Polyglandular Autoimmune Syndrome (PGA)

-Summary:

The polyglandular autoimmune syndrome (PGA), also abbreviated APS is a group of syndromes that have in common to be the association of two or more diseases of the endocrine system associated with other pathologies of immune cause.
The functional alterations of two or more glands are associated other non-endocrine autoimmune disorders, being the cutaneous the most common.

-Discussion:

Generally, cases of autoimmune polyendocrine syndrome type I appear in childhood and early adolescence, requires the coexistence of 2 of the following: hypoparathyroidism (80% to 85%); mucocutaneous candidiasis (70% to 80%); Addison’s disease (60% to 70%); type 1 diabetes (20%); hypogonadism (12%), thyroid disease (10%).
Various studies have shown that the AIR gene (autoimmune regulator), located on the short arm of chromosome 21, is mutated in this autoimmune disease.
So far, about 60 different mutations have been described. It is a potentially under-diagnosed syndrome due to the rarity and enormous variability in its presentation.
The diagnosis is made by searching for antibodies against interferon-omega or interferon-alpha.
It is also called, Autoimmune Polyendocrinopathy Syndrome type 1, or known as Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy.
Unlike the type II autoimmune polydrocrine syndrome, whose manifestations begin in adulthood and its onset tends to be insidious and with a variable frequency of presentation.
The autoimmune polyendocrine syndrome type II is the most frequent, with an incidence of 1 to 2 cases per 10,000 per year, unlike the autoimmune polyendocrine syndrome type I which is a very rare entity, with an incidence of 1 case per 100,000 per year.
Autoimmune polyglandular syndrome type 2 or PGA-II, is an autoimmune disease that affects many hormone-producing (endocrine) glands, also called Schmit’s syndrome.
It occurs primarily in adulthood, usually around the third and fourth decades of life. Middle-aged women have shown a higher prevalence.
It is associated with HLA-DR3 and/or HLA-DR4 haplotypes, the HLA region is located on the short arm of chromosome 6 and the inheritance pattern is autosomal dominant with variable expressiveness.
It is characterized by the presence of Addison’s disease (adrenal insufficiency) along with autoimmune thyroid disease (such as Hashimoto’s disease) and/or type 1 diabetes.
CYP21 appears to be the main autoantigen in isolated Addison’s disease and Addison’s disease associated with PGA-II.
The most frequent components of the type II autoimmune polyendocrine syndrome are: thyroid disease (70 to 75%), type 1 diabetes (50% to 60%) and Addison’s disease (40%).
Therefore, the most relevant diagnostic approach may include the measurement of antithyroperoxidase and thyroid stimulating hormone receptor antibodies for autoimmune thyroid disease, glutamic acid decarboxylase and pancreatic islets for type 1 diabetes.
Finally antibodies against 21-hydroxylase for Addison’s disease or even primary hypogonadism (orchitis or autoimmune oophoritis).
More often, type II autoimmune polyendocrine syndrome diseases will occur sequentially rather than at the same time, so one strategy is to measure antibodies as the diseases appear.
Type III, typically affecting women during middle age, is due to the failure of several glands in the body to produce hormones. It does not affect the adrenal cortex, but includes 2 of the following: thyroid deficiency, pernicious anemia, type 1 diabetes mellitus, vitiligo and alopecia.
In PGA III, autoimmune thyroiditis, occurs with another organ-specific autoimmune disease, but the syndrome cannot be classified as PGA I or II.
In the context of PGA III, the autoimmune diseases most often grouped with autoimmune thyroiditis are immune-mediated diabetes mellitus and celiac disease.
PGA III can be further classified into the following three subcategories:
PGA IIIA – Autoimmune Thyroiditis with Autoimmune Diabetes Mellitus (also known as a variant of polyglandular autoimmune syndrome type 3)
PGA IIIB – Autoimmune Thyroiditis with Pernicious Anemia
PGA IIIC – Autoimmune Thyroiditis with Vitiligo and/or Alopecia and/or a Specific Autoimmune Disease of Other Organs
The management of these disorders requires collaboration among multiple specialties due to the multiplicity of affected organs.

-Conclusions:

The identification of patients with positive autoimmunity for any of the components of an EGP is the beginning to establish the diagnosis, or the risk of suffering from it.
The presence of an antibody and/or an autoimmune disease can be indicative, for the diagnosis of these complex syndromes, in relation to adrenal insufficiency, but also in terms of diseases such as diabetes, celiac disease or hypothyroidism, where the lack of early diagnosis can disturb the evolution of each one, with vital risk.
The diagnosis of latent forms of adrenal insufficiency can prevent serious complications that can lead to death. The current resources are a simple way to establish a diagnosis or a risk of evolution to declared disease.
Genetic studies, while not routinely indicated, should be conducted to identify family cases, especially when they are made up of children and youth.
The positivity of the 21-hydroxylase antibody may be an indicator of the risk of adrenal insufficiency, which may never appear.
It can also be a marker of the presence or risk of any of the components of an

-Conclusions:

The identification of patients with positive autoimmunity for any of the components of an EGP is the beginning to establish the diagnosis, or the risk of suffering from it.
The presence of an antibody and/or an autoimmune disease can be indicative, for the diagnosis of these complex syndromes, in relation to adrenal insufficiency, but also in terms of diseases such as diabetes, celiac disease or hypothyroidism, where the lack of early diagnosis can disturb the evolution of each one, with vital risk.
The diagnosis of latent forms of adrenal insufficiency can prevent serious complications that can lead to death. The current resources are a simple way to establish a diagnosis or a risk of evolution to declared disease.
Genetic studies, while not routinely indicated, should be conducted to identify family cases, especially when they are made up of children and youth.
The positivity of the 21-hydroxylase antibody may be an indicator of the risk of adrenal insufficiency, which may never appear.
It can also be a marker of the presence or risk of any of the components of an EGP ( know also as APS), in the short or long term, being higher in the presence of other related antibodies.
Polyglandular deficiency syndromes involve deficiencies in the function of several endocrine glands, which may occur simultaneously or sequentially.
Non-endocrine organs may also be affected.
Most cases are autoimmune, the triggers are often unknown.
Polyglandular deficiency syndromes are distinguished by the glands affected.
Treatment consists of replacement of the deficient hormones.
References:
-Eisenbarth, GS, Gottlieb, PA Autoimmune polyendocrine syndromes. N Engl J Med 2004; 350:2068
-Aung K. Type III Polyglandular Autoimmune Syndrome.Medscape Reference. 2017
Keywords:
autoimmune polyglandular syndrome and adrenal insufficiency, Hashimoto’s thyroiditis and autoimmune polyglandular syndrome, autoimmune polyglandular syndrome and chromosome 21, HLA system and autoimmune polyglandular syndrome, autoimmune polyglandular syndrome and leukocyte antigen system, autoimmune polyglandular syndrome and chromosome 6, hypoparathyroidism and autoimmune polyglandular syndrome, alpha and omega interferons and autoimmune polyglandular syndrome, anti hydroxyprogesterone antibody and autoimmune polyglandular syndrome, AIR gene and autoimmune polyglandular syndrome, polymorphisms of the main complex of histocompatibility and autoimmune polyglandular syndrome, Schmit syndrome, PGE or APS syndromes.

 

Deja una respuesta

Tu dirección de correo electrónico no será publicada. Los campos obligatorios están marcados con *

es_ESSpanish
en_GBEnglish es_ESSpanish