Risks

Hashimoto’s rarely travels alone

14.3% of Hashimoto’s and 9.67% of Graves’ patients have another autoimmune disease ↗︎

This database shows evidence-based relative risks (RR) for conditions associated with autoimmune thyroid disease. Primary source: Boelaert et al., Am J Med 2010 (UK cohort: 495 Hashimoto’s and 2,791 Graves’ patients, self-reported diagnoses).

Top conditions by relative risk

Risk in Hashimoto’s women vs. general population

Addison's
130.1×
Pernicious Anemia
34.2×
Vitiligo
25.6×
Celiac
21.7×
SLE
14.6×
MG Not statistically significant
11.7×
RA
4.4×
T1DM
3.4×

Relative risk vs. general population, log scale. Grey bars: 95% CI includes 1 (not statistically significant).

Detailed comorbidity database

organ autoimmune

Addison's Disease

0.01% UK women
1.17% Women with Hashimoto’s
130.1× Relative risk

95% CI: 42.4–301.3 · p <.001

Clinical details
Symptoms
Profound fatigue Weight loss Hyperpigmentation Salt craving Postural hypotension Hyponatremia Hyperkalemia
Diagnostic tests
  • Morning cortisol (8-9 AM)
  • ACTH stimulation test (Synacthen)
  • 21-hydroxylase antibodies
  • Electrolytes (Na, K)
When to screen
  • Unexplained weight loss in Hashimoto's
  • Postural symptoms
  • Hyperpigmentation
  • BEFORE starting/increasing levothyroxine if APS-2 suspected
  • Type 1 diabetes with Hashimoto's
Clinical pearls
  • CRITICAL: Untreated Addison's + LT4 initiation can precipitate adrenal crisis ↗︎
  • TSH may falsely elevate in untreated Addison's (resolves with steroid replacement)
  • Component of APS-2 (Schmidt syndrome) with Hashimoto's and T1DM
  • Median diagnostic delay: 1-3 years

Source: Boelaert et al., Am J Med 2010 ↗︎

organ autoimmune

Pernicious Anemia

0.13% UK women
4.45% Women with Hashimoto’s
34.2× Relative risk

95% CI: 20.8–52.8 · p <.001

Clinical details
Symptoms
Fatigue Brain fog Memory problems Paresthesias (tingling) Glossitis Pallor
Diagnostic tests
  • Vitamin B12 (with MMA if borderline)
  • Anti-parietal cell antibodies
  • Anti-intrinsic factor antibodies
  • CBC with MCV
  • Gastrin (elevated in autoimmune gastritis)
When to screen
  • All Hashimoto's patients at diagnosis
  • Rising TSH on stable levothyroxine dose
  • Persistent fatigue despite normal TSH
  • Macrocytic anemia
  • Repeat every 2-3 years
Clinical pearls
  • Risk in Hashimoto's women: 34× general population ↗︎
  • Hypochlorhydria from autoimmune gastritis impairs LT4 absorption
  • Iron deficiency precedes B12 deficiency in early autoimmune gastritis
  • Up to 40% of autoimmune atrophic gastritis patients have Hashimoto's
  • Elevated gastric carcinoid tumor risk - endoscopic surveillance warranted

Source: Boelaert et al., Am J Med 2010 ↗︎

organ autoimmune

Vitiligo

0.11% UK women
2.81% Women with Hashimoto’s
25.6× Relative risk

95% CI: 13.3–44.2 · p <.001

Clinical details
Symptoms
Depigmented patches on skin Often symmetric distribution Hands, face, around orifices Hair depigmentation in affected areas
Diagnostic tests
  • Visual examination (Wood's lamp)
  • TSH and TPO antibodies
When to screen
  • All Hashimoto's patients - dermatological exam
  • New skin pigmentation changes
  • Bidirectional: thyroid screen all vitiligo patients
Clinical pearls
  • Vitiligo meta-analysis: AITD OR 5.88 (Fan et al. 2018) ↗︎
  • Thyroid-specific autoantibodies in 20.8% of vitiligo patients (Vrijman 2012) ↗︎
  • British/Dutch guidelines: thyroid screening in all vitiligo patients

Source: Boelaert 2010; Fan Eur J Dermatol 2018 ↗︎

organ autoimmune

Celiac Disease

0.05% UK women
1.17% Women with Hashimoto’s
21.7× Relative risk

95% CI: 7.1–50.2 · p <.001

Clinical details
Symptoms
Diarrhea or constipation Bloating Iron deficiency Fatigue Often asymptomatic
Diagnostic tests
  • Tissue transglutaminase IgA (tTG-IgA)
  • Total IgA (rule out IgA deficiency)
  • Endomysial antibodies (EMA)
  • Duodenal biopsy (gold standard)
When to screen
  • All Hashimoto's patients at diagnosis
  • Unexplained iron deficiency
  • Rising LT4 requirements
  • GI symptoms
Clinical pearls
  • Roy 2016 meta-analysis: biopsy-confirmed celiac disease in 1.6% (95% CI 1.3-1.9%) of AITD patients, about 1 in 62 ↗︎
  • Higher in children (6.2%) than adults (2.7%) (Roy 2016) ↗︎
  • Gluten-free diet may reduce LT4 dose requirements
  • Test BEFORE starting gluten-free diet

Source: Boelaert 2010; Roy Thyroid 2016 ↗︎

systemic autoimmune

Systemic Lupus Erythematosus

0.05% UK women
0.70% Women with Hashimoto’s
14.6× Relative risk

95% CI: 3.0–47.5 · p <.001

Clinical details
Symptoms
Malar (butterfly) rash Photosensitivity Joint pain Fatigue Hair loss Mouth ulcers
Diagnostic tests
  • ANA (high sensitivity)
  • Anti-dsDNA
  • Anti-Smith antibodies
  • Complement (C3, C4)
  • Urinalysis
When to screen
  • Multisystem symptoms
  • Photosensitive rash
  • Unexplained cytopenias
  • Recurrent miscarriages
Clinical pearls
  • Risk in Hashimoto's women: 14.6× general population ↗︎
  • Up to 25% of SLE patients have AITD
  • Female:male ratio 9:1
  • Hashimoto's can be presenting feature of SLE

Source: Boelaert 2010 ↗︎

systemic autoimmune

Myasthenia Gravis

Not statistically significant
0.02% UK women
0.23% Women with Hashimoto’s
11.7× Relative risk

95% CI: 0.3–64.9 · p .082

Clinical details
Symptoms
Muscle weakness (worsens with activity) Ptosis (drooping eyelids) Diplopia Difficulty swallowing Difficulty speaking
Diagnostic tests
  • Acetylcholine receptor antibodies
  • MuSK antibodies
  • Edrophonium (Tensilon) test
  • Single-fiber EMG
When to screen
  • Fluctuating weakness
  • Eyelid drooping
  • Diplopia
  • Bulbar symptoms
Clinical pearls
  • RR 105× in male Graves' patients (Boelaert 2010)
  • 10-15% of MG patients have AITD
  • Symptoms worsen in evening
  • Crisis is medical emergency

Source: Boelaert 2010 ↗︎

systemic autoimmune

Rheumatoid Arthritis

1.07% UK women
4.68% Women with Hashimoto’s
4.4× Relative risk

95% CI: 2.7–6.7 · p <.001

Clinical details
Symptoms
Symmetric joint pain and swelling Morning stiffness > 1 hour Small joints of hands and feet Fatigue
Diagnostic tests
  • Rheumatoid factor (RF)
  • Anti-CCP antibodies (more specific)
  • ESR and CRP
  • Joint imaging
When to screen
  • Persistent joint symptoms
  • Morning stiffness
  • Symmetric joint involvement
Clinical pearls
  • Most common coexisting autoimmune disease in Hashimoto's (4.24%) ↗︎
  • Bidirectional association: TPO antibodies common in RA
  • Early DMARD therapy critical

Source: Boelaert 2010 ↗︎

autoimmune polyglandular

Type 1 Diabetes

0.34% UK women
1.17% Women with Hashimoto’s
3.4× Relative risk

95% CI: 1.1–8.0 · p .016

Clinical details
Symptoms
Polyuria Polydipsia Weight loss Fatigue Blurred vision
Diagnostic tests
  • Fasting glucose
  • HbA1c
  • GAD antibodies
  • IA-2 antibodies
  • C-peptide
When to screen
  • Hashimoto's at diagnosis (HbA1c)
  • Symptoms of hyperglycemia
  • Family history of T1DM
  • Annual screening if APS-2 features
Clinical pearls
  • Up to 25% of T1DM patients have positive TPO antibodies
  • Component of APS-2 (Schmidt syndrome)
  • Higher rate in men than women with Graves' disease (Boelaert 2010) ↗︎
  • Genetic overlap: HLA-DR3, CTLA-4, PTPN22

Source: Boelaert 2010 ↗︎

sleep

Obstructive Sleep Apnea

22.00% Men, AHI ≥ 5 (17% in women)
Clinical details
Symptoms
Excessive daytime sleepiness Loud snoring Witnessed apneas Morning headaches Brain fog Resistant hypertension
Diagnostic tests
  • STOP-Bang questionnaire
  • Epworth Sleepiness Scale
  • Polysomnography (gold standard)
  • Home sleep apnea test (HSAT)
When to screen
  • Daytime fatigue despite normal TSH
  • Snoring or witnessed apneas
  • Obesity (BMI > 30)
  • Resistant hypertension
  • Atrial fibrillation
Clinical pearls
  • An estimated 936 million adults aged 30-69 have OSA (AHI ≥5); 425 million moderate to severe (Benjafield 2019) ↗︎
  • In a 1997 US cohort, 82% of men and 93% of women with moderate to severe sleep apnea were undiagnosed (Young 1997) ↗︎
  • Hypothyroidism (US adults, NHANES 2007-2008): adjusted OR 1.88 (95% CI 1.24-2.84) for diagnosed sleep apnea (Thavaraputta 2019) ↗︎
  • Hypothyroidism increases OSA risk via macroglossia, pharyngeal myopathy
  • Often more impactful than thyroid optimization for fatigue
  • Women under-diagnosed - may present without snoring

Source: Benjafield Lancet Respir Med 2019; Thavaraputta J Clin Endocrinol Metab 2019 ↗︎

nutritional

Vitamin D Deficiency

47.90% Worldwide, vitamin D below 50 nmol/L
Clinical details
Symptoms
Fatigue Muscle weakness Bone pain Mood changes Often asymptomatic
Diagnostic tests
  • 25-OH Vitamin D (preferred)
  • Calcium
  • PTH
When to screen
  • All Hashimoto's at diagnosis
  • Annual monitoring
  • Northern latitudes
  • Limited sun exposure
Clinical pearls
  • 47.9% of people worldwide have 25(OH)D below 50 nmol/L (Cui 2023) ↗︎
  • AITD patients more often vitamin D deficient: OR 2.99 (95% CI 1.88-4.74), meta-analysis (Wang 2015) ↗︎
  • Modulates Treg/Th17 balance, immunologically relevant
  • Higher TPO titers correlate with lower vitamin D (causality unproven) ↗︎
  • Target 25(OH)D ≥50 nmol/L (20 ng/mL)
  • Some experts recommend ≥75 nmol/L for AITD

Source: Wang et al. Nutrients 2015; Cui et al. Front Nutr 2023 ↗︎

nutritional

Iron Deficiency

10.00% US women of childbearing age (9–11%)
Clinical details
Symptoms
Fatigue Exercise intolerance Hair loss Brittle nails Restless legs Brain fog
Diagnostic tests
  • Ferritin (most sensitive)
  • Transferrin saturation
  • CBC with MCV
When to screen
  • All Hashimoto's at diagnosis
  • Menstruating women
  • Persistent fatigue despite normal TSH
  • Hair loss
Clinical pearls
  • Can cause symptoms at ferritin <30 ng/mL even without anemia
  • Iron is required for thyroid hormone synthesis (TPO contains heme) ↗︎
  • Iron supplements separate from levothyroxine by 4 hours ↗︎
  • Pernicious anemia and celiac may underlie persistent iron deficiency ↗︎

Source: Hu & Rayman, Thyroid 2017 ↗︎

Medically reviewed · Last reviewed