Hypothyroidism%20(pediatric) Diagnosis

Differentiating Between Primary, Central and Subclinical Hypothyroidism

• Overt primary hypothyroidism: Low free thyroxine (FT₄) and elevated serum thyroid-stimulating hormone (TSH)
• Subclinical primary hypothyroidism: Elevated TSH and normal FT₄
• Repeat thyroid function test should be done after 3-6 months to confirm the diagnosis
• Central hypothyroidism: Low FT₄ and low, normal or mildly elevated serum TSH

• Prolonged gestation
• Maternal history of thyroiditis (transient neonatal hypothyroidism)
• Maternal exposure to radioiodine or intake of goitrogens (eg Amiodarone, antithyroid drugs)
• Family history of hypothyroidism
• Thyroid treatment for hyperthyroidism (eg Thionamides, radioiodine or surgery)
• Viral infection followed by a painful thyroid gland with signs and symptoms of hyperthyroidism, later on manifesting signs and symptoms of hypothyroidism (subacute thyroiditis)
• Iodine sources (Iodine deficiency/endemic goiter)
• Excessive iodide intake (eg Kelps, radiocontrast dyes)
• Intake of goitrogens (eg Lithium, Amiodarone, thionamides)
• Head and neck radiation

• Patient’s age must be considered in the interpretation of thyroid function results

Confirmation of Hypothyroidism

• Serum thyroid-stimulating hormone (TSH): Most valuable test for detecting hypothyroidism
• Free thyroxine (FT₄) levels also useful for confirmation
• TSH and FT₄ concentrations are higher in children, especially in the 1st week of life and throughout the 1st year

Other Thyroid Tests

• Thyroid autoantibodies: Antithyroid peroxidase and antithyroglobulin autoantibodies
• Thyroid scan, ultrasound
• Fine needle aspiration (FNA): Recommended for all palpable solitary or dominant nodules, independent of size
  
  • FNA is preferred over thyroid scan or ultrasonography as the initial diagnostic test for thyroid nodules, although a previous ultrasound may aid the physician in performing the aspiration

Acquired Hypothyroidism

• If suspected, the entire function of the hypothalamic-pituitary axis should be evaluated with appropriate tests
  
  • Once confirmed imaging studies of the brain and pituitary gland should be performed

Congenital Hypothyroidism

• Most infants appear unaffected at birth; signs and symptoms may be delayed until 6-12 weeks of age or older
• Newborn screening for congenital hyperthyroidism is crucial for early detection and treatment
  
  • Delaying treatment after 6 weeks of life is associated with increased risk of delayed cognitive development
  • Abnormal laboratory results must be communicated immediately so that empirical thyroid hormone replacement can be initiated even while waiting for confirmatory studies

• Cranial imaging such as magnetic resonance imaging (MRI) is recommended in patients with confirmed central hypothyroidism

• Present or absent femoral/tibial epiphyses in radiographic imaging of the knee may help assess the severity of intrauterine hypothyroidism
• Scintigraphy and ultrasonography may also be used to assess the patient’s thyroid function and cause of the disease
  
  • Performing both scintigraphy and ultrasound is highly suggested in neonates with high thyroid-stimulating hormone (TSH) levels

Newborn Screening for Congenital Hypothyroidism

• Goals of screening: To identify and treat patients at risk for the health consequences of thyroid dysfunction before they become clinically apparent
• Additional indications and ideal time for screening:
  
  • Normal hospital delivery at term: 2-4 days of age
  • Infants in neonatal intensive care units (NICU), preterm babies, home births: Within 7 days of age
  • Maternal history of thyroid medication or family history of congenital hypothyroidism: Cord blood for screening

Types of Newborn Screening

• Primary thyroid-stimulating hormone (TSH), backup free thyroxine (FT₄): May miss thyroid-binding globulin deficiency, central hypothyroidism, hypothyroxinemia with delayed TSH elevation
• Primary T₄, backup TSH: May miss delayed TSH elevation with initial normal T₄
• Primary T₄ and TSH: Ideal screening approach

Interpretation of Newborn Screening Results

• Elevated TSH and low T₄: Congenital hypothyroidism
• Normal TSH and low T₄: Transient hypothyroxinemia, central hypothyroidism, thyroid-binding globulin deficiency, isolated low T₄
• Elevated TSH and normal T₄: Transient/permanent mild congenital hypothyroidism, delayed maturation of hypothalamic/pituitary axis, thyroid hormone resistance, Down syndrome, subclinical hypothyroidism
• Delayed TSH elevation and low T₄: Low or very low-birth weight infants, preterm infants, sick term newborn

Confirmation of Results

• Infants with abnormal or borderline screening results should have free T₄ and TSH drawn for definitive testing
  
  • Thyroid hormone replacement may be empirically initiated while awaiting confirmatory results

Secondary Screening for Congenital Hypothyroidism

Recommended for the following:

• Preterm neonates
• Infants with low-birth weight (LBW)
• Infants with very low-birth weight (VLBW)
• Unhealthy infants/preterm neonates previously admitted in the NICU
• Newborn screening done within 1st 24 hours after birth
• Multiple pregnancy