Of the many forms of thyroid disease in children, hypothyroidism remains the most common. Since the 1970s with the advent of neonatal screening for thyroid disease in most industrialized countries, the incidence of congenital hypothyroidism has increased from about 1 in 6700 live births to about 1 in 2500 births.
Reviewed by Andrew J Bauer, MD, FAAP.
Of the many forms of thyroid disease in children, hypothyroidism remains the most common. Since the 1970s with the advent of neonatal screening for thyroid disease in most industrialized countries, the incidence of congenital hypothyroidism has increased from about 1 in 6700 live births to about 1 in 2500 births.1 Acquired hypothyroidism is also common in children and emerges as a child ages.
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Accurate detection and early treatment of congenital hypothyroidism in infants is critical to preventing the neurodevelopmental deficits that can occur if the disease is left untreated. As pointed out in a recent study, congenital hypothyroidism is one of the most common preventable causes of mental retardation with neurodevelopmental outcome inversely related to age of diagnosis and treatment.2
Whereas early treatment is important for neurodevelopment in infants, early detection and treatment of acquired hypothyroidism in children is important in terms of linear growth. These children will present with linear growth deficiencies.
“The thyroid is important early on for brain development, and after the first 3 years of life the thyroid is more important for linear growth or how tall a child is getting,” says Andrew J. Bauer, MD, FAAP, associate professor of pediatrics, University of Pennsylvania, Philadelphia, and director, Thyroid Center, Children’s Hospital of Philadelphia.
As such, he emphasizes that the goal of treatment is to identify hypothyroidism and initiate treatment within 2 weeks. “This can be done by the pediatrician, or in partnership with a pediatric endocrinologist,” he says.
At the recent American Academy of Pediatrics (APP) National Conference and Exhibition in October, Bauer spoke on pediatric thyroid disease. In his presentation, he highlighted key issues in the evaluation and management of congenital and acquired hypothyroidism in children based on the latest evidence.3 This article summarizes key issues for pediatricians to bear in mind when evaluating and managing an infant or child with hypothyroidism, and when to consider referral to an endocrinologist.
Most cases of congenital hypothyroidism (85%) are caused by the failure of the thyroid gland to develop or migrate properly, a situation that is often associated with decreased thyroid function and that might be associated with additional congenital malformations including heart, lung, kidney, and others.
Because most newborns with congenital hypothyroidism will not show any clinical symptoms of disease for several weeks or even months after they are born (by which time neurodevelopmental deficits may have occurred), neonatal screening is now established in most industrialized countries. Early detection and treatment of congenital hypothyroidism through screening has helped prevent severe neurodevelopmental deficits.1 Given that, updated recommendations published in 2014 highlight the importance of screening worldwide (Table 1).1
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What screening also has done, however, is pick up many more mild cases of hypothyroidism. Many of these infants with mild elevations in thyroid-stimulating hormone (TSH) that persist beyond 2 to 3 weeks of life will have transient hypothyroidism, says Bauer, and may be able to go off treatment within 3 years.
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The need to confirm abnormal thyroid screening with a venous sample is therefore imperative to confirm a diagnosis of the disease and its severity as well as to select which infants should begin treatment (Table 2).1-3 Once laboratory results confirm the diagnosis, the goal is to initiate treatment as soon as possible, ideally within 2 weeks, and to normalize the thyroid hormone levels within the first month of life. Pediatricians can either start treatment with levothyroxine (L-T4; 10-15 mcg/kg/day) immediately upon receiving a confirmatory lab report and then refer the infant to a pediatric endocrinologist, or immediately send the infant to a pediatric endocrinologist who will initiate treatment, says Bauer.
An X-ray of the knee may be performed to assess the severity of exposure to intrauterine hypothyroidism, and thyroid ultrasound and/or thyroid scintigraphy (using technetium-99m) may be used to determine if the thyroid gland is in a normal anatomic position. “Imaging is important but can be performed within 7 days of initiation of thyroid hormone treatment,” says Bauer, emphasizing, however, that imaging should not delay initiation of treatment.
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For pediatricians who initiate treatment before referral, Bauer emphasizes that in the United States the only approved form of thyroid hormone replacement therapy is in a pill form. “There is no stable liquid form of thyroid hormone in the United States,” he says, noting that a liquid form, regardless of the method used for compounding, does not provide a consistent suspension, and dosing is unpredictable. Despite this, he still occasionally evaluates patients with abnormal thyroid hormone levels after a well-intended attempt to compound the pill into liquid form. Treatment recommendations are shown in Table 3.1-3
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The goal of treatment is to normalize thyroid levels targeting the TSH in the low-mid normal range (normal range, 0.45 to 4.5 mU/L; target between 1-3 mU/L) and fT4 in the mid-upper normal range (normal range, 0.9-1.6 ng/dL) within the first 30 days of life.
NEXT: Acquired hypothyroidism
The most common form of acquired hypothyroidism is autoimmune hypothyroidism, known by the eponym of Hashimoto thyroiditis. Other causes include radiation or tumor induced (central disease); deficiencies or excess in iodine; medication-induced (lithium and others); syndromes (Down, Turner, or Klinefelter syndromes); and surgical removal (thyroidectomy) or radioiodine ablation (for treatment of thyroid nodules, thyroid cancer or definitive treatment of autoimmune hyperthyroidism, known by the eponym Graves’ disease).
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Bauer says that acquired hypothyroidism should be considered based on family risk, physical exam, and laboratory tests (Table 4).3-5 In highlighting family risk, he says that autoimmune diseases often cluster in families but the risk does not follow a specific predictable pattern (eg, does not follow a Mendelian pattern of inheritance). He says that children often have thyroid function tests sent because of nonspecific complaints (fatigue and increasing weight are 2 of the most common) and in early stages of the disease the patient may have positive antithyroid antibody levels (antithyroglobulin or antithyroid peroxidase) but normal thyroid function. These patients often are referred to endocrinologists to determine when to initiate treatment. “Pediatricians need to be aware that we don’t treat patients who only have positive antibodies. We wait to treat until there is evidence that the thyroid is not working,” he says.
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In terms of physical exam, Bauer stressed a simple and quick method for completing a thyroid exam. (See “Performing an easy, complete thyroid exam”) The sign most consistent with acquired hypothyroidism is decreased linear growth, he says, emphasizing the need to document linear growth in children during both well and sick visits. However, he says he and his colleagues see many more patients referred because of a slight elevation in their TSH found after thyroid levels were sent secondary to complaints of increased weight and fatigue. “The excess weight in overweight children causes the mild elevation in TSH (in the 5 to 10 mIU/L range) rather than the ‘mild hypothyroidism’ causing the increased weight,” he says, adding that data show that if these children can lose weight through decreased calories and increased exercise, the TSH will normalize without medication.6
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A key distinguisher between these 2 situations, Bauer says, is that the excess weight is typically associated with an increase in linear growth velocity (height). “If hypothyroidism were severe enough to cause increased weight, it should also cause decreased linear growth,” he says. “This later finding is the situation that should trigger pediatricians to think of an endocrine problem.”
Treatment of acquired hypothyroidism is shown in Table 5.3-5 Bauer points out that for children with severe hypothyroidism, initiation of treatment can be associated with hyperactivity, pseudotumor cerebri, or rapid advancement through puberty with attenuated final height.
Implementation of neonatal screening for congenital hypothyroidism has improved early detection and treatment for many newborns with subsequent prevention of neurodevelopmental deficits. However, in an effort to ensure that all at-risk patients are identified and treated, lower cutoff points for triggering abnormal thyroid levels have increased the diagnosis of mild and transient hypothyroidism.
All newborns with an abnormal thyroid screen must undergo confirmatory venous thyroid function assessment (TSH and fT4), and imaging with a thyroid ultrasound and/or thyroid scan should be considered to determine the diagnosis and likelihood of needing lifelong thyroid hormone replacement therapy. Once confirmed, treatment should commence within 2 weeks with the goal of achieving normal thyroid levels by day 30. Imaging can be performed within 7 days of starting L-T4 treatment and should not delay initiation of treatment.1
For children with acquired hypothyroidism, a physical exam that includes assessment of linear growth as well as a complete thyroid exam is essential to make the diagnosis. Although many overweight children are referred to pediatricians and endocrinologists for suspected hypothyroidism, hypothyroidism actually may be secondary to obesity and not the cause. In these children, TSH levels will normalize with weight loss.
For both congenital and acquired hypothyroidism, treatment should be given only in pill form because any liquid form is unstable and does not provide consistent dosing. Pediatricians should partner with a pediatric endocrinologist in the management of these patients to ensure optimal treatment and avoidance of unintended delayed treatment effects.
1. Léger J, Olivieri A, Donaldson M, et al; ESPE-PES-SLEP-JSPE-APEG-APPES-ISPAE; Congenital Hypothyroidism Consensus Conference Group. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab. 2014;99(2):363-384.
2. LaFranchi SH. Approach to the diagnosis and treatment of neonatal hypothyroidism. J Clin Endocrinol Metab. 2011;96(10):2959-2967.
3. Bauer AJ. Thyroid gland: too little or too much. Session F2004; F1070. Presented at: American Academy of Pediatrics National Conference and Exhibition; October 24, 2015; Washington, DC. Available at: http://aap.planion.com/EvalCenter/AAP/Blobs/150290_1_150318_1_150318_1_F1070&F2004Bauer_Thyroi.pdf. Accessed April 8, 2016.
4. de Vries L, Bulvik S, Phillip M. Chronic autoimmune thyroiditis in children and adolescents: at presentation and during long-term follow-up. Arch Dis Child. 2009;94(1):33-37.
5. Jonklaas J, Bianco AC, Bauer AJ, et al; American Thyroid Association Task Force on Thyroid Hormone Replacement. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Task Force on Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670-1751.
6. Pacifico L, Anania C, Ferraro F, Andreoli GM, Chiesa C. Thyroid function in childhood obesity and metabolic comorbidity. Clin Chim Acta. 2012;413(3-4):396-405.
Ms Nierengarten, a medical writer in Minneapolis, Minnesota, has over 25 years of medical writing experience, authoring articles for a number of online and print publications, including various Lancet supplements, and Medscape. She has nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article.