Polyglandular Autoimmunity: Two Cases of Type 1 diabetes (T1D) accompanied by Addison’s disease (AD)




Borrego, Natali
Bommakanti, Maalini
Radack, Jill
Hamilton, Luke
Wilson, Don


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Type 1 diabetes (T1D), present in ~1:500 children, is often accompanied by other autoimmune conditions, notably chronic lymphocytic thyroiditis. Involvement of other endocrine organs, however, is rare. Autoimmune impairment of more than one endocrine system is referred to as an autoimmune polyglandular syndrome (APS), categorized as type 1 (APS-1) or type 2 (APS-2). In addition to T1D, APS-1 is characterized by 1 or more of the following: candidiasis, hypoparathyroidism, and/or AD; while APS-2 involves AD and/or chronic thyroiditis2. The lifetime risk of developing a 2nd endocrine autoimmune condition in individuals with T1D is ~1:5, and usually occurs during adulthood. While children may be affected, such reports are unusual and generally limited to case studies. APS-2 is rare in childhood, with a prevalence of ~ 1:100,0004. We present two children with APS-2.

Case Information:

Case 1: A 6-year-old Caucasian male, who was diagnosed with T1D at 3 years-of-age, presented with persistent vomiting which required hospitalization. Although his diabetes was reasonably well controlled prior to his hospitalization, the child was noted to be overly sensitive to insulin during this admission, during which he experienced several episodes of hypoglycemia. Laboratory testing revealed metabolic acidosis, hyponatremia, and hypocortisolemia. Appropriate testing confirmed primary adrenal insufficiency; the latter, along with his T1D, being consistent with APS-2.

Case 2: A 15-year-old Caucasian male experienced an unexplained 20 lb. weight loss. After developing fever, routine laboratory tests were reported to be characteristic of diabetic ketoacidosis (DKA) - hyponatremia, metabolic acidosis and hyperglycemia. With treatment, his DKA resolved, and he began conventional insulin therapy. However, follow-up laboratory tests demonstrated persistent hyponatremia. Additional studies confirmed the presence of AD, consistent with APS-2.


These previously healthy children developed T1D accompanied by AD, characteristic of APS-2. The presence of both conditions significantly increases the risk of potential life-threatening complications in affected children5. Individuals with both T1D and AD have a 2.5-fold increased risk of adrenal crises, compared to those with isolated AD6. Timely diagnosis of polyglandular autoimmunity is critical to help inform clinical decision-making, and to avoid adverse outcomes. The diagnosis of APS is often hampered by common symptoms such as: fatigue and weakness, unexplained weight loss, increased thirst, frequent urination, irritability, nausea and abdominal pain, and changes in appetite2. Management is complicated by the effects of glucocorticoid levels on insulin sensitivity. For example, these patients have a risk of increased insulin sensitivity and hypoglycemia in the early morning hours prior to the next glucocorticoid dose1. Patient education is key for understanding the interactions between the two conditions as well as the effects of diet, physical activity, and emotional stress2. While the onset of APS is variable, most patients tend to develop autoimmunity sequentially over a period of many years2. APS-2 has been linked primarily to genes coding for major histocompatibility complex, particularly DR3-DQ2 and DR4-DQ8 variants6. Physicians should be vigilant in assessing children with autoimmune-related conditions, such as T1D, and although rare, aware of the potential for additional autoimmune-mediated organ failure in some.