Page 263 - TNFlipTest

Toronto Notes 2019 Thyroid
Investigations
• triplebolustest
■ stimulates release of all anterior pituitary hormones in normal individuals
■ rapid sequence of IV infusion of insulin, GnRH, and TRH
■ insulin (usual dose 0.1 unit/kg of human regular insulin) → hypoglycemia → increased GH and
ACTH/cortisol
■ GnRH(100μgIVpush)→increasedLHandFSH
■ TRH(200μgIVpushover120s)→increasedTSHandPRL(nolongeravailableinCanada)
■ GnRH and TRH stimulation tests are very limited in their utility; the insulin tolerance test is the
Endocrinology E21
only truly useful test in the triple bolus assessment
Thyroid
Thyroid Hormones
Section of the Thyroid Gland
Follicular cell
C-cell Capillary
Thyroid follicle
Follicular cell Capsule
Colloid
Extra-Thyroidal Factors Impacting Thyroid Hormone Homeostasis: A Review
JRM 2015;4(1):40-49
• Mostperipheralthyroidmetabolismoccursinthe
liver and the kidneys, thus severe liver disease
and CKD can significantly alter T3:T4 ratio.
• Alcoholdependenceresultsinhypothalamic-
pituitary-thyroid axis dysfunction demonstrated
by decreased TSH, T4, and T3 levels.
• Smoking is associated with lower TSH levels in a
dose-dependent manner: with heavy smoking (8- 12 cigarettes/day) having more TSH suppression than light smokers (<4 cigarettes/day).
• Heavymetalexposureincludinglead,mercury, andcadamiumhasbeenshowntoalterthyroid hormone function and peripheral metabolism.
I–
TP
–
Tg+I +H2O2
DIT
DIT
Na+
NIC
T4
T3
DIT
MIT
T3
I–
Blood vessel
T4
Coupling enzymes
Tg
L
T4 T3
L
DIT = diiodotyrosine; L = lysosome; MIT = monoiodotyrosine; Tg = thyroglobulin; NIC = sodium iodide cotransporter T3 = triiodothyronine; T4 = thyroxine (tetraiodothyronine); TP = thyroid peroxidase enzyme
Figure 9. Thyroid hormone synthesis
Synthetic Function of Thyroid Gland
© Stefania Spano 2012
• thesynthesisofthyroidhormonesT4(thyroxine)andT3(triiodothyronine)bythethyroidgland involves trapping and oxidation of iodide, iodination of thyroglobulin, digestion of thyroglobulin, and release of T3 and T4
• freeT4(0.03%)andfreeT3(0.3%)representthehormonallyactivefractionofthyroidhormones ■ the remaining fraction is bound to thyroxine binding globulin (TBG) and albumin, and is
biologically inactive
• T3 is more biologically active (3-8x more potent), but T4 has a longer half-life
• 85% of T4 is converted to T3 or reverse T3 (RT3) in the periphery by deiodinase enzymes
• RT3ismetabolicallyinactivebutproducedintimesofstresstodecreasemetabolicactivity
• most of the plasma T3 pool is derived from the peripheral conversion of T4
• calcitonin,apeptidehormone,isalsoproducedinthethyroid,bytheparafollicularcellsorCcells
■ calcitonin functions by inhibiting osteoclast activity and increasing renal calcium excretion
Role of Thyroid Hormones
• thyroidhormonesactprimarilythroughmodifyinggenetranscriptionbybindingtonuclearreceptors • actionofthesehormonesisdiffuse,affectingnearlyeveryorgansystem
• thyroidhormoneshavedifferenttissue-specificeffectsdeterminedbytheexpressionofthetypesof
thyroid receptor isoform and the local production of T3
• theyincreasethebasalmetabolicrateincluding:increasedNa+/K+ATPaseactivity,increasedO2
consumption, increased respiration, heat generation, and increased cardiovascular activity • whenpresentathigherthannormallevelsitpotentiatestheactionsofGH,catecholamines
(epinephrine, norepinephrine), glucagon and cortisol, resulting in increased gluconeogenesis, ketogenesis and proteolysis. These actions mimic what happens in starvation
Patterns of Hormone Levels
TSH T3, T4
1°Hyper   2°Hyper   1°Hypo  
Colloid
2°Hypo
 
T T3 4
T T3 4