Early Clinical Indicators of Addison Disease in Adults With Type 1 Diabetes: A Nationwide, Observational, Cohort Study

Context: Patients with type 1 diabetes mellitus (T1DM) have an increased risk of Addison disease (AD) development, but prediction of those at risk is not possible. Objective: To determine whether there are early clinical indicators that may denote the development of AD in adults with T1DM. Design: Observational, matched-cohort study. Setting: Patient data from Swedish national registries [National Diabetes Register (NDR), Inpatient Register, and Prescription Drug Register]. Participants: All patients with T1DM diagnosed with concomitant AD (n = 66) among the 36,514 adult patients with T1DM in the NDR between 1998 and 2013. Each case was matched to five controls with T1DM alone (n = 330). Main Outcome Measures: Clinical data and drug prescriptions were assessed prior to baseline (inclusion into the study) and prior to AD diagnosis. Analysis of covariance and estimated group proportions were used for comparisons. Results: Prior to baseline, cases had a higher frequency of thyroid/antithyroid drug prescription than controls (9.1% vs 1.8%). Prior to AD diagnosis, cases had higher frequencies of diabetic retinopathy (12.1% vs 2.1%), infections requiring hospital admission (16.7% vs 2.1%), thyroid/antithyroid drug prescription (28.8% vs 7.0%), and glucagon prescription (18.2% vs 6.4%). There was no difference in glycated Hb between the groups prior to baseline or prior to AD diagnosis. Conclusions: These data suggest that medical treatment of thyroid disease, a severe infection, and glucagon prescription for severe hypoglycemia should raise the suspicion of AD development in adults with T1DM. Development of diabetic retinopathy might also be associated with glucocorticoid deficiency and the development of AD among patients with T1DM.