Endocrine 4 (Thyroid) Flashcards
What hormones are secreted by the Thyroid Gland
Thyroxine T4
Tr-Iodothyronine
Calcitonin
Synthesis of Thyroid Hormone
- Plasma iodide is taken up by follicle cells
- Iodination of Thyroglobulin
- Thyroperoxidase + H2O2 oxidizes iodine and incorporates iodine into Tyrosine residues of thyroglobulin - Secretion of Thyroid Hormone
Regulation of Thyroid Hormone
Thyrotropin-Releasing Hormone (TRH) and Protirelin (Synthetic Tripeptide) causes anterior pituitary to release Thyroid Stimulating Hormone (TSH)
TRH + Protirelin = TSH Release
Action of TSH
- Receptor
TSH acts on GPCRS in Thyroid Follicle Cells
- Increase in CAMP
- Activation of PI3K
Action of TSH
- Trophic Action
Increases Na+/I- Symporter
- More iodine into cell
Synthesis of Thyroglobulin
Secretion of Thyroglobulin into Follicle
Generation of H2O2
- Greater stimulus of thyroperoxidase to incorporate iodide into tyrosine of thyroglobulin
Endocytosis of Thyroglobulin
Secretion of T3 and T4
Increased blood flow through the gland
Vascularity of the Thyroid Gland
Heavily vascularized
- Uptake in the thyroid gland is very rapid
Causes of Hypothyroidism
Hashimoto’s Disease
- Antibodies against thyroglobulin leading to decreased thyroid hormone secretion
Symptoms of Hypothyroidism
Low metabolic rate
Slow speech
Bradycardia
Sensitivity to cold
Myxedema (Severe Cases)
- Waxlike consistency and thickening of skin
Thyroid Replacements
- MOA
Treats Hypothyroidism by replacing action of T3/T4
When no T3 (Natural Conformation):
- Histone Deacetylation (Loose)
- Does not interact with transcription factors
- Transcriptional Repression
When T3 Present
- Histone Acetylation (Tight)
- Interacts with transcription factors
- Transcriptional Activation
Thyroid Replacements
- T3 vs T4
T4 is deiodinated to T3 (By Dio1)
T4 is a pro-hormone
- Slower acting, large reserves
T3 is turned over more rapidly, smaller pool
Thyroid Replacements
- Effects
T3:
Metabolism:
- Increased Body Temp
- Decreased Weight
Cardiovascular:
- Increased Heart Rate
- Increased Blood Pressure
GI
- Increased Motility
Musculoskeletal
- Skeletal Development
- Peak Bone Mass
Reproductive
- Enhance Ovulation
- Enhance Spermatogenesis
Does not have a direct effect, rather affects other hormones that have secondary impact
Thyroid Replacements
- Adverse Effects
- Tachycardia
- Atrial Fibrillation
Causes of Hyperthyroidism
Grave’s Disease AKA Diffuse Toxic Goitre
- Antibodies against thyrotropin receptor lead to overstimulation and an increase of thyroid hormone secretion
Hyperthyroidism = Thyrotoxicosis
Symptoms of Hyperthyroidism
High Basal Metabolism
- Increased Appetite
- Weight Decrease
Increased Skin Temperature
Heat Intolerance
Sweating
Nervousness and Tremor
Tachycardia
Radioiodine
- MOA
Treats Hyperthyroidism
1st Line Treatment using (131)I
Taken up like normal iodine by the thyroid
Beta Particles of Isotope have a:
- Short range (Weakly penetrating), and only stay within the thyroid
- Cytotoxic action, destroys the thyroid gland
Takes a month before it takes action
Radioiodine
- Considerations
Avoid use in children
Avoid use in pregnancy
After destruction of gland individual becomes hypothyroid and needs administration of Levothyroxine (T4)
Antithyroids (Thioamides)
- MOA
Thiocarbamide (S-C-N) has antithyroid activiy
- Prevents synthesis of thyroid hormone
Inhibits Thyroperoxidase
Block Iodine Oxidation
Block Coupling of Iodinated Tyrosine
Inhibit Peripheral Deiodination of T4 to T3
Antithyroids (Thioamides)
- Adverse Effects
Skin Rash (Common)
Neutropenia (More serious but rare)
Agranulocytosis (More serious but rare)
Do not use if Pregnant
Antithyroids (Excess Iodine)
Lugol Iodine
- Solution of potassium iodide + iodine in water
- Used in severe thyrotoxicosis or preparation for surgery
Antithyroids (Excess Iodine)
- MOA
Lugol Iodine will cause an excess amount of iodide resulting in a negative feedback that inhibits thyroid hormone secretion
- Reduces vascularity of thyroid gland
- Reduce H2O2
–> Inhibits iodination of thyroglobulin
