Hashimoto’s thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is the most common autoimmune thyroid disease, first reported in 1912 by the Japanese scholar HakaruHashimoto as a type of autoimmune thyroiditis (AIT). Atrophic thyroiditis (AT) without goiter has also been classified as Hashimoto’s thyroiditis.
The prevalence of Hashimoto’s thyroiditis is reported to be 3-4% abroad. The incidence is 0.08% in men and 0.35% in women. The prevalence in women is 3 to 4 times higher than that in men. The prevalence rate reported in China is 1.6%. The morbidity rate is 0.69%. If patients with subclinical hypothyroidism are included, the prevalence in the female population can be as high as 3.3-10%, and the prevalence increases significantly with age.
Hashimoto’s thyroiditis is a recognized organ-specific autoimmune disease with a genetic predisposition that can coexist with other autoimmune diseases such as pernicious anemia, dry syndrome, chronic active hepatitis, and systemic lupus erythematosus.
Hashimoto’s thyroiditis is currently considered to be the result of a combination of genetic and environmental factors. The more recognized cause is an abnormal autoimmune epidemic function. Specific antibodies against thyroid tissue, including thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb), and thyroid stimulation blocking antibodies (TSBAb), appear in the patient’s serum.
The pathogenesis of Hashimoto’s thyroiditis is still not fully understood. TPOAb has both antibody-dependent and complement-mediated cytotoxic effects. Cytotoxic T cells and helper (Th1) cytokines are also involved in the process of thyroid cell apoptosis and injury. tsBAb occupies TSH receptors and promotes thyroid atrophy and hypofunction. Iodine intake is an important environmental factor influencing the development of Hashimoto’s thyroiditis, and the incidence of the disease increases significantly with increased iodine intake. In particular, increased iodine intake can promote the development of clinical hypothyroidism in patients with latent Hashimoto’s thyroiditis.
Pathological manifestations of Hashimoto’s thyroiditis patients have an enlarged, hard thyroid gland. The normal thyroid follicular structure is extensively replaced by lymphocytes, plasma cells, and lymphopoietic centers. The thyroid follicles are isolated and small, with small, atrophic follicles and sparse gliosis. As the disease progresses, the follicles become smaller and atrophied, with less glial material in the lumen, and the epithelial cells swell and increase in size, with a marked eosinophilic staining of the cytoplasm, called Askanazy cells. Ninety percent of thyroid follicles have been destroyed by the time hypothyroidism occurs.
The course of Hashimoto’s thyroiditis can be divided into three stages: recessive stage (early stage): normal thyroid function, no goiter or mild goiter, positive TPOAb, and lymphocytic infiltration in the thyroid gland. Subclinical hypothyroidism stage: massive lymphocyte infiltration in the thyroid gland and follicular destruction. Clinical hypothyroidism: follicular destruction and thyroid atrophy.
Clinical manifestations: High incidence age 30-50 years. The onset of the disease is insidious and the progression is slow. Early clinical manifestations are atypical, asymptomatic, and may only show positive thyroid autoantibodies. Most patients are first diagnosed with goiter or hypothyroidism. Clinical hypothyroidism appears in the late stage. Patients show typical symptoms such as fear of cold, fatigue, dry skin, bradycardia, constipation and even mucinous edema and often discomfort in the throat or mild swallowing difficulties. There is sometimes a feeling of neck pressure and occasional localized pain. The signs include a moderate enlargement of the thyroid gland, which is diffuse, lobulated or nodular, with a mostly firm texture and no adhesion to the surrounding tissues, or an atrophied thyroid gland in the case of AT.
Hashimoto’s thyroiditis and Graves’ disease (Graves’ disease) can coexist in a condition called Hashimoto’s thyrotoxicosis. The presence of thyroid-stimulating antibodies (TSAb) and TPOAb in the serum and histology of both Hashimoto’s thyroiditis and Graves’ disease are present. The clinical presentation alternates between hyperthyroidism (hyperthyroidism) and hypothyroidism, which may be associated with a predominant role of TSAb or TSBAb. The symptoms of hyperthyroidism are similar to Graves’ disease, and the self-conscious symptoms may be less severe than in Graves’ disease alone, requiring regular antithyroid medication, but hypothyroidism is likely to occur during treatment. In some patients, the hyperthyroidism is a transient leaky thyrotoxicosis.
Patients with Hashimoto’s thyroiditis may also have concomitant other autoimmune disorders and can be a component of the endocrine polyglandular autoimmune syndrome, i.e., with hypothyroidism, type 1 diabetes, hypoparathyroidism, and hyperaldosteronism. In recent years, autoimmune thyroiditis-associated encephalitis, thyroid amyloidosis and lymphocytic interstitial pneumonia associated with this disease have also been identified.
Laboratory tests
1. Thyroid function and autoantibody determination: When thyroid function is normal, a significant increase in serum TPOAb and TgAb titers is the most meaningful and the only diagnostic indicator, belonging to the occult phase of Hashimoto’s thyroiditis. The destruction of thyroid follicles results in a subclinical hypothyroid phase (elevated serum TSH and normal free T4), which finally progresses to clinical hypothyroidism (elevated serum TSH and reduced free T4).
TgAb has the same significance as TPOAb, and the TPOAb positivity rate is higher than TPOAb, with a reported TPOAb positivity rate of over 95% and TgAb of 80%. The antibody positivity rate is low in young patients.
2. Ultrasonography: Hashimoto’s thyroiditis shows on ultrasound as goiter with uneven echogenicity, which may be accompanied by multiple hypoechoic or thyroid nodules.
3. Nuclear thyroid scan and iodine uptake measurement: Nuclear thyroid scan may show uneven and sparse thyroid nuclei resolution or “cold nodular” changes. This is a non-routine test. The iodine uptake rate of the thyroid gland may be normal or even elevated in the early stages, but decreases after destruction of thyroid follicular cells. The accompanying GD is usually elevated. Most people believe that this test has no practical significance for diagnosis.
4. Fine needle aspiration cytology (FNAC) of the thyroid gland: It helps to establish the diagnosis of Hashimoto’s thyroiditis. It is usually not routinely used for Hashimoto’s thyroiditis.
V. Diagnosis and differential diagnosis To date, the ATA, AACE and other authorities have only developed diagnostic criteria for hypothyroidism or hyperthyroidism, and there are no corresponding guidelines for Hashimoto’s thyroiditis.
The diagnosis of Hashimoto’s thyroiditis can be established if there is a significant increase in serum TPOAb and TgAb titers, but patients with AT do not have an enlarged thyroid, but have a significant increase in antibody titers, and have hypothyroidism. Some of the thyroid glands are hard and must be differentiated from thyroid cancer.
Treatment
1. Limiting iodine intake in a safe range (urinary iodine at 100-200 μg/L) may help to slow down the progress of thyroid autoimmune destruction. Levothyroxine has been reported to reduce the level of thyroid antibodies, but there is no evidence that it can stop the progression of the disease.
2. Treatment is generally not needed for those with goiter only and no hypothyroidism.
3. Treatment is mainly directed at the symptoms of hypothyroidism and goiter compression. There is a consensus to implement thyroxine replacement therapy in clinically hypothyroid individuals. Levothyroxine is recommended and there is no need to use T3 or T3/T4 mixed dosage form.
The goal of treatment is to restore serum TSH and thyroid hormone levels to normal ranges and requires lifelong medication. The therapeutic dose depends on the patient’s condition, age, weight and individual differences. The average dose for adults is 125 μg/day, 1.6 to 1.8 μg/(kg?day) by body weight, with elderly patients requiring a lower dose of approximately 1.0 μg/(kg?day).
Dosage: Take one dose in the morning on an empty stomach. Start with a small dose, especially for elderly patients with cardiovascular disease, longer duration of disease, and severe disease. Those younger than 50 years old with no history of heart disease can reach the full replacement dose as soon as possible. Those over 50 years old taking levothyroxine tablets should have their heart status routinely checked, generally starting with 25-50 μg per day and increasing by 25 μg every 1-2 weeks until the goal of full replacement is reached. Those with heart disease are advised to start with 12.5~25μg per day and increase by 12.5~25μg every 2 weeks to avoid triggering and aggravating the heart disease condition.
Since the half-life of levothyroxine is 7 days and it generally takes 4~6 weeks to re-establish the balance of hypothalamic-pituitary-thyroid axis, the hormone index can be reviewed every 4~6 weeks when levothyroxine is initially taken, and then the levothyroxine dose can be adjusted according to the results until the treatment target is reached. After reaching the treatment target, the hormone index can be rechecked every 6~12 months and thyroid ultrasonography if necessary.
Those who have obvious compression symptoms and are not relieved by medication may consider surgery, but postoperative hypothyroidism or worsening of hypothyroidism mostly occurs.
4. The treatment of Hashimoto’s thyroiditis with suboptimal hypothyroidism is the most controversial. There is no consensus on the TSH value for starting treatment, the advantages and disadvantages of treatment, and the population to be treated. For those with TSH >10 mIU/L levothyroxine treatment is generally advocated. Given that evidence from evidence-based medicine is insufficient to determine the rationality and effectiveness of thyroxine replacement therapy, and that overtreatment can bring about a series of adverse effects, such as cardiovascular disease and osteoporosis, most scholars propose that follow-up is sufficient for patients with TSH between 4.5 and 10 mIU/L, especially for elderly patients of advanced age. However, the expert consensus of ATA and AACE in the United States and other institutions believes that it is also desirable to give levothyroxine appropriately as long as the dose of medication is mastered and overtreatment is prevented. Of course, levothyroxine needs to be used routinely for hypothyroidism in patients with significant symptoms, TPOAb-positive patients, those who wish to become pregnant, pregnant women, and children and adolescents.