Lecture 37: Thyroid Hormones Flashcards
Thyoid gland
-in the neck
Thyroid hormones
-Thyroxine (T4) x10
-Triiodothyronine (T3) mor potent
Effect of thyroid hormones on growth and development
-essential for brain development
-promote protein synthesis (skeletal/muscle)
-anabolic at normal levels but catabolic at high levels
Cretinism caused by
-absent T3
Effects of thyroid hormones on metabolism
-increase BMR
-inc oxygen consumption
-starvation lowers T3 and thyroid receptor
Starvation lowers levels of
-T3 hormone
-thyroid receptors
-to dec BMR to save energy
Effect of thyroid hormones on Thermogenesis
-inc resting heat production
-inability to adjust to environmental temp is characteristic symptom of hyper/hypo thyroidism
Effect of thyroid hormones on cardiovascular system
-inc catcholamine sensitivity
- makes heart beat more
Biosynthesis of Thyroid hormones
- Dietary Iodine
- NIS transport
- Pendrin transport and oxidation by thyroid peroxidase
- thyroglobulin transport
- Iodide Organification
- Coupling
- Retrievement
- Cleavage
- Dietary Iodine (I2)
-turned to iodide (I-) in tummy
- Na+-I- symporter (NIS)
-transports iodide into follicular cell
- Pendrin transport and Oxidation
-iodide passes down electrochemical gradient into follicular COLLOID w help from PENDRIN transporter
-oxidized to I0 at apical membrane by throid peroxidase
Pendrin
-apical transport protein
-helps iodide into follicular colloid for oxidation
- iodide-free throglobulin transported to
apical membrane
- Iodide organification
-thyroglobulin iodinated at 1 or 2 positions by thyroid peroxidase
-Monoiodotyrosine and di-iodotyrosine (MIT and DIT)
- Coupling
-MIT + DIT = T3
-DIT + DIT = T4
-dependent on thyroid peroxidase
- Thyroglobulin Retrieval
-thyroid hormone-containing thyroglobulin is retrieved back into cytosol of follicular cell as colloid droplets by pinocytosis
- Cleavage
-Lysosomal exopeptidases cleave T4 or T3 from thyroglobulin
=release hormone into circulation where T4 can be converted to more potent T3 by 5’deiodinase
thyroid peroxidase
-oxidizes iodide
-iodinates thyroglobulin to MIT or DIT
-couples MIT and DIT
5’ deiodinase
-converts T4 to T3
-happens in circulation
Hypothalamus-pituitary-thyroid axis
-hypothalamus releases TRH
-stimulates anterior pituitary to relase TSH
-stimulates thyroid to release T3 and T4
negative feedback loop
-T3 and T4 inhibit hypothalamus and anterior pituitary directly
-which indirectly inhibits thyroid gland
TRH
thyrotropin releasing hormone
TSH
thyrotropin
Iodine
-used for synthesis of thyroid hormones
-routinely added to table salt
best natural food source for iodine
-fish
-seaweed
Iodine deficiency
-endemic in inland populations
-goiter and crentinism
goiter
enlargement of thyroid gland due to persistent rise in TSH but no iodine to make hormone
crentinism
-severely stunted physical and mental growth
Thyroid hormone transport
-Thyroxine-binding globulin (TBR) (primary)
-Transthyretin (TTR)
-Albumin
Primary transport protein of thyroid hormones
TBG
transport proteins have a greater affinity to
-T4
T4 in the body
-only 0.04% is free
-longer half life than T3 but slower onset
-serves as a storage pool (2-3 months)
Thyroid hormone mech of action
-belong to nuclear receptor family
-similar to steroid
-bind nuclear and inc transcription
Metabolism of Thyoid hormones
-deiodination
-conjugation to form glucuronide or sulfate w phenolic group
-excreted via bile
-some hydrolyzed by bacteria
-marginal enterhepatic circulation
structures
slide 14
HYPOthyroidism
-deficiency of thyroid hormones
Symptoms of HYPOthyroidism
-dec metabolism = fatigue, mental dullness, lethargy, inattention
-defective thermoreg
-may occur w goiter
-dwarfism/cretinism in infants and children
-Myxoedema coma
myxoedema coma
-end state of untreated HYPOthyroidism
-water intoxication
-shock
-death
Causes of HYPOthyroidism
-Hashimoto’s thyroiditis
-destruction/removal of gland (no goiter)
-idodine deficiency (goiter)
-congenital cretinism
-secondary: TSH deficiency
Hashimoto’s thyroditis
-most common cause of HYPOthyroidism
-autoimmune disease that destroys thyroid gland
Secondary cause of HYPOthyroidism
-TSH deficiency
HYPERthyroidism
-excessive levels of thyroid hormones (thyrotoxicosis)
Symptoms of HYPERthyroidsism
-excessive metabolism
-poor thermoreg and weight loss
-inc HR and cardiac output
Causes of HYPERthyroidism
-Graves’ disease
-Toxic uninodular goiter and toxic multinodular goiter
-Subacute thyroiditis
Graves’ Disease
-most common cause of HYPERthyroidism
-autoimmune
-thyroid stimulating IgG
-toxic goiter
Toxic uni/multi nodular goiter
-adenoma producing excess T3
-mostly in older women
-causes HYPERthyroidism
Subacute Thyroiditis
-viral infection of thyroid gland
-transient release of store thyroid hormones
-HYPERthyroidism
HYPOthyroid skin
-pale
-cool
-puffy
HYPERthyroid skin
-warm
-moist
-sweaty
HYPOthyroid eyes
-droopy eyelids
HYPERthyroid eyes
-retraction of upper lids
-exophthalmos
HYPOthyroidsim CV effects
-BRADYcardia
-dec CO
-inc vasc resistance
HYPERthyroid CV effects
-TACHYcardia
-inc CO
-dec vasc resistance
HYPOthyroid CNS
-lethargy
HYPERthyroidism CNS
nervousness
HYPOthyroidism metabolism
-dec appetite
-dec BMR
-hYPOglycemia
-inc cholesterol and triglycerides
-dec drug metabolism
HYPERthyroid metabolism
-inc appetit
-inc BMR
-HYPERglycemia
-dec cholesterol and triglycerides
-inc drug metabolism
Hypothyroidism treatment
-Thyroid Hormone Replacement Therapy
Thyroid Hormone Replacement Therapies
-Natural Thyroid hormone preparations (not FDA approved)
-Levothyroxine (T4)
-Liothyronine (T3)
-Liotrix (disc)
Natural Thyroid hormone preparations
-not FDA approved
-HYPOthyroidism treatment
-dessicated thyroid and thyroglobulin (bovine or porcine)
-variable T4/T3 blood levels due to inconsistencies in sources
Levothyroxine (T4!)
-HYPOthyroidism treatment
-converted to T3 intracellularly
-slow onset
-long half-life (week)
-6-8 weeks to reach steady state levels
Liothyronine (T3!)
-HYPOthyroidism treatment
-rapid onset
-short duration (24h)
-need multiple daily doses
-greater cardiotoxicity risk
-difficult to monitor via lab tests
Liotrix (disc)
-4:1 T4 to T3 ratio
-more expensive
-not more effective than T4 admin alone
-discontinued
HYPERthyroidism drugs
-Thioamides
-131I
-Iodide
Thioamides
-HYPERthyroidism treatment
-antithyroid
-treat thyrotoxicosis
-inhibit thyroid peroxidase
=block iodine organification and coupling
-slow onset (3-4 weeks)
-require depletion of stored T4
Thioamide drugs
-Methimazole
-Propylthiouracil
131I
-HYPERthyroidism
-radioactive iodine
-emit B particles and gamma rays
-8 day half life
-localized destruction of thyroid follicles
-admin orally in solution as Na131I
problems w 131I
-HYPOthyroidism occurs in 80% of patients
-potential inc in some cancer
-radiation thyroiditis in rare cases (storm?!) = prevent w pretreatment of antithyroid drugs
-radioactive urine
131I contraindication
-not for pregnant or breastfeeding
131I advantage
-no surgery
-lower cost
Iodide treatment
-for HYPERthyroidism
-lots of I- inhibits own uptake , organification, and release of thyroid hormones
-dec vascularity of thyroid gland
-not for long term use
Lugol’s solution
-aq solution of I and KI
-iodide treatment for HYPERthyroidism
Iodide clinical uses
-prep for thyroidectomy
-severe thyrotoxicosis
-protection from radioactive iodine fallout (nuclear/military exposure)
Iodide side effects
-HYPOthyroidism
-sensitivity to idodine in some patitents (angioedema)
