Chronic Autoimmune Thyroiditis or Hashimoto’s Thyroiditis(HT) is an inflammatory disease characterized by diffuse lymphocytic infiltration, fibrosis, and parenchymal atrophy. Hashimoto’s Thyroiditis is the most common cause of primary - Functional Medicine Houston

hypothyroidism which continues to be a common problem, especially in women.

Circulating autoantibodies against thyroglobulin and thyroid peroxidase (TPO) were present in almost all patients with autoimmune hypothyroidism. Thyroid Stimulating Hormone Receptor Antibody (TSH-R Ab) blocks the receptor instead of stimulating it as in graves’ diseases. In some cases of Hashimoto’s Thyroiditis, the exact mechanisms underlying autoimmune thyroiditis are not fully understood. The hypothesis relies on both genetic and environmental involvement.

Clinically, the disease can present as gradual thyroid failure, with or without goitre formation due to autoimmune-mediated apoptosis of the thyroid epithelial cells. 

The typical markers of the disease, found in almost all cases are the antibodies against one or more thyroid antigens, diffuse lymphocytic infiltration of the thyroid (predominantly thyroid-specific Band T cells), and follicular destruction, which is the characteristic sign of thyroiditis.

The epidemiology of Hashimoto’s Thyroiditis is related to other autoimmune diseases affecting other endocrine organs. However, Hashimoto’s Thyroiditis is by far the most common endocrine autoimmune disease. 

Hashimoto’s Thyroiditis also primarily affects middle-aged women, can occur in men and women of all ages as well as children, and has recently been recognized as the most common cause of pediatric thyroid disease. Autoimmunity review by Cooper et al. in 2003 83% of cases were estimated to be female.

Autoimmune thyroid diseases (AITD) result from the complex interplay of exogenous and endogenous factors. The cause of Hashimoto’s thyroiditis is thought to be a mix between genetic susceptibility and environmental factors. 

The familial association with Graves’ disease (GD) and the undeniable fact that Graves’ Disease and Hashimoto’s Thyroiditis may sometimes evolve into one another proves that the two disorders are closely related. It is observed that many patients are prone to familial aggregation of Hashimoto’s thyroiditis. 

Genetic factors have been related to susceptibility in 70% to 80% while environmental factors have been demonstrated only in 20% to 30% of cases of Autoimmune Thyroid Disease. Relatives of Autoimmune Thyroid Disease patients carry a high risk of contracting the disease themselves.

Genetic Factors

Advances in genetic techniques have led to significant advances in the diagnosis of complex diseases using new genetic techniques.  In the diagnosis of complex autoimmune diseases, such as Autoimmune Thyroid Disease, four phases are described: Phase 1- candidate gene analyses; Phase 2  is a genome-wide linkage study; Phase 3- genome-wide association studies (GWAS); Phase 4  is whole genome sequencing. In Autoimmune Thyroid Disease, major thyroid antigens are implicated in thyroid autoimmunity. 

TSH-R mRNA has also been detected in other tissues, and although the role of TSH in most tissues is unclear, data suggest that TSH  may regulate bone cell and adipocyte function. Post-ocular expression of TSH-R is associated with thyroid eye disease (graves orbitopathy) and anterior tibialmyxoma  (thyroid dermatopathy).

Other genes such as HLA-DR3 and, in some cases, HLA-DR4 are susceptible to Graves’ Disease and Hashimoto’s Thyroiditis.  The cytotoxic T lymphocyte-associated protein 4 (CTLA-4) genes, a member of the immunoglobulin family, are also associated with Hashimoto’s Thyroiditis.  The mechanism is to encode a protein that sends an inhibitory signal to the T cell. Mutations in this gene have been associated with T1D, Graves’ Disease, Hashimoto’s Thyroiditis, celiac disease, systemic lupus erythematosus(SLE), and other autoimmune diseases. It is reported that high production of IFN-gamma and low production of IL-4  are more common in patients with severe Hashimoto’s Thyroiditis than in patients with mild H.

New analytical approaches will reveal many other genes that may represent small etiological contributions to clinical symptom variability. For example, combinations of novel genetic markers have been investigated, and the results show an association of TPO-Ab positivity with an increased risk of hypothyroidism. The MAGI3 gene has been studied as a marker that can predict whether TPO-Ab- positive patients are particularly at risk of developing clinical thyroid dysfunction. The importance of genetic factors causing autoimmune hypothyroidism is indicated by the frequent presence of thyroid antibodies and other autoimmune diseases in relatives. Scientific data has been demonstrated in twin studies showing a high concordance rate (0.55) in identical twins.

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