What further tests should be performed in a 10‑year‑old with unexplained weight loss to screen for autoimmune diseases such as celiac disease, type 1 diabetes, autoimmune thyroiditis, Addison disease, or inflammatory bowel disease?

Diagnostic Testing for Autoimmune Diseases in a 10-Year-Old with Weight Loss

Screen immediately for type 1 diabetes with fasting glucose or HbA1c, celiac disease with IgA tissue transglutaminase antibodies (plus total IgA), and thyroid dysfunction with TSH plus thyroid antibodies, as these three conditions are the most common autoimmune causes of weight loss in this age group and frequently coexist. 1

Priority Testing Panel

First-Line Screening Tests

Type 1 Diabetes Assessment:

• Fasting plasma glucose or HbA1c to detect hyperglycemia 1
• If diabetes is confirmed, test for pancreatic autoantibodies (GAD65, IA-2, insulin autoantibodies, ZnT8) to confirm autoimmune etiology 1
• Random glucose if symptomatic (polyuria, polydipsia, polyphagia) 1

Celiac Disease Screening:

• IgA tissue transglutaminase (tTG) antibodies with documentation of normal total serum IgA levels 1
• If IgA deficient, use IgG tTG and deamidated gliadin peptide antibodies instead 1, 2
• Celiac disease causes weight loss through malabsorption and occurs in 1-16% of children with type 1 diabetes versus 0.3-1% in the general population 1

Thyroid Function Assessment:

• TSH measurement when clinically stable 1
• Anti-thyroid peroxidase (TPO) antibodies and anti-thyroglobulin antibodies, as testing TPO alone misses 6-25% of cases with isolated anti-thyroglobulin positivity 1, 3
• Free T4 if TSH is abnormal 3
• Autoimmune thyroid disease occurs in 17-30% of patients with type 1 diabetes 1

Second-Tier Testing (If Initial Screening Suggests Multiple Autoimmune Conditions)

Addison Disease (Primary Adrenal Insufficiency):

• Morning cortisol and ACTH levels 1
• 21-hydroxylase antibodies if symptoms of adrenal insufficiency present (hyperpigmentation, salt craving, hypotension, hypoglycemia) 3, 4
• Consider ACTH stimulation test if morning cortisol is borderline 4

Inflammatory Bowel Disease Screening:

• Complete blood count (anemia, thrombocytosis) 4
• Erythrocyte sedimentation rate and C-reactive protein 4
• Fecal calprotectin if gastrointestinal symptoms present 4
• Albumin level (hypoalbuminemia suggests protein-losing enteropathy) 4

Critical Timing Considerations

Avoid these common pitfalls:

• Do not delay celiac testing—antibodies must be measured while the child is still consuming gluten, as starting a gluten-free diet prematurely makes diagnosis impossible and imposes unnecessary burden 1, 2
• Thyroid function tests may be misleading if performed during acute metabolic stress (ketoacidosis, severe hyperglycemia), so recheck after stabilization if initially abnormal 1
• If type 1 diabetes is diagnosed, screen for other autoimmune conditions soon after diagnosis when clinically stable 1

Confirmatory Steps for Positive Results

If Celiac Antibodies Are Positive:

• Duodenal biopsy with at least 4-6 specimens from the second part of duodenum and bulb to confirm diagnosis before initiating gluten-free diet 2
• Biopsy confirmation is especially important in asymptomatic children to avoid unnecessary dietary restrictions 1, 2

If Thyroid Antibodies Are Positive:

• Recheck TSH every 1-2 years or sooner if symptoms develop (growth failure, unexplained glycemic variability, fatigue) 1, 3
• Monitor growth rate closely as thyroid dysfunction affects linear growth 1

Genetic and Additional Screening

HLA Typing:

• Consider HLA-DQ2/DQ8 testing to stratify future celiac disease risk, as absence of both alleles effectively rules out celiac disease 2
• This is particularly useful if initial antibody testing is negative but clinical suspicion remains high 2

Nutritional Deficiency Assessment:

• Iron studies (ferritin, iron, TIBC) for iron deficiency anemia 4
• Vitamin D, vitamin B12, and folate levels, especially if celiac disease or inflammatory bowel disease is suspected 4
• These deficiencies commonly accompany malabsorptive conditions causing weight loss 4

Autoimmune Clustering Considerations

The presence of one autoimmune condition significantly increases risk for others—this is critical in a 10-year-old with weight loss:

• 10-30% of patients with celiac disease have thyroid and/or type 1 diabetes antibodies 5
• 5-7% of patients with autoimmune thyroid disease or type 1 diabetes have positive celiac antibodies 5
• The HLA-DQ2 and HLA-DQ8 alleles (linked to DR3 and DR4) are shared genetic risk factors for type 1 diabetes, celiac disease, and autoimmune thyroid disease 6, 5, 7
• Less common autoimmune conditions like Addison disease, autoimmune hepatitis, and autoimmune gastritis occur more frequently in children with type 1 diabetes than in the general population 1

Follow-Up Screening Protocol

If Initial Testing Is Negative:

• Repeat celiac screening within 2 years, then again at 5 years 1, 2
• Repeat thyroid screening every 1-2 years if antibodies are negative 1
• Screen more frequently if symptoms develop or if another autoimmune condition is diagnosed 1, 2