A 6-week-old girl, who was born at home and was not screened at birth for congenital hypothyroidism, presented to her pediatrician with signs of jaundice and was found to be hypothyroid with an elevated TSH (Figure 191-1). She was started on levothyroxine and her dose was titrated until her TSH was normal. At her 1 year old visit she was a normal healthy child with a normal developmental exam.

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  Hypothyroidism is a condition caused by lack of thyroid hormone and usually develops as a result of thyroid failure from intrinsic thyroid disease. The most common cause of nonendemic goitrous hypothyroidism in both children and adults is chronic lymphocytic (Hashimoto) thyroiditis, also called autoimmune thyroiditis.¹

  
  
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  Congenital hypothyroidism (CH) is decreased or absent thyroid function and thyroid hormone production that is present at birth. Historically this was due to lack of iodine. In iodine-replete countries, most cases of CH are caused by defects in embryonic development (e.g., congenitally absent, underdeveloped, or ectopic thyroid gland). Other causes include inherited enzymatic defects in the synthesis of thyroxine (T4), prematurity, and anti-thyroid drugs taken during pregnancy.

  
  
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  Goiter is a spectrum of changes in the thyroid gland ranging from diffuse enlargement to nodular enlargement depending on the cause. In the US, the most common cause of goiter with normal thyroid function or transient dysfunction is thyroiditis.

  
  
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  Subclinical thyroid disease refers to a patient with no or minimal thyroid-related symptoms but abnormal laboratory values (elevated TSH and thyroxine level within the normal range).

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  Based on a population study in Scotland, the prevalence of hypothyroidism in children (<22 years of age) is 0.135 percent; the prevalence is 0.113 percent in children aged 11 to 18 years.² These values are twice those of previous estimates. The most common cause of acquired hypothyroidism was autoimmune disease.

  
  
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  CH occurs in about 1 per 3000 to 4000 births in the US with a female to male ratio of 2: 1. It is the most preventable cause of cognitive impairment in children.³ There is a higher incidence of CH in some ethnic groups such as Greek Cypriots (1 per 1800) and Asians (1 per 918 in Northern England).^4,5

  
  
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  In a New Zealand population study, the overall incidence of CH rose from 2.6 to 3.6 per 10,000 live births over an 18-year period thought to be due to a shift in population with proportionately more Asian and Pacific Island births.⁶

  
  
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  Worldwide, goiter is the most common endocrine disorder with rates of 4 to 15 percent in areas of adequate iodine intake and more than 90 percent where there is iodine deficiency.⁷ Endemic goiter is defined as goiter that affects more than 5 percent of the population (Figure 191-1).

  
  
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  Most goiters are not associated with thyroid dysfunction.

  
  
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  The prevalence of goitrous hypothyroidism varies from 0.7 to 4 percent of the population. Among adolescents, the incidence of Hashimoto thyroiditis during adolescence is approximately 1 to 2 percent.³

  
  
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  Subclinical hypothyroidism is present in 3 to 10 percent of population groups.^8,9

  
  
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  Prevalence rates of hypothyroidism and subclinical hypothyroidism are higher for children with certain conditions including Down syndrome (10.8% of children with Down syndrome in one 11-year population study filled a new prescription for thyroid medication),¹⁰ Turner syndrome, type 1 diabetes mellitus (7.2% of children in one study had subclinical hypothyroidism),¹¹ celiac disease, and cystic fibrosis (CF) (108/129 children with CF in one study were iodine deficient and 11.6 percent had subclinical hypothyroidism).¹² Autoimmune thyroid disease is also more common in individuals with vitiligo. In a recent report of 104 Iranian children age 5 to 15 years referred with migraine headache, 24 percent had subclinical hypothyroidism.¹³

Hypothyroidism can be caused by disease of the thyroid gland itself (e.g., Hashimoto thyroiditis or thyroid dysgenesis), treatment of hyperthyroidism (e.g., anti-thyroid medication or radioiodine thyroid ablation in the patient or mother during pregnancy, or thyroidectomy), high-dose head and neck radiation therapy, medications (e.g., lithium or alpha-interferon) or, rarely, by pituitary or hypothalamic disorders (e.g., tumors, inflammatory conditions, infiltrative diseases, infections, pituitary surgery, pituitary radiation therapy, and head trauma).⁸

Hashimoto thyroiditis is caused by thyroid peroxidase (TPO) antibodies.

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  There is marked lymphocytic infiltration of the thyroid in Hashimoto thyroiditis; the infiltrate is composed of activated CD4+ and CD8+ T cells, as well as B cells.

  
  
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  Thyroid destruction in Hashimoto thyroiditis is believed to be primarily mediated by CD8+ cytotoxic T cells.

CH can be either permanent or temporary.

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  Permanent causes include defective embryonic development resulting in congenitally absent, underdeveloped, or ectopic thyroid gland (85%); inherited enzymatic defect in the synthesis of thyroxine (T4) caused by an autosomal recessive gene (10%); abnormal function of hypothalamus or pituitary, or thyroid hormone resistance (<5%). In the New Zealand study previously cited, of 330 new cases of CH over an 18-year period, 86 percent of cases had a scintiscan of which 67 percent showed thyroid dysgenesis (female to male ratio 5:1), and 33 percent demonstrated dyshormonogenesis (female to male ratio 0.9:1.0).⁶

  
  
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  About 2 percent of thyroid dysgenesis is familial. In one case series, TSHR was found to be the main causative locus in autosomal recessively inherited thyroid dysgenesis.¹⁴

  
  
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  Among cases of temporary hypothyroidism, causes include antithyroid drugs taken during pregnancy, prematurity, and iodine deficiency or excess.

Contributing factors for goiter are:

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  Iodine deficiency or excess (Figures 191-2 and 191-3).

  
  
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  TSH stimulation.

  
  
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  Drugs, including lithium, amiodarone, anticonvulsants, and α-interferon.

  
  
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  Autoimmunity/heredity.

Other risk factors for hypothyroidism include²:

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  Symptoms of thyroid hormone deficiency.

  
  
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  Goiter.

  
  
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  Personal or family history of thyroid disease.

  
  
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  Personal treatment of thyroid disease.

  
  
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  History of an autoimmune disease, especially diabetes mellitus.

Clinical Features

Many children with autoimmune thyroiditis are asymptomatic at diagnosis.¹⁵ Classic signs and symptoms of hypothyroidism are³:

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  A decrease in linear growth.

  
  
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  Fatigue and/or weakness.

  
  
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  Dry and cool skin (Figure 191-4).

  
  
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  Increased body hair.

  
  
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  Difficulty concentrating with poor school performance.

  
  
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  Bradycardia.

  
  
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  Delayed deep tendon reflex relaxation.

  
  
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  Weight gain despite poor appetite.

  
  
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  Constipation.

  
  
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  The most useful signs in adults for diagnosing hypothyroidism in one study were puffiness (likelihood ratio positive [LR+] 16.2) and delayed ankle reflex (LR+ 11.8).¹⁶

  
  
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  Clues to a central cause of hypothyroidism include a history of pituitary/hypothalamic surgery or radiation, headache, visual field defects, or ophthalmoplegia.⁸

Among infants with CH, the vast majority (95%) has few clinical manifestations.³ Features suggestive of CH include:³

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  An open posterior fontanelle in a term baby.

  
  
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  Lethargy or hypotonia.

  
  
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  Hoarse cry.

  
  
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  Feeding problems or macroglossia.

  
  
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  Constipation.

  
  
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  Umbilical hernia (Figure 191-5).

  
  
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  Dry skin.

  
  
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  Hypothermia.

  
  
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  Prolonged jaundice.