J Med Cases
Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
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Case Report

Volume 3, Number 1, February 2012, pages 1-3


A Significant Discrepancy Between Endocrinological and Clinical Phenotype and Immunological Phenotype in Autoimmune Polyglandular Syndrome Type 3

Hidetaka Hamasakia, Hidekatsu Yanaia, b, c, Chika Hiraishia, Sumie Moriyamaa

aDepartment of Internal Medicine, National Center for Global Health and Medicine Kohnodai Hospital, Chiba, Japan
bClinical Research Center, National Center for Global Health and Medicine Kohnodai Hospital, Chiba, Japan
cCorresponding author: Hidekatsu Yanai, Department of Internal Medicine, Clinical Research Center, National Center for Global Health and Medicine Kohnodai Hospital, 1-7-1 Kohnodai, Ichikawa, Chiba 272-8516, Japan

Manuscript accepted for publication July 29, 2011
Short title: Phenotype and Immunological Phenotype
doi: https://doi.org/10.4021/jmc262w

Abstract▴Top 

Autoimmune polyglandular syndrome (APS) is made up of a group of autoimmune disorders of the endocrine glands. In APS type 3, autoimmune thyroiditis occurs with another organ-specific autoimmune disease. APS type 3 is also associated with systemic autoimmune diseases such as sarcoidosis, Sjogren's syndrome and rheumatoid arthritis. We describe a 53-year-old woman with APS type 3 who showed a significant discrepancy between endocrinological and clinical phenotype and immunological phenotype.

Keywords: Autoimmune thyroiditis; Autoimmune polyglandular syndrome; Rheumatoid arthritis; Sjögren's syndrome; Type 1 diabetes

Introduction▴Top 

In autoimmune polyglandular syndrome (APS) type 3, autoimmune thyroiditis occurs with another organ-specific autoimmune disease, but not with autoimmune adrenalitis [1]. Other systemic autoimmune diseases can include type 1 diabetes mellitus, Sjögren's syndrome, and rheumatoid arthritis. Here, we report a patient with APS type 3 who showed a significant discrepancy between endocrinological and clinical phenotype and immunological phenotype.

Case Report▴Top 

A 53-year-old woman was diagnosed as having autoimmune thyroiditis due to the swelling of thyroid and the positivity for anti-thyroid peroxidase antibody (anti-TPO ab) and anti-thyroglobulin antibody (anti-TG ab) 25 years ago, however, she did not require thyroxin substitution because her thyroid function test was normal. She was also diagnosed as having Sjögren's syndrome due to dryness of eye and mouth and the positivity for anti-SSA/Ro antibody (anti-SSA/Ro ab) and anti-SSB/La antibody (anti-SSB/La ab) 4 years ago, and she has been treated by cevimeline hydrochloride hydrate. She was referred to our hospital due to hyperglycemia. Her body weight was 62.9 kg and height 157.4 cm (BMI 25.4 kg/m2). Plasma glucose (335 mg/dL) and HbA1c (8.8%) levels were significantly elevated. Although titers of anti-TPO ab and anti-TG ab were significantly high, serum levels of free triiodothyronine, free thyroxine and thyroid stimulating hormone were within normal range. The titers of both anti-glutamic acid decarboxylase antibody (anti-GAD ab) and anti-insulinoma-associated protein-2 antibody (anti-IA-2 ab) were remarkably high, however, the urinary C-peptide level was within normal range (Table 1), suggesting the preserved beta-cell function. Her blood glucose levels were 101 - 167 mg/dL by using 2 units of insulin glulisine before each meal. Her adrenal function was normal. Although she has been diagnosed as having APS type 3, she was euthyroid and insulin-independent. Further, titer of rheumatoid factor (RF) was remarkably high, however, she did not show arthritis and her serum anti-cyclic citrullinated peptide antibody (anti-CCP ab) and C-reactive protein (CRP) were negative (Table 1).

Table 1.
Click to view
Table 1. Clinical, Immunological, and Endocrinological Characteristics of Our Patient with Autoimmune Polyglandular Syndrome Type 3
 
Discussion▴Top 

APS is made up of a group of autoimmune disorders of the endocrine glands [2]. APS shows failure of the glands to produce their hormones. APS type 3, in contrast to APS type 1 and 2 [3], does not involve the adrenal dysfunction (Table 2) [1]. In APS type 3, autoimmune thyroiditis occurs with another organ-specific autoimmune disease (Table 2) [1]. APS type 3 can be further classified into the 3 subgroups. Autoimmune thyroiditis with type 1 diabetes mellitus which developed in my patient is categorized as APS type 3A. APS type 3 is associated with organ-specific autoimmune diseases such as Celiac disease and myasthenia gravis, and systemic autoimmune diseases such as sarcoidosis, Sjögren's syndrome and rheumatoid arthritis [1].

Table 2.
Click to view
Table 2. Major Component Diseases and Minor Autoimmune Diseases in Each Type of Autoimmune Polyglandular Syndrome [1]
 

Most patients with APS type 3 show abnormal thyroid function and decreased insulin secretion [4-6]. We experience a very rare APS type 3 middle-aged patient who showed normal thyroid and preserved beta-cell function in spite of the existence of remarkably high titer of autoantibodies (anti-TPO ab, anti-TG ab, anti-GAD ab and anti-IA-2 ab). Further, she presented with symptoms of Sjögren's syndrome (dryness of eye and mouth) and has been treated, showing the positivity for anti-SSA/Ro antibody and anti-SSB/La antibody. However, in spite of remarkably high titer of RF, she did not show arthritis and her serum anti-CCP ab and CRP were negative (Table 1).

APS is diverse, and its diversity is a characteristic that is both clinically important and very informative to understand its underlying basic immunological mechanisms and features [7-9]. An accumulation of similar cases to our patient may prompt us to understand the pathogenesis for APS.


References▴Top 
  1. Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev. 2002;23(3):327-364.
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  9. Ahonen P, Myllarniemi S, Sipila I, Perheentupa J. Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med. 1990;322(26):1829-1836.
    pubmed doi


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Journal of Medical Cases, monthly, ISSN 1923-4155 (print), 1923-4163 (online), published by Elmer Press Inc.        
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