre and 2 for high-risk lesion at US. At histology, 35 carcinomas and 58 benign lesions were found. Cancer prevalence was 16.7% in EU-TIRADS 4 and 60% in EU-TIRADS 5. Overall, 18 F-FDG PET/CT was positive in 33/35 cancers (94.5% sensitivity) and negative in 31/58 benign lesions (53.4% specificity). When considering only EU-TIRADS 4, 18 F-FDG PET/CT was positive in 7/8 cancers and negative in 20/40 benign lesions; among these, there were 36 cases with FNAC indication according to dimensional cut-off (ie >1.5 cm), and 18 F-FDG PET/CT showed 85.7% sensitivity and 41.4% specificity. CONCLUSIONS: 18 F-FDG PET/CT may have a role in stratifying the cancer risk of thyroid nodules with an intermediate ultrasound assessment. More specifically, thyroid lesions classified as EU-TIRADS 4 and with no 18 F-FDG uptake could be ruled out from further examination, similar to other anamnestic and clinical suspicious factors of patients. Further prospective and cost-effectiveness studies are needed.


Asunto(s)
Tomografía de Emisión de Positrones/normas , Medición de Riesgo/normas , Nódulo Tiroideo/diagnóstico por imagen , Nódulo Tiroideo/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Fina , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos , Estudios Retrospectivos , Nódulo Tiroideo/cirugía , Tiroidectomía , Ultrasonografía
5.
Eur J Clin Invest ; 47(5): 341-347, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28226412

RESUMEN

BACKGROUND: Polymorphisms of the receptor for advanced glycation end products (RAGE) gene have been studied in various autoimmune disorders, but not in Hashimoto's thyroiditis. Also, increased oxidative stress has been described in patients with Hashimoto's thyroiditis. The aim of this study was to investigate the possible role of two common RAGE polymorphisms (-429T>C, -374T>A) in Hashimoto's thyroiditis; in parallel, we studied oxidative stress levels. MATERIALS AND METHODS: A total of 300 consecutive euthyroid women were examined and classified into three groups: Hashimoto's thyroiditis with treatment (n = 96), Hashimoto's thyroiditis without treatment (n = 109) and controls (n = 95). For a rough evaluation of oxidative stress, total lipid peroxide levels in serum were measured. The -429T>C AluI and -374T>A MfeI polymorphisms of RAGE were studied in genomic DNA. RESULTS: Significant association of the RAGE system with Hashimoto's thyroiditis was found only with regard to the prevalence of the -429T>C, but not with -374T>A polymorphism. The levels of oxidative stress were significantly elevated in Hashimoto's thyroiditis patients under treatment. Further analysis demonstrated that an oxidative stress cut-off value of 590 µmol/L is associated with an increased risk of progression of Hashimoto's thyroiditis from euthyroidism to hypothyroidism; this risk is further increased in carriers of the RAGE -429T>C polymorphism. CONCLUSIONS: Our findings indicate that both examined risk factors may be implicated in the occurrence of Hashimoto's thyroiditis, but this covers only a fraction of the pathophysiology of the disease.


Asunto(s)
Antígenos de Neoplasias/genética , Enfermedad de Hashimoto/genética , Proteínas Quinasas Activadas por Mitógenos/genética , Estrés Oxidativo , Adulto , Anciano , Estudios de Casos y Controles , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Grecia , Enfermedad de Hashimoto/metabolismo , Humanos , Peróxidos Lipídicos/metabolismo , Persona de Mediana Edad , Polimorfismo Genético , Adulto Joven
6.
Eur Arch Psychiatry Clin Neurosci ; 267(7): 661-669, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27783216

RESUMEN

Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. However, visual paired associative learning (PAL) has been far less researched. Neurocognitive dysfunction in BD patients has been related to several clinical factors, but data on the effect of medication are relatively scarce and inconsistent. The aim of our study was to explore the effect of clinical and treatment-related parameters on executive functions and visual memory/learning, including PAL, in BD. Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using CANTAB battery tasks targeting spatial recognition memory, PAL and executive functions (set shifting, planning, inhibitory control). Bipolar patients showed poorer performance in PAL, set shifting, planning and inhibitory control than healthy subjects; however, only differences in PAL and planning survived correction for multiple comparisons. Number of previous manic episodes and illness duration predicted worse performance in set shifting and PAL, respectively, whereas current treatment with valproate predicted better performance in PAL. This is one of the first studies to assess clinical and treatment-related predictors of PAL in BD. We report a possibly beneficial effect of valproate on PAL, which warrants further investigation.


Asunto(s)
Aprendizaje por Asociación/fisiología , Trastorno Bipolar/complicaciones , Trastorno Bipolar/psicología , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Reconocimiento en Psicología/fisiología , Adulto , Análisis de Varianza , Atención/efectos de los fármacos , Inhibidores Enzimáticos/uso terapéutico , Función Ejecutiva/efectos de los fármacos , Femenino , Humanos , Inhibición Psicológica , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estimulación Luminosa , Escalas de Valoración Psiquiátrica , Estudios Retrospectivos , Ácido Valproico/uso terapéutico
7.
J Pediatr ; 166(2): 451-6.e2, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25453245

RESUMEN

OBJECTIVE: To compare clinical and histologic characteristics of papillary thyroid carcinomas (PTCs) ≤10 mm in patients ≤21 years old with larger ones and with microcarcinomas in adults. STUDY DESIGN: Retrospective study of patients with PTC diagnosed between 1983 and 2012. Medical records were reviewed and information about age, sex, tumor size, intra/extrathyroid extension, lymph node, and distant metastases were collected. RESULTS: Patients ≤21 years old (n = 93) and adults (n = 1235) with PTC were identified. Among the former, 34 had PTC ≤10 mm (37.4%) and among the latter, 584 had papillary thyroid microcarcinoma (PTM) (47.3%), P = .082. Patients with tumors ≤10 mm less frequently had extrathyroidal extension and lymph node metastases compared with larger tumors (8.8% vs 33.3%, P = .017, and 60.0% vs 95.2%, P = .001, respectively). The percentage of PTC ≤10 mm increased with age (7.1%, 32.0%, and 48.1% in age groups ≤15, 15-18, and >18 to ≤21 years old, respectively; P = .016). Mean tumor size was larger (6.8 ± 2.7 vs 5.8 ± 2.8 mm, P = .030), and lymph nodes metastases were more frequent (41.2% vs 18.6%, P = .003) in patients ≤21 years of age compared with adults with PTM. The frequency of multifocal cancers decreased between 1983-1992, 1993-2002, and 2003-2012 (66.7%, 53.6%, and 27.1%, respectively, P = .019). CONCLUSIONS: The frequency of PTC ≤10 mm is low in children, increases in adolescents, and reaches that of adults at 18-21 years of age. Mean tumor size is larger and metastases to regional lymph nodes more frequent in comparison with PTM in adults. Whether their treatment and follow-up could be based on guidelines used for PTM in adults is questionable.


Asunto(s)
Carcinoma/patología , Neoplasias de la Tiroides/patología , Adolescente , Adulto , Carcinoma/secundario , Carcinoma Papilar/patología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides/secundario , Carga Tumoral , Adulto Joven
8.
Clin Endocrinol (Oxf) ; 82(2): 197-204, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25040693

RESUMEN

OBJECTIVE: TSH suppression therapy in patients with differentiated thyroid cancer (DTC) has been associated with adverse effects on areal bone mineral density (aBMD) only in postmenopausal women. The purpose of study was to examine the effect of TSH suppression therapy on skeletal integrity using peripheral quantitative computed tomography (pQCT) at the radius and tibia in pre- and postmenopausal women with DTC and controls. STUDY DESIGN AND PATIENTS: Subjects included 80 women with DTC (40 pre- and 40 postmenopausal) and 89 (29 and 60, respectively) controls. pQCT was performed at the radius and tibia, Dual-energy X-ray absorptiometry (DXA) at the hip and lumbar spine, while samples were taken for calciotropic hormones and bone markers. RESULTS: No differences were observed concerning aBMD by DXA. In premenopausal women, there were no significant differences concerning vBMD, while cortical thickness was higher at the radius in patients with DTC (P < 0·01) compared with controls. In postmenopausal women with DTC trabecular bone mineral content (BMC), area and vBMD were lower at the radius (all P < 0·05), while at the tibia trabecular BMC and vBMD were lower at the mixed transition zone (14% from the distal end, P < 0·05) compared with controls. Cortical thickness was lower at the radius (P < 0·01) in postmenopausal patients compared with controls. Serum CTX was higher in postmenopausal women with DCT (P < 0·01), while in premenopausal patients, parathyroid hormone (PTH) was lower (P = 0·01) compared with controls. CONCLUSIONS: TSH suppression therapy is associated with higher bone resorption only in postmenopausal women; this adversely affects trabecular and cortical bone properties especially at nonweight-bearing sites such as the radius.


Asunto(s)
Densidad Ósea , Huesos/patología , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/tratamiento farmacológico , Tiroxina/uso terapéutico , Adulto , Densidad Ósea/efectos de los fármacos , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Estudios de Casos y Controles , Tomografía Computarizada de Haz Cónico , Femenino , Terapia de Reemplazo de Hormonas , Humanos , Menopausia/efectos de los fármacos , Persona de Mediana Edad , Tamaño de los Órganos , Neoplasias de la Tiroides/fisiopatología , Neoplasias de la Tiroides/cirugía , Tirotropina/antagonistas & inhibidores , Tomografía Computarizada por Rayos X/métodos
9.
Recent Results Cancer Res ; 204: 179-86, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26494389

RESUMEN

One of the components of trethe classical form of MEN2 syndromes is primary hyperparathyroidism (PHP). It occurs in 20-30% of the typical MEN2A syndrome. The prevalence is more rare in gene carriers as these frequently have familial MTC only. PHP is diagnosed more frequently in association with the exon 11, codon 634 mutation of the ret gene-so there is phenotype/genotype correlation. The clinical manifestations of PHP in MEN2 are usually mild and the peak age of diagnosis after the 3rd decade. The treatment is surgical excision of the enlarged gland(s). Although there can be multigland disease in the parathyroids, it is frequently the case that both hyperplasia and adenoma may coexist, or even a single adenoma may be found during the investigation and finally during the operation. Patients with MEN2 syndromes should be screened for PHP with serum calcium measurements. The intensity of the screening should be higher in those carrying the ret mutations most frequently associated with this manifestation.


Asunto(s)
Hiperparatiroidismo Primario/etiología , Neoplasia Endocrina Múltiple Tipo 2a/complicaciones , Neoplasia Endocrina Múltiple Tipo 2b/complicaciones , Biomarcadores de Tumor/genética , Calcio/sangre , Predisposición Genética a la Enfermedad , Humanos , Hiperparatiroidismo Primario/sangre , Hiperparatiroidismo Primario/diagnóstico , Hiperparatiroidismo Primario/cirugía , Neoplasia Endocrina Múltiple Tipo 2a/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2b/diagnóstico , Neoplasia Endocrina Múltiple Tipo 2b/genética , Mutación , Paratiroidectomía , Fenotipo , Proteínas Proto-Oncogénicas c-ret/genética
10.
Lancet Oncol ; 15(6): 648-55, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24745698

RESUMEN

BACKGROUND: The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. METHODS: This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. FINDINGS: 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent. INTERPRETATION: The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/cirugía , Neoplasia Endocrina Múltiple Tipo 2a/complicaciones , Neoplasia Endocrina Múltiple Tipo 2a/cirugía , Feocromocitoma/cirugía , Adolescente , Neoplasias de las Glándulas Suprarrenales/etiología , Neoplasias de las Glándulas Suprarrenales/mortalidad , Adrenalectomía/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasia Endocrina Múltiple Tipo 2a/mortalidad , Feocromocitoma/etiología , Feocromocitoma/mortalidad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
11.
Int J Gynecol Cancer ; 24(5): 851-6, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24844218

RESUMEN

OBJECTIVE: Thyroid-stimulating hormone (TSH) regulates normal thyroid function by binding to its receptor (thyroid-stimulating hormone receptor -TSHR) that is expressed at the surface of thyroid cells. Recently, it has been demonstrated that TSHR is abundantly expressed in several tissues apart from the thyroid, among them the normal ovarian surface epithelium. The role of TSHR expression outside the thyroid is not completely understood. The current study examines possible alterations of TSHR expression in ovarian carcinomas and its implication in ovarian carcinogenesis. MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction and immunohistochemistry analysis of TSHR expression were performed in 34 ovarian carcinoma specimens and 10 normal ovarian tissues (controls). RESULTS: Significant reduction in TSHR messenger RNA (mRNA) expression was detected in ovarian carcinomas (mean [SD]: 0.518 [0.0934] vs normal, 49.4985 [89.1626]; P < 0.001, Mann-Whitney U test), whereas TSHR protein levels were significantly increased (percentage of positive cells: cancer, 73.55% [20.09%], vs normal, 54.54% [21.14%]; intensity: cancer, 2.52 [0.508], vs normal 1 [0]; P = 0.012, Mann-Whitney U test). No significant differences in TSHR mRNA were found according to history of thyroid disease. CONCLUSIONS: Our study describes for the first time alterations in TSHR expression both at mRNA and protein levels in ovarian carcinomas. The discrepancy between the decreased levels of the TSHR mRNA and the increased protein expression has already been described in thyroid carcinomas and might be due to alterations in its degradation by the ubiquitin system or other unknown mechanisms. Further analysis could elucidate the role of these findings in ovarian carcinogenesis.


Asunto(s)
Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias Ováricas/genética , Neoplasias Ováricas/metabolismo , Receptores de Tirotropina/genética , Receptores de Tirotropina/metabolismo , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patología , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patología , Adulto , Anciano , Estudios de Casos y Controles , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/patología , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Clasificación del Tumor , Neoplasias Ováricas/patología , Pronóstico , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
12.
J Perinat Med ; 42(1): 69-74, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23985426

RESUMEN

OBJECTIVE: The aim of the study was to evaluate the significance of the presence of thyroid peroxidase autoantibodies (anti-TPO Abs) in type 1 diabetes mellitus (DM1) pregnant women relative to the course of pregnancy and, especially, with regard to metabolic control, thyroid function, maternal complications and neonatal outcome. METHODS: In a prospective observational study of 91 DM1 women with singleton pregnancies, anti-TPO, anti-thyroglobulin, thyroid-stimulating hormone (TSH), and free thyroxine index (T4/thyroid binding capacity) were measured in each trimester. At each visit, HbA1c, body mass index, and units of insulin per kilogram were recorded, as were complications and pregnancy outcome. RESULTS: Twenty-one (27%) of the 78 women who met the inclusion criteria presented with positive anti-TPO Abs. There were no differences regarding glycemic control (HbA1c) or insulin dose. First-trimester TSH levels were significantly higher in the anti-TPO-positive group than in the anti-TPO-negative group. Finally, no differences were observed regarding diabetic or obstetric complications and neonatal outcome. CONCLUSION: One fourth of DM1 pregnant women presented with positive anti-TPO Abs. However, the presence of anti-TPO Abs does not seem to be related with worse metabolic control or adverse pregnancy outcome. Further investigation is needed; meanwhile, the effort for early treatment of thyroid dysfunction and strict metabolic control in all DM1 women should be continued.


Asunto(s)
Autoanticuerpos/sangre , Autoantígenos/inmunología , Diabetes Mellitus Tipo 1/inmunología , Yoduro Peroxidasa/inmunología , Proteínas de Unión a Hierro/inmunología , Resultado del Embarazo , Embarazo en Diabéticas/inmunología , Adulto , Biomarcadores/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/enzimología , Femenino , Estudios de Seguimiento , Humanos , Embarazo , Embarazo en Diabéticas/sangre , Embarazo en Diabéticas/enzimología , Estudios Prospectivos
13.
Artículo en Inglés | MEDLINE | ID: mdl-38614119

RESUMEN

Summary: Struma ovarii is an ovarian teratoma that comprises 2-5% of all ovarian teratomas. Malignant transformation of struma ovarii occurs in less than 5% of all cases, and metastatic disease is even rarer. We report two cases initially diagnosed with benign struma ovarii that presented malignant transformation, specifically highly differentiated follicular carcinoma of the ovary (HDFCO), some years after the first diagnosis. Case 1 concerns a 37-year-old female featuring HDFCO of the right ovary with multiple metastatic foci, who was diagnosed with benign struma ovarii 14 years ago. Case 2 concerns a 26-year-old female diagnosed with HDFCO of the left ovary. This patient was initially diagnosed with benign struma ovarii 6 years ago that recurred 4 years after the diagnosis. Both patients were treated with surgery, adjunctive total thyroidectomy, and radioactive iodine (131I) therapy. Learning points: Malignant transformation of struma ovarii is very rare (<5%). Diagnosis of HDFCO without extra ovarian dissemination is difficult due to the resemblance of its histological appearance with normal thyroid tissue. There is no consensus on the postoperative treatment of malignant struma ovarii (MSO). Clinical and histological features of MSO should be assessed for the postoperative treatment decisions. TSH suppression and thyroglobulin level measurements are necessary for patient follow-up.

14.
Endocrine ; 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39217207

RESUMEN

BACKGROUND: Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines. PURPOSE: To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice. METHODS: Online survey on the use of TH for growing SG among thyroid experts from 28 European countries. RESULTS: The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41-50, 51-60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03-1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33-0.48), Northern Europe (OR 0.28, 95% CI 0.22-0.36) and Western Asia (OR 0.16, 95% CI 0.11-0.24) compared to Western Europe. Associations with respondents' sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak. CONCLUSIONS: Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention.

15.
Thyroid ; 34(4): 429-441, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38368541

RESUMEN

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.


Asunto(s)
Hipotiroidismo , Tirotropina , Humanos , Femenino , Hipotiroidismo/tratamiento farmacológico , Hipotiroidismo/epidemiología , Tiroxina , Triyodotironina , Demografía
16.
Gynecol Endocrinol ; 29(8): 784-7, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23763623

RESUMEN

Several studies have examined the association of the PvuII polymorphism of the estrogen receptor alpha gene with the risk of stroke. Data linking the polymorphism with the severity and outcome of cerebrovascular disease are lacking. In this study, we evaluated 285 postmenopausal Caucasian patients suffering an acute stroke, hospitalized in two tertiary hospitals over a period of 2 years, and searched for associations between the PvuII polymorphism and the one-month outcome and the neurological severity on admission. The prevalence of CC genotype was 21%, CT 50% and TT 29%. Estradiol levels were higher with increasing frequencies of the C allele (p = 0.04). There was no difference in the short-term functional outcome and mortality and the neurological severity on admission among the three genotypes. We did not find a significant association of the PvuII polymorphism with intracerebral hemorrhage and classical stroke risk factors. An association of the CC genotype with venous thromboembolism history was recorded (p 0.05). There was no association between the PvuII polymorphism and stroke severity and short-term outcome in the studied female stroke population. It is possible that the long-term estrogenic action, reflected by the genetic polymorphism, is not a major determinant of disease severity and prognosis in older age.


Asunto(s)
Receptor alfa de Estrógeno/genética , Accidente Cerebrovascular/genética , Anciano , Anciano de 80 o más Años , ADN-Citosina Metilasas/metabolismo , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología
17.
Endocrine ; 80(3): 570-579, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36626081

RESUMEN

PURPOSE: MTC has varying clinical course. In cases with metastatic disease (meta-MTC) further therapeutic modalities (locoregional and/or Tyrosine-Kinase-Inhibitors, TKIs) are needed. Clinical features, disease progression, response to therapy and possible factors predisposing to TKIs response-resistance in meta-MTCs were investigated. METHODS: Out of 338 MTC patients 54 had meta-MTC and were followed for 0.7-46 years (median 10.5); therapeutic interventions and response to therapy were recorded retrospectively. RESULTS: Of 54 meta-MTC patients, 34/54 were men, 44/54 sporadic (age-at-diagnosis 47 ± 17.4 years, range: 5-78). Distant metastases at diagnosis were present in 12/54 (≥2 loci in 8/12), 7/12 received TKIs; During follow-up metastases occurred in 42/54 (within 0.6-25 years from diagnosis, median 5 yrs). Locoregional therapies were administered to 44/54 (81.5%) and TKIs to 40/54 (74.1%). Vandetanib was administered in 30 patients (24 as first-line therapy). The median progression-free-survival, PFS) was 48 months (range 4-120), partial response (PR): 26.7%, stable disease (SD): 23.3%, progressive disease (PD): 50.0%, cancer-specific survival: 44.8%, (16 in ongoing-therapy). More favorable disease course was recorded in familial-MTC compared to sporadic (p = 0.02) and in those patients with serious-adverse-events (SAEs) under treatment (p = 0.027). Those with biochemical progression under vandetanib, later showed more frequently structural progression (p = 0.007). Ten patients received cabozantinib (8/10 as second-line therapy, median PFS:11 months (3-36 months), 8/10 died). Three RET-mutant patients received selpercatinib; all showed PR. Within the total follow-up period, the response to therapy was: PR: 8/54 (14.8%), SD: 15/54 (27.8%), PD: 31/54 (57.4%), cancer-specific survival 46.3%. Mortality was higher in older patients (≥60 years) compared to younger ones (<60 yrs) (83.3 vs 45.2%, p = 0.021). Outcome was better in familial-MTC vs sporadic (PR: 50 vs 6.8%, SD: 20 vs 29.5%, PD: 30 vs 59.1%, p = 0.007). CONCLUSIONS: Meta-MTCs treatment results in disease stabilization in 42.6% during a median 10.5 year follow-up. Combination of locoregional and systemic therapies may result in more favorable PFS. Family history, younger age, SAEs may predict better response; biochemical escape under TKI needs to be followed-up closely as it may indicate disease progression.


Asunto(s)
Carcinoma Neuroendocrino , Neoplasias de la Tiroides , Masculino , Humanos , Anciano , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/diagnóstico , Carcinoma Neuroendocrino/tratamiento farmacológico , Carcinoma Neuroendocrino/diagnóstico , Piperidinas/uso terapéutico , Progresión de la Enfermedad , Resistencia a Medicamentos
18.
Biomedicines ; 11(2)2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36831140

RESUMEN

High-dose intravenous steroid treatment (HDIST) represents the first choice of treatment for multiple sclerosis (MS) relapses. Chronic oral glucocorticoid (GC) administration correlates with bone loss whereas data regarding HDIST in MS are still conflicting. Twenty-five newly diagnosed MS patients (NDMSP) (median age: 37 years) were prospectively studied for the effects of HDIST on bone mineral density (BMD) and bone metabolism. Patients received 1000 mg methylprednisolone intravenously every day for 5 days followed by oral prednisolone tapering over 21 days. Bone metabolism indices were determined prior to GC, on days 2, 4, 6, and 90, and at months 6, 12, 18, and 24 post GC therapy. Femoral, lumbar-spine BMD, and whole-body measurement of adipose/lean tissue were assessed prior to GC-administration and then every six months. Ten patients completed the study. N-terminal-propeptide-procollagen-type-1 and bone-specific alkaline phosphatase showed a significant increase at day-90 (p < 0.05). A transient non-significant fall of BMD was observed at 6 months after GC-administration, which subsequently appeared to be restored. We conclude that HDIST seems not to have long-term negative effects on BMD, while the observed transient increase of bone formation markers probably indicates a high bone turnover phase to GC-administration. Additional prospective studies with larger sample size are needed.

19.
Front Endocrinol (Lausanne) ; 14: 1225202, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38027187

RESUMEN

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.


Asunto(s)
Hipotiroidismo , Renta , Humanos , Femenino , Persona de Mediana Edad , Masculino , Factores Socioeconómicos , Encuestas y Cuestionarios , Europa (Continente) , Hipotiroidismo/epidemiología , Hipotiroidismo/terapia
20.
Immunology ; 135(3): 245-53, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22098450

RESUMEN

We have previously reported that the 20-mer peptide p2340 (amino acids 2340-2359), of human thyroglobulin (Tg) has the unique feature that it causes experimental autoimmune thyroiditis (EAT) in mouse strains bearing high-responder (HR) or low-responder (LR) MHC haplotypes in Tg-induced EAT. In this study, we have employed fine epitope mapping to examine whether this property of p2340 is the result of recognition of distinct or shared minimal T-cell epitopes in the context of HR or LR MHC class II molecules. Use of overlapping peptides showed that a core minimal 9-mer epitope (LTWVQTHIR, amino acids 2344-2352) was recognized by p2340-primed T cells from both HR (H2(k,s) ) and LR (H2(b,d) ) strains, whereas a second 9-mer epitope (HIRGFGGDP, amino acids 2350-2358) was antigenic only in H2(s) hosts. Truncation analysis of LTWVQTHIR and HIRGFGGDP peptides delineated them as the minimal epitopes recognized by p2340-primed T cells from the above strains. Subcutaneous challenge of all mouse strains with the 9-mer core peptide LTWVQTHIR in adjuvant elicited specific lymph node cell proliferative responses and mild EAT only in HR hosts, highlighting this sequence as a minimal pathogenic Tg peptide in EAT. The 9-mer peptide HIRGFGGDP was not found to be immunogenic in H2(s) hosts. These data demonstrate that minimal T-cell epitopes, defined as autoantigenic in hosts of various MHC haplotypes, are not intrinsically immunogenic. Activation of naive autoreactive T cells may require contributions from flanking residues within longer peptide sequences encompassing these epitopes.


Asunto(s)
Fragmentos de Péptidos/inmunología , Tiroglobulina/inmunología , Secuencia de Aminoácidos , Animales , Autoantígenos/química , Autoantígenos/genética , Modelos Animales de Enfermedad , Mapeo Epitopo , Femenino , Antígenos H-2 , Haplotipos , Humanos , Complejo Mayor de Histocompatibilidad , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Especificidad de la Especie , Linfocitos T/inmunología , Tiroglobulina/química , Tiroglobulina/genética , Tiroiditis Autoinmune/inmunología
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