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1.
BMC Cancer ; 19(1): 325, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953466

RESUMO

BACKGROUND: For progressive metastatic medullary thyroid carcinoma (MTC), the available treatment options with tyrosine kinase inhibitors result in grade 3-4 adverse events in a large number of patients. Peptide Receptor Radionuclide Therapy (PRRT), which has also been suggested to be a useful treatment for MTC, is usually well tolerated, but evidence on its effectivity is very limited. METHODS: Retrospective evaluation of treatment effects of PRRT in a highly selected group of MTC patients, with progressive disease or refractory symptoms. In addition, a retrospective evaluation of uptake on historical 111In-DTPA-octreotide scans was performed in patients with detectable tumor size > 1 cm. RESULTS: Over the last 17 years, 10 MTC patients were treated with PRRT. Four out of 10 patients showed stable disease at first follow-up (8 months after start of therapy) whereas the other 6 were progressive. Patients with stable disease were characterized by a combination of both a high uptake on 111In-DTPA-octreotide scan (uptake grade ≥ 3) and a positive somatostatin receptor type 2a (SSTR2a) expression of the tumor by immunohistochemistry. Retrospective evaluation of historical 111In-DTPA-octreotide scans of 35 non-treated MTC patients revealed low uptake (uptake grade 1) in the vast majority of patients 31/35 (89%) with intermediate uptake (uptake grade 2) in the remaining 4/35 (11%). CONCLUSIONS: PRRT using 177Lu-octreotate could be considered as a treatment in those patients with high uptake on 111In-DTPA-octreotide scan (uptake grade 3) and positive SSTR2a expression in tumor histology. Since this high uptake was present in a very limited number of patients, this treatment is only suitable in a selected group of MTC patients.


Assuntos
Carcinoma Neuroendócrino/radioterapia , Octreotida/análogos & derivados , Radioimunoterapia/métodos , Receptores de Somatostatina/metabolismo , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Idoso , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/patologia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Octreotida/uso terapêutico , Seleção de Pacientes , Ácido Pentético/administração & dosagem , Ácido Pentético/análogos & derivados , Intervalo Livre de Progressão , Cintilografia/métodos , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
2.
BMC Gastroenterol ; 18(1): 84, 2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29902988

RESUMO

BACKGROUND: Neuroendocrine tumours (NET) consist of a heterogeneous group of neoplasms with various organs of origin. At diagnosis 21% of the patients with a Grade 1 NET and 30% with a Grade 2 NET have distant metastases. Treatment with peptide receptor radionuclide therapy (PRRT) shows a high objective response rate and long median survival after treatment. However, complete remission is almost never achieved. The liver is the most commonly affected organ in metastatic disease and is the most incriminating factor for patient survival. Additional treatment of liver disease after PRRT may improve outcome in NET patients. Radioembolization is an established therapy for liver metastasis. To investigate this hypothesis, a phase 2 study was initiated to assess effectiveness and toxicity of holmium-166 radioembolization (166Ho-RE) after PRRT with lutetium-177 (177Lu)-DOTATATE. METHODS: The HEPAR PLUS trial ("Holmium Embolization Particles for Arterial Radiotherapy Plus 177 Lu-DOTATATE in Salvage NET patients") is a single centre, interventional, non-randomized, non-comparative, open label study. In this phase 2 study 30-48 patients with > 3 measurable liver metastases according to RECIST 1.1 will receive additional 166Ho-RE within 20 weeks after the 4th and last cycle of PRRT with 7.4 GBq 177Lu-DOTATATE. Primary objectives are to assess tumour response, complete and partial response according to RECIST 1.1, and toxicity, based on CTCAE v4.03, 3 months after 166Ho-RE. Secondary endpoints include biochemical response, quality of life, biodistribution and dosimetry. DISCUSSION: This is the first prospective study to combine PRRT with 177Lu-DOTATATE and additional 166Ho-RE in metastatic NET. A radiation boost on intrahepatic disease using 166Ho-RE may lead to an improved response rate without significant additional side-effects. TRIAL REGISTRATION: Clinicaltrials.gov NCT02067988 , 13 February 2014. Protocol version: 6, 30 november 2016.


Assuntos
Antineoplásicos/uso terapêutico , Embolização Terapêutica/métodos , Hólmio/uso terapêutico , Neoplasias Hepáticas/terapia , Tumores Neuroendócrinos/terapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Biomarcadores Tumorais , Terapia Combinada , Hólmio/efeitos adversos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Metástase Neoplásica , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/secundário , Octreotida/uso terapêutico , Qualidade de Vida , Radioisótopos/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Indução de Remissão , Análise de Sobrevida
3.
Eur J Nucl Med Mol Imaging ; 43(3): 453-63, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26419852

RESUMO

PURPOSE: In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from (131)I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with (177)Lu-DOTA(0)-Tyr(3)-octreotate ((177)Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit. METHODS: The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined. RESULTS: Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0 × 10(9)/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67 ± 7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq (177)Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients. CONCLUSION: The incidence of subacute haematological toxicity after PRRT with (177)Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from (131)I, seems not to be valid for PRRT with (177)Lu-DOTATATE.


Assuntos
Lutécio/química , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/química , Radioisótopos/química , Receptores de Peptídeos/química , Idoso , Medula Óssea/efeitos da radiação , Feminino , Humanos , Iodo/química , Masculino , Pessoa de Meia-Idade , Países Baixos , Tumores Neuroendócrinos/mortalidade , Octreotida/efeitos adversos , Octreotida/química , Compostos Organometálicos/efeitos adversos , Prognóstico , Estudos Prospectivos , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Radioisótopos/efeitos adversos , Radiometria , Compostos Radiofarmacêuticos/uso terapêutico , Fatores de Risco , Resultado do Tratamento
4.
Eur J Nucl Med Mol Imaging ; 43(10): 1802-11, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27160225

RESUMO

PURPOSE: After peptide receptor radionuclide therapy (PRRT), renal toxicity may occur, particular in PRRT with (90)Y-labelled somatostatin analogues. Risk factors have been identified for increased probability of developing renal toxicity after PRRT, including hypertension, diabetes and age. We investigated the renal function over time, the incidence of nephrotoxicity and associated risk factors in patients treated with PRRT with [(177)Lu-DOTA(0),Tyr(3)]-Octreotate ((177)Lu-Octreotate). Also, radiation dose to the kidneys was evaluated and compared with the accepted dose limits in external beam radiotherapy and PRRT with (90)Y-radiolabelled somatostatin analogues. METHODS: The annual decrease in creatinine clearance (CLR) was determined in 209 Dutch patients and the incidence of grade 3 or 4 renal toxicity (according to CTCAE v4.03) was evaluated in 323 patients. Risk factors were analysed using a nonlinear mixed effects regression model. Also, radiation doses to the kidneys were calculated and their association with high annual decrease in renal function were analysed. RESULTS: Of the 323 patients, 3 (1 %) developed (subacute) renal toxicity grade 2 (increase in serum creatinine >1.5 - 3.0 times baseline or upper limit of normal). No subacute grade 3 or 4 nephrotoxicity was observed. The estimated average baseline CLR (± SD) was 108 ± 5 ml/min and the estimated average annual decrease in CLR (± SD) was 3.4 ± 0.4 %. None of the risk factors (hypertension, diabetes, high cumulative injected activity, radiation dose to the kidneys and CTCAE grade) at baseline had a significant effect on renal function over time. The mean absorbed kidney dose in 228 patients was 20.1 ± 4.9 Gy. CONCLUSION: Nephrotoxicity in patients treated with (177)Lu-octreotate was low. No (sub)acute grade 3 or 4 renal toxicity occurred and none of the patients had an annual decrease in renal function of >20 %. No risk factors for renal toxicity could be identified. Our data support the idea that the radiation dose threshold, adopted from external beam radiotherapy and PRRT with (90)Y-labelled somatostatin analogues, does not seem valid for PRRT with (177)Lu-octreotate.


Assuntos
Complexos de Coordenação/uso terapêutico , Nefropatias/mortalidade , Neoplasias/mortalidade , Neoplasias/radioterapia , Octreotida/análogos & derivados , Lesões por Radiação/mortalidade , Radioterapia/mortalidade , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Humanos , Incidência , Masculino , Terapia de Alvo Molecular/mortalidade , Países Baixos/epidemiologia , Octreotida/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Dosagem Radioterapêutica , Fatores de Risco , Taxa de Sobrevida
5.
Eur J Nucl Med Mol Imaging ; 42(2): 222-30, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25267348

RESUMO

PURPOSE: The aim of this study was to find clinically relevant MIBG-avid metastatic patterns in patients with newly diagnosed stage 4 neuroblastoma. METHODS: Diagnostic (123)I-MIBG scans from 249 patients (123 from a European and 126 from the COG cohort) were assessed for metastatic spread in 14 body segments and the form of the lesions: "focal" (clear margins distinguishable from adjacent background) or "diffuse" (indistinct margins, dispersed throughout the body segment). The total numbers of diffuse and focal lesions were recorded. Patients were then categorized as having lesions exclusively focal, lesions more focal than diffuse, lesions more diffuse than focal, or lesions exclusively diffuse. RESULTS: Diffuse lesions affected a median of seven body segments and focal lesions a median of two body segments (P < 0.001, both cohorts). Patients with a focal pattern had a median of 2 affected body segments and those with a diffuse pattern a median of 11 affected body segments (P < 0.001, both cohorts). Thus, two MIBG-avid metastatic patterns emerged: "limited-focal" and "extensive-diffuse". The median numbers of affected body segments in MYCN-amplified (MNA) tumours were 5 (European cohort) and 4 (COG cohort) compared to 9 and 11, respectively, in single-copy MYCN (MYCNsc) tumours (P < 0.001). Patients with exclusively focal metastases were more likely to have a MNA tumour (60% and 70%, respectively) than patients with the other types of metastases (23% and 28%, respectively; P < 0.001). In a multivariate Cox regression analysis, focal metastases were associated with a better event-free and overall survival than the other types of metastases in patients with MNA tumours in the COG cohort (P < 0.01). CONCLUSION: Two metastatic patterns were found: a "limited and focal" pattern found mainly in patients with MNA neuroblastoma that correlated with prognosis, and an "extensive and diffuse" pattern found mainly in patients with MYCNsc neuroblastoma.


Assuntos
3-Iodobenzilguanidina , Neuroblastoma/diagnóstico por imagem , Proteínas Nucleares/genética , Proteínas Oncogênicas/genética , Compostos Radiofarmacêuticos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Imagem Multimodal , Proteína Proto-Oncogênica N-Myc , Metástase Neoplásica/diagnóstico por imagem , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Neuroblastoma/genética , Neuroblastoma/patologia , Tomografia por Emissão de Pósitrons , Valor Preditivo dos Testes , Prognóstico , Tomografia Computadorizada por Raios X
6.
Eur J Nucl Med Mol Imaging ; 40(12): 1843-52, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23877632

RESUMO

PURPOSE: The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). METHODS: In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. RESULTS: In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 ± 0.01 to 2.26 ± 0.02 mmol/l, p = 0.02). Eight patients (17%) showed a marked decrease in serum calcium levels with a nadir of ≤ 2.10 mmol/l. In five patients (11%), calcium substitution therapy was prescribed. PTH increased significantly (5.9 ± 0.6 to 6.7 ± 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 ± 3 to 77 ± 3 µmol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 ± 0.01 at baseline to a nadir of 2.24 ± 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22%) showed a serum calcium nadir of ≤ 2.10 mmol/l, and 11 (7%) received calcium substitution therapy. CONCLUSION: The mean serum calcium level decreased significantly after treatment with (177)Lu-octreotate, resulting in mild hypocalcaemia in about 20% of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate.


Assuntos
Hipocalcemia/sangue , Hipocalcemia/induzido quimicamente , Octreotida/análogos & derivados , Compostos Organometálicos/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Cálcio/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/radioterapia , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Compostos Organometálicos/uso terapêutico
7.
Neuroendocrinology ; 97(1): 74-85, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22237390

RESUMO

The primary treatment of gastroenteropancreatic neuroendocrine tumors (GEPNETs) is surgery with curative intent or debulking of the tumor mass. In case of metastatic disease, cytoreductive options are limited. A relatively new therapeutic modality, peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs, is currently available in a number of mostly European centers. Complete and partial responses obtained after treatment with [90Y-DOTA0,Tyr3]octreotide are in the same range as after treatment with [177Lu-DOTA0,Tyr3]octreotate (i.e. 10-30%). However, significant nephrotoxicity has been observed after treatment with [90Y-DOTA0,Tyr3]octreotide. Options to improve PRRT may include combinations of radioactive labeled somatostatin analogs, intra-arterial administration, and the use of radiosensitizing drugs combined with PRRT. Other therapeutic applications of PRRT may include additional therapy cycles in patients with progressive disease after benefit from initial therapy, PRRT in adjuvant or neoadjuvant setting, or PRRT combined with new targeted therapies, such as sunitinib or everolimus. Randomized clinical trials comparing PRRT with other treatment modalities, or comparing various radioactive labeled somatostatin analogs should be undertaken to determine the best treatment options and treatment sequelae for patients with GEPNETs.


Assuntos
Carcinoma Neuroendócrino/terapia , Neoplasias Gastrointestinais/terapia , Neoplasias Pancreáticas/terapia , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Receptores de Peptídeos/metabolismo , Humanos
8.
JAMA Surg ; 157(11): 991-999, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36069889

RESUMO

Importance: Several less-invasive staging procedures have been proposed to replace axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) in patients with initially clinically node-positive (cN+) breast cancer, but these procedures may fail to detect residual disease. Owing to the lack of high-level evidence, it is not yet clear which procedure is most optimal to replace ALND. Objective: To determine the diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy (RISAS), a targeted axillary dissection procedure. Design, Setting, and Participants: This was a prospective, multicenter, noninferiority, diagnostic accuracy trial conducted from March 1, 2017, to December 31, 2019. Patients were included within 14 institutions (general, teaching, and academic) throughout the Netherlands. Patients with breast cancer clinical tumor categories 1 through 4 (cT1-4; tumor diameter <2 cm and up to >5 cm or extension to the chest wall or skin) and pathologically proven positive axillary lymph nodes (ie, clinical node categories cN1, metastases to movable ipsilateral level I and/or level II axillary nodes; cN2, metastases to fixed or matted ipsilateral level I and/or level II axillary nodes; cN3b, metastases to ipsilateral level I and/or level II axillary nodes with metastases to internal mammary nodes) who were treated with NAC were eligible for inclusion. Data were analyzed from July 2020 to December 2021. Intervention: Pre-NAC, the marking of a pathologically confirmed positive axillary lymph node with radioactive iodine seed (MARI) procedure, was performed and after NAC, sentinel lymph node biopsy (SLNB) combined with excision of the marked lymph node (ie, RISAS procedure) was performed, followed by ALND. Main Outcomes and Measures: The identification rate, false-negative rate (FNR), and negative predictive value (NPV) were calculated for all 3 procedures: RISAS, SLNB, and MARI. The noninferiority margin of the observed FNR was 6.25% for the RISAS procedure. Results: A total of 212 patients (median [range] age, 52 [22-77] years) who had cN+ breast cancer underwent the RISAS procedure and ALND. The identification rate of the RISAS procedure was 98.2% (223 of 227). The identification rates of SLNB and MARI were 86.4% (197 of 228) and 94.1% (224 of 238), respectively. FNR of the RISAS procedure was 3.5% (5 of 144; 90% CI, 1.38-7.16), and NPV was 92.8% (64 of 69; 90% CI, 85.37-97.10), compared with an FNR of 17.9% (22 of 123; 90% CI, 12.4%-24.5%) and NPV of 72.8% (59 of 81; 90% CI, 63.5%-80.8%) for SLNB and an FNR of 7.0% (10 of 143; 90% CI, 3.8%-11.6%) and NPV of 86.3% (63 of 73; 90% CI, 77.9%-92.4%) for the MARI procedure. In a subgroup of 174 patients in whom SLNB and the MARI procedure were successful and ALND was performed, FNR of the RISAS procedure was 2.5% (3 of 118; 90% CI, 0.7%-6.4%), compared with 18.6% (22 of 118; 90% CI, 13.0%-25.5%) for SLNB (P < .001) and 6.8% (8 of 118; 90% CI, 3.4%-11.9%) for the MARI procedure (P = .03). Conclusions and Relevance: Results of this diagnostic study suggest that the RISAS procedure was the most feasible and accurate less-invasive procedure for axillary staging after NAC in patients with cN+ breast cancer.


Assuntos
Neoplasias da Mama , Iodo , Linfonodo Sentinela , Neoplasias da Glândula Tireoide , Humanos , Pessoa de Meia-Idade , Feminino , Biópsia de Linfonodo Sentinela/métodos , Axila , Terapia Neoadjuvante , Neoplasias da Mama/patologia , Radioisótopos do Iodo/uso terapêutico , Estudos Prospectivos , Iodo/uso terapêutico , Metástase Linfática/patologia , Neoplasias da Glândula Tireoide/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodo Sentinela/patologia
9.
Thyroid ; 30(4): 580-587, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31928168

RESUMO

Background: Although international guidelines have become more conservative on the use of radioactive iodine (RAI) therapy, it is still one of the cornerstones of the treatment of patients with advanced differentiated thyroid cancer (DTC). As a large proportion of females diagnosed with DTC is in their reproductive years, knowledge about the effect of RAI on their gonadal and reproductive function is important. Earlier studies evaluating Anti-Müllerian hormone (AMH) as a representative of ovarian reserve were either cross-sectional, had relatively low numbers, had no patients with multiple RAI therapies, or had a relatively short follow-up. The primary aim of our study was, therefore, to prospectively evaluate the effect of RAI on AMH in women undergoing treatment for DTC. Methods: We included females, aged 16 years until menopause, who were scheduled to undergo their first RAI treatment for DTC at our hospital. Serum AMH was measured before initial therapy and regularly thereafter. Repeated measurement analysis was used to assess the changes of AMH concentrations over time, and how this is influenced by age and cumulative RAI dose. Results: Longitudinal AMH assessments were available in 65 patients (mean age 32 years, median of five measurements during median follow-up of 34 months). AMH concentrations changed nonlinear over time, decreased until 12 months in the single RAI group (-55%), and stabilized thereafter. In the multiple RAI group, after stabilization, a further decrease occurred (-85% after 48 months). Age in both RAI groups significantly influenced AMH change over time, with younger patients (<35 years of age) showing a less steep decrease. Conclusions: In a population of female DTC patients treated with total thyroidectomy and a single RAI therapy, AMH concentrations significantly dropped during the first year after initial therapy, and thereafter they remained stable. In patients receiving multiple RAI therapies, a further decrease was seen. Age at baseline significantly influenced AMH change over time. These results support a less aggressive treatment with RAI in low-risk patients as is advocated in the current American Thyroid Association (ATA) guidelines, especially in females older than 35 years of age with the desire to have a child.


Assuntos
Hormônio Antimülleriano/sangue , Infertilidade Feminina/etiologia , Radioisótopos do Iodo/administração & dosagem , Reserva Ovariana/efeitos da radiação , Neoplasias da Glândula Tireoide/radioterapia , Adolescente , Adulto , Fatores Etários , Feminino , Humanos , Infertilidade Feminina/sangue , Radioisótopos do Iodo/efeitos adversos , Radioisótopos do Iodo/uso terapêutico , Estudos Longitudinais , Pessoa de Meia-Idade , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto Jovem
10.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31665318

RESUMO

CONTEXT: Current American Thyroid Association (ATA) Management Guidelines for the treatment of differentiated thyroid cancer (DTC) stratify patients to decide on additional radioiodine (RAI) therapy after surgery, and to predict recurring/persisting disease. However, studies evaluating the detection of distant metastases and how these guidelines perform in patients with distant metastases are scarce. OBJECTIVE: To evaluate the 2015 ATA Guidelines in DTC patients with respect to 1) the detection of distant metastases, and 2) the accuracy of its Risk Stratification System in patients with distant metastases. PATIENTS AND MAIN OUTCOME MEASURES: We retrospectively included 83 DTC patients who were diagnosed with distant metastases around the time of initial therapy, and a control population of 472 patients (312 low-risk, 160 intermediate-risk) who did not have a routine indication for RAI therapy. We used the control group to assess the percentage of distant metastases that would have been missed if no RAI therapy was given. RESULTS: Two hundred forty-six patients had no routine indication for RAI therapy of which 4 (1.6%) had distant metastases. Furthermore, among the 83 patients with distant metastases, 14 patients (17%) had excellent response, while 55 (67%) had structural disease after a median follow-up of 62 months. None of the 14 patients that achieved an excellent response had a recurrence. CONCLUSIONS: In patients without a routine indication for RAI therapy according to the 2015 ATA Guidelines, distant metastases would initially have been missed in 1.6% of the patients. Furthermore, in patients with distant metastases upon diagnosis, the 2015 ATA Guidelines are an excellent predictor of both persistent disease and recurrence.


Assuntos
Adenocarcinoma Folicular/prevenção & controle , Endocrinologia/normas , Guias de Prática Clínica como Assunto , Câncer Papilífero da Tireoide/prevenção & controle , Neoplasias da Glândula Tireoide/terapia , Adenocarcinoma Folicular/diagnóstico , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Endocrinologia/métodos , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Organizações sem Fins Lucrativos/normas , Seleção de Pacientes , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/normas , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/normas , Fatores de Risco , Sociedades Médicas/normas , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/epidemiologia , Câncer Papilífero da Tireoide/secundário , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia/normas , Estados Unidos/epidemiologia
11.
Eur J Endocrinol ; 181(6): 671-679, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31639771

RESUMO

OBJECTIVE: Earlier cross-sectional studies showed that patients with differentiated thyroid cancer (DTC) have a significant reduction of quality of life (QoL) compared to controls. However, recent longitudinal studies showed mixed results and had relative short follow-up or lacked knowledge about QoL before initial surgery. Therefore, we initiated a longitudinal study to assess changes of QoL in patients undergoing treatment for DTC. METHODS: We prospectively included patients, aged 18-80 years, who were treated for DTC at a Dutch university hospital. Using questionnaires, QoL was assessed before surgery, just before radioiodine (RAI) therapy, and regularly during follow-up. Repeated measurement analysis was used to assess changes of QoL over time, and we explored the influence of different characteristics on QoL. RESULTS: Longitudinal QoL assessments were available in 185 patients (mean age 47 years; 71% women). All patients were treated according to the Dutch guidelines with total thyroidectomy followed by RAI (83% after thyroid hormone withdrawal). Median time between baseline and final questionnaire was 31 months, and patients completed a median of three questionnaires. QoL at baseline was lower than that in the general population, developed non-linear over time, was lowest around RAI therapy, and recovered over time. Females, younger patients, and patients with persistent hypoparathyroidism had lower QoL scores. CONCLUSIONS: In a population of DTC patients, QoL before initial therapy is already lower than that in the general population. Thereafter, QoL develops non-linearly over time in general, with the lowest QoL around RAI therapy, while 2 to 3 years later, it approximates baseline values.


Assuntos
Neoplasias da Glândula Tireoide/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Adulto Jovem
12.
J Clin Endocrinol Metab ; 104(4): 1336-1344, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30566620

RESUMO

PURPOSE: Peptide receptor radionuclide therapy (PRRT) with the radiolabeled somatostatin analogue [Lutetium-177-DOTA0-Tyr3]octreotate (177Lu-DOTATATE) is widely applied for inoperable metastatic small intestinal and nonfunctioning pancreatic neuroendocrine tumors (pNETs). The aim of this study is to describe the safety and efficacy of the treatment of functioning pNETs. METHODS: Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gbq per cycle. Radiological (Response Evaluation Criteria in Solid Tumors 1.1), symptomatic, and biochemical response were analyzed retrospectively for all patients with a functioning pNET (insulinoma, gastrinoma, VIPoma, and glucagonoma) treated with 177Lu-DOTATATE. Quality of life (QOL) was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module questionnaire. RESULTS: Thirty-four patients with a metastatic functioning pNET (European Neuroendocrine Tumor Society grade 1 or 2) were included: 14 insulinomas, 5 VIPomas, 7 gastrinomas, and 8 glucagonomas. Subacute hematological toxicity, grade 3 or 4 occurred in 4 patients (12%) and a hormonal crisis in 3 patients (9%). PRRT resulted in partial or complete response in 59% of patients and the disease control rate was 78% in patients with baseline progression. 71% of patients with uncontrolled symptoms had a reduction of symptoms and a more than 80% decrease of circulating hormone levels was measured during follow-up. After PRRT, median progression-free survival was 18.1 months (interquartile range: 3.3 to 35.7) with a concurrent increase in QOL. CONCLUSION: Treatment with 177Lu-DOTATATE is a safe and effective therapy resulting in radiological, symptomatic and biochemical response in a high percentage of patients with metastatic functioning pNETs. Hormonal crises occur relatively frequent and preventive therapy should be considered before and/or during PRRT.


Assuntos
Complexos de Coordenação/administração & dosagem , Lutécio/administração & dosagem , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Neoplasias Pancreáticas/radioterapia , Radioisótopos/administração & dosagem , Adulto , Idoso , Complexos de Coordenação/efeitos adversos , Feminino , Gastrinas/sangue , Gastrinas/metabolismo , Glucagon/sangue , Glucagon/metabolismo , Humanos , Insulina/sangue , Insulina/metabolismo , Lutécio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/sangue , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Octreotida/efeitos adversos , Pâncreas/metabolismo , Pâncreas/patologia , Pâncreas/efeitos da radiação , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Qualidade de Vida , Doses de Radiação , Radioisótopos/efeitos adversos , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Peptídeo Intestinal Vasoativo/sangue , Peptídeo Intestinal Vasoativo/metabolismo
13.
Thyroid ; 29(8): 1073-1079, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31140385

RESUMO

Background: The 2015 American Thyroid Association (ATA) Risk Stratification System for differentiated thyroid cancer (DTC) is designed to predict recurring/persisting disease but not survival. Earlier studies evaluating this system evaluated the 2009 edition, comprised a low number of patients with ATA high-risk, had low numbers of patients with follicular thyroid cancer (FTC), or did not distinguish between papillary and FTC. Therefore, we evaluated the prognostic value of the 2015 ATA Risk Stratification System in a large population of high-risk thyroid cancer patients, which included a substantial proportion of FTC patients. Methods: We retrospectively studied adult patients with DTC who were diagnosed and/or treated at a Dutch university hospital between January 2002 and December 2015. All patients fulfilled the 2015 ATA high-risk criteria. Overall survival and disease-specific survival (DSS) were analyzed using the Kaplan-Meier method. Logistic regression and Cox proportional hazards models were used to estimate the effects of DTC subtype and ATA high-risk criteria on response to therapy, recurrence, as well as survival. Results: We included 236 patients with high-risk DTC (32% FTC) with a mean age of 56 years. Median follow-up was 6 years. At final follow-up, 69 patients (29%) had excellent response, while 120 (51%) had structural disease. All high-risk criteria, except large pathologic lymph nodes, were inversely related to excellent response and positively related to structural disease at final follow-up. During follow-up, 14% of the 79 patients who achieved excellent response developed a recurrence. Finally, 10-year DSS was much higher in the initial excellent response than in the initial structural disease group (100% vs. 61%, respectively). Conclusions: In a population of high-risk DTC patients harboring a large subset of FTC patients, the 2015 ATA Risk Stratification System is not only an excellent predictor of persisting disease but also of survival. As much as 14% of the high-risk patients who had an excellent response upon dynamic risk stratification experienced a recurrence during follow-up. Clinicians should thus be aware of the relatively high recurrence risk in these patients, even after an excellent response to therapy.


Assuntos
Adenocarcinoma Folicular/terapia , Adenoma Oxífilo/terapia , Recidiva Local de Neoplasia , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia , Adenocarcinoma Folicular/mortalidade , Adenocarcinoma Folicular/patologia , Adenoma Oxífilo/mortalidade , Adenoma Oxífilo/patologia , Adulto , Idoso , Neoplasias Ósseas/secundário , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Estimativa de Kaplan-Meier , Modelos Logísticos , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Países Baixos , Prognóstico , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/uso terapêutico , Radioterapia , Estudos Retrospectivos , Medição de Risco , Sociedades Médicas , Taxa de Sobrevida , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Tireoidectomia , Resultado do Tratamento , Carga Tumoral
14.
Eur J Endocrinol ; 181(1): 45-53, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31067510

RESUMO

OBJECTIVES: Inoperable or metastatic paragangliomas (PGLs) and malignant pheochromocytomas (PCCs) are rare tumours with limited options for systemic treatment. Aim of this study was to assess the safety and efficacy of the radiolabelled somatostatin analogue (177LutetiumDOTA0-Tyr3)octreotate (177Lu-DOTATATE) for the treatment of PGLs and PCCs. METHODS: Patients with histologically proven inoperable or malignant PGLs and PCCs treated with 177Lu-DOTATATE at our centre were retrospectively analysed. Patients were treated with up to four cycles of 177Lu-DOTATATE with an intended dose of 7.4 Gb per cycle. Response was assessed with use of RECIST 1.1. RESULTS: Thirty patients were included: 17 with parasympathetic, 10 with sympathetic PGLs and 3 with PCCs. Grade 3/4 subacute haematotoxicity occurred in 6 (20%) of patients. A reversible subacute adverse event due to cardiac failure following possible catecholamine release occurred in two patients. Best tumour response was partial response in 7 (23%) and stable disease in 20 (67%), whereas 3 (10%) patients had progressive disease. In 20 patients with baseline disease progression, tumour control was observed in 17 (85%); the median progression-free survival was 91 months in patients with parasympathetic PGLs, 13 months in patients with sympathetic PGLs and 10 months in patients with metastatic PCCs. CONCLUSION: This study suggests that PRRT with 177Lu-DOTATATE is a safe and effective treatment option for patients with inoperable or malignant PGL and PCC.


Assuntos
Neoplasias das Glândulas Suprarrenais/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Paraganglioma/radioterapia , Feocromocitoma/radioterapia , Radioisótopos/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Octreotida/uso terapêutico , Doses de Radiação , Receptores de Peptídeos/efeitos da radiação , Estudos Retrospectivos , Resultado do Tratamento
15.
Physiol Rep ; 6(20): e13883, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30350459

RESUMO

Thyroid hormone importantly affects the cardiovascular system. However, evaluation of stroke volume (SV) and its determinants is confounded by variations in volume status that occur along different thyroid states. This study applied the pressure-volume (PV) framework to obtain relatively load-independent estimates of cardiac function in hypothyroidism as compared to euthyroidism. Ten athyroid patients were assessed echocardiographically after 4 weeks in deep hypothyroid state, and again after supplementation with oral Levothyroxine (LT4) for 3 months. Thyroid hormone levels were assessed and noninvasive pressure-volume (PV) analysis based on dedicated repeated echocardiograms was performed. Changes were assessed using paired tests. Results are presented as medians and interquartile ranges. Hypothyroidism was associated with reduced stroke volume (SV: 67.6 ± 17 vs. 75.7 ± 20.6 mL, P = 0.024), preload (end-diastolic volume, EDV: 122.6 ± 32.5 vs. 135.7 ± 33.6 mL, P = 0.004), and contractility (end-systolic elastance, Ees : 1.7 ± 0.33 vs. 2.58 ± 1.33 mmHg/mL, P = 0.01). Afterload was constant (effective arterial elastance, Ea : 1.66 ± 0.32 vs. 1.79 ± 0.52 mmHg/mL, P = 0.43) and the total energy spent was lower (PVA∙HR: 86.7 ± 28 vs. 110.9 ± 32.1 J, P = 0.04). Hemodynamic manifestations of frank hypothyroidism in humans are characterized by reduced preload and contractility, and unchanged total afterload. LT4 therapy increased work efficiency and heart rate, but not the net energy expenditure. Noninvasive PV analysis may be useful to follow-up different thyroid states.


Assuntos
Coração/efeitos dos fármacos , Hipotireoidismo/fisiopatologia , Volume Sistólico , Tiroxina/farmacologia , Adulto , Feminino , Coração/fisiologia , Humanos , Hipotireoidismo/etiologia , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Projetos Piloto , Tireoidectomia/efeitos adversos , Tiroxina/administração & dosagem , Tiroxina/efeitos adversos
16.
Thyroid ; 28(8): 976-981, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29848239

RESUMO

BACKGROUND: Recently, the eighth edition of the American Joint Committee on Cancer (AJCC)/tumor node metastasis (TNM) staging system for differentiated thyroid cancer (DTC) was published. Studies evaluating this new edition have so far only comprised patients with papillary thyroid cancer (PTC) or made no distinction between PTC and follicular thyroid cancer (FTC). Therefore, this study evaluated the prognostic value of the eighth edition of the AJCC/TNM staging system in a European population with DTC, focusing on potential differences between PTC and FTC. METHODS: Adult patients with DTC who were diagnosed and/or treated at a Dutch university hospital between January 2002 and April 2016 were retrospectively studied. Overall survival (OS) and disease-specific survival (DSS) were analyzed for DTC and for PTC and FTC separately according to the seventh and eighth editions using the Kaplan-Meier method. Cox's proportional hazards model was used to compare the effect of PTC and FTC on survival. The statistical model performance was assessed using the C-index, Akaike information criterion (AIC), and the Bayesian information criterion. RESULTS: The study included 792 patients with DTC (79% PTC, 21% FTC) with mean age of 49 years. Median follow-up was 7.2 years. Reclassification using the eighth edition resulted in the downstaging of 282 (36%) patients, an increased number of patients in stages I and II, and an equivalent decrease in patients with stages III and IV. For DTC, as well as for PTC and FTC separately, stage at diagnosis was significantly related to both OS and DSS (p < 0.001). When using the seventh edition, FTC patients had a significantly lower survival rate than PTC patients in stage I and stage IV for OS, and in stage IV for DSS. This difference in survival rates disappeared using the eighth edition. In general, the statistical model performance was better for the eighth than for the seventh edition. CONCLUSIONS: In a European population of patients with DTC, the eighth edition of the AJCC/TNM staging system is a better predictor for both OS and DSS than the previous seventh edition for both PTC and FTC. Furthermore, differences in survival rates between PTC and FTC that were present using the seventh edition disappeared using the eighth edition, implying that this new edition is predicting well, regardless of DTC subtype.


Assuntos
Adenocarcinoma Folicular/patologia , Carcinoma Papilar/patologia , Metástase Neoplásica/patologia , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/mortalidade , Adulto , Idoso , Carcinoma Papilar/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade
17.
J Clin Endocrinol Metab ; 103(1): 169-178, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29069456

RESUMO

Context: Despite the well-recognized clinical features resulting from insufficient or excessive thyroid hormone (TH) levels in humans, it is largely unknown which genes are regulated by TH in human tissues. Objective: To study the effect of TH on human gene expression profiles in whole blood, mainly consisting of T3 receptor (TR) α-expressing cells. Methods: We performed next-generation RNA sequencing on whole blood samples from eight athyroid patients (four females) on and after 4 weeks off levothyroxine replacement. Gene expression changes were analyzed through paired differential expression analysis and confirmed in a validation cohort. Weighted gene coexpression network analysis (WGCNA) was applied to identify thyroid state-related networks. Results: We detected 486 differentially expressed genes (fold-change >1.5; multiple testing corrected P value < 0.05), of which 76% were positively and 24% were negatively regulated. Gene ontology (GO) enrichment analysis revealed that three biological processes were significantly overrepresented, of which the process translational elongation showed the highest fold enrichment (7.3-fold, P = 1.8 × 10-6). WGCNA analysis independently identified various gene clusters that correlated with thyroid state. Further GO analysis suggested that thyroid state affects platelet function. Conclusions: Changes in thyroid state regulate numerous genes in human whole blood, predominantly TRα-expressing leukocytes. In addition, TH may regulate gene transcripts in platelets.


Assuntos
Biomarcadores/metabolismo , Plaquetas/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Receptores dos Hormônios Tireóideos/metabolismo , Glândula Tireoide/metabolismo , Tiroxina/farmacologia , Plaquetas/efeitos dos fármacos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Masculino , Prognóstico , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/patologia
18.
PLoS One ; 13(4): e0194259, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29649216

RESUMO

BACKGROUND: Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone. OBJECTIVE: To study if serum miRNA profiles are changed in different thyroid states. DESIGN AND METHODS: We studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification. RESULTS: Mean age of the subjects was 44.0 years (range 20-61 years). Median TSH levels were 88.9 mU/l during levothyroxine withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1 µg/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment. CONCLUSION: Although we previously showed an up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle, the present study does not supply evidence that thyroid state also affects serum miRNAs in humans.


Assuntos
Hipotireoidismo/tratamento farmacológico , MicroRNAs/sangue , Glândula Tireoide/cirurgia , Hormônios Tireóideos/sangue , Tiroxina/uso terapêutico , Adulto , Biomarcadores/sangue , Feminino , Humanos , Hipotireoidismo/sangue , Masculino , Pessoa de Meia-Idade , Tireotropina/sangue , Tri-Iodotironina/sangue , Adulto Jovem
19.
Hematol Oncol Clin North Am ; 21(3): 561-73; x, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17548040

RESUMO

Treatment with radiolabeled somatostatin analogs is a promising new tool in the management of patients who have inoperable or metastasized endocrine tumors. Symptomatic improvement may occur with all (111)In-, (90)Y-, or (177)Lu-labeled somatostatin analogs that have been used for peptide receptor radionuclide therapy. The results that were obtained with [(90)Y-DOTA degrees ,Tyr(3)]octreotide and [(177)Lu-DOTA degrees ,Tyr(3)]octreotate are encouraging in tumor regression. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild. These data compare favorably with the limited number of alternative treatment approaches.


Assuntos
Neoplasias das Glândulas Endócrinas/radioterapia , Neoplasias Gastrointestinais/radioterapia , Octreotida/análogos & derivados , Neoplasias das Glândulas Endócrinas/diagnóstico , Neoplasias das Glândulas Endócrinas/tratamento farmacológico , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/tratamento farmacológico , Humanos , Radioisótopos de Índio , Lutécio , Octreotida/uso terapêutico , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/métodos , Radioisótopos de Ítrio
20.
Eur Thyroid J ; 6(5): 238-242, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29071235

RESUMO

BACKGROUND: Hypothyroidism has been associated with impaired urinary concentrating ability. However, previous reports on thyroid hormone and urinary concentrating ability in humans only studied a limited number of patients with autoimmune thyroid disease or used healthy controls instead of paired analysis within the same patients. OBJECTIVE: To study the urinary concentrating ability in athyreotic patients with differentiated thyroid cancer on and off levothyroxine treatment as they are exposed to different thyroid states as part of their treatment in the absence of an autoimmune disease. DESIGN AND METHODS: We studied 9 patients (mean age of 42.7 years) during severe hypothyroid state (withdrawal of levothyroxine before radioactive iodine therapy) and TSH-suppressed state (on levothyroxine therapy). At these two points, serum and urine samples were collected after 14 h of overnight fasting without any food or drink. RESULTS: Serum and urine osmolality were not significantly different between on and off levothyroxine treatment. Serum creatinine levels were significantly higher in patients off versus on levothyroxine treatment (87.0 vs. 71.0 µmol/L, respectively; p = 0.044) and, correspondingly, the estimated glomerular filtration rate was significantly lower (89.6 vs. 93.1 mL/min, respectively; p = 0.038). CONCLUSION: Short-term, severe hypothyroidism has no effect on urinary concentrating ability. Our study confirms the well-known effects of thyroid hormone on serum creatinine concentrations.

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