Condition

Acquired Hypothyroidism in Children

Editors: Nancie MacIver MD, PhD; Zbigniew Fedorowicz PhD, MSc, DPH, BDS, LDSRCS; Scott A. Barron MD, FAAP

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Background Information

Description

  • acquired hypometabolic state due to deficiency of thyroid hormone
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Definitions

  • overt (clinical) hypothyroidism - elevated thyroid-stimulating hormone (TSH) with low free thyroxine (free T4)
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  • subclinical hypothyroidism - elevated TSH with normal free T4
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  • central hypothyroidism - low to normal TSH with low free T4 due to hypopituitarism or hypothalamic lesion
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Types

  • primary - inability of thyroid gland to produce adequate thyroid hormone
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  • secondary - inadequate thyroid stimulation from pituitary damage or dysfunction
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  • tertiary - inadequate pituitary or thyroid stimulation from hypothalamic damage or dysfunction
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Epidemiology

Who Is Most Affected

  • usually occurs in children > 6 months old, but may present any time
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  • autoimmune thyroiditis is more common in female children (ratio 2:1)
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Incidence/Prevalence

  • autoimmune thyroiditis (also known as chronic lymphocytic thyroiditis or Hashimoto thyroiditis) is most common cause of acquired thyroiditis and accounts for 30%-40% of acquired hypothyroidism
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    • reported incidence of goitrous chronic lymphocytic thyroiditis is 1 in 50-100 in adolescents
    • most common acquired thyroid disease and cause of hypothyroidism in children
    • see Hashimoto Thyroiditis for details
  • STUDY SUMMARY
    about 3% prevalence of hypothyroidism in children and adults in Europe between 1975 and 2012
    SYSTEMATIC REVIEW: J Clin Endocrinol Metab 2014 Mar;99(3):923

Risk Factors

Associated Conditions

Etiology and Pathogenesis

Causes

  • primary causes in children
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    • autoimmunity
      • autoimmune thyroiditis (Hashimoto thyroiditis)
        • goitrous autoimmune disease due to thyroid gland destruction by infiltrating lymphocytes
        • in children it usually occurs in early to midpuberty, but may present as early as infancy
        • may be associated with chromosomes X and 21
      • atrophic thyroiditis (also called primary myxedema) - nongoitrous variant
    • infiltration
    • infection
    • thyroidectomy
    • thyroiditis due to
      • radioactive iodine (I-131) ablation (usually done for Graves disease)
      • external irradiation of nonthyroidal tumors such as lymphomas, brain tumors, or total body irradiation (usually for Hodgkin lymphoma or other lymphoma)
      • iodinated contrast exposure
        • incidence of hypothyroidism 1.33 per 1,000 person-months among children < 4 years old after exposure to iodinated contrast agent during diagnostic procedure in retrospective cohort study with 2,320 children (Invest Radiol 2019 May;54(5):296)
        • transient or long-lasting hypothyroidism reported in 15% of children ≤ 8 years old after exposure to iodinated contrast media during cardiac catheterization or computed tomography angiography in retrospective cohort study with 207 children (J Pediatr Endocrinol Metab 2020 Nov 26;33(11):1409)
    • iodine deficiency (usually presents with goiter)
    • excessive iodine intake
    • medications with antithyroid activity, including
      • thionamides (such as propylthiouracil, methimazole, and carbimazole)
      • lithium
      • antiseizure medications
      • sertraline
      • amiodarone
      • aminosalicylic acid
      • aminoglutethimide
      • tyrosine kinase inhibitors
    • goitrogens (such as cassava, water pollutants, cabbage, sweet potatoes, cauliflower, broccoli, and soy beans)
  • secondary (pituitary) and tertiary (hypothalamic) causes
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Pathogenesis

  • production and release of active thyroid hormone in thyroid gland is dependent on functioning hypothalamic-pituitary-thyroid axis, including adequate
    • production, release, and transport of active
      • thyrotropin-releasing hormone (TRH) from hypothalamus
      • thyroid-stimulating hormone (TSH) from pituitary gland
    • uptake and binding of
      • TRH to pituitary receptors to activate production of TSH
      • TSH to thyroid gland receptors to activate thyroid follicle to produce triiodothyronine (T3) and tetraiodothyronine (T4)
      • T3 and T4 to cellular receptors to control metabolism and growth
    • uptake of iodine into thyroid follicle to form T3 and T4
    • peripheral conversion of T4 to more active T3
    • binding to peripheral receptors to achieve effects
    • PubMed23772479Clinical laboratory science : journal of the American Society for Medical TechnologyClin Lab Sci20130401262112-7112 Reference - Clin Lab Sci 2013 Spring;26(2):112
  • acquired hypothyroidism may be due to
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    • inability to produce adequate thyroid hormone (T3 and/or T4) from
      • lymphocytic infiltration (chronic lymphocytic thyroiditis)
      • damage to thyroid gland from radiation, trauma, infection, or infiltration by accumulation of abnormal metabolic products
      • inadequate or excessive iodine
      • antithyroid medications or goitrogens
    • lack of thyroxine from removal or destruction of thyroid gland
    • inadequate stimulation of thyroid hormone production from damage to pituitary gland or hypothalamus from
      • local infection or trauma
      • tumors or lesions pressing on hypothalamus/pituitary
      • infiltration by accumulation of abnormal metabolic products
Primary and secondary hypothyroidism comparison

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Primary and secondary hypothyroidism comparison

Left: Primary hypothyroidism, in which the thyroid cannot produce enough thyroid hormones (thick green arrow). Right: Secondary hypothyroidism, in which the thyroid is not stimulated by the pituitary gland to produce necessary hormone levels (thin green arrow).

Hormone changes occurring during development of primary hypothyroidism

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Hormone changes occurring during development of primary hypothyroidism

In mild thyroid failure, the only detectable abnormality is a mildly elevated serum TSH level. Moderate hypothyroidism is characterized by further elevation of serum TSH and a reduction in serum T4, but the T3 level is relatively preserved by enhanced T4 to T3 conversion. In severe hypothyroidism, the TSH level is very high, the T4 level is further reduced, and the serum T3 level becomes low. Abbreviation: TSH, thyroid-stimulating hormone.

Hormone changes occurring during development of central hypothyroidism

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Hormone changes occurring during development of central hypothyroidism

Because this disorder is due to impaired pituitary TSH secretion, the serum TSH level does not rise and thus there is no signal of mild thyroid failure. When central hypothyroidism is moderate, the serum T4 level becomes low, the serum T3 level remains normal and the serum TSH is low or low-normal. Severe central hypothyroidism is characterized by very low serum T4 level, low serum T3 level, and a low or low-normal serum TSH level. Abbreviation: TSH, thyroid-stimulating hormone.

  • effects of hypothyroidism on metabolism may include
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    • decreasing heart rate and myocardial contractility
    • reduced oxygen consumption and generation of body heat
    • reduction in glycogen synthesis, glucose uptake and utilization, glycogenolysis, and gluconeogenesis
    • reduction in synthesis of cholesterol and its metabolic conversion to biologically active compounds, such as hormones
    • reduction in cytokines, growth factors, and other factors to stimulate bone development and growth
    • reduction in protein catabolism
    • hypoplasia of cortical neurons, delayed myelinization, and reduced central nervous system vascularization (most thyroid hormone-dependent brain development is complete after age 3 years)
    • PubMed23772479Clinical laboratory science : journal of the American Society for Medical TechnologyClin Lab Sci20130401262112-7112 Reference - Clin Lab Sci 2013 Spring;26(2):112
  • goiter in autoimmune thyroiditis may be a result of lymphocytic infiltration or as a result of compensatory increase in thyroid-stimulating hormone
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