Differentiating between primary, central & subclinical hypothyroidism

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

Additional thyroid tests may include the following

• Thyroid autoantibodies: Antithyroid peroxidase & 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

• 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 w/ signs & symptoms of hyperthyroidism, later on manifesting signs & 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 & 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 & FT₄ concentrations are higher in children, especially in the 1st week of life & throughout the 1st year

Acquired Hypothyroidism

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

Congenital Hypothyroidism

• Most infants appear unaffected at birth; signs & symptoms may be delayed until 6-12 weeks of age or older
• Newborn screening for congenital hyperthyroidism is crucial for early detection & treatment
  
  • Delaying treatment after 6 weeks of life is associated w/ 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

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

Newborn Screening for Congenital Hypothyroidism

• Goals of screening: To identify & treat patients at risk for the health consequences of thyroid dysfunction before they become clinically apparent
• Additional indications & 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 w/ delayed TSH elevation
• Primary T₄, backup TSH: May miss delayed TSH elevation w/ initial normal T₄
• Primary T₄ & TSH: Ideal screening approach

Interpretation of newborn screening results:

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

Confirmation of results

• Infants w/ abnormal or borderline screening results should have free T₄ & 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 w/ low-birth weight (LBW)
• Infants w/ very low-birth weight (VLBW)
• Unhealthy infants/preterm neonates previously admitted in the NICU
• Newborn screening done w/in 1st 24 hours after birth
• Multiple pregnancy