Autoimmune Thyroid Disease Flashcards
Functions of the thyroid gland
Produces thyroid hormones (T3 & T4)
Regulate vital body functions: breathing, HR, CNS/PNS, body WT, muscle strength, menstrual cycle, body temp, cholesterol levels
Hypothyroidism
Cannot produce enough thyroid hormone –> slows processes down
Hashimoto thyroiditis, trx of hyperthyroidism, thyroid surgery, radiation therapy, medications
Hyperthyroidism
Overproduction of thyroid hormone –> speeds process up
Graves disease
Thyroiditis
Thyroid adenomas
Autoimmune diseases of thyroid
Graves Disease
Hashimoto Thyroiditis
Autoimmunity susceptible genes: Hashimoto thyroiditis
HLA-DR3 & DR5
Autoimmunity susceptible genes: Graves Disease
HLA-B8 & DR3
Mechanisms → thyroid autoimmunity (1/2)
Tissue destruction:
Antibody-mediated
® Cytotoxic: antibody-dependent cellular cytotoxicity (ADCC)
® Non-cytotoxic: phagocytosis of microbes opsonized w/ complement fragments (C3b)
T-cell mediated (CD4 & CD8)
® Perforin/granzyme-mediated cell killing
® Fas/FasL-mediated killing
Mechanisms → thyroid autoimmunity (2/2)
Endocrine function alteration
Antibody-mediated: blocking or stimulating the ligand receptor
Hashimoto thyroiditis
Genetics
HLA-DR3 & DR5
Hashimoto thyroiditis
Environmental Triggers
Iodine intake
Infection, pregnancy
Cytokine therapy
Stress
Hashimoto thyroiditis
Pathogenesis
*CD8 T-cells attack thyroid → tissue destruction → release of thyroglobulin & thyroid proteins into blood → recognized as foreign
■ hyroglobulin: precursor for T3 & T4
■ TPO: enzyme that catalyzes binding of iodine to tyrosine residues in the thyroglobulin molecules to eventually form T3 & T4
*B-cells make antithyroglobulin & antithyroid peroxidase (TPO) antibodies → destruction of gland
Hashimoto thyroiditis
Hypersensitivity rxn
Type IV –> T-cell mediated
Hashimoto thyroiditis
Symptoms
Fatigue
WT gain
Constipation
Increased sensitivity to cold
Dry skin
Depression
Muscle aches
Reduced exercise tolerance
Irregular/heavy menses
May not have sx
Usually progress slowly
Levothyroxine (T4): MOA
Hormone replacement for T4
Most of T4 synthesized in thyroid (80%)
T4->T3 via deiodinases
Levothyroxine (T4): Indications
FIRST LINE: hypothyroidism
Less expensive
Longer t1/2
Levothyroxine (T4): SE
Related to excess hormone or insufficient replacement
Levothyroxine (T4): Contraindications
Lower dose in elderly & CVD pts
Take on an empty stomach
Variable absorption w/ other meds
Liothyronine (T3) MOA
Hormone replacement for T3
20% T3 synthesized in thyroid; 80% synthesized in target tissues
Liotrix: MOA
4:1 ratio of T4:T3 (mimics ratio seen in plasma)
Thionamides
Methimazole (MMI)
Propylthiouracil (PTU)
Thionamides: Methimazole (MMI) – MOA
Block incorporation of iodine ions by inhibiting peroxidases in thyroid gland
Slow onset of activity; 3-4 wks for effect
