Mild Hypothyroidism in Childhood

Who, When, and How Should Be Treated?

Maria Cristina Vigone; Donatella Capalbo; Giovanna Weber; Mariacarolina Salerno

Disclosures

J Endo Soc. 2018;2(9):1024-1039. 

In This Article

Management of Mild SH in Childhood

Current guidelines from the American Thyroid Association and the European Thyroid Association suggest offering L-T4 treatment to adults with TSH levels >10 mIU/L, as well as to those with TSH levels of 4.5 to 10.0 mIU/L in the presence of symptoms or signs of hypothyroidism and/or antithyroid antibodies and/or evidence of atherosclerotic cardiovascular disease.[89,90]

In children, the management of mild SH is still a matter of debate, and the need for therapy is questionable. Indeed, the potential effects of mild hypothyroidism on health outcomes are not clear, and current data do not suggest detrimental effects on neurocognitive and growth development.

A few studies have evaluated linear growth among children with untreated mild autoimmune[91,92] and nonautoimmune SH[53,64,93,94] and most of them reported normal height even after longstanding untreated SH.[53,92–94] Moreover, no appreciable effects after 2 years of L-T4 treatment on linear growth were detected among children with mild idiopathic SH.[95,96]

Data on the effect of SH on neurocognitive outcome in children are conflicting. Even though subtle abnormalities in attention have been reported in two small studies on SH children,[97,98] data from a large survey reported normal cognitive performance in SH adolescents.[51] Furthermore, a recent prospective case-control study among 30 children with mild but long-lasting idiopathic SH reported normal verbal, performance and full-scale IQ, comparable to euthyroid controls.[93]

No abnormalities in biochemical markers of bone metabolism, lumbar bone mineral density, and bone quality were detected in two studies evaluating the effects of untreated mild SH on bone health.[99,100]

Recently, concern has been raised on adverse cardiovascular (CV) outcome in patients with untreated SH. Coronary heart disease and heart failure seem to occur most frequently among adults with SH, particularly when the TSH levels exceed 10 mIU/L.[1,4]

Higher TSH levels have been associated with less favorable lipid levels, even in children.[3] Moreover, recent longitudinal case-control studies demonstrated that untreated mild SH in children can be associated with early CV risk factors such as mild dyslipidemia, increased visceral adiposity, increased levels of homocysteine, early markers of endothelial dysfunction, and preclinical alteration in left ventricular function.[94,96,101] L-T4 treatment was associated with beneficial effects on most biochemical markers of CV risk and cardiac and endothelial function.[96,101]

However, despite these subtle CV abnormalities, current data are not sufficient to recommend treatment of all children with mild SH,[3,96] and the decision to treat should be based on individual patient factors.

A schematic approach to the management of mild SH in children is summarized in Figure 1.

Figure 1.

Schematic approach to diagnosis and management of SH in children. (Adapted with permission from Salerno M, Capalbo D, Cerbone M, De Luca F. Sublinical hypothyroidism in childhood: current knowledge and open issues. Nat Rev Endocrinol. 2016; 12(12):734–746 [3].)

The first step in managing a child with a mild increase in TSH levels should be to rule out abnormal values caused by laboratory problems, diurnal variation in TSH concentration, and transient causes of SH (recovery phase from nonthyroidal illness or subacute thyroiditis). Persistent SH should be confirmed by reevaluation of the TSH levels at 4 to 12 weeks after the first test.

In children with persistent elevated TSH level, a diagnostic workup is recommended. The child's history should focus on the presence of neonatal hyperthyrotropinemia, autoimmune and/or genetic conditions, use of medications known to interfere with thyroid function, previous exposure to ionizing radiation, and endemic iodine deficiency. Attention should be given to the presence of SH, goiter, and endocrine, genetic, or autoimmune diseases in family members. Physical examination should focus on signs of hypothyroidism, goiter, weight gain, and clinical features suggestive of specific genetic conditions.

All patients should be screened for the presence of antithyroid antibodies. Thyroid ultrasound may provide additional information on gland morphology and structure. Further investigations can be considered on the basis of personal history, physical examination, and dysmorphic features. Urinary iodine excretion for those living in endemically deficient areas should be carried out. For cases arising in familial settings, genetic analysis can be considered. In patients with mild SH and risk factors such as a family history of hyperlipidemia, presence of acanthosis, or body mass index >90%, a screening lipid panel may be considered.

The subsequent management and the decision on treatment should depend on the etiology, the degree of TSH elevation, the risk of progression to overt hypothyroidism, and the presence of clinical symptoms or signs of mild thyroid impairment.

In the most common clinical scenario of autoimmune SH, treatment with L-T4 should be started for all children affected by severe forms (TSH level >10 mIU/L) or among those with mild SH in the presence of goiter or the signs or symptoms of hypothyroidism. In children with HT, a beneficial effect of L-T4 on goiter has been documented in several studies, even in patients with normal or subclinical thyroid dysfunction.[102–104]

In children with untreated HT, thyroid function (FT4 and TSH) should be monitored every 6 months. Repeated measurements of thyroid antibodies during the follow-up do not contribute to the management of SH. The frequency of imaging should be personalized based on signs and symptoms. Children with Turner syndrome and DS should be carefully monitored for the greater risk of progressive thyroid dysfunction.

The management of SH associated with other autoimmune diseases such as celiac disease and type 1 diabetes represents a difficult issue. Even though a recent study suggests that the presence of celiac disease in patients with HT and SH is a predictive factor for thyroid failure[58] there are no data on the effects of early L-T4 treatment in these children.

Studies in children and adolescents with type 1 diabetes suggest that mild SH may be associated with an increased risk of dyslipidemia[105] and symptomatic hypoglycemia,[106] whereas growth impairment has been documented only in children with severe overt thyroid dysfunction.[91]

In the absence of longitudinal studies on the benefits of early treatment with L-T4, the decision of treating mild SH associated with diabetes or celiac disease remains controversial.

Currently, data are insufficient to establish a specific TSH cutoff to treat these patients, and L-T4 treatment should be personalized, taking into account not only the presence of subtle signs or symptoms of thyroid failure but also the control of the underlying disease.

TSH resistance should be considered in the differential diagnosis of all patients with nonautoimmune, nongoitrous hyperthyrotropinemia, but the need for therapy is questionable, and intervention should depend on the child's age and the degree of TSH elevation. Therapy is recommended in case of overt hypothyroidism, whereas careful monitoring is suggested for mild and asymptomatic forms.

In children who are overweight or obese, diet and lifestyle changes should be recommended and thyroid function should be rechecked after weight loss. Iodine supplementation is recommended among children living in areas with endemic iodine deficiency and/or with documented reduced iodine excretion.

In children treated with medications that might interfere with thyroid function, treatment with L-T4 should be considered for children with a TSH level >10 mIU/L. A possible recovery of thyroid function should be evaluated at medication withdrawal.

Finally, in all forms of SH that resolve at any point during follow-up, a reevaluation of thyroid function should be considered later in life, particularly during adolescence and pregnancy.

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