From the Guidelines
Investigations for polyglandular autoimmune syndrome (PAS) should include comprehensive testing for multiple endocrine and non-endocrine autoimmune conditions, starting with screening for the most common associated disorders, such as thyroid function, adrenal function, and pancreatic function. This approach is crucial for early detection and management of potential autoimmune conditions that may arise in these patients. According to the consensus statement on the diagnosis, treatment, and follow-up of patients with primary adrenal insufficiency 1, the aetiology of primary adrenal insufficiency (PAI) should be determined, as it may affect treatment decisions and follow-up.
In the context of PAS, measuring anti-21-hydroxylase antibodies is essential for diagnosing an autoimmune cause of adrenal insufficiency, as autoimmunity accounts for approximately 85% of diagnoses of PAI in Western Europe 1. Additional testing should include:
- Thyroid function tests (TSH, free T4, anti-thyroid peroxidase, and anti-thyroglobulin antibodies)
- Adrenal function tests (morning cortisol, ACTH stimulation test, anti-21-hydroxylase antibodies)
- Pancreatic function tests (fasting glucose, HbA1c, anti-glutamic acid decarboxylase antibodies, anti-islet cell antibodies)
- Complete blood count to assess for pernicious anemia (vitamin B12 levels, anti-parietal cell, and anti-intrinsic factor antibodies)
- Liver function tests with anti-liver antibodies
- Calcium and phosphate levels for hypoparathyroidism
- Gonadal function tests (FSH, LH, estradiol or testosterone)
- Tissue transglutaminase antibodies for celiac disease
Genetic testing, particularly HLA typing and AIRE gene mutations for type 1 PAS, may also be valuable in certain cases, especially in young patients with multiple autoimmune conditions 1. Regular monitoring is essential, as additional autoimmune conditions may develop over time, even if initial screening is negative. The rationale for comprehensive testing is that early detection of subclinical disease allows for timely intervention before significant organ damage occurs, as these syndromes typically involve multiple autoimmune conditions that may develop sequentially rather than simultaneously.
From the Research
Investigations for Polyglandular Autoimmune Syndrome
Investigations for polyglandular autoimmune syndrome (PAS) involve a combination of clinical, serological, and genetic tests. The following are some of the key investigations:
- Serological measurement of organ-specific autoantibodies, such as those against thyroid, adrenal, and pancreatic islet cells 2, 3, 4, 5
- Functional testing to assess the function of endocrine glands, such as thyroid function tests and adrenal function tests 2, 4, 5
- Genetic testing to identify mutations in the autoimmune regulatory (AIRE) gene, which is associated with PAS type I 4, 6
- Human leukocyte antigen (HLA) typing to identify susceptibility genes associated with PAS type II and III 2, 4
- Screening for non-endocrine autoimmune diseases, such as vitiligo and alopecia, which are commonly associated with PAS 2, 5, 6
Diagnostic Criteria
The diagnosis of PAS is based on the presence of two or more autoimmune-mediated endocrinopathies, such as:
- Type 1 diabetes
- Autoimmune thyroid disease (e.g. Hashimoto's thyroiditis or Graves' disease)
- Addison's disease
- Hypoparathyroidism
- Vitiligo
- Alopecia
- Pernicious anemia 2, 3, 4, 5, 6
Screening and Monitoring
Regular screening and monitoring are essential for early detection and management of PAS. This includes:
- Screening for polyglandular autoimmunity in patients with monoglandular autoimmune disease and/or first-degree relatives of patients with PAS 5
- Functional screening every 3 years in subjects at risk for PAS 2
- Serological measurement of organ-specific autoantibodies and subsequent functional testing in patients with clinical disease 2, 4, 5