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1.
Mol Pharmacol ; 97(1): 2-8, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31704717

RESUMO

The thyrotropin (TSH) receptor (TSHR) signals via G proteins of all four classes and ß-arrestin 1. Stimulation of TSHR leads to increasing cAMP production that has been reported as a monotonic dose-response curve that plateaus at high TSH doses. In HEK 293 cells overexpressing TSHRs (HEK-TSHR cells), we found that TSHR activation exhibits an "inverted U-shaped dose-response curve" with increasing cAMP production at low doses of TSH and decreased cAMP production at high doses (>1 mU/ml). Since protein kinase A inhibition by H-89 and knockdown of ß-arrestin 1 or ß-arrestin 2 did not affect the decreased cAMP production at high TSH doses, we studied the roles of TSHR downregulation and of Gi/Go proteins. A high TSH dose (100 mU/ml) caused a 33% decrease in cell-surface TSHR. However, because inhibiting TSHR downregulation with combined expression of a dominant negative dynamin 1 and ß-arrestin 2 knockdown had no effect, we concluded that downregulation is not involved in the biphasic cAMP response. Pertussis toxin, which inhibits activation of Gi/Go, abolished the biphasic response with no statistically significant difference in cAMP levels at 1 and 100 mU/ml TSH. Concordantly, co-knockdown of Gi/Go proteins increased cAMP levels stimulated by 100 mU/ml TSH from 55% to 73% of the peak level. These data show that biphasic regulation of cAMP production is mediated by Gs and Gi/Go at low and high TSH doses, respectively, which may represent a mechanism to prevent overstimulation in TSHR-expressing cells. SIGNIFICANCE STATEMENT: We demonstrate biphasic regulation of TSH-mediated cAMP production involving coupling of the TSH receptor (TSHR) to Gs at low TSH doses and to Gi/o at high TSH doses. We suggest that this biphasic cAMP response allows the TSHR to mediate responses at lower levels of TSH and that decreased cAMP production at high doses may represent a mechanism to prevent overstimulation of TSHR-expressing cells. This mechanism could prevent chronic stimulation of thyroid gland function.


Assuntos
AMP Cíclico/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Receptores da Tireotropina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tireotropina/administração & dosagem , Relação Dose-Resposta a Droga , Regulação para Baixo , Dinamina I/genética , Dinamina I/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/antagonistas & inibidores , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Toxina Pertussis/administração & dosagem , Receptores da Tireotropina/genética , Transdução de Sinais/genética , beta-Arrestina 2/genética , beta-Arrestina 2/metabolismo
3.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(5): 305-311, mayo 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-182805

RESUMO

Objetivo: Determinar el riesgo de hipotiroidismo en gestantes con enfermedad tiroidea autoinmune y tirotropina (TSH) < 2,5 mUI/l al inicio del embarazo. Métodos: Estudio prospectivo longitudinal en gestantes de primer trimestre sin antecedentes de patología tiroidea y con TSH en primer trimestre < 2,5 mUI/l. Se determinaron TSH, tiroxina libre (T4l) y anticuerpos antiperoxidasa (TPO) y antitiroglobulina en los 3 trimestres. Se comparó la evolución de la función tiroidea y la aparición de hipotiroidismo gestacional (TSH > 4 mUI/l), entre las gestantes con autoinmunidad positiva y autoinmunidad negativa. Resultados: Se incluyeron 300 gestantes con TSH basal 1,3 ± 0,6 mUI/l (semana gestacional 9). El 17,7% (n = 53) tenían autoinmunidad positiva en el primer trimestre. Los títulos de anticuerpos TPO y antitiroglobulina disminuyeron entre el primer y el tercer trimestre un 76,8% y un 80,7% respectivamente. La evolución de la función tiroidea fue similar en el grupo con autoinmunidad positiva y el grupo con autoinmunidad negativa, y la aparición de hipotiroidismo fue del 1,9% (1/53) y del 2% (5/247) respectivamente. Las gestantes en las que la TSH aumentó por encima de 4 mUI/l (n = 6) tenían cifras superiores de TSH basal en comparación con las que mantuvieron TSH≤4 mUI/l a lo largo del embarazo (1,8 vs. 1,3 mUI/l; p = 0,047). Conclusión: En nuestra población, las mujeres con TSH < 2,5 mUI/l al inicio del embarazo tienen un riesgo mínimo de desarrollar hipotiroidismo durante la gestación, independientemente de la autoinmunidad tiroidea


Objective: To determine the risk of hypothyroidism in pregnant women with autoimmune thyroid disease and thyrotropin (TSH) < 2,5 mIU/l at the beginning of pregnancy. Methods: Prospective longitudinal study of pregnant women with no personal history of thyroid disease, and with TSH < 2.5 mIU/l in the first trimester. TSH, free thyroxine (FT4), anti peroxidase (TPO) and anti thyroglobulin antibodies were measured in the 3 trimesters of pregnancy. We compared thyroid function throughout pregnancy, and the development of gestational hypothyroidism (TSH >4 mIU/l) among pregnant women with positive thyroid autoimmunity and those with negative autoimmunity. Results: We included 300 pregnant women with mean baseline TSH 1.3 ± 0.6 mIU/l (9th gestational week). Positive thyroid autoinmunity was detected in 17.7% of women (n = 53) at the first trimester. Between the first and the third trimesters, TPO and anti thyroglobulin antibodies titers decreased 76.8% and 80.7% respectively. Thyroid function during pregnancy was similar among the group with positive autoimmunity and the group with negative autoimmunity, and the development of hypothyroidism was 1.9% (1/53) and 2% (5/247) respectively. Pregnant women in whom TSH increased above 4 mIU/l (n = 6), had higher baseline TSH levels compared to those who maintained TSH ≤4 mIU/l during pregnancy (1.8 vs. 1.3 mIU/l; p=.047). Conclusion: In our population, women with TSH levels <2.5 mIU/l at the beginning of pregnancy have a minimal risk of developing gestational hypothyroidism regardless of thyroid autoimmunity


Assuntos
Humanos , Feminino , Gravidez , Adulto , Doenças da Glândula Tireoide/complicações , Complicações na Gravidez , Hipotireoidismo/complicações , Tireotropina/administração & dosagem , Autoimunidade/efeitos dos fármacos , Doenças da Glândula Tireoide/diagnóstico , Estudos Prospectivos , Estudos Longitudinais , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Antitireóideos/uso terapêutico
4.
World J Pediatr ; 15(2): 124-134, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30734891

RESUMO

BACKGROUND: Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is, therefore, of utmost importance to optimize physical and neurodevelopmental outcomes. DATA SOURCES: A PubMed search was completed in Clinical Queries using the key terms "hypothyroidism". RESULTS: Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. CONCLUSIONS: To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first 2 weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH < 5 mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism.


Assuntos
Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/tratamento farmacológico , Triagem Neonatal , Tireotropina/administração & dosagem , Tiroxina/administração & dosagem , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Lactente , Recém-Nascido , Masculino , Medição de Risco , Fatores Sexuais , Testes de Função Tireóidea , Resultado do Tratamento
5.
J Clin Endocrinol Metab ; 104(4): 1020-1028, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30398518

RESUMO

CONTEXT: Recombinant human thyrotropin (rhTSH) has been shown to be an effective stimulation method for radioactive iodine (RAI) therapy in differentiated thyroid cancer, including in those with nodal metastases (N1 DTC). OBJECTIVES: To demonstrate the noninferiority of rhTSH vs thyroid hormone withdrawal (THW) in preparation to RAI regarding disease status at the first evaluation in the real-life setting in patients with N1 DTC. DESIGN: This was a French multicenter retrospective study. Groups were matched according to age (<45/≥45 years), number of N1 nodes (≤5/>5 lymph nodes), and stage (pT1-T2/pT3). RESULTS: The cohort consisted of 404 patients pT1-T3/N1/M0 DTC treated with rhTSH (n = 205) or THW (n = 199). Pathological characteristics and initially administrated RAI activities (3.27 ± 1.00 GBq) were similar between the two groups. At first evaluation (6 to 18 months post-RAI), disease-free status was defined by thyroglobulin levels below threshold and a normal ultrasound. Disease-free rate was not inferior in the rhTSH group (75.1%) compared with the THW group (71.9%). The observed difference between the success rates was 3.3% (-6.6 to 13.0); rhTSH was therefore considered noninferior to THW because the upper limit of this interval was <15%. At the last evaluation (29.7 ± 20.7 months for rhTSH; 36.7 ± 23.8 months for THW), 83.5% (rhTSH) and 81.5% (THW) of patients achieved a complete response. This result was not influenced by any of the known prognostic factors. CONCLUSIONS: A preparation for initial RAI treatment with rhTSH was noninferior to that with THW in our series of pT1-T3/N1/M0-DTC on disease-free status outcomes at the first evaluation and after 3 years.


Assuntos
Quimiorradioterapia Adjuvante/métodos , Radioisótopos do Iodo/administração & dosagem , Neoplasias da Glândula Tireoide/terapia , Tireotropina/administração & dosagem , Tiroxina/uso terapêutico , Adulto , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Testes de Função Tireóidea , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/efeitos da radiação , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Suspensão de Tratamento
6.
Medicine (Baltimore) ; 97(2): e9084, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29480822

RESUMO

Pituitary stalk interruption syndrome (PSIS) is associated with simultaneous or subsequent pituitary hormone deficiencies (PHDs). Although the clinical features of multiple PHDs are well known, the status of the thyrotrophic axis in PSIS has not been thoroughly investigated.The clinical data of 89 PSIS patients and 34 Sheehan syndrome (SS) patients were retrospectively analyzed.The prevalence of central hypothyroidism in the PSIS patients and the SS patients was 79.8% and 70.6%, respectively. The thyroid-stimulating hormone (TSH) levels in the PSIS patients were significantly higher in comparison with the SS patients (5.13 ±â€Š3.40 vs 1.67 ±â€Š1.20 mU/L, P < .05). TSH elevation (8.79 ±â€Š3.17 mU/L) was noticed in 29 of 71 (40.85%) hypothyroid PSIS patients but not in the 24 hypothyroid SS patients. The TSH levels in the hypothyroid PSIS patients were significantly higher in comparison with the euthyroid PSIS patients (5.42 ±â€Š3.67 vs 3.66 ±â€Š1.50 mU/L). Thyroid hormone replacement significantly reduced the TSH levels in the PSIS patients with elevated TSH levels from 7.24 ±â€Š0.98 to 1.67 ±â€Š1.51 mU/L (P < .05). The logistic regression analysis suggested that TSH level was not significantly associated with pituitary stalk status and height of the anterior pituitary gland.PSIS is a newly recognized cause of central hypothyroidism. The proportion and amplitude of TSH elevations are higher in PSIS than in other causes of central hypothyroidism.


Assuntos
Doenças da Hipófise/metabolismo , Tireotropina/metabolismo , Adulto , Feminino , Terapia de Reposição Hormonal , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Doenças da Hipófise/diagnóstico por imagem , Doenças da Hipófise/tratamento farmacológico , Doenças da Hipófise/epidemiologia , Hipófise/diagnóstico por imagem , Hipófise/efeitos dos fármacos , Hipófise/metabolismo , Prevalência , Estudos Retrospectivos , Tireotropina/administração & dosagem , Adulto Jovem
7.
Eur J Nucl Med Mol Imaging ; 45(7): 1218-1223, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29460027

RESUMO

PURPOSE: Current guidelines recommend thyroid hormone withdrawal (THW) of 3-4 weeks before radioiodine remnant ablation (RRA) of differentiated thyroid carcinoma (DTC). We aimed to evaluate (1) the reliability of a shorter THW (i.e., 14 days) to achieve adequate TSH levels (i.e., 30 mU/l), (2) the association between length of THW and response to therapy, and (3) the potential association between pre-ablation TSH levels and patients' outcome. METHODS: After thyroidectomy, all patients started LT4 therapy, which was subsequently discontinued in order to perform RRA. Patients were broken down into two groups according to the length of THW: group A, 2 weeks of THW, and group B, 3-4 weeks of THW. We used clinical, biochemical, and imaging data to evaluate patients' outcome. By means of univariate and multivariate analysis, including main DTC prognostic factors, we assessed the impact of THW length and TSH levels on patients' outcome. RESULTS: We evaluated 222 patients, 85 of whom were treated with RRA after a THW period of 2 weeks (group A). All other 137 patients underwent RRA after 3-4 weeks THW (group B). At the time of RRA all patients presented TSH levels ≥30 mU/l. After a median follow-up time of 3.4 years, we found 183 patients (82%) with excellent response to treatment and 39 patients (18%) showing incomplete response. Kaplan-Meier response to therapy curves showed that ablation-Tg, tumor size, and lymph node status were significantly associated with prognosis; no associations were found between THW length, TSH levels, and prognosis. Multivariate Cox model showed that only ablation-Tg was significantly associated with treatment response. CONCLUSIONS: Prior to RRA, a short 2-week THW is an effective method to stimulate TSH levels. No difference in terms of incomplete response to treatment was observed between DTC patients prepared for RRA with a short THW and those with the long THW.


Assuntos
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tireotropina/administração & dosagem , Feminino , Humanos , Radioisótopos do Iodo , Itália , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Hormônios Tireóideos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/radioterapia , Tireoidectomia , Resultado do Tratamento
8.
Am J Physiol Regul Integr Comp Physiol ; 314(5): R734-R740, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29351420

RESUMO

Besides its well-known action to stimulate thyroid hormone release, thyrotropin mRNA is expressed within the brain, and thyrotropin and its receptor have been shown to be present in brain areas that control feeding and gastrointestinal function. Here, the hypothesis that thyrotropin acts on receptors in the hindbrain to alter food intake and/or gastric function was tested. Fourth ventricular injections of thyrotropin (0.06, 0.60, and 6.00 µg) were given to rats with chronic intracerebroventricular cannulas aimed at the fourth ventricle. Thyrotropin produced an acute reduction of sucrose intake (30 min). The highest dose of thyrotropin caused inhibition of overnight solid food intake (22 h). In contrast, subcutaneous administration of corresponding thyrotropin doses had no effect on nutrient intake. The highest effective dose of fourth ventricular thyrotropin (6 µg) did not produce a conditioned flavor avoidance in a standardized two-bottle test, nor did it affect water intake or gastric emptying of glucose. Thyrotropin injected in the fourth ventricle produced a small but significant increase in rectal temperature and lowered plasma levels of tri-iodothyronin but did not affect plasma levels of thyroxine. In addition, there was a tendency toward a reduction in blood glucose 2 h after fourth ventricular thyrotropin injection ( P = 0.056). In conclusion, fourth ventricular thyrotropin specifically inhibits food intake, increases core temperature, and lowers plasma levels of tri-iodothyronin but does not affect gastromotor function.


Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Rombencéfalo/efeitos dos fármacos , Resposta de Saciedade/efeitos dos fármacos , Tireotropina/administração & dosagem , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Masculino , Ratos Sprague-Dawley , Receptores da Tireotropina/agonistas , Receptores da Tireotropina/metabolismo , Rombencéfalo/metabolismo , Fatores de Tempo , Tri-Iodotironina/sangue
9.
Wiad Lek ; 70(4): 778-783, 2017.
Artigo em Polonês | MEDLINE | ID: mdl-29064805

RESUMO

Thyroid diseases belong to the most common disorders of the ductless glands. Particular attention is paid to the growing morbidity of autoimmune affliction of the thyroid gland, including Hashimoto's thyroiditis. The main method of treatment is an oral substitution of thyroid hormones. However, the literature pays particular attention to supporting therapy with a diet rich in components essential for the proper functioning of this organ.


Assuntos
Doença de Hashimoto/tratamento farmacológico , Oligoelementos/administração & dosagem , Adulto , Feminino , Doença de Hashimoto/prevenção & controle , Humanos , Tireotropina/administração & dosagem
10.
Medicine (Baltimore) ; 96(29): e7512, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28723762

RESUMO

In patients with differentiated thyroid cancer, stimulated thyroglobulin (sTg) levels after thyroid hormone withdrawal (THW) at remnant ablation (RA) and at 6 to 12 months are known to have good prognostic value. This study aimed to evaluate the prognostic impacts and best cutoff values of sTg levels under recombinant human thyroid stimulating hormone (rhTSH) treatment at RA and at follow-up. A total of 151 patients were enrolled, of whom 77 were followed up with rhTSH-stimulated Tg (rhTSH-sTg) and 74 with THW-stimulated Tg (THW-sTg) at 6 to 12 months after rhTSH-aided RA. Risk stratification, response to treatment (excellent, indeterminate, biochemical incomplete, and structural incomplete response [SIR]), and clinical outcome were accessed by revised American Thyroid Association (ATA) guideline criteria. Seven out of 151 (4.6%) patients were confirmed to have SIR during the median follow-up of 79.0 months; 3 in the rhTSH group and 4 in the THW group. One hundred thirty-two out of 151 (87.4%) patients were confirmed to have excellent response; 68 (51.5%) in the rhTSH group and 64 (48.5%) in the THW group. The cutoff values of sTg for predicting SIR to treatment at rhTSH-aided RA, THW-sTg, and rhTSH-sTg were 4.64 ng/mL (sensitivity 85.7%, specificity 76.4%, negative predictive value [NPV] 99.2%), 2.41 ng/mL (sensitivity 100%, specificity 94.3%, NPV 100%), and 1.02 ng/mL (sensitivity 66.7%, specificity 94.6%, NPV 98.6%), respectively. sTg levels using rhTSH at both RA and follow-up has a high NPV and are as effective as using THW for predicting SIR. The risk classification according to the revised ATA guidelines can be used effectively to supplement rhTSH-aided sTg levels to predict better clinical outcomes.


Assuntos
Radioisótopos do Iodo/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Tireoglobulina/sangue , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/terapia , Tireotropina/administração & dosagem , Biomarcadores Tumorais/sangue , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Risco , Sensibilidade e Especificidade , Fatores de Tempo , Resultado do Tratamento
11.
Clin Nucl Med ; 42(4): 247-249, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28166158

RESUMO

OBJECTIVE: In patients with differentiated thyroid carcinoma scheduled to receive doses of I for diagnostic or therapeutic purposes, we compared patients prepared with thyroid hormone withdrawal (THW) versus recombinant human thyroid stimulating hormone (rh-TSH) to evaluate the incidence of cancelled procedures because of inadequate thyroid stimulation. METHODS: Thyroid cancer patients after thyroidectomy who were scheduled for diagnostic or therapeutic I procedures between January 2012 and June 2015 were retrospectively reviewed. Patients were divided based on preparation modality (THW vs rh-TSH), and the incidence of cancelled procedures was compared. RESULTS: Charts from 761 patients were reviewed, 292 THW and 569 rh-TSH. A total of 10 patients (3.4%) in the THW group had cancelled procedures because of insufficient thyroid stimulation (TSH < 20 mU/L). If a TSH threshold of 30 mU/L were used, 57 patients (17.1%) would have been cancelled. Comparing the groups with chi-squared analysis for both TSH thresholds yielded significantly more cancellations in the THW group (P < 0.001). CONCLUSIONS: Our study has shown that THW in preparation for I procedures leads to significantly more cancellations because of insufficient thyroid stimulation as compared with rh-TSH, which led to no cancellations. The added cost and inconvenience to this cancer population should therefore be considered when selecting a preparation modality. LEVEL OF EVIDENCE: Retrospective cohort-Level III.


Assuntos
Carcinoma/diagnóstico por imagem , Radioisótopos do Iodo/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Tireotropina/administração & dosagem , Tiroxina/administração & dosagem , Adulto , Idoso , Carcinoma/tratamento farmacológico , Carcinoma/radioterapia , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia/métodos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Tireotropina/efeitos adversos , Tireotropina/uso terapêutico , Tiroxina/efeitos adversos , Tiroxina/uso terapêutico
12.
J Nucl Med ; 58(7): 1146-1154, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28104741

RESUMO

Patients with metastatic differentiated thyroid cancer (DTC) may be prepared using either thyroid-stimulating hormone withdrawal (THW) or recombinant human thyroid-stimulating hormone (rhTSH) injections before 131I administration for treatment. The objective of this study was to compare the absorbed dose to the critical organs and tumors determined by 124I PET/CT-based dosimetry for 131I therapy of metastatic DTC when the same patient was prepared with and imaged after both THW and rhTSH injections. Methods: Four DTC patients at MedStar Washington Hospital Center were first prepared using the rhTSH method and imaged by 124I PET/CT at 2, 24, 48, 72, and 96 h after administration of approximately 30-63 MBq of 124I. After 5-8 wk, the same patients were prepared using the THW method and imaged as before. The 124I PET/CT images acquired as part of a prospective study were used to perform retrospective dosimetric calculations for 131I therapy for the normal organs with the dosimetry package 3D-RD. The absorbed doses from 131I for the lungs, liver, heart, kidneys, and bone marrow were obtained for each study (rhTSH and THW). Twenty-two lesions in 3 patients were identified. The contours were drawn on each PET image of each study. Time-integrated activity coefficients were calculated and used as input in OLINDA/EXM sphere dose calculator to obtain the absorbed dose to tumors. Results: The THW-to-rhTSH organ absorbed dose ratio averaged over 5 organs for the first 3 patients was 1.5, 2.5, and 0.64, respectively, and averaged over 3 organs for the fourth patient was 1.1. The absorbed dose per unit administered activity to the bone marrow was 0.13, 0.086, 0.33, and 0.068 mGy/MBq after rhTSH and 0.11, 0.14, 0.22, and 0.080 mGy/MBq after THW for each patient, respectively. With the exception of 3 lesions of 1 patient, the absorbed dose per unit administered activity of 131I was higher in the THW study than in the rhTSH study. The ratio of the average tumor absorbed dose after stimulation by THW compared with stimulation by rhTSH injections was 3.9, 27, and 1.4 for patient 1, patient 2, and patient 3, respectively. The ratio of mean tumor to bone marrow absorbed dose per unit administered activity of 131I, after THW and rhTSH, was 232 and 62 (patient 1), 12 and 0.78 (patient 2), and 22 and 11 (patient 3), respectively. Conclusion: The results suggest a high patient variability in the overall absorbed dose to the normal organs per MBq of 131I administered, between the 2 TSH stimulation methods. The tumor-to-dose-limiting-organ (bone marrow) absorbed dose ratio, that is, the therapeutic index, was higher in the THW-aided than rhTSH-aided administrations. Additional comparison for tumor and normal organ absorbed dose in patients prepared using both methods is needed before definitive conclusions may be drawn regarding rhTSH versus THW patient preparation methods for 131I therapy of metastatic DTC.


Assuntos
Radioisótopos do Iodo/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/secundário , Tireotropina/administração & dosagem , Contagem Corporal Total/métodos , Absorção de Radiação , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Pré-Medicação/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Proteínas Recombinantes/administração & dosagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Resultado do Tratamento
13.
Clin Endocrinol (Oxf) ; 86(2): 263-269, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27581500

RESUMO

OBJECTIVE: The use of thyrotropin (TSH) in the initial assessment of thyroid nodules is inefficient and leads to unnecessary assessment costs. We compared the total costs of thyroid nodule assessment with or without the use of TSH in the initial assessment. METHODS: A total of 1808 patients with thyroid nodules received TSH, fine-needle aspiration (FNA) and thyroid scintigraphy (TS) assessment, including 83 autonomously functioning thyroid nodule (AFTN) cases and 1725 non-AFTN cases. The total costs of the TSH strategy and non-TSH strategies were compared. The ratio of single-use costs of FNA to TS (CFNA/TS ) was used as the main outcome measure. RESULTS: Only when 6·03 ≤ CFNA/TS ≤ 27·17, the lowest total costs were associated with using the conventional TSH strategy. When CFNA/TS <6·03 or CFNA/TS >27·17, the lowest costs were found with FNA and TS, respectively. CONCLUSION: From the perspective of cost economics, in iodine-sufficient areas, we recommend that the decision on the use of TSH for the initial assessment of thyroid nodules should be based on the testing costs of FNA and TS in that medical unit.


Assuntos
Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/economia , Tireotropina/administração & dosagem , Biópsia por Agulha Fina , Custos e Análise de Custo , Tomada de Decisões , Feminino , Humanos , Masculino , Curva ROC , Cintilografia/economia , Sensibilidade e Especificidade , Nódulo da Glândula Tireoide/diagnóstico por imagem , Tireotropina/economia
14.
Rev Esp Med Nucl Imagen Mol ; 36(1): 7-12, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27422154

RESUMO

AIM: Stimulation with recombinant human thyrotropin (rhTSH) increases thyroid radioiodine uptake, and is an aid to 131I therapy in non-toxic multinodular goitre (MNG). However, there are not many studies using rhTSH prior to 131I in toxic multinodular goitre to improve hyperthyroidism and compressive symptoms. MATERIAL AND METHOD: A prospective study was conducted on patients with MNG and hyperthyroidism. Patients were recruited consecutively and divided into group I, stimulated with 0.3mg of rhTSH before radioiodine therapy, and a control group or group II, without stimulation. Thyroid function, radioiodine thyroid uptake, thyroid weight, and compressive symptoms were measured, and patients were followed-up for 9 months. RESULTS: Group I consisted of 16 patients (14 women), with a mean age 69.7 years, and group II with 16 patients (12 women), with a mean age 70.7 years. After stimulation with 0.3mg rhTSH in group I, 131I uptake (RAIU) at 24h increased by 78.4%, and the estimated absorbed dose by 89.3%. In group II, the estimated absorbed dose was lower than group I after stimulation with rhTSH (29.8Gy vs. 56.4Gy; P=0.001). At 9 months of follow-up, hyperthyroidism was controlled in 87.5% of patients in group I, and 56.2% in group II (P=0.049). The mean reduction in thyroid weight was higher in group I than in group II (39.3% vs. 26.9%; P=0.017), with a tendency towards subjective improvement of compressive symptoms in group I, although non-significant. Only 2 patients described tachycardias after rhTSH administration, which were resolved with beta-blockers. CONCLUSION: Stimulation with 0.3mg of recombinant human thyrotropin prior to radioiodine therapy achieves a reduction in thyroid weight and functional improvement in patients with hyperthyroidism and multinodular goitre with low uptake, and with no need for hospital admission.


Assuntos
Bócio Nodular/radioterapia , Radioisótopos do Iodo/uso terapêutico , Glândula Tireoide/efeitos dos fármacos , Tireotropina/farmacologia , Idoso , Transtornos de Deglutição/etiologia , Disfonia/etiologia , Feminino , Seguimentos , Bócio Nodular/complicações , Bócio Nodular/metabolismo , Estudo Historicamente Controlado , Humanos , Hipertireoidismo/etiologia , Hipertireoidismo/radioterapia , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/farmacocinética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/efeitos dos fármacos , Estudos Prospectivos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Glândula Tireoide/metabolismo , Tireotropina/administração & dosagem
15.
Horm Res Paediatr ; 86(6): 410-415, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27902975

RESUMO

BACKGROUND: Little objective pediatric data exist to guide the optimal time needed to achieve thyroid-stimulating hormone (TSH) levels ≥30 µIU/mL prior to performing 131I or 123I whole-body scan (WBS) imaging in children with thyroid cancer in the post-thyroidectomy period or after hormone discontinuation. METHODS: Retrospective study of patients aged 5-19 years who underwent WBS. Patient data collection included type and duration of withdrawal (liothyronine [L-T3], levothyroxine [L-T4], or post-thyroidectomy status without hormonal replacement) and TSH measured prior to WBS (level and timing). RESULTS: A total of 175 TSH level measurements were performed in 68 patients. Thirty-five TSH values were obtained 2-7 weeks postoperatively and 101 values were obtained 2-8 weeks post L-T4 withdrawal. One patient in each group had a TSH level <30 µIU/mL. There was no difference in TSH levels between 3 weeks and 4 weeks postoperatively (p = 0.14) or post L-T4 cessation (p = 0.21). Thirty-nine TSH measurements were obtained 1-28 days post L-T3 withdrawal. Three patients had to be rescheduled due to inadequate TSH levels, including one after 14 days L-T3 withdrawal. CONCLUSION: TSH levels ≥30 µIU/mL were achieved at 3 weeks post thyroidectomy or after L-T4 withdrawal and after at least 2 weeks following L-T3 cessation.


Assuntos
Radioisótopos do Iodo/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias da Glândula Tireoide , Tireotropina/administração & dosagem , Tiroxina/sangue , Tri-Iodotironina/sangue , Imagem Corporal Total , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/tratamento farmacológico
16.
Semin Reprod Med ; 34(6): 337-342, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27750362

RESUMO

The incidence of subclinical hypothyroidism (SCH) in pregnancy was classically thought to be low; however, with new definition of normal TSH range in pregnancy, there has been an increase in the percentage of women who meet classification for SCH. The diagnosis of SCH is important not only for monitoring for maternal conversion to overt hypothyroidism, but also for identifying obstetric and neonatal outcomes related to SCH. Although there have been proven associations between maternal overt hypothyroidism and adverse obstetric and neonatal outcomes, there has been conflicting data on the correlation between SCH and these outcomes. Recent data from a meta-analysis found an increased risk of pregnancy loss, placental abruption, premature rupture of membranes, and neonatal death for women with SCH compared to euthyroidism in pregnancy. Research studies have not demonstrated a distinct benefit from treatment of SCH, and the professional societies are divided on their recommendations for treating SCH. Additionally, universal screening of SCH is controversial at present.


Assuntos
Progressão da Doença , Hipotireoidismo/diagnóstico , Complicações na Gravidez/diagnóstico , Tireotropina/sangue , Biomarcadores/sangue , Feminino , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/epidemiologia , Hipotireoidismo/imunologia , Incidência , Infertilidade Feminina/sangue , Infertilidade Feminina/complicações , Programas de Rastreamento , Guias de Prática Clínica como Assunto , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/imunologia , Resultado da Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Valores de Referência , Risco , Tireotropina/administração & dosagem
17.
Endocr Pract ; 22(11): 1319-1326, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27482609

RESUMO

OBJECTIVE: Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled. METHODS: The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed. RESULTS: LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy. CONCLUSION: LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being. ABBREVIATIONS: AACE = American Association of Clinical Endocrinologists FT3 = free triiodothyronine FT4 = free thyroxine LT3 = levotriiodothyronine LT4 = levothyroxine MeSH = medicine medical subject headings QoL = quality of life TSH = thyroid-stimulating hormone.


Assuntos
Endocrinologistas/normas , Terapia de Reposição Hormonal/normas , Hipotireoidismo/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Sociedades Médicas/normas , Tireotropina/administração & dosagem , Tiroxina/administração & dosagem , Tri-Iodotironina/administração & dosagem , Humanos
18.
Nuklearmedizin ; 55(6): 228-235, 2016 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-27480576

RESUMO

The aim of the study was to investigate the effects of rhTSH stimulation before 131I treatment in patients with MNG. METHODS: Sources included the Cochrane Library, MEDLINE, EMBASE, and SCOPUS database (all until January 2016). Randomized controlled trials (RCTs) that assessed the efficacy of rhTSH-stimulated 131I treatment compared to placebo or 131I treatment alone were collected. Two authors performed the data extraction independently. RESULTS: Six RCTs involving 294 patients with MNG were included in this review. Altogether 168 patients were randomized to rhTSH-stimulated 131I therapy, and 126 to either placebo and 131I or 131I alone. rhTSH-stimulated 131I vs placebo and 131I or 131I alone for MNG showed no statistically significant difference in quality of life and all-cause mortality. rhTSH- (at a dose of 0.03 mg and above) stimulated 131I treatment for MNG showed significant benefits in thyroid volume reduction. 131I treatment with rhTSH stimulation at high doses (0.03 mg, 0.1 mg, 0.3 mg and 0.45 mg) for MNG caused significantly higher adverse effects and hypothyroidism. CONCLUSIONS: The overall results indicated that using rhTSH at high doses of 0.03-0.45 mg before 131I therapy resulted in a greater TVR than 131I therapy alone for patients with non-toxic MNG. However, an increased incidence of adverse effects and hypothyroidism was observed in patients receiving high-dose of rhTSH pretreatment than in patients who received low-dose rhTSH pretreatment. Therefore, a dose of 0.03 mg rhTSH pretreatment before 131I therapy may be more potent than 131I alone in treating patients with non-toxic MNG who either had a contraindication for or declined surgery.


Assuntos
Quimiorradioterapia/mortalidade , Bócio Nodular/mortalidade , Bócio Nodular/terapia , Radioisótopos do Iodo/administração & dosagem , Tireotropina/administração & dosagem , Humanos , Tolerância a Radiação/efeitos dos fármacos , Compostos Radiofarmacêuticos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/administração & dosagem , Taxa de Sobrevida , Resultado do Tratamento
19.
Thyroid ; 26(11): 1528-1534, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27558484

RESUMO

BACKGROUND: The role of thyrotropin (TSH) on the cardiovascular system has been poorly investigated. It is unknown whether the changes in the vasculature associated with thyroid diseases result from altered thyroid hormone action or whether they are a consequence of a direct effect of TSH on endothelial cells. The present study was designed to evaluate the endothelial response of coronary flow to TSH in patients with differentiated thyroid cancer (DTC) without cardiovascular risk factors. METHODS: The study population consisted of three men and seven women (Mage = 32.6 ± 8 years) who underwent total thyroidectomy for DTC. All were receiving therapy with L-thyroxine to maintain TSH within the reference range. No patient was obese, or had hypertension, diabetes, or dyslipidemia. Patients underwent standard echo-Doppler examination with evaluation of the coronary flow reserve (CFR) of the distal left anterior descending artery obtained by cold pressure test (CPT) before and 24 h after the second recombinant human TSH (rhTSH) injection. RESULTS: Left ventricular morphology and systolic and diastolic function were normal in all patients. Levels of thyroid hormones and thyroglobulin and antithyroglobulin antibodies did not differ significantly pre- versus post-rhTSH treatment, whereas TSH levels were higher after rhTSH administration. Blood pressure and heart rate were not affected by rhTSH. Coronary flow peak velocity at rest (22.3 ± 6 vs 23.2 ± 8.7; p = 0.66) did not differ between baseline and 24 h after rhTSH, while post-CPT velocity (29.3 ± 6.8 vs 34.4 ± 10.9; p < 0.05) and the CFR were higher after rhTSH administration (1.32 ± 0.2 vs. 1.53 ± 0.2; p < 0.01). CONCLUSIONS: rhTSH administration may improve the CFR after the non-pharmacological stressor CPT in DTC patients. The increase of coronary blood flow after rhTSH suggests that TSH may exert a protective effect on the coronary endothelium.


Assuntos
Circulação Coronária/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Proteínas Recombinantes/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tireotropina/uso terapêutico , Adulto , Pressão Sanguínea/efeitos dos fármacos , Diferenciação Celular , Terapia Combinada/efeitos adversos , Ecocardiografia Doppler/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Injeções Intramusculares , Masculino , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacocinética , Volume Sistólico/efeitos dos fármacos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tireotropina/administração & dosagem , Tireotropina/genética , Tireotropina/metabolismo , Tiroxina/uso terapêutico , Adulto Jovem
20.
Thyroid ; 26(11): 1614-1622, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27349131

RESUMO

BACKGROUND: MicroSPECT/CT imaging was used to quantitatively evaluate how iodide uptake in the mouse thyroid is influenced by (i) route of iodine administration; (ii) injection of recombinant human thyrotropin (rhTSH); and (iii) low iodide diet (LID) in euthyroid and triiodothyronine (T3)-treated mice. METHODS: Pertechnetate (99mTcO4-) and 123I thyroid uptake in euthyroid and T3-treated animals fed either a normal-iodine diet (NID) or an LID, treated or not with rhTSH, and radiotracer administered intravenously, subcutaneously, intraperitoneally or by gavage, were assessed using microSPECT/CT imaging. Western blotting was performed to measure sodium/iodide symporter expression levels in the thyroid. RESULTS: Systemic administration of radioiodide resulted in a higher (2.35-fold in NID mice) accumulation of iodide in the thyroid than oral administration. Mice fed LID with systemic radioiodide administration showed a further two-fold increase in thyroid iodide uptake to yield a ∼5-fold increase in uptake compared to the standard NID/oral route. Although rhTSH injections stimulated thyroid activity in both euthyroid and T3-treated mice fed the NID, uptake levels for T3-treated mice remained low compared with those for the euthyroid mice. Combining LID and rhTSH in T3-treated mice resulted in a 2.8-fold higher uptake compared with NID/T3/rhTSH mice and helped restore thyroid activity to levels equivalent to those of euthyroid animals. CONCLUSIONS: Systemic radioiodide administration results in higher thyroidal iodide levels than oral administration, particularly in LID-fed mice. These data highlight the importance of LID, both in euthyroid and T3-treated, rhTSH-injected mice. Extrapolated to human patients, and in the context of clinical guidelines for the preparation of differentiated thyroid cancer patients, our data indicate that LID can potentiate the efficacy of rhTSH treatment in T3-treated patients.


Assuntos
Radioisótopos do Iodo/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Glândula Tireoide/diagnóstico por imagem , Tri-Iodotironina/farmacocinética , Administração Oral , Animais , Dieta/efeitos adversos , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Injeções Subcutâneas , Iodo/administração & dosagem , Iodo/efeitos adversos , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/metabolismo , Camundongos Endogâmicos C57BL , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/metabolismo , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacologia , Pertecnetato Tc 99m de Sódio/metabolismo , Pertecnetato Tc 99m de Sódio/farmacocinética , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Tireotropina/administração & dosagem , Tireotropina/efeitos adversos , Tireotropina/farmacologia , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único , Tri-Iodotironina/administração & dosagem , Tri-Iodotironina/metabolismo
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