Can congenital hypothyroidism be diagnosed well after birth?

Can Congenital Hypothyroidism Be Diagnosed Well After Birth?

Yes, congenital hypothyroidism can be diagnosed well after birth, though this represents a failure of optimal screening and detection systems. While newborn screening programs are designed to identify most cases within the first days to weeks of life, some cases are missed by initial screening and only become apparent later through clinical symptoms or delayed testing 1, 2.

Why Late Diagnosis Occurs

Limitations of Single-Screen Programs

• Approximately 20% of congenital hypothyroidism cases cannot be efficiently identified by a single newborn screen alone, based on Utah's screening data from 2010-2016 3
• Among 130 diagnosed cases in Utah during this period, 25 cases (19%) had a normal first screen but abnormal second screen at approximately 2 weeks of age 3
• This demonstrates that even with screening programs in place, some infants will not be detected on initial testing 3

Subtle or Absent Clinical Manifestations at Birth

• Clinical manifestations are often subtle or not present at birth, likely due to transplacental passage of maternal thyroid hormone and residual thyroid function in some affected infants 1
• Most neonates born with congenital hypothyroidism have normal appearance and no detectable physical signs in the immediate newborn period 4
• Hypothyroidism in the newborn period is almost always overlooked without screening 4

Global Screening Gaps

• Seventy percent of neonates worldwide do not undergo newborn screening, meaning the majority of affected infants globally are diagnosed only when symptoms develop 2
• Newborn screening for hypothyroidism is not yet practiced in all countries 2

Clinical Presentation When Diagnosis Is Delayed

Common Symptoms That Emerge Over Time

• Decreased activity and increased sleep 1
• Feeding difficulty 1
• Constipation 1
• Prolonged jaundice 1

Physical Examination Findings

• Myxedematous facies 1
• Large fontanelles (particularly large posterior fontanelle) 1, 2
• Macroglossia (large tongue) 1, 2
• Distended abdomen with umbilical hernia 1, 2
• Hypotonia 1
• Lethargy and/or hypothermia 2

Critical Importance of Early Detection

Neurocognitive Consequences

• Untreated congenital hypothyroidism leads to intellectual disabilities and mental retardation 2, 4
• Lower neurocognitive outcomes occur in infants started on treatment after 30 days of age compared to those treated earlier 1
• Delayed diagnosis leads to the most severe outcome of congenital hypothyroidism—mental retardation—emphasizing the critical importance of newborn screening 4

Other Complications

• Growth complications including decreased height/length 3
• Untreated maternal hypothyroidism may have adverse effects on fetal neurocognitive development 5

When to Suspect Hypothyroidism Despite Normal Screening

Physicians must consider hypothyroidism when clinical symptoms and signs are present, even if newborn screening thyroid test results are normal 2. This is a critical clinical pitfall to avoid.

Indications for Testing Regardless of Screening Results

When the following clinical features are present, measurement of serum TSH and free T4 is indicated regardless of newborn screening results 2:

• Large posterior fontanelle
• Large tongue
• Umbilical hernia
• Prolonged jaundice
• Constipation
• Lethargy
• Hypothermia

Diagnostic Confirmation Process

Laboratory Testing

• Diagnosis should be confirmed by finding an elevated serum TSH and low T4 or free T4 level 1
• For congenital hypothyroidism, repeating the newborn screening analyte, possibly in conjunction with related analytes, is sufficient because consistently abnormal levels can be indicative of clinical disease 6

Additional Diagnostic Studies

Other diagnostic tests may help pinpoint the underlying etiology, though treatment may be started without these tests 1:

• Thyroid radionuclide uptake and scan
• Thyroid sonography
• Serum thyroglobulin determination

Treatment Initiation

Immediate Treatment Protocol

• Levothyroxine is the treatment of choice with a recommended starting dose of 10 to 15 mcg/kg/day 1, 2
• Treatment should be initiated immediately upon diagnosis to prevent adverse neurocognitive outcomes 1
• The immediate goals are to rapidly raise serum T4 above 130 nmol/L (10 μg/dL) and normalize serum TSH levels 1

Monitoring Requirements

Frequent laboratory monitoring in infancy is essential to ensure optimal neurocognitive outcome 1:

• Serum TSH and free T4 should be measured every 1-2 months in the first 6 months of life 1
• Every 3-4 months thereafter in the first year 1
• Every 2-3 months in the second and third years 7

Key Clinical Pitfalls to Avoid

• Do not rely solely on newborn screening results—clinical suspicion based on physical findings should prompt confirmatory testing even with normal screening 2
• Do not delay treatment while awaiting additional diagnostic studies—levothyroxine should be started immediately once diagnosis is confirmed by TSH and free T4 1
• Do not use inadequate initial dosing—lower levothyroxine doses than currently recommended (10-15 mcg/kg/day) are associated with worse neurocognitive outcomes 1
• Do not assume a single newborn screen is sufficient—approximately 20% of cases require a second screen for detection 3