Graves' Disease and Multiple Autoimmune Syndrome on the Rise

People with thyroid endocrine disorders require greater diagnostic and management investment.

with Alessandro Antonelli, MD, and Janet B. McGill, MD

The prevalence of multiple autoimmune syndrome (MAS)—the cascade of 3 or more autoimmune diseases presenting in a signal individual— is on the rise.1,2 With each additional autoimmune disorder, the ability to manage the more complex disease burden and plan an effective course of treatment will become a more vexing predicament for clinicians in the years ahead.

One such scenario, polyglandular syndromes—a clustering of autoimmune-specific diseases affecting endocrine glands with diabetes and celiac disorder the most prevalent. Yet, there is a growing body of evidence of an increased incidence of polyautoimmunity that has been expanding beyond known endocrine disorders to include autoimmune systemic rheumatologic diseases, gastrointestinal disorders, and neurological disorders.3-6

Patients with Graves' disease are likely to present with other autoimmune diseases.Clinicians should anticipate more patients presenting with multiple autoimmune syndrome, requiring greater diagnostic attention and targeted treatment. Photo: 123rf

Polyautoimmune Syndrome on the Rise in Patients with Endocrine-Related Diseases

Building on our existing understanding of polyautoimmunity, a group of Italian researchers examined the prevalence of non-glandular autoimmune disorders in patients affected by Graves’ disease with or without Graves’ ophthalmology,7 which was presented at the American Thyroid Association Symposium, in Washington, DC.

The investigators prospectively evaluated 3209 patients with Graves’ disease to assess for other autoimmune disorders as compared with three sex- and age-matched cohorts.7

What they found was an estimated 25% of patients who were diagnosed with an autoimmune thyroid disorder presented with at least one other autoimmune disorder including but not limited to:

  • alopecia
  • Addison’s disease
  • rheumatoid arthritis (RA)
  • chronic autoimmune gastritis
  • vitiligo
  • polymyalgia rheumatic
  • celiac disease
  • type 1 diabetes 
  • Sjogren’s syndrome
  • multiple sclerosis (MS)
  • systemic lupus erythematosus (SLE)
  • sarcoidosis/systemic sclerosis
  • myasthenia gravis

The presence of three autoimmune diseases (MAS) were reported in 1.5% of patients with confirmed Graves’ disease, and 1.4% of patients with autoimmune thyroiditis.7 Furthermore, the occurrence of multiple non-thyroid autoimmune disorders appeared significantly higher among patients with Graves’ ophthalmopathy than with those with Graves’ without eye disease.

Previously investigators reported polyautoimmunity in more than one-third of patients with one autoimmune disorder;2 typically, autoimmune thyroid disease and Sjogren’s syndrome are among the most frequently encountered diseases.1,8  Female gender, familial autoimmunity, and increasing age were all significantly associated with increased risk of polyautoimmunity.2,4,9

“The prevalence in female gender is higher than in men, and the gender ratio and age range appear to depend on the type of autoimmune diseases present," said study investigator, Alessandro Antonelli, MD, director of the Immuno-Endocrine Section of Internal Medicine, and professor of medicine and director of the Laboratory of Primary Human Cells in the Department of Clinical and Experimental Medicine at the University of Pisa School of Medicine in Italy.  

Type 1 Diabetes Elevates Risk for Multiple Autoimmune Syndrome

Although Type 1 diabetes (T1D) has been recognized as a common autoimmune disorder, minimal attention has focused on nondiabetes-related complications and comorbidities, particularly in adults.10

In a recent observational study of 1212 adults with T1D noted that more than 9% of the women with T1D also had systemic rheumatic diseases (SRD); further, 14% of women over age 50 years were diagnosed with T1D with co-occurring SRD.4

Older age of T1D onset (over 30 years) was associated with increased risk for additional autoimmune disorders.10 And, consistent with other studies, Hughes et al reported that thyroid diseases were most prevalent, affecting nearly 27% of patients.10

Similarly, a cross-sectional database study of 158,865 adults with a diagnosis of T1D found significant comorbidity with other autoimmune disorders: 20.1% had thyroid disease, 3.4% had systemic rheumatic diseases, 2% had RA, and 1.4% had gastrointestinal autoimmune diseases.9 Most of the autoimmune disorders were reported more frequently in women than men and increased in prevalence with age.

Janet B. McGill, MD, Professor of Medicine in the Division of Endocrinology, Metabolism, and Lipid Research at the Washington University School of Medicine in St. Louis, MO, and a co-author of the studies on adults with T1D discussed the findings reported by Ferrari et al in an interview with EndocrineWeb.

Given the findings reported at ATA,7 Dr. McGill reiterated the need for clinicians to increase their vigilance regarding the presence of multiple autoimmunities in any patient who receives a diagnosis for an initial autoimmune disorder, and who remains "unwell".

“patients with Hashimoto’s thyroiditis or Graves’ disease in the presence of symptoms and signs (for example, bilateral painful joints) should be tested for rheumatological disorders," Dr. Antonelli told EndocrineWeb.

In Autoimmune Management—Thyroid Disease, T1D Just the Beginning

According to Bliddal et al,8 autoimmune thyroid disease was described as the “tallest tree in the forest of polyautoimmunity,” noted Dr. McGill, because it occurs so often and represents the autoimmune disease that appears with the greatest frequency in patients with polyautoimmunity. 

Earlier publications have identified autoimmune thyroid disease, systemic lupus erythematosus (SLE) and Sjogren’s syndrome as the autoimmune disorders most often encountered.1,2

A yet another study of more than 5000 patients with SLE and nearly 25,100 matched controls found a significantly increased risk of hypothyroidism in patients with SLE than the controls (15.6% vs 5.75%).6 While Demirezer Bolat reported that 33% of patients (n = 145) with celiac disease had also been diagnosed polyautoimmunity.5  Among the risk factors identified for polyautoimmunity were female gender, family history for autoimmune disorders, and having any musculoskeletal disease.5

Referencing her own research,12 Dr. McGill stated that “like Graves’ disease, increased risk of other autoimmune diseases has been found in persons with type 1 diabetes mellitus. Women have a greater risk than men; however, in both sexes, the prevalence of other autoimmune disease increases with age.”

“We need research to better understand the pathogenesis of and risk factors for poly- or multiple- autoimmunity, as well as the need to educate both clinicians and patients about this growing concern [of multiple autoimmune syndrome],” Dr. McGill told EndocrineWeb.

She emphasized the growing likelihood of polyautoimmunity among middle- and older aged women, in particular, suggesting “the need for  endocrinologists to look past polyglandular autoimmunity and to think more broadly about elevated risks for systemic rheumatic and neurologic diseases, among other autoimmune conditions.” 

Continue Reading:
Similarities in Autoimmune Onset of Diabetes Revealed in Thyroid Disease
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