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Hashimotos

Disease

Hashimotos Disease
Aka Chronic Lymphocytic Thyroiditis
Autoimmune disease causing primary
hypothyroidism
Primary cause of hypothyroidism in US
1 in 1000

Third most prevalent autoimmune disease


in the US
Atleast 7 times more common in women
than men

Hakaru Hashimoto - 1912


First recognized autoimmune
disease
Discovered by Japanese specialist
Hakaru Hashimoto
Published in 1912

Symptoms

Fatigue
Weight gain
Pale/puffy face
Feeling cold
Joint/muscle pain
Constipation
Dry/thinning hair
Memory problems

Pathophysiology
Immune system attacks the thyroid gland, causing inflammation and preventing it from
producing thyroid hormones
T3 = triiodothyronine
T4 = thyroxine

Autoantibodies against thyroid peroxidase (TPO), thyroglobulin, TSH receptors attack


follicles of thyroid gland
Invasion of thyroid tissue by T-lymphocytes
Thyroid Stimulating Hormone (TSH) increases by pituitary as T4 decreases (no negative
feedback)
Enlargement of the thyroid is due to lymphocytic infiltration and fibrosis rather than
tissue hypertrophy.

Hashimotos Histology

Massive infiltration of lymphocytes + plasma cells into thyroid gland


Germinal centers form (not present in normal thyroid gland)
Thyroid follicles disappear (present in normal thyroid to produce T3/T4)

Contrast with Graves Disease (Hyperthyroid)


Both diseases result in antibodies attacking
thyroid gland, preventing negative feedback
Both cause goiter
Hashimotos is due to infiltration by lymphocytes
Graves is due to excessive T3/T4 production

One can progress to the other (often Graves ->


Hashimotos)

Risk Factors
Family history

HLA-DR5 gene
CTLA-4 gene (Cytotoxic T-lymphocyte Antigen-4) = negative regulation of T Cells
Also associated with Type 1 DM

Environmental Factors
High iodine intake?
Selenium deficiency

Chromosomal Disorders

Turners Syndrome, Down Syndrome, Klinefelter Syndrome

Other Autoimmune Diseases

Diagnosis
History + Physical exam + Presence of a goitre
Blood testing for Thyroid-Stimulating hormone (TSH), free T3/T4
High TSH and low T3/T4

Presence of antibodies (anti-Tg, anti-TPO, TPOab)


Fine Needle Aspiration to exclude malignancy
Often misdiagnosed as depression, chronic fatigue syndrome, anxiety
disorder, PMS,

Treatment
Thyroid Hormone Replacements (synthetic T4)
Levothyroxine, triiodothyronine, desiccated thyroid extract
Oral, once per day to keep TSH under 3.0
Must be checked ~every 6 months (too much can cause osteoporosis and
arrhythmias)

Other:
Selenium
Low-level laser therapy
Gluten free diet

Prognosis

Excellent with medication


5% progress to thyroid failure every year
Rarely progresses to hyperthyroid Basedow-Graves Disease
Higher risk of B cell lymphoma
Susceptible to other autoimmune diseases
Vitiligo, Rheumatoid arthritis, Addisons disease, DM Type 1,
Pernicious Anemia, Celiac Disease, Autoimmune Hepatitis

Sources
https://en.wikipedia.org/wiki/Hashimoto's_thyroiditis#Pathophysiology
http://www.niddk.nih.gov/health-information/health-topics/endocrine/hashimotosdisease/Pages/fact-sheet.aspx
http://www.omim.org/entry/140300
http://www.omim.org/geneMap/8/401?start=-3&limit=10&highlight=401
http://ghr.nlm.nih.gov/gene/HLA-DRB1
http://emedicine.medscape.com/article/120937-overview