Avaliação da administração de levotiroxina com a refeição e suas repercussões clínicas e laboratoriais no hipotireoidismo primário

Orientadora: Profª Drª Gisah Amaral de CarvalhoDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciencias da Saúde, Programa de Pós-Graduaçao em Medicina Interna. Defesa : Curitiba, 02/12/2011Bibliografia: fls. 42-47Resumo: O hipotireoidismo é uma doença prevalente, que compromete o organismo de forma global. O tratamento de reposição com levotiroxina (LT4) deve ser mantido indefinidamente na maioria dos pacientes. A eficácia da terapia depende da absorção adequada da LT4 administrada via oral e, atualmente é consenso que a LT4 seja administrada em jejum. Muitos pacientes têm menor aderência ao tratamento devido à necessidade de jejum mínimo de 30 minutos, pela interferência nas atividades diárias. O objetivo deste estudo foi avaliar pacientes com hipotireoidismo primário tratados com dose substitutiva de LT4 quanto ao efeito da administração da droga junto com a refeição matinal, no controle clínico e laboratorial. Realizou-se um estudo clínico prospectivo, randomizado, aberto, tipo cross-over, para avaliação de 45 pacientes portadores de hipotireoidismo primário compensado, em tratamento com doses substitutivas de LT4. Os pacientes foram submetidos a 2 fases de tratamento, recebendo a medicação por 3 meses em jejum (grupo controle) e por 3 meses junto com a refeição matinal (grupo intervenção), totalizando um acompanhamento por 6 meses. Foi realizada avaliação clínica e laboratorial (TSH, T4 livre e T3 Total) a cada 45 dias e recordatório alimentar para avaliação do consumo na refeição matinal. Quarenta e dois pacientes concluíram o protocolo. Os níveis de TSH foram mais altos com administração da LT4 com o café da manhã do que com a administração convencional em jejum (2,89 vs 1,90 mUI/L, p=0,028), mas com níveis médios de TSH mantendo-se no alvo terapêutico. Hipotireoidismo descompensado (TSH ? 3,5 mIU/L) ocorreu em 23,8% dos pacientes tomando LT4 na refeição matinal e em 14,4% no jejum (p=0,26). Não foram identificados fatores de risco para elevação do TSH. No presente estudo, a administração da LT4 junto com a refeição matinal não interferiu no controle clínico, mas interferiu no controle laboratorial do hipotireoidismo O uso da LT4 junto com a primeira refeição matinal pode ser considerado uma forma alternativa de tratamento a pacientes que apresentam má aderência devido à dificuldade em respeitar orientações rígidas de tomada da medicação em jejum. Como esta opção de tratamento é mais suscetível a oscilações nos níveis de TSH, o paciente deve ser seguido rigorosamente e deve-se estar ciente de que ajustes na dose da LT4 podem ser necessários. Nos pacientes onde uma meta específica de TSH é importante, a administração da LT4 em jejum é sempre recomendada.Abstract: Hypothyroidism is a prevalent disease that compromises the organism in a global way. The treatment with levothyroxine (LT4) replacement must be kept indefinitely in the majority of the patients. The effectiveness of this therapy depends on the adequate absorption of oral given LT4 and, it's currently a consensus that LT4 must be administered in fast state. Many patients have decreased adherence to treatment due the necessity of minimum 30 minutes fast, which interferes in daily activities. The objective of this study was to evaluate patients with primary hypothyroidism treated with LT4 substitutive doses and the effect of drug administration at breakfast, in clinical and laboratorial control. It was a prospective, randomized, open-label, cross over clinical trial involving 45 patients with stable primary hypothyroidism, properly treated with LT4 substitutive doses. Patients were randomly submitted to 2 different treatment phases: receive medication for 3 months in fast (control group) and for 3 months in breakfast (intervention group), with a total follow-up of 6 months. Clinical and laboratorial evaluation (TSH, free T4 and total T3) were performed in 45 days intervals and a questionnaire for evaluation of breakfast consumption was made. Forty-two patients concluded the protocol. The TSH levels were higher with levothyroxine administration during breakfast than with fasting state (2.89 vs 1.9 mUI/L. p=0.028) but TSH remained in therapeutic range. Uncontrolled hypothyroidism (TSH levels ? 3.5 mIU/L) occurred in 23.8% of patients taking LT4 in the breakfast and in 14.4% in fasting state (p = 0.26). No risk factors were identified for TSH elevation. In the present study, administration of LT4 with breakfast did not affect clinical control, but interfered with the laboratorial control of hypothyroidism. Levothyroxine administration with breakfast could be considered as an alternative regimen to patients who have adherence difficulties because of the strict orientation of fasting intake. As this therapeutic option is more susceptible to variability on TSH levels, the patient should be followed more closely and the clinician should be aware that adjustments in LT4 dose might be necessary. In patients that a specific serum TSH goal is important, the ingestion of LT4 in the fasting state is always recommende

The clinical use of thyroid function tests

Laboratory tests are essential for accurate diagnosis and cost-effective management of thyroid disorders. When the clinical suspicion is strong, hormonal levels just confirms the diagnosis. However, in most patients, symptoms are subtle and unspecific, so that only biochemical tests can detect the disorder. The objective of this article is to do a critical analysis of the appropriate use of the most important thyroid function tests, including serum concentrations of thyrotropin (TSH), thyroid hormones and antithyroid antibodies. Through a survey in the MedLine database, we discuss the major pitfalls and interferences related to daily use of these tests and recommendations are presented to optimize the use of these diagnostic tools in clinical practice.Exames laboratoriais são fundamentais para o diagnóstico acurado e o monitoramento custo-efetivo das disfunções tireoidianas. Quando há alta suspeita clínica, as dosagens hormonais apenas confirmam o diagnóstico. No entanto, na maioria dos pacientes, a sintomatologia é sutil e inespecífica, de forma que apenas testes bioquímicos podem detectar o transtorno. O objetivo deste artigo é fazer uma análise crítica do uso apropriado dos principais testes de função tireoidiana, entre eles a dosagem sérica do hormônio estimulante da tireoide (TSH), dos hormônios tireoidianos e dos anticorpos antitireoidianos. Mediante um levantamento na base de dados do MedLine, são discutidas as principais armadilhas e interferências relacionadas ao uso cotidiano desses testes e apresentadas recomendações para otimizar a utilização dessas ferramentas diagnósticas na prática clínica.19320

Stężenie TSH wiąże się z podwyższonym ryzykiem raka tarczycy u pacjentów z guzkami tarczycy

Introduction: Several studies have shown an increased risk of thyroid malignancies in patients with elevated TSH levels, even if these levels fell within the normal range. The aim of this study was to evaluate the relationship between TSH and risk of malignancy in patients with thyroid nodules. Material and methods: We included 622 patients with thyroid nodules evaluated by fine needle aspiration and/or thyroidectomy and diagnosed by cytology or histology. Clinical and laboratory data, such as gender, weight, ultrasound findings, serum TSH, and free T4, were obtained from medical records or collected during each patient's first visit to our centre, prior to any intervention. Results: Thyroid cancer was more prevalent in males (p = 0.012) and in patients with a solitary nodule (p < 0.01). Malignant tumours were predominantly solid, whereas benign tumours were solid or mixed (p = 0.053). The carcinoma risk in patients with thyroid nodules increased with increasing serum TSH concentration, with a significant elevation in patients with serum TSH levels above 1.64 mU/L (p < 0.001). This relationship persisted even when the subgroup of patients undergoing thyroidectomy was analysed separately. Patients with follicular lesions presented with significantly higher TSH levels compared to patients with benign cytology (p < 0.001). We also found correlation between elevated TSH and tumour size (p = 0.005). Conclusions: Our results suggest that in patients with nodular thyroid disease the carcinoma risk rose in parallel with serum TSH concentration, with significant increases evident in patients with serum TSH greater than 1.64 mU/L. (Endokrynol Pol 2015; 66 (6): 480–485)Wstęp: Niektóre badania wykazały zwiększone ryzyko wystąpienia guzów tarczycy u pacjentów z podwyższonym stężeniem TSH, nawet jeśli stężenie to przekracza zakres wartości referencyjnych. Celem niniejszego badania była ocena związku pomiędzy TSH i ryzykiem nowotworu u pacjentów z guzkami tarczycy. Materiał i metody: Badaniem objęto 622 pacjentów z guzkami tarczycy, którym wykonano biopsję aspiracyjną cienkoigłową i/Lub tyreoidektomię oraz zdiagnozowano cytologicznie lub histologicznie. Dane kliniczne i laboratoryjne, takie jak płeć, masa ciała, wyniki USG oraz stężenie TSH i fT4 w osoczu, pobrano przed jakąkolwiek ingerencją z dokumentacji medycznej lub zebrano podczas pierwszej wizyty każdego z pacjentów w centrum medycznym, w którym pracują autorzy artykułu. Wyniki: Rak tarczycy występował częściej u mężczyzn (p = 0,012) oraz u pacjentów z pojedynczym guzkiem (p < 0,01). Guzy złośliwe były głównie struktury litej, podczas gdy guzy łagodne miały charakter lity lub mieszany (p = 0,053). Ryzyko raka u pacjentów z guzkami tarczycy wzrastało wraz ze wzrostem stężenia TSH w osoczu, wraz ze znacznym wzrostem tego ryzyka u pacjentów ze stężeniem TSH powyżej 1,64 mU/L (p < 0,001). Związek ten utrzymał się nawet, gdy podgrupę pacjentów poddanych tyreoidektomii zanalizowano osobno. U pacjentów ze zmianami pęcherzykowatymi stwierdzono znacznie wyższe stężenie TSH w porównaniu z pacjentami z obrazem cytologicznym ilustrującym łagodną zmianę (p < 0,001). Odnotowano również związek pomiędzy podwyższonym stężeniem TSH i rozmiarem guza (p = 0,005). Wnioski: Wyniki badania sugerują, że u pacjentów z guzkami tarczycy, ryzyko raka wzrasta równolegle do stężenia TSH w osoczu, ze znacznym wzrostem ryzyka u pacjentów ze stężeniem TSH w osoczu powyżej 1,64 mU/L. (Endokrynol Pol 2015; 66 (6): 480–485

TSH levels are associated with increased risk of thyroid carcinoma in patients with nodular disease

Introduction: Several studies have shown an increased risk of thyroid malignancies in patients with elevated TSH levels, even if these levels fell within the normal range. The aim of this study was to evaluate the relationship between TSH and risk of malignancy in patients with thyroid nodules. Material and methods: We included 622 patients with thyroid nodules evaluated by fine needle aspiration and/or thyroidectomy and diagnosed by cytology or histology. Clinical and laboratory data, such as gender, weight, ultrasound findings, serum TSH, and free T4, were obtained from medical records or collected during each patient's first visit to our centre, prior to any intervention. Results:Thyroid cancer was more prevalent in males (p = 0.012) and in patients with a solitary nodule (p < 0.01). Malignant tumours were predominantly solid, whereas benign tumours were solid or mixed (p = 0.053). The carcinoma risk in patients with thyroid nodules increased with increasing serum TSH concentration, with a significant elevation in patients with serum TSH levels above 1.64 mU/L (p < 0.001). This relationship persisted even when the subgroup of patients undergoing thyroidectomy was analysed separately. Patients with follicular lesions presented with significantly higher TSH levels compared to patients with benign cytology (p < 0.001). We also found correlation between elevated TSH and tumour size (p = 0.005). Conclusions: Our results suggest that in patients with nodular thyroid disease the carcinoma risk rose in parallel with serum TSH concentration, with significant increases evident in patients with serum TSH greater than 1.64 mU/L