Clinical and laboratory observation

Iodine-induced alterations of thyroid function in newborninfants after prenatal and perinatal exposure to povidone iodine

La découverte d'un goitre fœtal est un événement peu fréquent dont les conséquences néonatales ne sont pas toujours prévisibles. À propos de trois observations de goitres hypothyroïdiens découverts in utero, les auteurs décrivent la prise en charge thérapeutique encore mal codifiée de cette situation et insistent sur l'importance de l'examen échographique pour le diagnostic du goitre et son retentissement et pour le contrôle de l'efficacité du traitement. Ils discutent également des indications de l'injection intra-amniotique de L-Thyroxine^® et insistent sur la nécessité d'une évaluation thyroïdienne sûre après la naissance pour justifier une abstention thérapeutique pour le nouveau-né.

Fetal goiter is a rare occurrence of which neonatal consequences are not always predictable. Concerning three cases of goiters associated with hypothyroidism discovered in utero, the authors describe the way to take care of in this bad codified situation. They insist upon the major role of ultrasound for goiter diagnosis and its impacts and for control of treatment efficiency. They also discuss intra amniotic L-Thyroxine^® injection and insist upon the necessity to obtain quick and definite thyroid evaluation after birth before decision to abstain from neonatal therapy.

Los contrastes iodados pueden bloquear la síntesis de hormonas tiroideas. Nuestros objetivos fueron estudiar la incidencia de alteraciones tiroideas poscateterismo en niños con cardiopatía congénita, y analizar los factores predisponentes al desarrollo de hipotiroidismo postangiografía y evaluar la duración de éste.

Entre febrero de 1993 y abril de 1997 se analizaron los niveles de tirotropina (TSH) y tiroxina libre (FT4) previos al cateterismo y en las dos semanas siguientes a éste, en 99 niños cardiópatas menores de tres años. En aquellos que presentaron elevación de la TSH postangiografía se repitieron semanalmente las determinaciones hasta observar su normalización, o hasta que se indicó tratamiento sustitutivo. Tanto los datos de los pacientes (edad, exposición previa a contrastes, cardiopatía, malformaciones asociadas, insuficiencia renal, gravedad, tratamiento, etc.) como los datos del cateterismo (cantidad y tipo de contraste, etc.) se sometieron al análisis univariante.

En la primera semana poscateterismo se observó elevación de la cifra media de TSH y disminución de la cifra media de FT4, ambas significativas (p < 0,01), respecto a los valores basales. Diecinueve pacientes (19,2%) presentaron patrón de hipotiroidismo (cifras de TSH > 10 mUI/ml), mantenido más de tres semanas en 6 casos. La presencia de síndromes polimalformativos fue el factor de riesgo más claramente asociado tanto al desarrollo de hipotiroidismo postangiografía (p < 0,01) como a la mayor duración de éste.

En los pacientes portadores de síndromes polimalformativos debería realizarse un control de función tiroidea tras la realización de angiocardiografía con contrastes iodados.

Iodinated contrast agents can block thyroid hormone synthesis. The aims of this study were: 1st) to study the incidence of thyroid function disturbances in children with congenital heart disease after cardiac catheterization, 2nd) to analyze the predisposing factors that may lead to the development of hypothyroidism after angiography, and 3rd) to determine the duration of these hypothyroidism states.

From february 1993 to April 1997 thyrotropine (TSH) and free thyroxine (FT4) serum values were analyzed before cardiac catheterization and in the two following weeks, in 99 children under three years of age, with congenital cardiac disease. Those patients who showed any postangiography increase in TSH were further evaluated by weekly measures of serum thyroid hormones and TSH until normal values were obtained or until the initiation of hormonal replacement therapy. The patients’ data (age, previous exposure to contrast agents, cardiac disease, associated extracardiac malformations, renal failure, severity of illness, treatment) and the catheterism data (the dose and type of contrast and the fluoroscopy time) were included in the univariant analysis.

We observed a clear increase in the mean value of TSH and a decrease in the mean value of FT4 (p < 0,01) in the first postangiograpy week both significant in comparison to the basal values. Nineteen patients (19,2%) showed a hypothyroidism pattern (TSH > 10 mUI/ml), that persisted beyond three weeks in six cases. The occurrence of multiple malformation syndromes was the most clearly associated risk factor (p < 0,01) not only in the development of postangiography hypothyroidism but also in longer hormonal dysfunction.

Thyroid function should be tested in every patient with multiple malformation syndrome that undergo angiocardiography with iodinated contrast agents.

Mutations in dual oxidase (DUOX2) have been proposed as a cause of congenital hypothyroidism. Previous reports suggest that biallelic mutations of DUOX2 cause permanent congenital hypothyroidism and that monoallelic mutations cause transient congenital hypothyroidism.

To clarify the inheritance of hypothyroidism, we looked at the DUOX2 gene in patients with transient congenital hypothyroidism.

DUOX2, thyroid peroxidase, Na⁺/I⁻ symporter and dual oxidase maturation factor 2 genes were analyzed in eight patients with transient congenital hypothyroidism, using the PCR-amplified direct sequencing method.

The eight patients were found by a neonatal screening program. Six of these patients belonged to two independent families; the other two were unrelated. Their serum TSH values varied from 24.8–233.0 mU/liter. Six of the eight patients had a low serum freeT₄ level (0.19–0.84 ng/dl). Seven of the eight patients were treated with thyroid hormone replacement therapy, which ceased to be necessary by 9 yr of age.

Eight novel mutations were detected in the DUOX2 gene. Four patients in one family were compound heterozygous for p.L479SfsX2 and p.K628RfsX10. Two patients in a second family were compound heterozygous for p.K530X and p.[E876K;L1067S]. The two remaining unrelated patients were also compound heterozygous, for p.H678R/p.L1067S and p.A649E/p.R885Q, respectively.

All eight patients had biallelic mutations in the DUOX2 gene. We find that loss of DUOX2 activity results in transient congenital hypothyroidism and that transient congenital hypothyroidism caused by DUOX2 mutations is inherited as an autosomal recessive trait.