Overview
Definition:
Hypothyroidism in children is a condition characterized by insufficient production of thyroid hormones (thyroxine - T4 and triiodothyronine - T3) by the thyroid gland
This deficiency leads to a generalized slowing of metabolic processes, impacting growth, development, and organ function
Congenital hypothyroidism (CH) is diagnosed at birth, while acquired hypothyroidism can develop at any age
The management involves lifelong thyroid hormone replacement therapy, primarily with levothyroxine (LT4).
Epidemiology:
Congenital hypothyroidism affects approximately 1 in 2000 to 1 in 4000 live births worldwide, with screening programs in place to detect it early
Acquired hypothyroidism is less common but can occur due to autoimmune thyroiditis (Hashimoto's thyroiditis), post-surgical hypothyroidism, or radiation therapy
The incidence varies based on iodine intake and the prevalence of autoimmune diseases.
Clinical Significance:
Untreated hypothyroidism in pediatrics can lead to severe consequences, including impaired cognitive development and growth retardation, resulting in cretinism in severe congenital cases
Adequate and timely diagnosis and management are crucial for normal physical and intellectual development
Weight fluctuations, particularly weight gain, are common physiological changes in growing children and necessitate regular reassessment of levothyroxine dosage to maintain euthyroidism and optimize outcomes.
Clinical Presentation
Symptoms:
In infants: Poor feeding
Prolonged jaundice
Constipation
Umbilical hernia
Hypothermia
Lethargy
Hoarse cry
Large fontanelles
In older children: Slowed growth and development
Weight gain despite normal or decreased appetite
Fatigue and lethargy
Cold intolerance
Constipation
Dry skin and hair
Delayed puberty
Poor school performance
Cognitive deficits.
Signs:
Physical examination may reveal dry, coarse skin
Puffy face
Periorbital edema
Sparse hair
Brittle nails
Thickened tongue
Slowed reflexes
Bradycardia
Goiter (in some acquired cases)
Short stature
Delayed skeletal maturation.
Diagnostic Criteria:
Diagnosis is typically based on elevated Thyroid Stimulating Hormone (TSH) levels and low free thyroxine (fT4) levels in serum
TSH is the primary screening test, and confirmation requires fT4 measurement
For congenital hypothyroidism, screening is usually performed via heel prick blood tests within the first few days of life
Etiological workup may involve thyroid ultrasound, thyroid antibody testing (anti-TPO, anti-thyroglobulin), and sometimes thyroid scans.
Diagnostic Approach
History Taking:
Detailed birth history for infants (gestational age, birth weight, maternal thyroid status)
Family history of thyroid disease or autoimmune disorders
History of neck surgery or radiation
Onset and progression of symptoms
Dietary history including iodine intake
Growth patterns (height and weight charts)
Pubertal development status.
Physical Examination:
Assess growth parameters (height, weight, head circumference) against standard growth charts
Examine skin for dryness, pallor, and edema
Assess hair and nail quality
Evaluate for goiter, umbilical hernia, and facial features suggestive of hypothyroidism
Check reflexes, heart rate, and auscultate for cardiac murmurs
Assess for signs of delayed puberty.
Investigations:
Initial: TSH, free T4 (fT4)
Confirmatory: Repeat TSH and fT4
Etiological: Thyroid antibodies (anti-TPO, anti-thyroglobulin) to assess for autoimmune cause
Thyroid ultrasound to assess thyroid gland morphology and position
Bone age X-ray of the wrist and hand to assess skeletal maturation
Consider TRH stimulation test in ambiguous cases, though rarely needed in routine practice.
Differential Diagnosis:
Constitutional delay of growth and puberty
Short stature of other etiologies (e.g., growth hormone deficiency, genetic syndromes)
Other causes of constipation (e.g., dietary, Hirschsprung's disease)
Depression or behavioral issues
Obesity
Malnutrition.
Management
Initial Management:
Immediate initiation of thyroid hormone replacement therapy with levothyroxine (LT4) is crucial, especially for congenital hypothyroidism, to prevent irreversible neurological damage
Dose is calculated based on weight.
Medical Management:
Levothyroxine (LT4) is the drug of choice
The initial dose for congenital hypothyroidism is typically 10-15 mcg/kg/day
For acquired hypothyroidism, doses are generally lower, starting at 25-50 mcg/day or 1-2 mcg/kg/day, adjusted based on TSH and fT4 levels
Dosing is usually once daily in the morning on an empty stomach, at least 30-60 minutes before breakfast or 2-3 hours after the evening meal, to optimize absorption
Tablets should be crushed and mixed with a small amount of water, breast milk, or formula
Avoid co-administration with calcium, iron, soy-based formulas, and antacids which can impair absorption.
Dose Adjustment By Weight Gain:
Children are growing and their weight is dynamic, necessitating regular dose adjustments
The goal is to maintain TSH within the age-appropriate reference range (e.g., 0.5-4.0 mIU/L for most ages, though lower limits may be targeted in very young infants) and fT4 within the normal range for age
As a child gains weight, the LT4 dose typically needs to be increased to maintain euthyroidism
A common practice is to re-evaluate TSH and fT4 levels every 6-12 months or more frequently if there are significant weight changes (e.g., >10-20% change) or clinical signs/symptoms of subclinical or overt hypothyroidism or hyperthyroidism
For example, if a child gains 2-4 kg, a dose increase of approximately 10-15% of the current daily dose might be considered, followed by biochemical reassessment
Precise adjustments should be guided by serial laboratory monitoring and clinical assessment
Some guidelines suggest increasing the dose by 1-2 mcg/kg/day for a significant weight gain.
Monitoring And Follow Up:
Regular monitoring of TSH and fT4 is essential
For infants with CH, TSH and fT4 are checked 2-4 weeks after initiating therapy, then monthly until stable, and then every 3-6 months until 3 years of age
Thereafter, monitoring is typically every 6-12 months
Growth, development, and pubertal status should be assessed at each visit
Thyroid antibody levels should be checked annually in cases of autoimmune hypothyroidism.
Complications
Early Complications:
In congenital hypothyroidism: Severe neurological impairment, developmental delay, growth failure, developmental delay in motor and cognitive milestones.
Late Complications:
Inadequate treatment can lead to impaired linear growth and short stature, delayed puberty, cognitive deficits, obesity, cardiovascular issues (e.g., dyslipidemia), and reduced quality of life
Poorly controlled hypothyroidism can also exacerbate other chronic conditions.
Prevention Strategies:
Universal newborn screening for congenital hypothyroidism
Prompt diagnosis and initiation of LT4 therapy within the first few weeks of life
Regular monitoring of thyroid function tests and appropriate dose adjustments based on growth and weight changes
Patient and family education on medication adherence and importance of regular follow-up.
Prognosis
Factors Affecting Prognosis:
The most critical factor is the age at which treatment is initiated
Earlier treatment, particularly in congenital hypothyroidism, leads to better neurocognitive outcomes
Degree of thyroid hormone deficiency, adherence to therapy, and effectiveness of dose adjustments are also crucial
Genetic factors can also play a role.
Outcomes:
With timely and appropriate treatment, children with hypothyroidism can achieve normal growth and development, and lead healthy lives
Neurocognitive development in infants treated early for CH is generally good, though some subtle deficits may persist
Acquired hypothyroidism is often manageable, allowing for normal development with consistent therapy.
Follow Up:
Lifelong follow-up is generally recommended
Regular monitoring of thyroid function tests (TSH, fT4), growth parameters, and developmental milestones is crucial
Frequency of follow-up depends on age and stability of thyroid status, typically every 6-12 months in older children and adolescents
Transition to adult endocrinology care is necessary at the appropriate age.
Key Points
Exam Focus:
Understand the typical weight-based dosing for levothyroxine in pediatric hypothyroidism
Know the initial dosing ranges for congenital versus acquired hypothyroidism
Recognize the importance of serial monitoring of TSH and fT4 and how weight gain influences dose adjustments
Differentiate between neonatal screening targets and older child targets for TSH.
Clinical Pearls:
Always administer levothyroxine on an empty stomach for optimal absorption
Counsel parents on avoiding concomitant medications and supplements that interfere with absorption
Be vigilant for subtle signs of under- or overtreatment, especially during rapid growth phases or significant weight changes
Remember that dose adjustments are iterative and require patience and consistent monitoring.
Common Mistakes:
Underestimating the need for frequent dose adjustments in growing children
Inconsistent administration of levothyroxine
Incorrect interpretation of TSH and fT4 values without considering the age-specific reference ranges
Not accounting for factors affecting absorption like co-ingestion of certain foods or medications
Delaying reassessment after significant weight gain or loss.