Organ - Specific Autoimmune Diseases Flashcards
Normal Thyroid Function
thyrotropin-releasing hormone (TRH) is secreted from hypothalamus & acts on pituitary -> releases thyroid stimulating hormone (TSH) –> acts on thyroid to release thyroid hormones T3 & T4
Thyroid Hormone Function
metabolism, growth & maturation
Biosynthesis of Thyroid Hormones
- TSH binds to TSH receptor
- TSH causes iodine to be taken up into the thyroid
- iodine is oxidized to iodide by thyroid peroxidase (TPO)
- iodide is coupled to thyrooglobulin (TG)
- TG is converted to T3 or T4
- T4 is metabolized to T3
Throxine binding globulin (TBG)
serum protein that binds most circulating T3/T4
bound T3/T4 is inactive
Thyroid Feedback Mechanisms
low T3/T4 - piuitary gland produces TSH to stimulate more hormons
high T3/T4 - pituitary gland stops producing TSH
Thyroid autoantibodies
thyroid peroxidase antibody (TPOAb)
thyroglobulin antibody (TgAb)
thyroid stimulating hormone receptor antibody (TRAb)
Thyroglobulin (Tg)
protein produced exclusively by the thyroid gland
precursor to T3/T4
Anti-Tg antibodies
10-20% of ‘normal’ people have it
50-60% of patients w/ Hashimoto’s thyroiditis are +
>116 IU/ml is clinically relevant
Anti-TPO antibodies
50% + in thyroid inflammation
90% + in Hashimoto’s thyroiditis
75% + in Grave’s Disease
>75 IU/ml is clinically relevant
Anti TSH receptor antibodies
essentially all Grave’s patients are +
very difficult to test for so anti- TPO is normally ordered instead
Hashimoto’s thyroiditis
autoimmune process in which development of circulated cytotoxic Ab targets thyroid antigens
cellular damage & decreased production of thyroid hormones occur - hypothyroidism
Clinical Features of Hashimoto’s
30-60 yrs
5x more common in females
decreased T4 & increased TSH
Symptoms of Hashimoto’s
enlarged/lumpy thyroid
loss of energy, slowed metabolism, overweight, tiredness, constipation, cold sensitivity, slow pulse, dry skin, deep voice, dry hair, depression
Treatment for Hashimoto’s
synthetic T4 replacement (Synthroid)
Grave’s Disease
hyperthyroidism
mimics normal action of TSH by binding to & activating TSH receptors
increase T3/T4 & decrease in TSH
Clinical Features of Graves’
20-50 yrs 10x more common in females enlarged thyroid nervousness fatigue weightloss bulging eyeballs (!)
Lab testing for Graves’
increased T3/T4
low TSH
>75% have anti-TPO abs
Treatment for Graves’
anti-thyroid drugs, surgery, radioactive iodine ablation
Type 1 diabetes mellitus
hyperglycemia due to deficiency of insulin secretion -due to autoimmune pancreatic islet beta cell destruction
Lab diagnosis for Diabetes type 1
increase in serum glucose
glucose present in urine
HbA1C >6%
elevated serum ketones
Celiac Disease
inflamed small intestine -> malabsorption of food
chronic diarrhea
small stature / growth
genetic inappropriate immune response to gluten/gliadin
Celiac Disease testing
perform an ELISA for the IgA-TTG
‘confirmatory’- colon biopsy; wide short villi & infiltration of lymphs are diagnostic
Inflammatory Bowel Disease
marked chronic inflammation in the gut
abdominal pain, weight loss
Ulcerative colitis
affects the colon, inflammation in mucosal area
positive p-ANCA seriology
Crohn’s Disease
affects whole intestine
all layers inflammed w/ monocytes/macrophages
produce antibodies that react w/ baker’s yeast C. cerevisiae
Anti-Neutrophil Cytoplasmic Antibody Testing (ANCA)
indirect IFA just like for ANAs but uses neutrophils instead of Hep-2 cells
c-ANCA - cytoplasmic; antibodies against proteinase -3
p- ANCA- peripheral; antibodies against myeloperoxidase
Multiple Sclerosis
involves the CNS
autoantibodies against myelin basic protein
Myasthenia Gravis
involves nerve cells in skeletal muscles
autoantibodies against acetylecholine receptors
Goodpasture’s Syndrome
involves kidney glomeruli
autoantibodies against glomerular basement membrane
