Iodinated contrast media and risk of hypothyroidism (particularly in infants)

HSA would like to bring to the attention of healthcare professionals, rare overseas cases of hypothyroidism following iodinated contrast media (ICM) exposure, particularly in full term and preterm infants. If left untreated, this might result in severe delays in growth and development, including mental development. As such, thyroid function evaluation and monitoring for infants exposed to ICM is recommended, with initiation of treatment for abnormal thyroid function, if needed.

Background

ICM products are generally used to enhance visualisation of vascular structures and organs during radiographic procedures such as angiography and computed tomography. As ICM products contain iodine, they may interfere with thyroid hormone production, which may in turn affect proper growth and development (including mental development) in infants and proper metabolic activity in children and adults.

Hypothyroidism following ICM administration might be attributed to the Wolff-Chaikoff effect, an autoregulatory mechanism whereby a large amount of ingested iodine acutely inhibits thyroid hormone synthesis within the follicular cells.¹ In most individuals, the decreased production of thyroid hormones is transient and resumes after adaptation to the Wolff-Chaikoff effect (known as an “escape” phenomenon). However, certain susceptible populations, such as infants (especially those born preterm), the elderly and those with pre-existing thyroid disease, might be at an increased risk of failure to escape from the Wolff-Chaikoff effect, leading to development of iodine-induced thyroid dysfunction. 

There are 21 ICM products registered locally since 1991, comprising nine active ingredients namely, iopamidol, iohexol, ioversol, iopromide, iomeprol, meglumine ioxitalamate, iodixanol, iobitridol, and ethyl esters of iodised fatty acids of poppy-seed oil. 

International regulatory actions

In April 2017, Health Canada (HC) issued a safety alert on the rare potential risk of hypothyroidism with the use of ICM in certain patients, particularly infants.² HC had identified 10 international reports of hypothyroidism causally associated with ICM, of which six involved infants less than one year of age. As hypothyroidism in infants might have a detrimental effect on their growth and mental development, HC recommended updating and harmonising the prescribing information for all ICM products to include this safety information.

The US Food and Drug Administration (US FDA) had also issued an alert earlier in November 2015 advising that rare cases of hypothyroidism had been reported in infants following the use of ICM.³ A search of the US FDA’s adverse events database identified 11 cases of hypothyroidism reported with ICM, of which 10 involved infants younger than four months of age. The infants were either premature (n=4) or were born full term with major cardiac abnormalities (n=6). All of them were diagnosed with underactive thyroid within a month of receiving ICM. US FDA’s review of the available evidence had concluded that this was a rare occurrence which was usually temporary and would resolve without treatment or any lasting effects.

Local situation and HSA’s advisory

To date, HSA has not received any local adverse drug reaction reports of thyroid dysfunction associated with the use of ICM. The Singapore package inserts for ICM products will be updated on the warnings regarding ICM-induced thyroid function changes.

Healthcare professionals are advised to evaluate and monitor thyroid function in infants exposed to ICM.

References

1. J Clin Endocrinol Metab 2015; 100: 376-383
2. http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2017/63086a-eng.php
3. https://www.fda.gov/Drugs/DrugSafety/ucm472782.htm

Published: 14 Sep 2018

Safety Alerts