**5.5 Autoimmune gastritis and type 1 diabetes**

Autoimmune gastritis is rarely encountered in children and adolescents with type 1 diabetes, since the prevalence of parietal cell antibodies increases with age and with longer duration of disease. It is noteworthy that even young patients with type 1 diabetes are positive for parietal cell antibodies, with a frequency about 4%, which is higher than in controls (1.9%) (De Block et al., 2008). On the other hand, autoimmune gastritis is more frequent in children and adolescents with autoimmune thyroid disorder (Fig. 3 ).

Fig. 3. Atrophic gastritis and sessile antral polyp with signs of esophageal candidiasis (personal data)

Autoimmune Disorders Associated to Type 1 Diabetes Mellitus in Children and Adolescents 19

procedures (Aaron et al., 2008). In some cases supplementation with mineralcorticoids in

In adolescents with type 1 diabetes Addison's disease is rarely encountered, and symptoms are sometimes aspecific. Addison's disease usually follows type 1 diabetes diagnosis, being more frequently observed within the Autoimmune Polyendocrine Syndrome type 1 and type 2 (Kordonouri et al., 2009). Correct diagnosis of Addison's disease requires a high degree of clinical suspicion and since the disease is a life-threatening condition, several investigators recommend periodical screening of Addison's disease in all young patients since type 1 diabetes diagnosis (Brewer et al., 1997). In an adolescent with type 1 diabetes, Addison's disease should be suspected in case of recurrent hypoglycemic episodes, unexplained decrease of insulin requirement and improvement of metabolic control, fatigue, weight loss, hyponatriemia and hyperkaliemia. Diagnosis confirmation requires low cortisol levels after ACTH stimulation test. Screening procedures allow to detect asymptomatic children and adolescents with positive adrenal antibodies; where raised ACTH levels suggest the presence of adrenal insufficiency. Risk factors for Addison's disease in patients with type 1 diabetes include a history of other autoimmune conditions, in particular thyroid disease, and a positive family history for autoimmunity, as reported in a case series of 4 adolescents with pre-existing type 1 diabetes who developed Addison disease (Thomas et al., 2004). Three out of 4 patients showed unexplained hypoglycemia and the other one showed unawareness hypoglycemia; all cases reported unexplained improvement in diabetes control. Two out of 4 patients reported skin hyperpigmentation. In all 4 patients a positive personal and family history of other autoimmune conditions has been reported, in particular celiac and/or thyroid autoimmune diseases and Autoimmune Polyendocrine Syndrome type 2. A more recent study in 491 newly diagnosed children with type 1 diabetes aimed to define the prevalence of additional autoimmune conditions reported 1% positivity of antibodies to 21-hydroxylase, while overt Addison's disease was found only in 20% of the positive patients (Triolo et al.; 2011). Noteworthy, all young patients with type 1 diabetes and adrenal autoantibodies develop Addison's disease during the follow-up period, with a progression to overt adrenal failure much more rapid than in adults, indicating that different autoimmune responses may be evoked at different age periods (Betterle et al.,

mandatory.

1997).

in recognizable clinical clusters.

endocrinopathies and HLA typing.

**6.5 Addison's disease and type 1 diabetes** 

**7. The Autoimmune Polyglandular Syndromes (APS)** 

From the time of Addison's original description of his disease onwards, it has been apparent that multiple autoimmune endocrine disease can affect individual patients and their families

Twenty years ago, the autoimmune polyglandular syndromes (APS) were classified into three basic types based on the patient's age at onset, their clinical associations with specific

**Type I APS**, called also APECED (Autoimmune PolyEndocrinopathy-Candidiasis-Ectodermal Dystrophy) is a rare autosomal recessive disorder originally identified through the typical association of mucocutaneous candidiasis with Addison's disease and hypoparathyroidism. These symptoms usually constitute the first manifestation of the
