Hypothyroidism as a Cause of Short Stature
Hypothyroidism is a well-established pathologic cause of short stature in children and must be excluded in any child presenting with growth failure through TSH and free T4 testing. 1, 2
Mechanism and Clinical Presentation
Hypothyroidism impairs skeletal maturation and mineralization during childhood, leading to:
- Delayed bone age (>2 years behind chronological age), which distinguishes it from familial short stature where bone age matches chronological age 1, 2, 3
- Reduced height velocity with crossing downward through multiple percentile lines on growth charts 1
- Disproportionate skeletal development with increased head circumference relative to stature in untreated cases 4
- Low serum T4 (present in 36.7% of short stature cases) coupled with elevated TSH 5
In epidemiologic studies, primary hypothyroidism accounts for approximately 9.6% of children referred for short stature evaluation, making it one of the more common endocrine causes after growth hormone deficiency 6.
Diagnostic Algorithm
When evaluating short stature (height <3rd percentile or <-1.88 SD), the workup must include:
- TSH and free T4 measurement as part of the initial biochemical panel to exclude hypothyroidism 2
- Left wrist radiograph for bone age to identify the characteristic delayed bone maturation 1, 2
- Growth velocity calculation over 4-6 months to document pathologic deceleration 1
- IGF-1 measurement (compared to Tanner-, sex-, and age-matched ranges) because hypothyroidism can falsely lower IGF-1 levels 2
Critical pitfall: Hypothyroidism must be corrected before interpreting IGF-1 levels or pursuing growth hormone stimulation testing, as thyroid hormone deficiency independently suppresses the GH-IGF-1 axis 2.
Treatment Approach
Levothyroxine Replacement
Initiate levothyroxine at 1.6 mcg/kg/day for new-onset hypothyroidism in children with confirmed thyroid dysfunction 7:
- For infants 0-3 months at risk for cardiac complications: start at a lower dose and increase every 4-6 weeks based on TSH and free T4 response 7
- For children at risk for hyperactivity: start at one-fourth the full replacement dose and increase weekly by one-fourth increments until reaching full dosage 7
Monitoring During Treatment
- Measure TSH and total or free T4 at 2 and 4 weeks after initiating treatment, then 2 weeks after any dose adjustment 7
- Once stabilized, monitor every 3-12 months with routine assessment of development, mental and physical growth, and bone maturation 7
- Target normalization of serum TSH while maintaining free T4 in the upper half of the normal range 7
Expected Growth Response
When thyroid hormone replacement is initiated early (before 1 year of age):
- Complete normalization of head circumference, height, bone age, and weight occurs with adequate treatment 4
- Catch-up growth in height and bone age is observed in children treated after 1 year, though mean height may remain below normal even after 8 years of therapy in late-treated cases 4
- Restoration of euthyroid status reverses the impaired skeletal maturation and allows resumption of normal growth velocity 3
Special Considerations
Van Wyk-Grumbach syndrome: Severe, long-standing untreated hypothyroidism can paradoxically cause isosexual precocious puberty alongside short stature, which completely reverses with thyroid hormone replacement 8. Look for this rare presentation in children with both growth failure and early pubertal development.
Timing is critical: The earlier treatment begins, the better the final height outcome. Children treated before 1 year of age achieve complete height normalization, while those treated after 1 year show persistent height deficits despite catch-up growth 4.