Overview
Definition:
Congenital hypothyroidism (CH) is a condition present at birth characterized by insufficient production of thyroid hormones by the thyroid gland
Thyroid hormones are essential for normal growth and development, particularly of the brain
Untreated CH can lead to irreversible intellectual disability and stunted growth.
Epidemiology:
CH is one of the most common preventable causes of intellectual disability
The incidence varies globally, with estimates ranging from 1 in 1500 to 1 in 4000 live births
Newborn screening programs have significantly reduced the incidence of severe intellectual disability due to CH
Familial forms and specific ethnic or geographical predispositions exist.
Clinical Significance:
Early diagnosis and prompt treatment of CH are crucial to prevent severe neurodevelopmental deficits
However, the potential for overtreatment with supraphysiological doses of levothyroxine poses its own set of risks, necessitating careful monitoring and individualized management strategies
Understanding these nuances is vital for pediatricians preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
In newborns, signs are often subtle and may include prolonged jaundice
Persistent symptoms in infants can manifest as poor feeding
Lethargy
Constipation
Hypotonia
Large fontanelles
Macroglossia
Umbilical hernia
Delayed milestones
Cold mottled skin
Bradycardia
Hoarse cry
Significant overtreatment may lead to irritability
Rapid weight gain
Excessive sweating
Tachycardia
Poor sleep
Diarrhea
Fine tremor
Rapid growth.
Signs:
Physical examination may reveal a puffy face, dull expression, dry skin, and a protruding tongue
Umbilical hernia is common
Prolonged hypothermia may be noted
In overtreatment, signs of hyperthyroidism like accelerated linear growth, precocious puberty, and widened sutures can be observed.
Diagnostic Criteria:
Diagnosis is primarily based on elevated thyroid-stimulating hormone (TSH) and low free thyroxine (fT4) levels in newborn screening
Confirmatory testing includes repeat TSH and fT4
Genetic testing may be indicated for persistent or familial cases
Diagnostic confirmation typically involves TSH > 10-20 mIU/L and fT4 < 1.0-1.5 ng/dL (depending on assay and age), with higher TSH levels and lower fT4 indicating more severe hypothyroidism
Overtreatment is usually diagnosed based on laboratory findings (suppressed TSH, normal or elevated fT4/T3) and clinical signs.
Diagnostic Approach
History Taking:
Detailed family history is important, looking for thyroid disorders or consanguinity
Maternal thyroid status and any iodine exposure during pregnancy are relevant
Assess for symptoms suggestive of hypothyroidism or hyperthyroidism in the infant
In older children, inquire about growth, school performance, and behavioral changes.
Physical Examination:
A thorough physical examination focusing on dysmorphic features, fontanel size, tongue size, abdominal reflexes, skin texture, and signs of cardiac compromise
Assess growth parameters (height, weight, head circumference) and compare with standardized charts
Look for signs of hyperthyroidism in suspected overtreatment cases.
Investigations:
Initial investigations include serum TSH and free T4
If hypothyroidism is confirmed, further workup may involve thyroid autoantibodies (anti-TPO, anti-thyroglobulin), radioiodine uptake and scan (to determine gland location and function, though less common in screening era), and thyroid ultrasound to assess gland morphology
Genetic analysis for specific gene mutations may be performed in complex cases
Overtreatment is primarily diagnosed with suppressed TSH levels (<0.1 mIU/L) and normal or elevated free T4 levels
Monitoring involves serial TSH and free T4 measurements every 2-3 months initially, then every 3-6 months, and annually thereafter.
Differential Diagnosis:
Transient hypothyroidism (due to maternal antibodies, iodine deficiency/excess, or certain medications)
Central hypothyroidism (secondary or tertiary) characterized by low TSH with low fT4, requiring assessment of other pituitary hormones
Conditions mimicking hypothyroidism in newborns include Down syndrome, prematurity, and transient familial hypothyroidism
Mimics of overtreatment can include anxiety, prematurity, or other causes of increased metabolism.
Management
Initial Management:
Initiate treatment with levothyroxine (L-T4) as soon as diagnosis is confirmed, ideally within the first few weeks of life
The goal is to normalize thyroid hormone levels rapidly to promote optimal neurocognitive development
Dosage is weight-based.
Medical Management:
Levothyroxine (L-T4) is the treatment of choice
The initial dose for newborns is typically 10-15 mcg/kg/day, aiming to achieve TSH < 5-10 mIU/L and fT4 in the upper half of the reference range
Doses are adjusted based on serial biochemical monitoring and growth parameters
Overtreatment is managed by reducing the L-T4 dose, aiming for TSH within the normal range (0.5-4.0 mIU/L) and fT4 in the mid-normal range
Gradual reduction is preferred to avoid rebound hypothyroidism.
Surgical Management:
Surgery is generally not indicated for congenital hypothyroidism itself, but may be required for associated anomalies like thyroglossal duct cysts or in rare cases of thyroid tumors later in life.
Supportive Care:
Nutritional support is crucial, ensuring adequate caloric intake for growth
Psychosocial support for families is important
Educate parents on medication administration, recognition of symptoms of undertreatment and overtreatment, and the importance of regular follow-up.
Overtreatment Risks
Cardiovascular Effects:
Supraphysiological doses of L-T4 can lead to tachycardia, palpitations, increased cardiac output, and potentially supraventricular tachycardia or atrial fibrillation in susceptible individuals
Long-term, it may contribute to premature closure of the epiphyses.
Neurodevelopmental Impact:
While undertreatment is devastating, overtreatment can also negatively impact neurodevelopment
This includes behavioral issues like irritability, hyperactivity, anxiety, and sleep disturbances
Rapid growth and early puberty can also be consequences.
Skeletal Implications:
Excessive thyroid hormone can accelerate bone maturation and lead to premature epiphyseal closure, potentially impacting final adult height
This is a critical concern when dosing
Overtreatment can lead to bone age advancement.
Metabolic And Other Effects:
Other risks include significant weight loss, diarrhea, excessive sweating, tremors, and potentially impaired nutrient absorption
Increased metabolic rate can also affect other organ systems
Overtreatment can mask underlying adrenal insufficiency if growth is stunted.
Follow Up
Monitoring Frequency:
Close follow-up is essential, especially in the first few years of life
Initially, monitoring of TSH and fT4 every 2-4 weeks after dose initiation and adjustment
Once stable, every 3-6 months until age 3, then every 6-12 months annually
In adolescence, assessment of bone age and monitoring for psychosocial issues may be needed.
Target Parameters:
The goal of follow-up is to maintain TSH within the target range (typically 0.5-2.0 mIU/L for infants up to 3 years, and 0.5-4.0 mIU/L thereafter) and free T4 in the mid-normal range for age
Avoid consistently suppressed TSH levels (<0.1 mIU/L) which indicate overtreatment
Monitor growth parameters closely, ensuring appropriate velocity and pattern.
Long Term Surveillance:
Long-term follow-up should include assessment of neurocognitive function, academic performance, psychosocial adjustment, and growth
Regular review of medication adherence and potential side effects is crucial
Annual thyroid function tests are recommended throughout life for individuals with CH
Consider monitoring for related autoimmune conditions.
Transition To Adult Care:
A structured transition from pediatric to adult endocrine care is vital
This ensures continuity of care, continued monitoring, and management of any emerging issues
Patients need to understand their condition and lifelong treatment needs.
Key Points
Exam Focus:
Know the initial treatment dose of L-T4 for CH (10-15 mcg/kg/day)
Understand the target TSH and fT4 levels for monitoring
Be aware of the common causes of CH and the importance of newborn screening
Recognize the signs and symptoms of overtreatment, especially cardiovascular and neurodevelopmental effects
Differentiate congenital hypothyroidism from central hypothyroidism.
Clinical Pearls:
Always confirm hypothyroidism with repeat TSH and fT4 before initiating treatment, unless newborn screening values are critically abnormal
Adjust L-T4 dose based on TSH, fT4, and clinical assessment, not solely on TSH
Use liquid L-T4 preparations for neonates and infants for easier dosing
Monitor bone age annually in children receiving L-T4 to detect overtreatment
Educate parents thoroughly on medication handling and importance of regular follow-up.
Common Mistakes:
Over-treating by aiming for suppressed TSH levels, which can lead to iatrogenic hyperthyroidism
Under-treating by using insufficient L-T4 doses
Failing to adequately monitor growth and development
Not reassessing L-T4 dose after significant weight changes or illness
Delayed diagnosis due to reliance on clinical signs alone in newborns.