What is the initial diagnostic test to order for a pediatric patient with Down syndrome (DS) presenting with constipation and irritability?

Thyroid Function Testing (TFT) Should Be Ordered

For a pediatric patient with Down syndrome presenting with constipation and irritability, thyroid function testing (TFT) is the appropriate initial diagnostic test, as hypothyroidism is highly prevalent in this population and can present with these exact symptoms. 1

Rationale for TFT as First-Line Test

High Prevalence of Thyroid Dysfunction in Down Syndrome

• Children with Down syndrome have a significantly elevated risk of thyroid disorders, with studies showing thyroid dysfunction in 30-40% of cases 2, 3
• Hypothyroidism is the most common thyroid abnormality, occurring in approximately 38% of children with Down syndrome 3
• It is reasonable to perform thyroid function studies (thyroxine [T4] and thyroid-stimulating hormone) as part of the general laboratory evaluation for children with low tone or neuromuscular weakness, even without classic signs of thyroid disease 1

Clinical Presentation Matches Hypothyroidism

• Constipation is a cardinal symptom of hypothyroidism and would be expected with thyroid dysfunction 1
• Irritability can represent the behavioral manifestation of untreated hypothyroidism in children
• The clinical features of Down syndrome can mask the presenting signs and symptoms of hypothyroidism, making biochemical screening essential 4

Timing and Screening Considerations

• Thyroid dysfunction can develop at any age in children with Down syndrome, with preschool children showing particularly high prevalence 4
• Recent prospective data demonstrates that 30% of infants with Down syndrome develop thyroid disorders in the first year, with many cases occurring between routine screening intervals 2
• Diagnosis of thyroid disorders occurred in 11%, 17%, and 22% of infants by 30,60, and 90 days of life respectively 2

Why Not Abdominal Ultrasound First?

• While constipation warrants evaluation, abdominal ultrasound is not the first-line test for chronic constipation without alarm features 1
• In the absence of alarm symptoms (blood in stools, anemia, weight loss, abdominal mass), structural evaluation is not immediately indicated 1
• A complete blood cell count should be performed as initial testing, but metabolic tests including thyroid function are reasonable given the specific Down syndrome context 1

Practical Testing Approach

• Order TSH and free T4 (or total T4) as the initial thyroid function panel 1
• Capillary dried blood spot TSH sampling is feasible, less invasive, and acceptable for screening in children with Down syndrome 4
• Consider thyroid antibodies (anti-thyroid peroxidase, anti-thyroglobulin) as part of initial evaluation, particularly given the high rate of autoimmune thyroid disease in this population 5

Common Pitfall to Avoid

• Do not assume normal newborn screening rules out thyroid disease - 50% of children with Down syndrome who develop thyroid dysfunction were unscreened since neonatal screening 4
• Subclinical hypothyroidism (elevated TSH with normal T4) accounts for approximately 33% of cases and may still cause symptoms 3
• Some cases of subclinical hypothyroidism spontaneously normalize (11%), while others persist (14%), requiring longitudinal monitoring 3

Additional Considerations After TFT

• If TFT is normal, then consider complete blood count and evaluate for functional constipation with dietary/behavioral interventions 1
• If constipation persists despite normal TFT and initial management, consider colonic transit studies or evaluation for Hirschsprung disease, though this is less common 1
• The 4-month duration of constipation makes a metabolic/endocrine cause more likely than an acute structural problem