What is associated with Hashimoto's?

Hashimoto's Thyroiditis: Associations and Clinical Implications

Hashimoto's thyroiditis is the most common cause of hypothyroidism in industrialized nations, affecting women 7-10 times more often than men, and is associated with multiple autoimmune disorders, metabolic abnormalities, and quality of life impacts even in euthyroid patients. 1, 2

Etiology and Pathophysiology

• Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by lymphocytic infiltration of the thyroid gland, leading to progressive destruction of thyrocytes 2
• Development occurs due to genetic susceptibility, X-chromosome inactivation patterns modulated by environmental factors, and microbiome composition, resulting in an imbalance of self-tolerance mechanisms 2
• The autoimmune response is mediated by antibodies against thyroid peroxidase (TPOAbs) and thyroglobulin (TgAbs) 2, 3

Clinical Presentations

Hashimoto's thyroiditis can present in three main clinical states:

• Thyrotoxicosis (Hashitoxicosis): When stored thyroid hormones are released into circulation from destroyed thyroid follicles 2
• Euthyroidism: When preserved thyroid tissue compensates for destroyed thyrocytes 2
• Hypothyroidism: When thyroid hormone production becomes insufficient due to extensive thyroid damage 1, 2

Associated Conditions

Autoimmune Disorders

• HT is frequently associated with other organ-specific and non-organ-specific autoimmune disorders 4
• Common autoimmune comorbidities include:
  • Type 1 diabetes mellitus 1, 5
  • Systemic lupus erythematosus 1
  • Celiac disease 5

Metabolic Abnormalities

• Excess body weight and metabolic disorders are common even in euthyroid HT patients 3
• Insulin resistance and type 2 diabetes mellitus are associated with HT 1
• Dyslipidemia is frequently observed in HT patients 3

Reproductive Health Issues

• Presence of TPOAbs is associated with a 2-4 fold increase in risk of recurrent miscarriages and preterm birth in pregnant women 2
• Fertility problems may occur in both women and men with HT 2, 4

Neuropsychiatric Manifestations

• Neuropsychological and psychiatric deficits are common in HT patients, even with normal thyroid function 4
• Depression, anxiety, cognitive impairment, and reduced quality of life have been reported 6, 4

Cardiovascular Implications

• Decreased left ventricular performance has been observed in HT patients independent of thyroid function 4
• Increased risk of atherosclerosis and cardiovascular disease 3

Gastrointestinal Issues

• Disorders of the gut and altered microbiome composition 2, 4
• Functional gastrointestinal symptoms are common 4

Malignancy Risk

• HT is associated with 1.6 times higher risk of papillary thyroid cancer compared to the general population 2
• 60 times higher risk of thyroid lymphoma than the general population 2

Nutritional Deficiencies

• Vitamin D deficiency is common in HT patients 3
• Other frequent deficiencies include selenium, magnesium, iron, and vitamin B12 3

Diagnosis

• Diagnosis requires a detailed medical history, thyroid ultrasonography, and blood analysis of thyroid function and thyroid antibodies 6
• TSH testing is the recommended initial test for screening and evaluating patients with suspected thyroid dysfunction 1
• TSH and free T4 testing should be performed in patients with suspected hypothyroidism 1
• Elevated TPOAbs and/or TgAbs confirm the autoimmune nature of the disease 2, 3

Management

Thyroid Hormone Replacement

• Levothyroxine (LT4) is the standard treatment for hypothyroidism due to HT 2
• Dosing is based on the degree of preserved thyroid functionality and lean body mass, typically ranging from 1.4 to 1.8 mcg/kg/day 2
• In pregnancy, only levothyroxine is indicated as T3 does not sufficiently cross the fetal blood-brain barrier 2

Nutritional Interventions

• Several studies have shown benefits of vitamin D and selenium supplementation in HT patients 3
• An anti-inflammatory diet rich in vitamins and minerals and low in animal foods may have protective effects 3
• There is insufficient evidence to support a gluten-free diet for all HT patients 3

Monitoring

• Periodic TSH measurements are necessary to assess for progression from euthyroidism to hypothyroidism 2
• Regular monitoring of thyroid function is required during levothyroxine therapy to maintain optimal dosing 1
• Screening for associated conditions may be warranted, particularly in patients with persistent symptoms despite normal thyroid function 4

Special Considerations

• HT patients often experience symptoms even when thyroid parameters are within normal range 4
• Poor response to therapy despite normal TSH levels may be due to comorbidities, nutritional deficiencies, or pharmacokinetic factors affecting levothyroxine bioavailability 6
• The relationship between thyroid function, mental status, and psychiatric disorders is complex and requires further research 6