Published: 2 March 2017
2 March 2017
Monitoring finishes 30 September 2017.
Medsafe is highlighting a possible association between exposure to iodine-containing contrast agents (ICAs) and the development of hypothyroidism in infants (aged less than 12 months).
This follows an FDA review of ten cases of hypothyroidism in infants exposed to ICAs - six in full term infants with major cardiac abnormalities and four in premature infants (1). In these reports hypothyroidism was diagnosed 7 to 30 days after receiving an ICA. Improvement was documented in eight cases – four of which required treatment with thyroxine. No reports of hypothyroidism associated with ICAs have been reported to the Centre for Adverse Reactions Monitoring (CARM) in New Zealand.
ICAs are known to increase the risk of hyperthyroidism, particularly in those with a history of thyroid disease(2). Most New Zealand data sheets include advice regarding this risk. Observational studies have demonstrated that adults and children exposed to ICAs are at increased risk of developing hypothyroidism(3-5). However, studies in infants and neonates are limited by small numbers, a lack of control group and possible confounding by the use of topical iodine products. Therefore, little is known about this risk in infants and neonates.
ICAs are medicines used to enhance the ability of blood vessels and organs to be seen on medical imaging such as CT scans. ICAs can be administered intravascularly (intravenously or intra-arterially) or enterally.
Table 1: Iodine-containing contrast agents approved for use in New Zealand
|Brand name||Ingredient name||Sponsor|
|Lipiodol||Iodised oil||Obex Medical|
|Urografin and Gastrografin||Diatrizoate meglumine with sodium amidotrizoate||Bayer NZ|
|Ioscan||Diatrizoate sodium||Regional Health|
As of 1 January 2017, PHARMAC funds Lipiodol, Visipaque, Omnipaque, Urografin and Gastrografin through the hospital medicines list (Table 1).
ICAs are general sales medicines, therefore data sheets are not required. Of those products with data sheets, only the Omnipaque data sheet identifies hypothyroidism as a potential adverse effect.
ICAs provide iodine doses well in excess of recommended maximum daily doses for all age groups (2). In healthy individuals, exposure to excess iodine triggers the Wolff-Chaikoff effect which temporarily inhibits the formation and release of thyroid hormones. Normal thyroid function resumes within 1-2 weeks if the source of excess iodine is withdrawn. Failure to adapt to the Wolff-Chaikoff effect is thought to be the mechanism by which excess iodine can cause hypothyroidism (6).
As thyroid hormones are crucial to brain development (7), the consequences of even short periods of hypothyroidism could be more significant for infants (and children up to age 3) than other age groups. Infants may be more susceptible to hypothyroidism due to thyroid gland immaturity (particularly in premature infants), reduced renal clearance of iodine and increased skin absorption if iodine is also applied topically. In addition, sick infants may be less able to regulate their iodide balance and may require multiple scans using ICAs (8).
Symptoms of hypothyroidism in infants can include lethargy, hoarse cry, feeding problems, needing to be woken to feed, constipation, puffy face, hypotonia, dry skin, hypothermia and prolonged jaundice (9). As these symptoms are non-specific, hypothyroidism may be difficult to diagnose clinically in infants.
Medsafe considers the overall benefit-risk balance for ICAs remains positive; therefore no changes to the use of these products in infants are recommended.
Healthcare professionals should consider the possibility of hypothyroidism in infants presenting with unexplained non-specific symptoms, or deterioration in their clinical condition following imaging where an ICA was administered. Premature infants and those undergoing multiple imaging procedures are likely to be at increased risk. If ICAs are to be used in neonates or infants (less than 12 months of age), the suggested monitoring is thyroid-stimulating hormone (TSH) +/- free thyroxine (FT4) 5-7 days post contrast.
Parents and caregivers should discuss any concerns they may have with their baby's doctor.
More information about iodine-containing products can be found in the data sheets.
Medsafe is placing this safety concern on the medicines monitoring scheme to gain more information about this safety concern. Please report any cases of hypothyroidism in infants or children exposed to ICAs. Please include information on the severity and duration of hypothyroidism; whether treatment was required; and whether hypothyroidism was diagnosed clinically or upon routine screening.
Medsafe will continue to monitor this issue and will produce updated advice for healthcare professionals and consumers as necessary.
Consumers and healthcare professionals are encouraged to send reports of suspected adverse reactions to the Centre for Adverse Reactions Monitoring (CARM)
Medsafe cannot give advice about an individual's medical condition. If you have any concerns about a medicine you are taking Medsafe encourages you to talk to your healthcare professional.