Autoimmune Polyglandular Syndrome
Introduction
Autoimmune polyglandular syndromes (APS) are generally characterized by the failure of multiple endocrine glands responsible for secreting hormones or other biologically active substances. However, these syndromes represent a much more complex group of rare, genetically determined immune system disorders that affect various endocrine glands and eventually lead to their dysfunction.
APS is often diagnosed late because of its wide spectrum of clinical manifestations. Several types of the syndrome have been identified, the most common being type 1 APS, which is associated with younger age; type 2 APS (also known as Schmidt syndrome), which is associated with older age; and type 3 APS, which excludes adrenal cortical insufficiency but includes type 1 diabetes mellitus, vitiligo, thyroid insufficiency, pernicious anemia, and alopecia.
An additional type has also been identified following cancer treatment with specific immunotherapeutic agents, in which altered cells evade immune responses and become antigens capable of triggering an autoimmune reaction.
Patients who are at risk of developing APS and have already been diagnosed with an autoimmune disease are 30–50 times more likely to develop another autoimmune disease than individuals in the general population.
It has been estimated that individuals diagnosed with one autoimmune disease have a 25% probability of developing another similar condition.
These syndromes are classified according to the classification proposed by Neufeld and Blizzard in 1980 (Table 1) [1].
Table 1. Classification of Autoimmune Polyglandular Syndromes According to Neufeld and Blizzard
| APS Type | Diagnostic Characteristics |
|---|---|
| Type 1 APS | Chronic mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease (at least two must be present) |
| Type 2 APS | Addison's disease (always present) + autoimmune thyroid disease and/or type 1 diabetes mellitus |
| Type 3 APS | Autoimmune thyroid disease combined with another autoimmune disorder (excluding Addison's disease and hypoparathyroidism) |
| Type 4 APS | Various combinations of autoimmune diseases not included in the other types |
The greatest attention is given to the two most common forms, types 1 and 2 APS. Although the diseases included in this classification may appear identical, their treatment focuses on replacing the function of the affected organ or providing replacement therapy, while the syndromes differ in their etiology, pathogenesis, and clinical course.
The general differences between the most common types of APS are presented in Table 2 [2].
Table 2. Main Differences Between the Most Common Types of APS
| Characteristic | Type 1 APS | Type 2 APS |
|---|---|---|
| Prevalence | Very rare | Relatively common (1–2 per 10,000 population) |
| Male-to-female ratio | 3:4 | 1:3 |
| Age at onset | Childhood | Up to middle age |
| Autoimmune endocrine diseases | Hypoparathyroidism (80–85%); Addison's disease (60–70%); type 1 diabetes mellitus; hypogonadism (12%); thyroid disease (10%) | Thyroid disease (70–75%); type 1 diabetes mellitus (50–60%); Addison's disease (40%); hypoparathyroidism (3%) |
| Associated conditions | Mucocutaneous candidiasis | No candidiasis |
| Other associated conditions | Autoimmune gastritis, pernicious anemia, celiac disease, autoimmune hepatitis, vitiligo, alopecia, myasthenia | — |
DM – diabetes mellitus.
In patients with type 1 APS, damage to the parathyroid glands and adrenal glands predominates, while thyroid involvement is relatively rare, occurring in approximately 10% of cases.
In type 2 APS, the thyroid gland is affected in 80% of cases, adrenal involvement is observed in approximately 50%, and pancreatic damage is pronounced.
Figure 1 illustrates the frequency of different manifestations among the various types of the syndrome.
Summary
In recent years, improved understanding of autoimmune processes has led to an increase in clinical studies investigating different forms of APS.
Early detection of various antibodies allows the disease to be identified even at the subclinical stage. Genetic mutation testing is not yet widely available, but it is performed in high-risk populations, particularly when a patient has already been diagnosed with the condition and close relatives need to be evaluated.
For patients already diagnosed with type 1 or type 2 APS, it is important to determine whether they carry the relevant genetic alterations.
When characteristic genetic changes are identified, specialist consultation is necessary before clinical manifestations of autoimmunity develop, with the aim of reducing disease-related symptoms.
Once clinical symptoms have developed, patients should be monitored for the progression of complications. Appropriate replacement therapy is used to compensate for adrenal and thyroid insufficiency.
In cases of infection, trauma, or stressful situations, it is important to increase the dose of replacement medication. Without dose adjustment, the prognosis of survival decreases, particularly when pneumonia develops.
Because of the considerable diversity of clinical symptoms, timely diagnosis of this condition is particularly important.
Patients should also be monitored for symptoms suggestive of other autoimmune disorders. It is essential to recognize that these conditions may not occur as isolated diseases but may represent part of a broader syndrome, making early specialist consultation important.
Benediktas Krinickas, MD, Allergist and Clinical Immunologist, and Kotryna Linauskienė, MD, Allergist and Clinical Immunologist
Clinic of Chest Diseases, Immunology and Allergology, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University
Read more in Internistas, supplement Allergy. Asthma. Immunology, 2018.
