What serum work‑up is appropriate for a 14‑year‑old female with chronic diffuse pain and constant gastrointestinal distress, normal complete blood count, comprehensive metabolic panel, thyroid‑stimulating hormone, tissue transglutaminase IgA, normal vitamin B12, folate, iron, slightly low total iron‑binding capacity, and mildly elevated C‑reactive protein and lymphocyte count, to investigate a possible autoimmune disorder?

Serum Evaluation for Suspected Autoimmune Disorder in a 14-Year-Old Female

Given the chronic diffuse pain, persistent gastrointestinal distress, mildly elevated CRP, and already negative celiac screening, the next prudent step is to obtain anti-thyroid peroxidase antibodies, anti-parietal cell antibodies, and a comprehensive autoimmune panel including ANA, anti-smooth muscle antibodies, and ganglionic acetylcholine receptor antibodies. 1, 2

Rationale for Thyroid Autoimmunity Testing

• Anti-thyroid peroxidase (anti-TPO) antibodies are the single most predictive marker for autoimmune thyroid disease, which occurs in 17-30% of pediatric patients with type 1 diabetes and is the most common autoimmune comorbidity in this age group. 1
• Anti-TPO is more predictive than anti-thyroglobulin antibodies in multivariate analysis for identifying thyroid dysfunction. 1
• Autoimmune thyroid disease can present with diffuse pain, gastrointestinal symptoms, and unexplained glycemic variability or growth abnormalities. 1
• The mildly elevated CRP (23) supports ongoing systemic inflammation consistent with autoimmune thyroiditis. 1

Rationale for Gastric Autoimmunity Testing

• Anti-parietal cell antibodies should be obtained to evaluate for autoimmune atrophic gastritis, which causes chronic gastrointestinal distress, impaired iron absorption (explaining the slightly low TIBC at 15), and can present with diffuse abdominal pain. 1, 3
• Autoimmune atrophic gastritis destroys parietal cells in the gastric body, leading to hypochlorhydria that interferes with nutrient absorption and causes persistent GI symptoms. 1
• This condition is associated with other autoimmune diseases and requires systemic evaluation, as it increases risk for gastric neuroendocrine tumors and gastric cancer. 3
• Anti-intrinsic factor antibodies should also be checked if anti-parietal cell antibodies are positive, though B12 is currently normal. 1

Rationale for Autoimmune Gastrointestinal Dysmotility Testing

• Ganglionic acetylcholine receptor (gAChR) antibodies are critical to evaluate, as autoimmune gastrointestinal dysmotility presents with chronic GI distress, diffuse pain, and can occur idiopathically in adolescents. 4, 2
• This condition is under-recognized but treatable with immunotherapy when identified early. 4
• Neuronal voltage-gated calcium channel antibodies (N-type and P/Q-type) and neuronal voltage-gated potassium channel antibodies should also be considered if initial testing suggests autoimmune dysautonomia. 2
• The combination of chronic GI symptoms with diffuse pain in a young female with elevated inflammatory markers fits the profile of autoimmune gastrointestinal dysmotility. 4, 2

Rationale for Broader Autoimmune Screening

• Antinuclear antibodies (ANA) should be obtained to screen for systemic lupus erythematosus and other connective tissue diseases that commonly present with diffuse pain and GI symptoms in adolescent females. 1
• Anti-smooth muscle antibodies are indicated to evaluate for autoimmune hepatitis, which occurs more commonly in patients with other autoimmune conditions and can present with abdominal pain and systemic symptoms. 1
• The lymphocyte count of 7 (mildly elevated) suggests active immune dysregulation warranting comprehensive autoimmune evaluation. 1

Additional Considerations Based on Celiac Disease Evaluation

• Although tTG IgA was negative, HLA-DQ2/DQ8 typing should be considered if there is strong clinical suspicion for celiac disease, as negative HLA typing effectively rules out celiac disease with nearly 100% negative predictive value. 1
• The American Gastroenterological Association notes that celiac disease is present in 5-10% of children with other autoimmune diseases, and familial occurrence is common with 7.5% risk in first-degree relatives. 1
• However, given the already negative tTG IgA with documented normal total IgA, celiac disease is less likely unless symptoms worsen or growth parameters decline. 1

Critical Pitfalls to Avoid

• Do not delay autoimmune evaluation waiting for symptoms to worsen—early detection of autoimmune conditions allows for therapeutic intervention before irreversible complications develop. 3
• Do not assume the slightly low TIBC is insignificant; in the context of chronic inflammation (elevated CRP), this may indicate impaired iron absorption from autoimmune gastritis even with normal ferritin. 1
• Do not overlook the possibility of multiple concurrent autoimmune conditions, as clustering of autoimmune diseases is well-documented in adolescents. 1
• If initial autoimmune screening is negative but symptoms persist, consider referral to immunology for evaluation of primary immunodeficiency, which can present with chronic GI symptoms and recurrent infections. 5

Monitoring Strategy

• Repeat thyroid function testing (TSH, free T4) once metabolic stability is achieved if thyroid antibodies are positive, as initial testing can be misleading in the context of systemic inflammation. 1
• If anti-parietal cell antibodies are positive, obtain fasting gastrin level and consider upper endoscopy with gastric body and antral biopsies to confirm autoimmune atrophic gastritis. 1, 3
• If ganglionic acetylcholine receptor antibodies are positive, consider gastric emptying study and small bowel transit scintigraphy to document dysmotility, as objective evidence supports immunotherapy trials. 4, 2