Abstract
Iodine deficiency is rare in the United States today, and this is largely due to the effectiveness of iodization in the general food supply. Recent trends among specific populations of children in the United States include adopting food restrictions, such casein-free and gluten-free diets. Although the effect of these types of diets on overall nutrition status and certain micronutrients has been studied in children with autism spectrum disorder, the effect of these limitations on iodine levels in children has not been assessed. We present here 2 cases of iodine deficiency resulting from severe food restriction and associated primary hypothyroidism. In 1 case a classic presentation with a goiter was seen. These children were able to discontinue thyroid hormone treatment once iodine levels were normalized. There were no adverse events or unanticipated outcomes. The occurrence of these cases of iodine deficiency in the United States points to the need for thyroid function testing in children with severe food restrictions, especially those who have limited exposure to dairy, baked goods, and table salt.
- T4 —
- thyroxine
- TPO —
- thyroid peroxidase
- UIC —
- urinary iodine concentration
Iodine is essential for production of the thyroid hormones, thyroxine (T4) and triiodothyronine. Iodine deficiency may lead to goiter, hypothyroidism, poor growth, and neurocognitive impairments.1 After the introduction of salt iodization in the 1920s, US dietary iodine has been largely adequate.2 The Americas have the smallest proportion of individuals with insufficient iodine intake at 13.7%.3 According to NHANES in 2009–2010, the median urinary iodine concentration (UIC) in individuals aged 6 years or older in the United States remained appropriate at 144 µg/L, though this was significantly decreased from 164 µg/L in 2007–2008.4 Notably, school-aged children, who usually consume the largest amount of milk, consistently have higher UICs than adults.4
Common sources of dietary iodine in the United States include iodized salt, dairy foods (secondary to use of iodine-based cleansers and iodine in cattle feed), and commercially produced bread (secondary to use of iodate as a bread conditioner).5 However, there is no mandate in the United States to iodate salt, and food iodine content is not listed on packaging.5 Iodine levels in the United States have likely declined because of substitution of noniodized salt and recommendations to reduce dietary salt intake.5 Given the importance of specific dietary sources of iodine, children on medically restricted diets (such as allergen-free), children with severe food selectivity, and parent-selected food restrictions may be at risk for deficiency. Iodine deficiency in children and adults with limited diets has been reported.6–9 This article highlights 2 cases of pediatric patients with iodine deficiency from voluntarily restricted diets and emphasizes the importance of assessing for iodine deficiency in cases of antibody negative primary hypothyroidism.
Case 1
A 5-year-old boy presents to his pediatrician with fatigue and constipation, having 1 bowel movement per week.
His past medical history was significant for speech delay and autism spectrum disorder. He was born at term and weighed 3.6 kg. The pregnancy was complicated by admissions for bronchospasm and pyelonephritis. The family history was significant for hypothyroidism in the maternal grandmother and type 1 diabetes in his brother. His mother has inflammatory bowel disease.
On examination, the patient was noted to have a goiter. Laboratory testing was significant for an elevated thyrotropin 355 mIU/mL (reference 0.47–4.53), low free T4 0.18 ng/dL (reference 0.84–2.26), and normal free triiodothyronine 2.59 pg/mL (reference 2.00–5.00). Thyroid peroxidase (TPO) antibodies were negative.
Upon referral to pediatric endocrinology, he was found to have a markedly enlarged thyroid gland and dry skin. The remainder of his examination was nonrevealing. Repeat laboratories confirmed previous results (Table 1). Autoimmune hypothyroidism was thought the most likely diagnosis given the family history of autoimmunity; however, his TPO antibody was negative. A thyroid ultrasound demonstrated an enlarged hyperemic gland, suggesting Hashimoto’s thyroiditis. He was started on levothyroxine.
Case 1 Management Timeline
Repeat testing demonstrated improvement (Table 1) and thyroglobulin antibody was negative. Given the lack of evidence for autoimmune hypothyroidism and after discussion with the patient’s mother, the possibility of iodine deficiency arose. Since age 2, the patient consumed only organic, gluten- and casein-free foods. The family used noniodized sea salt rarely. The patient underwent two 24-hour urine collections, which revealed low iodine levels of 11 and 16 µg/L with urine volumes of 994 and 1036 mL, respectively.
The patient was started on 160 µg/day of iodine and his thyroid function improved (Table 1). Furthermore, a repeat 24-hour urine iodine level normalized. Levothyroxine was gradually decreased then discontinued 4 months after initiating iodine supplementation. He remains euthyroid on supplemental iodine.
Case 2
A 2-year-old boy presented to his pediatrician’s office for a well-child examination with parental concerns about limited diet. This was his first physician visit since age 4 months. His mother reported that he ate few foods and disliked items that required chewing. In addition, she removed cows’ milk from his diet over concerns about eczema and substituted coconut milk.
Past medical history was significant for atopic dermatitis. He was born at term and weighed 2.83 kg. Pregnancy was significant for an elevated 1-hour glucose tolerance test; however, follow-up testing was declined.
Growth evaluation revealed weight at the 0.02nd percentile, length at the 0.15th percentile, and head circumference at the 50th percentile. On physical examination, he appeared small and appropriately interactive. His thyroid was normal in size and texture. Laboratories were significant for free T4 0.20 ng/dL (reference 0.76–1.70), thyrotropin 222.43 mIU/L (reference 0.30–5.50), parathyroid hormone 626 pg/mL (reference 10–65), and TPO antibodies <10 IU/mL. In addition, he was noted to be severely vitamin D and calcium deficient, with radiographic evidence of rickets. Levothyroxine 12.5 µg/day was initiated. After an outpatient trial to increase dietary intake, he was admitted to the hospital to further manage failure to thrive.
During hospitalization, the patient had minimal dietary intake of primarily infant rice cereal and occasional bananas, rice, beans, and spaghetti. The parents reported avoiding processed foods and only cooked with sea salt. Twenty-four-hour urine iodine collection was low at 20 µg/L.
The patient was also found to have strong oral aversion. Nasogastric tube was placed and feeds were initiated with formula that contained adequate iodine to meet daily needs. Follow-up spot urine iodine revealed improvement to 237 µg/L. He demonstrated appropriate catch-up growth and thyroid function improved; therefore, levothyroxine was weaned and eventually discontinued (Table 2).
Case 2 Management Timeline
Discussion
Despite significant improvements in iodine status of populations worldwide, iodine deficiency continues to be the primary cause of preventable mental retardation affecting almost 2 billion people.10 Although iodine deficiency disorders are thought to impact developing nations, they can also affect those with easy access to iodine.
The cases presented here had diets lacking the primary sources of iodine in the United States: dairy, bread, and iodized salt. Iodine enters dairy products through both animal feed and iodine-based cleansers used in milking.2,11 In case 2, the patient substituted coconut milk, which contains negligible amounts of iodine.12 Breads are another primary source of iodine due to use of iodate dough conditioners, but the content varies significantly by manufacturer.13 Both patients had minimal bread intake. Finally, both patients exclusively used sea salt, resulting in no exposure to the primary intervention used to prevent iodine deficiency disorder.
Because 90% of iodine is renally excreted, urinary iodine measurements are used to assess iodine status.2 Urinary iodine is a sensitive indicator of iodine intake in the magnitude of days.14 Although single spot urine iodine samples from individuals are useful to evaluate populations, 10 or more spot urine iodine samples or 24-hour urine collections may be needed to better assess individual iodine status because of diurnal variability in intake and excretion.5,15,16 In the cases presented here, this number of collections proved difficult, with only 1 to 2 collected before the patients required active clinical management. Standards for 24-hour urine iodine have not been established for children under age 6, but the World Health Organization has established cutoff values for population mean UIC as they relate to public health significance in school-aged children (Table 3).15
World Health Organization Guidelines for Population Mean UIC as an Indicator of Iodine Status17
The cases presented here exhibit moderate and severe iodine deficiency accompanied by the hormone pattern for primary hypothyroidism. Although 1 patient had a goiter, the other did not, consistent with variability in goiter development.15 The differential diagnosis of iodine deficiency goiter includes Pendred syndrome, but normal hearing in case 1 makes this unlikely.
In the above cases, diets were restricted by a combination of parental choice, perceived food allergies, and oral aversion. The patient in case 1 had autism spectrum disorder. In the Autism Treatment Network, 19% of participants followed a gluten-free casein-free diet.18 A study of these children did not reveal micronutrient deficiencies when on a multivitamin; however, iodine status was not assessed19 and the majority of multivitamins in the United States do not contain iodine.20 Typical iodine stores may be able to maintain normal thyroid function for up to 3 months, after which a decline in function may manifest.18
With the growing popularity of voluntarily restricted diets, we recommend obtaining a thorough dietary history in cases of primary hypothyroidism without evidence of autoimmunity. Deficiencies of selenium, iron, and vitamin A should also be investigated as they can worsen the effects of iodine deficiency.15 In patients identified to have diets that restrict iodine, providers should recommend daily iodine supplementation and should screen for symptoms of hypothyroidism.
Footnotes
- Accepted March 23, 2016.
- Address correspondence to Brigid Gregg, MD, Department of Pediatrics, Division of Endocrinology, University of Michigan C.S. Mott Children’s Hospital, D1205 MPB 1500 E Medical Center Dr, Ann Arbor, MI 48109. E-mail: greggb{at}med.umich.edu
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.
References
- Copyright © 2016 by the American Academy of Pediatrics
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