Iodine excess in children with kidney disease: are we missing hypothyroidism?

Abstract

The thyroid gland has evolved mechanisms to enable ongoing normal thyroid hormone production in the situation of iodine toxicity. Iodine excess exerts its effect on the thyroid gland in two ways. Firstly, when the intracellular iodide concentration reaches over 10 M, hormone synthesis is shut down. This is called the Wolff-Chaikoff effect. Subsequently, the sodiumiodide symporter, which transports iodide into thyroid cells, ceases to function. This means that the level of intracellular iodide drops and thyroid hormone production normalises after 24 to 48 h [2]. However, in some situations, there is a continuing deficiency in thyroid hormone production and hypothyroidism persists. Hypothyroidism may continue if the source of iodine is not removed and/or if renal clearance is abnormal. Hypothyroidism is common in neonates with congenital heart disease, who may be frequently exposed to iodine and in whom the link between iodine and hypothyroidism is well described. Such neonates can be exposed to large doses of intravenous (IV) iodinated contrast media during angiography, cardiac surgery and IV line insertions; iodine exposure may continue as iodine-soaked dressings may be applied to the sternum if it is not closed at the time of surgery. The iodine can then be absorbed into the circulation. Ongoing hypothyroidism occurs in around 25% of infants with congenital heart disease, and it has been suggested that the neonatal thyroid gland is immature, and particularly unable to restore normal thyroid function after an episode of iodine excess [3]. Of course, renal function is also immature in the neonate even without acute kidney injury, which is common in such infants. However, we know that hypothyroidism occurs after exposure to excess iodine in children of all ages and in adults too, particularly in situations of reduced renal function [4]. Reports of the incidence and duration of hypothyroidism following iodine excess vary from no effect, to an increase in TSH within 3–5 days with no effect on T4 and T3, to hypothyroidism between 50 and 294 days, to permanent hypothyroidism [5]. This variability is affected by the cumulative iodine dose received, whether the thyroid gland is normal or not, patient age (neonates are particularly vulnerable) and renal function. Iodine is excreted by glomerular filtration, with a half-life of around 2 h when renal function is normal. In a study in adults with normal renal function, looking at urinary iodine excretion following iodinated contrast medium administration for CT scans, the peak urinary iodine concentration occurred at 1.1 weeks and normalised by 5.2 weeks. Thyroid dysfunction developed in 22% [6]. Half-life increases as the GFR falls and can be as long as 30 h when renal function is severely impaired [5], so patients with CKDwill have prolonged exposure to high blood levels of iodine after excess iodine exposure.