Publication: Optimización de la dosis de levotiroxina en pacientes con hipotiroidismo congénito durante los primeros siete años de vida
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2017-02-27
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Universidad Complutense de Madrid
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Abstract
Introducción: La instauración de los programas de detección precoz del hipotiroidismo congénito (HC) ha permitido superar la discapacidad intelectual asociada al mismo. Sin embargo, existe un grupo de pacientes en los que persiste una disfunción cerebral mínima. Algunos autores han asociado esta disfunción con la falta de optimización del tratamiento durante los primeros años de vida. Objetivos: Describir la dosis de LT4 recibida por los pacientes con HC durante los primeros siete años de vida y realizar una propuesta de dosis óptima, de forma global y diferenciando en función de la morfología tiroidea (agenesia tiroidea, tiroides ectópico y tiroides eutópico). Pacientes, material y métodos: Estudio retrospectivo de los pacientes con HC diagnosticados y seguidos en la Unidad de Diagnóstico y Seguimiento del Programa de Detección Precoz de HC de la Comunidad de Madrid, nacidos entre los años 2000 y 2012, hasta los 7 años de edad. Para la propuesta de la posología de LT4 se definió la dosis óptima como la dosis que maximiza la probabilidad de que la concentración de T4L esté en el rango de valores objetivo y se realizó la búsqueda de un modelo matemático que relacionase la dosis recibida de LT4 y los valores de T4L mediante el programa R 3.2, paquete lms4. Resultados: Se incluyeron 305 niños (124 tiroides eutópicos, 139 ectópicos, 36 agenesias, 6 hemiagenesias), con un total de 6315 determinaciones de la función tiroidea (TSH y T4L). La edad de inicio del tratamiento y la dosis inicial de LT4 se ajustaron a las recomendaciones de las últimas guías de diagnóstico y tratamiento del HC (12,5 ± 6,5 días y 11,8 ± 2,6 μg/kg/día) y en todos los pacientes se realizó una prueba de imagen al diagnóstico (en el 97% gammagrafía). La mayoría de los pacientes normalizaron la función tiroidea en el primer control analítico tras el inicio del tratamiento, aunque aproximadamente una quinta parte de los pacientes presentaron hipertiroxinemia transitoria sin repercusión clínica. Posteriormente la mayor parte de las determinaciones mostraron valores de TSH y T4L dentro de objetivos, aunque se describieron pacientes con sobre e infratratamiento en todos los grupos etarios. Durante todo el seguimiento, la dosis por kg de LT4 recibida por los pacientes con tiroides eutópico fue inferior a la recibida por los pacientes con tiroides ectópico y agenesia tiroidea. Para establecer la dosis óptima, en primer lugar se obtuvo un modelo multinivel de la cinética de la T4L en función la dosis recibida por kg de peso, la edad y la morfología tiroidea. La dosis óptima se determinó estableciendo como valores deseados de T4L aquellos situados en el punto medio del intervalo objetivo para cada edad y fijando un nivel de confianza del 90%. A partir de los datos de los pacientes, se estimaron los parámetros del modelo y se obtuvo una ecuación que permite calcular explícitamente la dosis óptima para cada edad en función de la morfología tiroidea así como de forma global...
Introduction: Congenital hypothyroidism (CH) screening programs prevent intellectual disability related to this condition. However, there is a group of patients in which subtle neurocognitive dysfunction persists. Some authors have related this dysfunction with the lack of optimization of the treatment during the first years of life. Objectives: Describing levothyroxine (LT4) dosage received by patients with CH up to seven years old and proposing an optimum dosage of LT4, either globally and taking into consideration thyroid morphology (athyreosis, ectopic gland and in situ thyroid) Patients, material and methods: Retrospective study of patients with CH diagnosed and followed in the Clinic Unit of the CH Screening Program of the Community of Madrid, born between 2000 and 2012, up to seven years of age. To optimize the dosage of LT4, optimum dose was defined as the dose that maximizes the probability of presenting a FT4 concentration within the target values and search for a mathematical model that relates the dose of LT4 with FT4 levels and age, using R program 3.2, lms4 package. Results: 305 children were included (124 in situ gland, 139 ectopic, 36 athyreosis, 6 hemiathyreosis), with a total of 6315 determinations of thyroid function (TSH and FT4). Age at onset of treatment and initial dosage of LT4 followed the recommendations of the latest guidelines for diagnosis and management of CH (12.5 ± 6.5 days y 11.8 ± 2.6 μg/kg/day). All the patients underwent an imaging study (97% scintigraphy). Most of the children normalized thyroid function in the first follow-up examination after the initiation of LT4 treatment, although approximately a fifth presented transient hyperthyroxinemia, without any clinical impact. Blood test revealed that most of the patients were euthyroid during the follow-up, although patients with over and undertreatment were described in all age groups. During the first seven years of life, patients with in situ thyroid received lower dose per kg that patients with ectopic thyroid and athyreosis. To establish the optimal dose a multilevel model of FT4 kinetics was obtained, considering the dose per kg, age and thyroid morphology. The optimal dose was determined by the establishment of the desired values of FT4 as those at the midpoint of the target range for every age with a confidence level of 90%. The model parameters were inferred from the patients data and an equation that allows to explicitly calculate the optimal dosage for each age, considering thyroid morphology and also globally was developed...
Introduction: Congenital hypothyroidism (CH) screening programs prevent intellectual disability related to this condition. However, there is a group of patients in which subtle neurocognitive dysfunction persists. Some authors have related this dysfunction with the lack of optimization of the treatment during the first years of life. Objectives: Describing levothyroxine (LT4) dosage received by patients with CH up to seven years old and proposing an optimum dosage of LT4, either globally and taking into consideration thyroid morphology (athyreosis, ectopic gland and in situ thyroid) Patients, material and methods: Retrospective study of patients with CH diagnosed and followed in the Clinic Unit of the CH Screening Program of the Community of Madrid, born between 2000 and 2012, up to seven years of age. To optimize the dosage of LT4, optimum dose was defined as the dose that maximizes the probability of presenting a FT4 concentration within the target values and search for a mathematical model that relates the dose of LT4 with FT4 levels and age, using R program 3.2, lms4 package. Results: 305 children were included (124 in situ gland, 139 ectopic, 36 athyreosis, 6 hemiathyreosis), with a total of 6315 determinations of thyroid function (TSH and FT4). Age at onset of treatment and initial dosage of LT4 followed the recommendations of the latest guidelines for diagnosis and management of CH (12.5 ± 6.5 days y 11.8 ± 2.6 μg/kg/day). All the patients underwent an imaging study (97% scintigraphy). Most of the children normalized thyroid function in the first follow-up examination after the initiation of LT4 treatment, although approximately a fifth presented transient hyperthyroxinemia, without any clinical impact. Blood test revealed that most of the patients were euthyroid during the follow-up, although patients with over and undertreatment were described in all age groups. During the first seven years of life, patients with in situ thyroid received lower dose per kg that patients with ectopic thyroid and athyreosis. To establish the optimal dose a multilevel model of FT4 kinetics was obtained, considering the dose per kg, age and thyroid morphology. The optimal dose was determined by the establishment of the desired values of FT4 as those at the midpoint of the target range for every age with a confidence level of 90%. The model parameters were inferred from the patients data and an equation that allows to explicitly calculate the optimal dosage for each age, considering thyroid morphology and also globally was developed...
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Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Pediatría, leída el 23/10/2015