Type III Polyglandular Autoimmune Syndrome Workup

Updated: Sep 22, 2017
  • Author: KoKo Aung, MD, MPH, FACP; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Workup

Laboratory Studies

Laboratory studies to diagnose polyglandular autoimmune syndrome (PAS) III include (1) serological tests for autoantibodies, (2) assessment of end-organ function, and (3) genetic tests.

Serological tests for autoantibodies

  • Some experts argue that measurement of levels of circulating antibodies may not be very useful, because many individuals have these antibodies without clinical manifestations. In a study by Hunger-Battefeld et al involving 139 patients with IMD, 63% of the patients were found to have 1 or more pathologically increased antibody titers associated with an autoimmune endocrine disease other than diabetes; however, only 31% of the patients presented with symptoms of this additional disease. In the study, thyropathy was the most prevalent autoimmune disease accompanying IMD. The authors recommended that patients with IMD be screened for other autoimmune endocrine diseases. [22]
  • Serological tests may be helpful in the following circumstances:
    • They can be used to verify the autoimmune nature of disease.
    • They can be used to identify patients affected by an isolated glandular failure in which polyglandular failure is likely to develop.
    • They can be used to screen asymptomatic family members of patients with PAS III.
  • Some autoantibodies appear to predict the development of glandular failure. This may allow the initiation of immunomodulatory treatment before the development of overt disease.
  • The following list delineates autoantibodies detected in each glandular disease:
    • For autoimmune thyroiditis, autoantibodies may include antithyroglobulin antibodies, antithyroid microsomal antibodies/antithyroid peroxidase antibodies (peroxidase is the microsomal antigen).
    • For IMD, they may include anti – islet cell antibodies and antibodies to glutamic acid decarboxylase.
    • For PA, antiparietal cell antibodies and anti – intrinsic factor antibodies may be present.
    • In vitiligo, antimelanocyte antibodies are found.

Assessment of end-organ function

  • Autoimmune thyroiditis
  • Immune-mediated diabetes
    • A fasting blood glucose level higher than 125 mg/dL, a random blood glucose level higher than 200 mg/dL in the presence of classic symptoms of diabetes mellitus, or a 2-hour postprandial blood glucose level higher than 200 mg/dL in an oral glucose tolerance test is diagnostic of diabetes mellitus.
    • Glycosylated hemoglobin level is more useful for monitoring of the progress of disease than for diagnostic purposes.
  • Pernicious anemia
    • CBC count is one of the most important diagnostic tests. Macrocytic anemia (mean cell volume >100 fL) with marked anisopoikilocytosis and hypersegmented neutrophils observed on peripheral blood films is characteristic. Serum vitamin B-12 level is very low.
    • Other laboratory findings include megaloblastic bone marrow and abnormal vitamin B-12 absorption test (Schilling test), corrected with the addition of intrinsic factor.
  • Vitiligo: Skin biopsy from the affected area reveals an absence of melanocytes and mild inflammatory cell infiltrate.

Genetic testing: Mutations in the HLAD gene should be analyzed in patients with PAS III and in siblings with symptoms of component glandular diseases. HLA-DR oligotyping and HLA-DQ oligotyping by polymerase chain reaction are commercially available through Associated Regional and University Pathologists Laboratories. HLA-DR typing of loci 1 and loci 2 also is available through Specialty Laboratories.

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Procedures

Perform fine-needle aspiration biopsy of the thyroid gland to exclude malignancy if a suggestive nodule (ie, dominant nodule) is present or if the goiter is growing rapidly.

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Histologic Findings

Histopathology of involved endocrine glands in PAS III demonstrates lymphocytic infiltration. For autoimmune thyroiditis, clumps of oxyphilic thyroid follicular cells surrounded by lymphocytes (struma lymphomatosa) are present. For vitiligo, melanocytes are absent and mild lymphocytic infiltrate is present.

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