Autoimmune Polyendocrinopathy

Abstract

Context This mini-review offers an update on the rare autoimmune polyendocrinopathy (AP) syndrome with a synopsis of recent developments. Design and Results Systematic search for studies related to pathogenesis, immunogenetics, screening, diagnosis, clinical spectrum, and epidemiology of AP. AP (orphan code ORPHA 282196) is defined as the autoimmune-induced failure of at least two glands. AP is divided into the rare juvenile type I and the adult types II to IV. The prevalence is 1:100,000 and 1:20,000 for types I and types II to IV, respectively. Whereas type I (ORPHA 3453) is a monogenetic syndrome with an autosomal recessive transmission related to mutations in the autoimmune regulator (AIRE) gene, types II to IV are genetically complex multifactorial syndromes that are strongly associated with certain alleles of HLA genes within the major histocompatibility complex located on chromosome 6, as well as the cytotoxic T lymphocyte antigen 4 and the protein tyrosine phosphatase nonreceptor type 22 genes. Addison disease is the major endocrine component of type II (ORPHA 3143), whereas the coexistence of type 1 diabetes and autoimmune thyroid disease is characteristic for type III (ORPHA 227982). Genetic screening for the AIRE gene is useful in patients with suspected type I, whereas serological screening (i.e., diabetes/adrenal antibodies) is required in patients with monoglandular autoimmunity and suspected AP. If positive, functional endocrine testing of the antibody-positive patients as well as serological screening of their first-degree relatives is recommended. Conclusion Timely diagnosis, genetic counseling, and optimal long-term management of AP is best offered in specialized centers.

Prevalence of other autoimmune diseases in polyglandular autoimmune syndromes type II and III

“…The mean age of the PAS patients at the time of diagnosis in our work was 34.7 years, which is unexpectedly high [38,39]. It is well known that PAS are more common in females [1,12] and this was confirmed by our study as well. As opposed to the common belief, PAS III was more prevalent than PAS II [25].…”

“…PAS is a complex and heterogeneous disorder. The fact that these conditions are so rare and that the number of variations is so high make the use of evidence-based approach difficult [1,7]. The screening and diagnostic protocol of these patients is a hard task for clinicians [34].…”

“…Autoimmune polyglandular syndromes (PAS) are complex, heterogeneous disorders in which various autoimmune diseases can occur, affecting both endocrine and non-endocrine organs. The diagnosis of PAS can be established if at least two organs are damaged by the autoimmune process [1]. PAS can be further divided into four subgroups based on the affected organs [2].…”

“…Further classifications can also be found in the literature. Authors Frommer et al and Kahaly et al proposed a distinction between juvenile (I) and adult (II-IV) forms of PAS [1,7]. Their definition of PAS III is also different, as they consider the presence of both AITD and T1DM (without AD) obligatory for this group [1,7].…”

Hyperpigmentation and ACTH – an overview of literature

“…low cortisol causes an aCtH increase based on a feedback mechanism between pituitary and adrenal glands while hyperpigmentation at the level of skin (including scars) and mucosa is one of the main clinical features (9). Others skin conditions like vitiligo may be associated in cases with polyglandular autoimmune syndrome (10). Primary adrenal insufficiency may be lethal if adequate substitution is not provided (9).…”