Thyroid function Flashcards
Circulating forms of thyroid hormone & thyroid transport proteins (don’t need to know % numbers)
Free form (<1%): fT4 & fT3
TBG (72%): T4 -, T3-thyroid binding globulin
Albumin: T4< T3 (7% < 28%)
T4-TBPA (1-7%): Thyroid binding pre-albumin
Thyroid hormone regulation
S: low fT4, fT3 1. Hypothalamus release TRH 2. Ant. Pit. secrete TSH 3. Thyroid secrete T4, T3 F: inc fT4, fT3 = ve FB
General physiological effects of T3/T4 (7)
- Inc Metabolic rate (inc Na/K/ATPase activity) & thermogenesis
- Inc GIT absorption (Carbohydrates => energy)
- Dec P-Cholesterol = Inc LDL-R expression
- Inc Cardiac output, HR, BP
- Inc responsiveness
- Lipolysis (=> energy)
- Promote Growth & development
6 Clinical features of hyper (and hypothyroidism - opposite effect)
- Tachycardia
- Heat tolerance
- Diahorrhea & weight loss
- Inc appetite
- Anxiety (bc brain stimulated)
- CK lvls slightly raised
BOTH: fertility & menstrual irreg. & muscle weakness
Why is it prudent to measure both TSH and thyroid hormone concentrations?
- difficulties in measuring fT4/fT3 so measure WITH TSH
- fT4 can be misleading
(if having complications w/ fT4 then measure total thyroid)
Thyroid hormone synthesis of T3 & T4
T3: TGL-T1 + TGL-T2 (via coupling enzymes) = TGL-T3 (storage form in follicle) => Thyroglubulin protease replace TGL = T3
T4: TGL-T2 + TGL-T2 (via coupling enzymes)= TGL-T4 (storage form in follicle) => Thyroglubulin protease replace TGL = T4
* Iodine is added to TGL structure via Tyrosine Iodinase
Define: Euthyroid Sick euthyroid Subclinical hyperthyroidism Subclinical hypothyroidism
Euthyroid: Normal thyroid function
Sick euthyroid: Thyroid function is ok but test says bad)
Subclinical hyper: T4, T3 are ok but TSH is low (suppressed)
Subclinical hypo: T4, T3 are ok but TSH is elevated
Causes and types of hypERthyroidism (5)
- Graves disease: autoimmune- TSH receptor Aby => stiumulate receptor = release
- Toxic adenoma & toxic multinodular goiter
- Thyroditis: inflammation => leakage
- T3 toxicosis: Hi T3, Lo T4 from Iodine def. or (first 2 points)
- iatrogenic: Iodine (treat for hypo)
Causes and types of hypOthyroidism (6)
- Hashimoto’s disease: autoimmune thyroiditis => destruction
- Treatment of hypERthyroid: surgery, drugs
- Severe Iodine def.
- hypopituitarism
- Iatrogenic: lithium therapy
- Congenital defects:
a) in synthesising thyroid hormones
b) absence/poorly formed thyroid gland
Tests used to dx Grave’s & Hashimoto
Grave’s: Radioactive iodine uptake, TSH receptor Aby, Thyroperoxidase Aby
Hasimoto: Thyroperoxidase aby
Describe the 4 tests options for Ix of thyroid functiiion
- Total T4 or T3 +TBG
- Radioactive iodine uptake: indicative of inc thyroid hormone synthesis
- TSH receptor Aby:
- Thyroperoxidase Aby: suscept. to AutoImm. Thyroid disease and Establish risk of thyroid disease w/ medication (e.g. Amiadrone, Li)
Influence of these drugs on thyroid
a) Amiadarone (anti-synthetic drug)
b) Lithium
c) Glucocorticoids & dopamine
a) Amiadarone: => Hyper/Hypothyroidism & reduced T4 ->T3 conversion
b) Lithium: inhibits I- uptake & T4, T3 release => Hypothyroidism & thyrotoxicosis
c) Glucocorticoids & dopamine: supress TSH
a) How can heparin treatment (infusion) interfere w/ fT4/fT3 assays?
b) how do you approach this situation
a) Heparin infusion -> Inc release Lipoprotein lipase from BV wall -> breaksdown pTG to FFA + Gly-OH => FFA displaces T4 & T3 from Alb = Inc fTH
b) delay sampling & assay promptly
What’s functional sensitivity?
concentration that results in a CV= 20%. It measures an assays precision on low analyte lvls
Describe the Siemans comp/Titrimetric chemiluminescnet ELISA for measuring fT4
Solid phase: Anti-T4 coated beads 1. Add Pt's sample (fT4 & Prtn-T4) 2. Incubate 3. Add ALP labelled T4 ?4. Add arcidinium labelled T4? 5. Spin out unreacted components (wash) 6. Add ALP substrate (phosphorylated dioxetane complex) => light signal
Describe the Abbott Architect comp/Titrimetric chemiluminescnet immunoassay 2-step for measuring fT4
Solid: Anti-T4 coated magnetic particles
- Add Pt’s sample (fT4 & Prtn-T4)
- Incubate & Wash
- Add arcidinium labelled T4?
- Wash
- Add H2O2 & NaOH => light
Describe the Titrimetric Roche chemiluminescnet fT4 assay
- Add Pt’s sample (fT4 & Prtn-T4) & Ru2+ anti-T4 Aby
- Add T4 biotin conjugate (comp) & Streptavidin (St) coated magnet beads
- Biotin on T4-biotin-Ru complex binds to St beads
- Wash step
- Add TPA & voltage => light signal (for T4-biotin-Ru complex)
How would results be affected with these Roche fT4 assay intereferences
a) Hi dose Biotin
b) Hi Streptividin
c) Hi ruthenium Aby
d) blocking, heterophilic Aby
a) Hi dose Biotin= Think fT4 is low
b) Hi Streptividin= Think fT4 is low
c) Hi ruthenium Aby= Think fT4 is low
d) blocking, heterophilic Aby = Think fT4 is Hi bc Aby R biotin binding to St = dec signal = think Hi fT4
a) Briefly discuss the challenge that would be faced in interpreting thyroid function tests on a patient in intensive care.
b) In such circumstances, what would be the most reliable test for thyroid function?
a) effect of non-thyroidal illness or sick euthyroid syndrome on thyroid hormones bc stress, medications, glucocorticoid therapy
b) Test: measure TSH
How can you tell a TSH assay is sensitive for dx
- Functional sensitivity of assay
- precision profile of assay
- plot of CV (y axis) against measured concentration (x-axis)
How can drugs interfere with fT4 &fT3 assays
drugs displace fT4/fT3 from binding proteins => underestimate fT4/fT3
effects of drugs, stress & illness on T4 & T3
- influences deiodinases activity (remove I-) => interpretive difficulties
- decrease TBG
why is Thyroid function testing avoided in the acutely ill?
illness influence fT3/fT4 (deiodinase activated). relationship to TSH, T4 -> T3/rT3 conversion
