endocrine - thyroid Flashcards
DIT plus DIT
Tetraiodithyronine or T4
Biosynthesis of T3 and T4
- Dietary iodide ingestion by follicular cells
- Active transport and uptake of iodide into colloid by thyroid gland
- Oxidation of I and iodination of Tg tyrosine residues
- Coupling of Iodotyrosine residues (MIT & DIT) to form T3 and T4
- Proteolytic of Tg with release of T3 and t4 into circulation
DIT plus MIT
Triiodothyronine T3
Indispensable component of thyroid hormone comprising 65% of T4 and 58% of T3’s weight.
Iodine
Required daily intake of iodine in 0-7y/o.
90 ug/d
Required daily intake of iodine in 7-12y/o.
120 ug/d
Required daily intake of iodine in teenager and adults
150 ug/d
Required daily intake of iodine in pregnant and lactating women
25o ug/d
Iodine intake not more than
1100 ug/d
Excess iodine
Wolff chaikoff effect
Jodbasedow phenomenon
Excess iodine with transient shut down of thyroid hormone production (normally).
When increasing doses of iodide inhibit organification and hormonogenesis of thyroid hormone.
Wolff chaikoff effect
In some pts with HAshimoto’s thyroiditis, they may stay hypothyroid because of inability to escape this effect
Wolff-chaikoff effect
Thyroid hyperfunction induced by excess iodine ingestion in pts with various thyroid disorder (grave’s disease)
Jod-basedow phenomenon
Dietary iodine reaches the circulation as
Iodide anion
Iodide active transport by thyroid Is mediated by this membrane protein
Sodium-iodide symporter or NIS
It functions as iodide concentrating mechanism that enables iodide to enter the thyroid for hormone biosynthesis
NIS
Iodide trapping by the aid of
NIS
Iodide must be first ___ to be able to iodinate tyro sly residues of Tg
Oxidized
Iodination of tyrosyl residues then forms monoiodotyrosine and diiodotyrosine which are then coupled to form either T3 or T4. Both reactions are catalyzed by
Thyroperoxidase
Thyroperoxidase Catalyzes oxidation steps involved in:
I- activation
Iodination of Tg tyrosyl residues
Coupling of iodotyrosyl residues
TPO uses ___ as the oxidant to activate I- to hypoiodate the iodination species
H2O2
To liberate t3 and t4, Tg is resorted into follicular cells in the form of ___ which fuse with lysosomes to form phagolysosome
colloid droplets
Primary secretory product of thyroid gland
T4
Thyroid secretes approximately how many grams of thyroxine daily
70-90 ug/d
Total daily production rate of t3
15-30 ug/d
T3 is derived from 2 processes
- 80% of circulating T3 comes from deiodination of T4 on peripheral cells
- 20% comes directly from thyroid secretion.
Pro hormone for T3
T4
T4 is biologically inactive in target tissues
True. Until converted to T3
T4 is converted to T3 by
5-deiodination of outer ring of T4
T3/T4 which is biologically active responsible for the majority of thyroid hormone effects
T3
Major extrathyroidal T4 conversion site for production of T3
Liver
Some occurs in kidney and other tissue
Normal disposition of T4
41% is converter to T3
38% is converter to rT3
21% is metabolized via other pathways (conjugation on liver and excretion in bile)
Normal circulating concentration of t4
4.5-11 ug/dl
Normal circulating concentration of t3
60-180 ng/dl
T3/4: Produced only in thyroid gland
T4
T3/4: 80% are from peripheral conversion
T3
Half life of t4
7 days
Half life of t3
One day
T3/4: only free hormones are active
T4
3-8x more potent
T3
More than 99% of circulating T3 and t4 is bound to plasma protein Carrier proteins which are
TBG 75%
Transthyretin TTR / thyroxine-binding prealbumin TBPA 10-15%
Albumin 7%
HDL 3%
Decrease or increase TBG effects on total serum T3 and T4 level and free T3 and T4.
Decrease or increase TBG will decrease/increase total serum T3 and T4 level.
While free T3 and T4 remain unchanged
Drugs that increase TBG
Oral contraceptives Methadone Clofibrate 5-fluorouracil Heroin Tamoxifen
Conditions that increase TBG
Pregnancy Infectious/chronic active hepatitis HIV infection Biliary cirrhosis Acute intermittent porphyria Genetic factors
Drugs that decrease serum t3 and t4 by decreasing TBG conc
Glucocorticoids Androgens L-asparaginase Mefenamic acid Furosemide
Drugs that decrease serum t3 and t4 by decreasing binding
Antiseizure medications
Salicylates
Decreased thyroid hormone concentration may lead to alteration of ___. May develop impairment of attention, slowed motor function, and poor memory
cognitive function.
Thyroid hormone influences cv hemodynamics by
Increase HR and decrease systemic vascular resistance thus increase CO = improve cardiac performance Elevate blood volume Local vasodilators Decrease diastolic blood pressure Cardiac chronotropy and inotropy
Thyroid hormone is critical for normal bone Growth and development
T3 regulates sk maturation at growth plate.
T3 participates in osteoblasts differentiation and proliferation and chondrocytes maturation loading to bone ossification.
Major regulator of mitochondrial activity
T3
Thyroid hormone is a major regulator of mitochondria activity
T3 induces early transcription and increases TFA expression.
T3 stimulates O2 consumption.
Thyroid hormone stimulates mitochondrial activity in most tissue
T3 increases basal metabolic rate, body heat production and O2 consumption.
Metabolic effects of T3
- Lipolysis- FA + glycerol
- expression of lipogenic enzymes
- cholesterol catabolism into BA
- Rapid removal of LDL from plasma
- Carbohydrate and protein catabolism