Delayed Diagnosis of Diabetes Type 1 in the Context of Autoimmune Polyglandular Syndrome Type 3: A Case Report

Diabetes type 1 (T1DM) is characterized by autoimmune destruction of pancreatic islet beta cells, while diabetes type 2 (T2DM) is by peripheral insulin resistance and decreasing the production of insulin. Usually, T1DM is primarily thought to occur in younger people, while T2DM presents in adulthood. The vast majority of diabetes cases that occur in adulthood are T2DM and presumed adult-onset diabetes type 2. Given varying clinical presentations and ultimate treatment approach it is important to promptly make the correct diagnosis.  

When T1DM occurs with another autoimmune-mediated endocrinopathy it is referred to as part of a polyglandular autoimmune syndrome (PAS) and shown to have a strong genetic background. PAS is grouped by heterogeneous organ-specific combinations with the most prevalent being the combination of type 1 diabetes with autoimmune thyroid disease. PAS type 3 is distinguished by the exclusion of Addison's disease and/or hypoparathyroidism (1). Here we describe a case of type 3 where the diagnosis of T1DM was delayed for various reasons. 

Case Description :

We present a 31-year-old obese female with uncontrolled diabetes diagnosed at age 15, complicated with dietary indiscretions and treatment non-adherence.  She was diagnosed with Graves’ disease when she became symptomatic at age 26 with TSH antibody 5.4 (ref range: 0.27-4.20µUI/ml) with thyrotoxicosis, insomnia, orbitopathy, palpitations, and diaphoresis. She was treated successfully with Methimazole and went into remission after about a year of treatment. Her diabetes was thought to be Type 2, though she was requiring insulin since diagnosis. Last Hemoglobin A1C was 8.6.  Her treatment regimen through the years included basal-bolus insulin in addition to multiple oral agents including metformin, nateglinide, glipizide, and sitagliptin. 

Given her young age at diagnosis of diabetes and a concurrent autoimmune Graves’ disease, the decision was made to rule out T1DM. GAD 65 Ab was 17.5 (ref range: < 0.02nmol/L) and Zinc Transporter 8 Ab were checked and found to be positive with greater than 500 (ref range: < 15U/ml) confirming her diagnosis of T1DM. All oral glucose control agents were discontinued, and pre-meal insulin was added along with continuing nightly basal insulin

Discussion :

This case demonstrates the importance and difficulty of an accurate and timely diagnosis for this rare disorder. Furthermore, treatment with insulin is essential to avoid complications such as DKA and microvascular diseases secondary to sustained hyperglycemia. It is an example of how a case of PAS and the diagnosis of type 1 diabetes can be missed due to the late presentation, obese body habitus, treatment, and diet-adherence, and most importantly the lack of detailed family history to clarify the illness of the other immediate family members.