Published: December 2025
Medically reviewed by:
Mercè Tena Campos, Scientific Affairs Manager
Polyautoimmunity refers to the presence of two or more autoimmune diseases in the same patient.1 Because symptoms overlap, many patients experience prolonged diagnostic journeys before the correct diagnosis is made. Early recognition and first-line testing in primary care can reduce time to diagnosis and prevent complications.2,3
Why Graves’ and Hashimoto’s often coexist with other autoimmune diseases
- Autoimmune thyroid diseases (AITDs) commonly co-occur with other autoimmune conditions. Cohort and systematic review data show that between one in three and one in six autoimmune thyroid patients also had another autoimmune disease, most often celiac disease, autoimmune gastritis/pernicious anemia, rheumatoid arthritis, vitiligo, type 1 diabetes, or Sjögren’s syndrome.4,5
| Additional autoimmune condition | All AITD patients | Hashimoto’s thyroiditis patients | Graves’ disease patients | |
|---|---|---|---|---|
| More common | Type 1 diabetes mellitus | 3.6 % | 4.4 % | 2.9 % |
| ↓ | Autoimmune gastritis | 3.4 % | 3.5 % | 3.3 % |
| ↓ | Rheumatoid arthritis | 2.6 % | 2.4 % | 2.6 % |
| ↓ | Celiac disease | 2.3 % | 2.7 % | 1.2 % |
| ↓ | Vitiligo | 2.4 % | 2.7 % | 2.1 % |
| ↓ | Pernicious anemia | 1.8 % | 3.9 % | 1.4 % |
| Less common | Sjögren’s syndrome | 1.2 % | 1.2 % | 0.8 % |
- Many patients with autoimmune thyroid diseases continue to feel unwell even when their thyroid treatment is correct. One of the reasons could be the presence of other autoimmune conditions, known as polyautoimmunity.6
- Risk factors for multiple autoimmune diseases include family history, female gender and genetic predisposition.7,8
Red flags for thyroid patients
Recognized signs and symptoms
- Unexplained iron-deficiency anemia or macrocytosis9,10
- Persistent gastrointestinal problems: bloating, diarrhea, malabsorption9,11
- Symmetrical small-joint pain or stiffness; sicca symptoms; Raynaud’s phenomenon12,13
- Depigmented skin or hair14-16
- Recurrent polyuria, hypoglycemia, or unexplained weight change17
Less obvious but important
- Chronic fatigue, anxiety, or low mood despite normal thyroid levels6,18
- Cognitive “brain fog”6
- Glossitis or burning tongue; persistent dyspepsia19,20
- Subtle rashes or very dry skin9,13
- Recurrent miscarriage or infertility problems9,11
Common autoimmune conditions to consider in thyroid patients
Classic symptoms: Diarrhea, steatorrhea, failure to thrive, features of malnutrition or malabsorption, abdominal pain, weight loss, bloating, indigestion, flatulence, nausea/vomiting, constipation.9
Non-classic and other shared symptoms: Unexplained iron deficiency anemia, peripheral neuropathy (tingling, numbness, pain in hands and feet), neurological symptoms (headaches, cognitive issues), osteoporosis, infertility, dermatitis herpetiformis, vitamin deficiencies (folic acid and B12), chronic migraine, chronic fatigue, difficulty losing weight, dental enamel defects.11,21
What can be done in primary care: Screen thyroid patients who have gastrointestinal red flags, other relevant symptoms or family history.9,11 Ensure the patient is eating gluten before testing; refer to gastroenterology if serology is positive.9
Recommended tests:
- tTG-IgA plus total IgA.9
- Pediatric no-biopsy pathway if tTG ≥10x ULN plus EMA positive.22
- In adults, very high tTG-IgA ± EMA may support no-biopsy diagnosis in selected centers per local protocol.23,24
Why it matters: Many celiac patients present with extra-intestinal features (anemia, osteoporosis, infertility) rather than diarrhea. Missed diagnoses prolong suffering and risk complications.25,26 Testing from primary care is simple and cost-effective.9,27
Classic symptoms (disease dependent): Joint pain, skin rashes, organ dysfunction, fatigue, dry eyes or mouth.12,13,28
Non-classic and other shared symptoms: Raynaud’s phenomenon, pleurisy, arthralgia, myopathy, malaise, weight loss, alopecia, sclerodactyly, telangiectasia.13,28
What can be done in primary care: Early detection and urgent referral are crucial.29,30
Recommended tests:
- Order rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP, ACPA or CCP); double positivity indicates priority referral.29
- ANA as first-line for systemic rheumatic autoimmune diseases;31 interpret using guidance from laboratory.
Why it matters: Combined RF IgM isotype and anti-CCP positivity is highly predictive of rheumatoid arthritis, while a single RF isotype may not be associated with a significant risk to develop rheumatoid arthritis.29,32-33 Sjögren’s syndrome frequently clusters with thyroid autoimmunity; sicca symptoms plus thyroid disease should raise suspicion.5 Early rheumatology referral improves outcomes and prevents joint damage.29
Classic symptoms: Often asymptomatic at first.10,28 Later: iron or vitamin B12 deficiency, anemia/pallor, glossitis, diarrhea, peripheral numbness, loss of vibratory sense.28
Non-classic and other shared symptoms: Fatigue, weakness, dyspepsia, neurological problems.10
What can be done in primary care: Consider in older patients with macrocytosis; test for antibodies against parietal cells and intrinsic factor, serum gastrin and antibodies against Helicobacter pylori.20,28,34 Positive or suspicious results → refer for endoscopy.20
Why it matters: Autoimmune gastritis and pernicious anemia are part of the “thyrogastric disease” spectrum.35 Gastric cancer risk must be remembered.34 Screening for thyroid autoimmunity is recommended in autoimmune gastritis.34 Early detection avoids irreversible neurologic complications from B12 deficiency.10
Classic symptoms: Polyuria, polydipsia, blurred vision, weight change.36
Non-classic and other shared symptoms: Impaired wound healing, increased infections, fatigue.28,36
What can be done in primary care: Glucose is the first and most relevant test; if unstable, start fluids/electrolytes/insulin and refer immediately.28,36
Why it matters: Patients with autoimmune thyroid diseases are at higher risk for type 1 diabetes and latent autoimmune diabetes should be considered in adults.17 Untreated hyperglycemia or delayed recognition can lead to diabetic ketoacidosis, which is life-threatening.36
Classic symptoms: Skin, hair, and oral depigmentation.14,15
Non-classic/other shared symptoms and impact: Psychosocial impact.16
What can be done in primary care: Classic cases can be diagnosed in primary care; atypical cases → dermatology. In adults with vitiligo, consider thyroid function tests.14
Why it matters: Vitiligo is the most common cause of acquired depigmentation.15 It is often the earliest visible autoimmune sign and can precede thyroid disease.15 Several chemicals (hair dyes, cleaning products, cosmetics) have been reported as triggers.16
The value of early recognition and testing
Early testing in primary care can shorten the diagnostic journey, improve care and avoid unnecessary referrals. Patients with persistent symptoms could feel unheard if their complaints are dismissed as “just thyroid.” By considering polyautoimmunity and testing for other autoimmune diseases, you can validate patient concerns and improve outcomes.2,3 Early action also reduces costs and prevents complications.37
You don’t have to be an autoimmune specialist to make a difference. Your role as a GP is to:
- Recognize red flags, including relevant symptoms and family history
- Test appropriately (celiac disease: tTG-IgA + total IgA; systemic rheumatic diseases: rheumatoid factor + anti-CCP ± antinuclear antibody screening)
- Refer to gastroenterology, rheumatology or other specialists if test results are positive or if clinical suspicion remains high
Thermo Fisher Scientific provides reliable autoimmune testing solutions and resources that can help you simplify decision-making, improve patient journeys and deliver coordinated care.
