Diabetes and Atypical Autoimmune Polyglandular Syndrome Type 3: A Paediatric Case Report Case

thyroiditis at 7 years. Her personal history was complicated by necrotizing glomerulonephritis ANCA-associated with important effects on glycaemic control and other autoimmune comorbidities. Conclusion: we analyse a multifaceted case, in a very young girl, characterized by the coexistence of different autoimmune diseases influencing endocrine functions and metabolic control, during the different phases of a complex therapy.


Introduction
Type 1 Diabetes (T1DM) is an autoimmune, multifactorial, disease caused by beta cells destruction induced by immune response [1]. The pathophysiology of T1DM is still unclear but genetic predisposition is a landmark of this condition. HLA and non-HLA genes are involved in the risk of autoimmunity onset and many of these genes are shared by different autoimmune settings; thus, children affected by T1DM are at increased risk of other autoimmune comorbidities [2,3].In particular, T1DM could be part of autoimmune polyglandular syndrome cluster.
In 1980 Neufled and Blizzard proposed a classification of the autoimmune polyendocrine syndromes (APS) Table 1 [4]. These conditions are characterized by lack of self-tolerance and by induction of immune responses directed against self-structures with the coexistence, in the same patient, of more than one autoimmune disease [5]. The term polyendocrine is not completely appropriate, because several non-endocrine scenarios could be part of the clinical picture of these autoimmune syndromes [5,6].
Here, we report the case of a girl affected by APS type 3 and the course of the different diseases' diagnosis in her young life. consolidation therapy at a mycophenolate as "600 mg/mq/die administered twice daily, with maintenance of negative proteinuria, although the dose was subsequently reduced for the onset of leukopenia [7,8]. During the follow up period, the girl presented some other transient phases of hyper-and hypo-thyroidism, in spite of the compliance to GFD. The strange course of thyroid autoimmunity during these phases is described in Figure 1.

Discussion
Type 1 Diabetes is an autoimmune disease in which genetic and environmental factors interact to define not only determinism of its pathophysiology but also the susceptibility to other autoimmune conditions [3].
Often the cluster of autoimmune diseases could be present in the same person and so the diagnosis of autoimmune polyglandular syndrome could be made [9]. In our patient, Autoimmune  [5].However, beyond all type of classification, our patient's history was characterized by an uncommon association in her clinical picture.  of ANCA-associated vasculitis [11]. In particular, the patient HLA genotype could explain her susceptibility to ANCA associated vasculitis [7]. MF is now adolescent and her clinical history is, probably, similar to an iceberg in which we can observe only the visible part, we don't know the submerged one at this time and we don't know what else could happen in her next future.
In particular, one important teaching from this case is the influence and complex interactions of autoimmunity on endocrine functionality. At first, the strange instability of thyroid function was one prominent feature in our patient. Transient phases of hypothyroidism and hyperthyroidism were recorded: each phase was accompanied by modification in thyroid autoimmunity subset, as showed in Figure 1, and every phase of hypothyroidism was preceded by hyperthyroidism, as to indicate an autoimmune attack to the gland. Probably, the autoimmune system, the therapies used, and the stress could be the reading key of these complex immuneendocrine interactions. These might lead to the lack of recovery equilibrium typical of autoimmune thyroiditis course [12]. The effects of autoimmune comorbidities on glycaemic control has also been experimented: hypoglycemia and hyperglycemia were clearly complications observed in our patient management [13].
Last but not least, moreover, this lesson: Nephropathy in Diabetic Children is not only «Diabetic». Renal biopsy played a fundamental role in the diagnosis, prognosis and in our therapeutic decisions [14]. Our case report highlights the importance of a strict clinical and laboratory monitoring in these complex pediatric patients, in a multidisciplinary approach, giving the right attention to the appearance of new signs or symptoms, even if they could be related to the first diagnosis.

Funding Source
No external funding for this manuscript.

Financial Disclosure
The authors have no financial relationships relevant to this article to disclose.

Conflict of Interests
The authors have no potential conflicts of interest to disclose.