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Endocrine System

Hashimoto’s thyroiditis

Typical, organ-specific, autoimmune disease, characterized by autoimmune-mediated destruction of the thyroid gland.

Typical, organ-specific, autoimmune disease, characterized by autoimmune-mediated destruction of the thyroid gland.

  • Also known as chronic lymphocytic/autoimmune thyroiditis
  • M/C cause of hypothyroidism in developed countries (inadequate dietary intake of iodine M/C cause worldwide)
  • ♀:♂::10:1
  • Associated with gastric disorders (10-40% cases): Thyrogastric syndrome: Polyglandular autoimmune syndrome (PAS)
    • Thyroid gland develops from the primitive gut, and therefore the thyroid follicular cells share similar characteristics with parietal cells of the same endodermal origin.

Autoimmune thyroid disease (AITD):

Prototypical organ-specific autoimmune disease
  • Hyperthyroid Graves disease
  • Hypothyroid autoimmune thyroiditis
  • Subtle subclinical thyroid dysfunctions

History

It was first described by the Japanese physician Hakaru Hashimoto in 1912. In 1957 it was recognised as an autoimmune disorder.

In 1912, Dr Hakaru Hashimoto described 4 patients with a chronic disorder of the thyroid, which he termed struma lymphomatosa. The thyroid glands of these patients were characterized by diffuse lymphocytic infiltration, fibrosis, parenchymal atrophy, and an eosinophilic change in some of the acinar cells. Clinical and pathologic studies of this disease have appeared frequently since Hashimoto’s original description. The disease has been called Hashimoto’s thyroiditis, chronic thyroiditis, lymphocytic thyroiditis, lymphadenoid goiter, and recently autoimmune thyroiditis.

Etiology

Genetic susceptibility:

  • Human Leukocyte Antigen (HLA) Genes
  • Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) Gene
  • Protein Tyrosine Phosphatase Nonreceptor-Type 22 (PTPN22) Gene
  • Thyroglobulin Gene
  • Vitamin D Receptor (VDR) Gene
  • Cytokine Genes and other Immune-Related Genes

Endogenous triggers:

  • Female sex: ♀:♂::10:1
  • Pregnancy and Postpartum period: Tolerance of the fetal semi-allograft during pregnancy is enabled by the state of immunosuppression which is a result of hormonal changes and trophoblast expression of key immunomodulatory molecules. The pivotal players in regulation of the immune response are Tregs, which rapidly increase during pregnancy. Postpartum rapid decrease of Tregs and re-establishment of the immune response to the pre-pregnancy state may lead to the occurrence or aggravation of the autoimmune thyroid disease.
  • Fetal Microchimerism (28-83% cases): Presence of fetal cells in maternal tissues which are transferred in the maternal circulation during pregnancy. The fetal immune cells, settled in the maternal thyroid gland, may become activated in the postpartum period when the immunotolerance ceases, representing a possible trigger that may initiate or exaggerate the autoimmune thyroid disease. 

Environmental triggers:

  • Excessive iodine intake
  • Drugs: Interferon α (IFN-α), lithium, amiodarone
  • Infection: Hepatitis C, parvovirus, rubella, herpes simplex virus, Epstein Barr virus, and HTLV type 1
  • Chemicals: Polyaromatic hydrocarbons or polyhalogenated biphenyls
Mechanisms of thyroid autoimmunity in HT. In individuals with certain genetic background, several endogenous and environmental factors may trigger thyroid autoimmunity, causing increased antigen presentation in the thyroid and consequently leading to reduced immune tolerance. As a result, different cytokines are produced by immune and thyroid cells leading to predominantly Th1 response with increased Th1/Th2 ratio. Lately, also Th17 effector T cells have been implicated in thyroid autoimmunity. Increased production of cytokines, such as interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), and interleukin 1 (IL-1), may lead to apoptotic processes which combined with CD8+ mediated cytotoxicity, impairment of cell junctions, and complement activation slowly induce thyroid destruction. | Zaletel, K., & Gaberšček, S. (2011). Hashimoto’s Thyroiditis: From Genes to the Disease. Current Genomics, 12(8), 576–588. https://doi.org/10.2174/138920211798120763

Pathophysiology

Intrathyroidal lymphocytic (T-cell) infiltration followed by a gradual destruction and fibrous replacement of the thyroid parenchymal tissue which may lead to subclinical or overt hypothyroidism.
  • Thyroid peroxidase (TPO): TPO antigen, located at the apical membrane of the thyrocyte, is essential for thyroid hormone synthesis, catalysis of iodine oxidation, iodination of tyrosine residues in Tg, and coupling of the iodothyronine into thyroxine (T4) and triiodothyronine (T3).
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Presentation

Classically, the disease occurs as painless, diffuse enlargement of the thyroid gland in a young or middle-aged woman. It is often associated with hypothyroidism.

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Complications:

  • Thyroid MALToma
  • Diffuse large B-cell lymphoma (DLBCL)

Diagnosis

Diagnosis is made by the finding of a diffuse, smooth, firm goiter in a young woman, with strongly positive titers of TG Ab and/or TPO Ab and a euthyroid or hypothyroid metabolic status.

Diagnostic algorithm:

Diagnosis of Hashimoto’s thyroiditis (chronic thyroiditis) | Akamizu T, Amino N. Hashimoto’s Thyroiditis. [Updated 2017 Jul 17]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK285557/

Serology:

Low total T4 or free T4 level in the presence of an elevated TSH level confirms the diagnosis of primary hypothyroidism.
  • ↑ Thyroid-stimulating hormone (TSH) (best initial test)
  • ↓ Thyroxine (T4) levels (T3 levels have no place in the diagnosis of hypothyroidism)
  • ↑ Anti-thyroid peroxidase (anti-TPO) antibodies (90%)
  • ↑ Antithyroglobulin (anti-Tg) (80%) and TSH receptor-blocking antibodies (TBII)

Needle biopsy (M/accurate test) & ultrasound (USG):

A) Ultrasound image of euthyroid Hashimoto thyroiditis. A representative ultrasound is shown of an asymptomatic, euthyroid patient’s thyroid nodule cytologically diagnosed Hashimoto thyroiditis. Note the minimal color flow Doppler identified within the nodule. B) Cytopathology. Cytological characteristics of a thyroid nodule with typical diagnostic features of Hashimoto’s thyroiditis (i.e. lymphocytic infiltrate, Hurthle cells, lymphoglandular bodies and crushed lymphocytes). | Staii, A., Mirocha, S., Todorova-Koteva, K., Glinberg, S., & Jaume, J. C. (2010). Hashimoto thyroiditis is more frequent than expected when diagnosed by cytology which uncovers a pre-clinical state. Thyroid Research, 3(1), 11. https://doi.org/10.1186/1756-6614-3-11

Fluorescent thyroid scan:

Fluorescent thyroid scan in thyroiditis. The normal thyroid scan (left) allows identification of a thyroid with normal stable (127I) stores throughout both lobes. A marked reduction in 127I content is apparent throughout the entire gland involved with Hashimoto’s thyroiditis (right). | Akamizu T, Amino N. Hashimoto’s Thyroiditis. [Updated 2017 Jul 17]. In: Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK285557/

Differential diagnosis:

  • Graves’ disease
  • Nontoxic nodular goiter

Management

Life-long disorder with no cure.

Thyroid hormone replacement agents:

  • Levothyroxine (DOC)
  • Triiodothyronine
  • Desiccated thyroid extract
Whole Family Wellness Center. (2017). Hashimoto’s Specialist Portland Oregon. [online] Available at: http://wfwcenter.com/thyroid-and-autoimmune-disease/hashimotos-treatment/ [Accessed 2 Jul. 2017].

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