Autoimmune thyroiditis

Overview

Hashimoto thyroiditis is an autoimmune disorder that causes thyroid cell destruction by immunological mechanisms mediated by cells and antibodies. It is the most common cause of hypothyroidism in developed countries.

In contrast, a shortage of iodine in the diet is the most common cause of hypothyroidism worldwide. Chronic lymphocytic thyroiditis and chronic autoimmune thyroiditis are other names for this condition. The condition's pathophysiology is defined by the formation of anti-thyroid antibodies, which attack thyroid tissue and produce progressive fibrosis.

Patients may develop signs, symptoms, and laboratory results of hyperthyroidism or normal levels early in the course of the disease. This is because thyroid gland cell death can be intermittent. The thyroid gland can swell over time, causing a painless goiter. Hypothyroidism can cause weight gain, fatigue, constipation, depression, hair loss, and general aches and pains in certain people.

Diagnosis is usually difficult, and symptoms may not appear until late in the disease's progression. The most common laboratory findings are elevated thyroid-stimulating hormone (TSH) levels, low free thyroxine (fT4) levels, and increased antithyroid peroxidase (TPO) antibodies.

The size of the thyroid normally decreases over time. One of the probable outcomes is thyroid lymphoma. Furthermore, because untreated Hashimoto's patients usually develop hypothyroidism, further consequences can include, but are not limited to, high cholesterol, heart disease, heart failure, high blood pressure, myxedema, and potential pregnancy complications.

Levothyroxine is a frequent treatment for Hashimoto's thyroiditis. If hypothyroidism is not present, some doctors may advise against treatment, while others may recommend it to reduce the size of the goiter. Those who are affected should avoid taking large amounts of iodine; nonetheless, enough iodine is required, especially during pregnancy. Surgery is seldom required to treat a goiter.

Worldwide demographics of Autoimmune thyroiditis

Autoimmune thyroiditis

With adequate iodine consumption, Hashimoto's thyroiditis is the most common cause of hypothyroidism in the United States and other areas of the world after the age of six. The annual incidence is predicted to be 0.8 per 1000 males and 3.5 per 1000 females. According to twin research, monozygotic twins had a greater concordance of autoimmune thyroiditis than dizygotic twins. According to Danish study, concordance rates in monozygotic twins were 55%, compared to just 3% in dizygotic twins.

According to this study, genetic variables account for 79% of propensity, with the remaining 21% attributed to environmental and sex hormone influences. In general, the prevalence of thyroid disease increases with age.

Women suffer disproportionately. The female-to-male ratio is at least ten to one. Although some sources say that diagnosis is more common in the fifth decade of life, the majority of women are diagnosed between the ages of 30 and 50.

Pathophysiology of Autoimmune thyroiditis

Autoimmune thyroiditis Pathophysiology

The beginning of Hashimoto disease is thought to be autoimmune, with lymphocyte infiltration and fibrosis being typical problems. The current diagnosis is based on clinical symptoms that match with test results that demonstrate elevated TSH levels with normal to low thyroxine levels. There is, however, minimal evidence to support the role of anti-thyroid peroxidase (anti-TPO) antibodies in the development of autoimmune thyroid disease.

Anti-TPO antibodies can fix complement and have been shown to bind to and kill thyrocytes in vitro. To present, no link has been shown in human studies between the severity of sickness and the level of anti-TPO antibody concentration in the blood. A high amount of anti-TPO antibodies in the blood, on the other hand, coincides with the active phase of the disease.

Risk factors for Autoimmune thyroiditis

Autoimmune thyroiditis Risks

Investigations on monozygotic twins demonstrate a concordance of 38–55 %, with an even higher concordance of circulating thyroid antibodies unrelated to clinical presentation (up to 80 percent in monozygotic twins). Neither outcome was shown in dizygotic twins to the same extent, demonstrating a significant preference for a high genetic etiology. There are several risk factors for the development of autoimmune thyroiditis, including:

Medications:

Certain treatments or substances have been linked to changes in thyroid function. There are two basic methods of interference that these medications can have:

When a drug alters thyroid hormone serum transfer proteins, one of the interference processes is triggered. Estrogen, tamoxifen, heroin, methadone, and perphenazine all raise thyroid binding globulin (TBG) concentrations. Androgens, anabolic steroids like danazol, glucocorticoids, and delayed release nicotinic acid all lower TBG concentrations. Furosemide, fenoflenac, mefenamic acid, salicylates, phenytoin, diazepam, sulphonylureas, and heparin all impede thyroid hormone binding to TBG and/or transthyretin.
Another way that medications can interfere with thyroid function is through affecting thyroid hormone extra-thryoidal metabolism. T4 and T3 conversion is known to be decreased by propylthiouracil, glucocorticoids, propanolol, iondinated contrast agents, amiodarone, and clomipramine. Phenobarbital, rifampin, phenytoin, and carbamazepine all enhance hepatic metabolism. Finally, cholestryamine, colestipol, aluminum hydroxide, ferrous sulphate, and sucralfate are all medications that either decrease or increase T4 absorption.

HLA genes:

The first gene locus related to autoimmune thyroid disease was the major histocompatibility complex (MHC) region on chromosome 6p21. Specific HLA alleles have a higher affinity for autoantigenic thyroidal peptides, which can lead to the development of autoimmune thyroid disease.

In Hashimoto's disease, aberrant expression of HLA II on thyrocytes has been observed. They are capable of presenting thyroid autoantigens and thereby initiating autoimmune thyroid disease. In Hashimoto's disease, susceptibility alleles are inconsistent. Several alleles have been related to the disease among Caucasians, including DR3, DR5, and DQ7.

CTLA-4 genes:

This gene is the second most significant immune-regulatory gene associated with autoimmune thyroid disease. CTLA-4 gene polymorphisms may contribute to reduced T-cell proliferation inhibition and an increased susceptibility to autoimmune reactions. CTLA-4 is a gene that increases the risk of thyroid autoantibodies. A whole-genome linkage research discovered a correlation between the CTLA-4 region and thyroid autoantibody prevalence. The major locus for thyroid autoantibodies has been identified as CTLA-4.

Iodine:

Excessive iodine consumption is a well-documented environmental risk that can lead to thyroid autoimmunity. Thyroid autoantibodies are more prevalent in areas with a higher iodine supply. Several hypotheses have been advanced to explain how iodine may promote thyroid autoimmunity. Iodine enhances thyroglobulin iodination, which boosts immunogenicity by creating new iodine-containing epitopes or disclosing cryptic epitopes. It has the potential to boost APC presentation, improve T-cell receptor binding affinity, and activate specific T-cells.

Iodine exposure has been shown to increase the quantity of reactive oxygen species. They boost the expression of the intracellular adhesion molecule-1 on thyroid follicular cells, perhaps recruiting immunocompetent cells to the thyroid gland.

Iodine is toxic to thyrocytes because highly reactive oxygen species can adhere to membrane lipids and proteins. It causes thyrocyte destruction and the release of autoantigens. Iodine also affects immunological cells and hastens follicular cell death (augmented maturation of dendritic cells, increased number of T cells, stimulated B-cell immunoglobulin production).

Gender:

A study of healthy Danish twins divided into three groups (monozygotic and dizygotic same sex, and opposite sex twin pairs) estimated that genetic contribution to TPO susceptibility was 61 % in males and 72 % in females, and contribution to thyroglobulin antibodies susceptibility was 39 % in males and 75% in females.

The female predominance of thyroid autoimmunity may be attributed to the X chromosome. It contains sex and immune-related genes, both of which are involved in immunological tolerance. Patients with a higher prevalence of X chromosome monosomy in peripheral white blood cells were more likely to have thyroid autoimmunity.

Another proposed mechanism is skewed X-chromosome inactivation, which results in the escape of X-linked self-antigens from thymus presentation and the loss of T-cell tolerance.

Other autoimmune diseases are a risk factor for getting Hashimoto's thyroiditis, and vice versa. Celiac disease, type 1 diabetes, vitiligo, and alopecia are the most prevalent autoimmune illnesses related with Hashimoto's thyroiditis.

The genes involved varies between ethnic groups, and the frequency is higher in persons with chromosomal diseases such as Turner, Down, and Klinefelter syndromes, which are typically linked with autoantibodies against thyroglobulin and thyroperoxidase. The progressive depletion of these cells as a result of the cytotoxic immune response results in greater degrees of primary hypothyroidism, characterized by low T3/T4 levels and compensatory TSH increases.

Causes of Autoimmune thyroiditis

Causes of Autoimmune thyroiditis

The exact etiology of Hashimoto's disease is uncertain. The vast majority of people develop antibodies against thyroid antigens, the most common of which being anti-thyroid peroxidase (anti-TPO). Many persons produce antithyroglobulin (anti-Tg) antibodies as well as TSH receptor-blocking antibodies.

These antibodies cause thyroid tissue injury, which leads to inadequate thyroid hormone production. Serum antibody-negative people constitute just a small percentage of the population, accounting for no more than 10-15% of individuals with clinically visible illness. TPO antibody positivity indicates the development of clinical disease.

It is linked to type 2 Polyglandular Autoimmune Syndrome, autoimmune adrenal insufficiency, and type 1 diabetes. Hashimoto thyroiditis has been associated to a variety of other autoimmune conditions, such as pernicious anemia, adrenal insufficiency, and celiac disease.

Autoimmune thyroiditis signs and symptoms:

Autoimmune thyroiditis signs

The organ system manifestations of Hashimoto thyroiditis differ due on the nature of the disease. Patients may initially have hyperthyroid symptoms, since the first loss of thyroid cells may result in a higher release of thyroid hormone into the blood. Individuals get hypothyroidism symptoms when the antibody response has caused enough harm. These signs and symptoms are subtle and diverse, affecting nearly every organ system in the body.

The most frequent skin symptom linked with hypothyroidism is myxedema, an edema-like skin disease caused by increased glycosaminoglycan deposition. This, however, is exceptional and occurs only in extreme cases. Extensor surfaces, palms, and soles may have scaly and dry skin. Histologic examination reveals epidermal thinning. Increased cutaneous mucopolysaccharides cause water retention and pale skin.

Hair growth ceases, and hair can become dry, coarse, thin, and fragile. It is not uncommon to suffer from widespread or partial alopecia.

Reduced thyroid function can increase peripheral vascular resistance by up to 50% to 60% and decrease cardiac output by up to 50%. Bradycardia may be produced by a reduction in the chronotropic effect of thyroid hormone on sinoatrial cells. The majority of patients, however, encounter a few symptoms that are directly connected to the cardiovascular system.

Exhaustion, exertional dyspnea, and exercise intolerance are most likely the result of a combination of reduced pulmonary and cardiac reserve, as well as lower muscular strength or increased muscle fatigue. Hypothyroid rats have been shown to have reduced endurance. This group's biochemical changes have showed decreased muscle pyruvate and palmitate oxidation, increased glycogen store consumption, and decreased fatty acid mobilization. Muscle weakness and myopathy are both serious signs.

It is possible that the manifestation is subclinical. Early symptoms include constipation, tiredness, dry skin, and weight gain. Some of the more advanced symptoms include cold intolerance, decreased sweating, nerve deafness, peripheral neuropathy, decreased energy, depression, dementia, memory loss, muscle cramps, joint pain, hair loss, apnea, menorrhagia, and pressure symptoms in the neck from goiter enlargement, such as voice hoarseness.

On rare occasions, individuals may develop an accumulation of fluid in the pleural and pericardial regions. The most severe clinical symptom is myxoedema coma, which must be managed as an endocrine emergency in the context of patient care.

Diagnostic work-up for Autoimmune thyroiditis

Autoimmune thyroiditis Diagnostic

The presence of significant amounts of antithyroid peroxidase antibodies in the serum is often used to make the diagnosis, however seronegative thyroiditis (no circulating autoantibodies) is also conceivable.

Because the symptoms of early hypothyroidism are so vague, Hashimoto's thyroiditis is frequently misdiagnosed as depression, cyclothymia, premenstrual syndrome, chronic fatigue syndrome, fibromyalgia, and, less frequently, erectile dysfunction or an anxiety disorder.

On gross examination, a hard goiter that is not painful to the touch is common; other symptoms seen with hypothyroidism, such as periorbital myxedema, are dependent on the current state of progression of the response, especially given the usually gradual development of clinically relevant hypothyroidism.

TSH, free T3, free T4, and anti-thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO), and anti-microsomal antibodies are all important in the diagnosing procedure.

TSH secretion from the anterior pituitary increases in response to a decrease in negative feedback inhibition secondary to decreased serum thyroid hormones; earlier assessment of affected individuals may present with elevated levels of thyroglobulin attributed to transient thyrotoxicosis, as inflammation within the thyroid causes damage to the integrity of thyroid follicle storage of thyroglobulin; T4 is the most commonly used thyroid hormone test for hypothyroidism.

The body's exposure to high amounts of previously separated thyroid enzymes is likely to aggravate tolerance breakdown, resulting in more severe symptoms later in the illness.

A thyroid ultrasound evaluates thyroid size, echotexture, and the presence of thyroid nodules; nevertheless, it is typically not required for identifying the problem in the majority of cases.

Lymphocytic infiltration of thyrocyte-associated tissues commonly leads to the establishment of histologically significant germinal centers inside the thyroid gland.

Treatment of Autoimmune thyroiditis

Treatment of Autoimmune thyroiditis

The cornerstone of hypothyroidism treatment is thyroid hormone replacement medication. Orally given titrated levothyroxine sodium is the preferred medication. It has a 7-day half-life and can be used on a regular basis. It should not be used with iron or calcium supplements, aluminum hydroxide, or proton pump inhibitors to avoid poor absorption. Take it first thing in the morning on an empty stomach for best absorption.

The normal daily dosage is 1.6 - 1.8 mcg/kg, however this varies from patient to patient. Those under the age of 50 should begin with the full dose; however, patients with cardiovascular problems and the elderly should begin with lower doses. A starting dose of 25 mcg/day is recommended for people over the age of 50, with a re-evaluation after six to eight weeks.

To maintain euthyroid state, the amount of thyroxine must be increased by 30% during pregnancy, and greater doses of levothyroxine are necessary in persons with short-bowel syndrome.

Consequences & prognosis of Autoimmune thyroiditis

prognosis of Autoimmune thyroiditis

The most common complication is overt, symptomatic thyroid dysfunction, with around 5% of individuals suffering from subclinical hypothyroidism and chronic autoimmune thyroiditis progressing to thyroid failure each year.

Transient bouts of thyrotoxicosis (thyroid overactivity) can occur, and the condition can progress to full hyperthyroid Graves' disease with active orbitopathy on rare occasions (bulging, inflamed eyes).

Rare cases of fibrous autoimmune thyroiditis induce significant shortness of breath and swallowing difficulty, comparable to aggressive thyroid malignancies, however such symptoms are invariably resolved with surgery or corticosteroid therapy.

Although primary thyroid B-cell lymphoma affects less than one in 1000 people, it is more likely to strike those who have had autoimmune thyroiditis for a long period, as patients with Hashimoto's thyroiditis have a 67 to 80 times higher risk of acquiring primary thyroid lymphoma.

Conclusion

Autoimmune thyroiditis

Hashimoto thyroiditis is an autoimmune disease characterized by insufficient thyroid hormone production as a result of lymphocyte infiltration and injury to the thyroid gland. It is assumed to be caused by a combination of hereditary and environmental factors. Patients begin asymptomatic or hyperthyroid, then progress to hypothyroidism as the thyroid parenchyma deteriorates.

With appropriate iodine consumption, Hashimoto's thyroiditis is the most prevalent cause of hypothyroidism beyond the age of six in the United States and other parts of the world. The estimated yearly incidence is 0.8 per 1000 men and 3.5 per 1000 females.

The presence of diffuse goitre, anti-thyroid antibodies, sonographic characteristics, and lymphocytic infiltration on cytological examination is used to make the clinical diagnosis of Hashimoto thyroiditis.

The mainstay of treatment is hormone replacement therapy with levothyroxine, and the amount of thyroxine must be increased by 30% during pregnancy, and greater doses of levothyroxine are necessary in patients with short-bowel syndrome to maintain euthyroid state.

Autoimmune thyroiditis can be complicated by unfavorable outcomes such as transient episodes of thyrotoxicosis, and the disease can rarely progress to complete hyperthyroid Graves' disease with active orbitopathy, fibrous autoimmune thyroiditis with severe shortness of breath and swallowing difficulties, similar to aggressive thyroid cancers, and finally the most feared complication, primary thyroid B-cell lymphoma.