Efeito dos inibidores multiquinase na terapia de reposição de levotiroxina em pacientes com carcinoma de tireoide

Abstract

Introdução: Os inibidores de multiquinase (IMK) têm sido utilizados no tratamento do câncer de tireoide (CT) avançado. Em pacientes recebendo terapia de reposição com levotiroxina, o IMK pode aumentar a necessidade de hormônio da tireoide.Objetivo: Investigar os efeitos do IMK na terapia de reposição com hormônio tireoidiano em uma coorte de pacientes com CT. Metodologia: Foram incluídos pacientes com CT em uso de IMK acompanhados em um centro de referência. Para os pacientes com câncer diferenciado de tireoide (CDT), o objetivo do tratamento era atingir níveis séricos de TSH < 0,1 mUI/mL. Para os pacientes com câncer medular de tireoide (CMT), o objetivo da reposição era manter os níveis sérios de TSH dentro da faixa de valores normais (0,35-4,9 mUI/mL). A dose inicial de levotiroxina foi calculada considerando o peso do paciente (mcg/kg) e posteriormente ajustada para atingir esses objetivos. A dose de levotiroxina antes do início do IMK foi considerada a dose basal e a dose máxima durante o uso do IMK foi considerada a dose máxima. Resultados: Foram incluídos 26 pacientes, 11 (42,3%) com CDT e 15 (57,7%) com CMT. O tratamento com IMK de primeira linha para CDT foi sorafenibe e para CMT foi vandetanibe. A duração média do uso de IMK foi de 21 meses (P25-75 11-49) e todos os pacientes tiveram pelo menos um efeito colateral, sendo as reações cutâneas o efeito mais comum (80,7%). Após uma mediana de 12 meses (P25-75 8-20) do uso de IMK, 23 pacientes dos 25 analisados (92%) necessitaram de algum incremento na dose de reposição de levotiroxina com um aumento mediano de 38% (P25-75 18-57). Os fatores de risco para elevação mais proeminente da dose de levotiroxina foram idade mais jovem, uso mais prolongado do IMK e maior número de sítios com metástases. Conclusão: A maioria dos pacientes com CT que utilizam IMK necessitam de aumento da dose de reposição de levotiroxina. Portanto, o monitoramento da reposição com levotiroxina deve ser feito com cuidado nesse grupo de pacientes, com aferições mais frequentes dos níveis de TSH especialmente nos pacientes mais jovens, com maior tempo de uso do IMK e doença mais extensa.

In this study, the anticonvulsant potential of the anti-inflammatory drug dexamethasone (DEXA) was evaluated in the pentylenetetrazole-induced (PTZ) kindling animal model. In this chronic model, the animals received daily treatments: saline (0.9% NaCl), dexamethasone (DEXA) 1mg, 2mg or 4mg / kg or diazepam (2mg / kg) for 14 days and every other day. PTZ (20 mg / kg). On the days they received PTZ, seizure intensity was classified according to Racine (1973). Animals were euthanized on the fifteenth day and serum, hippocampus and cortex were collected for interleukin 1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) cytokines by ELISA. DEXA-treated animals in the PTZ-induced seizure model at all concentrations had reduced seizure intensity according to the Racine scale when compared to the saline-treated group. There was no significant difference between DEXA-treated and diazepam-treated animals, indicating that the anti-inflammatory drug was effective as an anticonvulsant agent. Moreover, DEXA treatment did not alter the locomotor and exploratory capacity of the animals evaluated by the open field test, demonstrating the safety of the proposed treatment. Introduction: Multikinase inhibitors (MKI) have been used to treat advanced thyroid cancer (TC). In patients receiving levothyroxine replacement therapy, MKI may increase the need for thyroid hormone. Objective: To investigate the effects of MKI on thyroid replacement therapy in a cohort of TC patients. Methodology: Patients with TC using MKI followed in a referral center were included. For those patients with differentiated thyroid cancer (DTC), the goal of TSH was <0.1 mIU/mL and for those with medullary thyroid cancer (MTC), the normal range of TSH values (0.35-4.9 mIU/mL). Initial levothyroxine dose was calculated considering the patient weight (mcg/kg) and adjusted to reach these goals. The dose of levothyroxine before the start of MKI was considered the basal dose and the maximal dose during the MKI use was the maximal dose. Results: 26 patients were included, 11 (42.3%) with DTC and 15 (57.7%) with MTC. First-line MKI treatment for DTC was sorafenib and for MTC was vandetanib. The mean duration of MKI's use was 21 months (P25-75 11-49) and all patients had at least one side effect, being the most common skin reactions (80.7%). After a median of 12 months (P25-75 8-20) of MKI's use, 92% (n=23) needed increases on the levothyroxine replacement dose with a median dose increase of 38% (P25-75 18-57). Risk factors for more prominent elevation in levothyroxine dose were younger age, longer use of MKI treatment and more sites of distant metastasis. Conclusion: The majority of TC patients using MKI need increases in the levothyroxine replacement dose. The monitoring should be done carefully with more frequents TSH dosages in those patients with younger age, longer time on MKI and more extensive disease.