Background: Autoimmune disease (AD) occurs due to loss of immunological tolerance to self-antigens and can be organ specific or systemic. One in four patients with a single AD may develop another AD. The presence of three or more AD is described as multiple autoimmune syndrome (MAS) in which Type 3 subset includes autoimmune thyroiditis and T1D, but not autoimmune hepatitis. Type 2 Autoimmune Polyendocrine Syndrome can be diagnosed when T1D and autoimmune thyroiditis coexist. The association of autoimmune thyroiditis and T1D is well recognised but the co-existence of autoimmune hepatitis is unusual and the co-presentation of all three diseases, to our knowledge, has not been reported.
Case Presentation: 7-year old Caucasian female referred with a 2 week history of weight loss, polyuria and polydipsia. Investigations confirmed T1D with blood glucose 27 mmol/L, blood ketones 4.0mmol/L and normal pH 7.36. Anti-GAD antibodies were >2000 and HbA1c was 105 mmol/mol (20-41). Thyroid function tests were abnormal (TSH 8.07 (0.35-4.94mU/L), Free T4 14 (9-20pmol/L), TPO Antibodies >3000). Thyroid ultrasound revealed abnormal echogenicity, confirming autoimmune thyroiditis. Coeliac screen was negative. Short synacthen test was normal. Unexpectedly, liver enzymes were raised (ALT 1297 (<41U/L), AST 1616 (<37U/L), GGT 156 (<45 U/L)) as were IgG and IgM Immunoglobulins (27.3 (4.9-16.1g/L) and 3.77 (0.5-1.8g/L) respectively). Clotting, viral serology, alpha-1 antitrypsin, caeruloplasmin, serum copper and abdominal ultrasound scan were normal. Anti-neutrophil cytoplasmic antibodies were positive with elevated Proteinase 3 Antibody (21.27 (<3.5U/ml)) and low complement C4 (0.11 (0.14-0.54g/L). Anti-liver/kidney microsome antibody (anti LKM) and antibody to liver cytosol (anti LC-1) were both positive. Liver biopsy revealed features in keeping with severe acute hepatitis. Given high IgG and positive liver autoantibodies, autoimmune hepatitis was diagnosed. She was commenced on a Basal/Bolus insulin regime for diabetes control, Levothyroxine for thyroiditis and Prednisolone daily for 8-12 weeks for autoimmune hepatitis. Liver function was monitored weekly with a weaning steroid plan. Her insulin requirement has increased markedly because of steroids, consequently her diabetes monitoring and follow up has been increased given the expected ongoing impact.
Conclusions: This case highlights the need for clinicians to have a low threshold for investigations into other AD (dependent on clinical features) when one AD already exists. National guidelines advise performing screening tests for autoimmune thyroiditis and coeliac disease in patients with newly diagnosed T1D. This case raises the question of whether further autoimmune conditions should form part of this initial screening.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology