Physiology Block 3 Week 14 10 Thyroid Hormone Flashcards
Anatomy of Thyroid Gland
Follicles:
-balls consisting of a shell made of cells filled with colloid
Parafollicular cells:
-synthesize calcitonin
Amino Acid Precursor of Thyroid Hormone Synthesis
What is added?
Tyrosine
Addition of iodine
Monoiodotyrosine (MIT) DIT T3: Triiodothyronine (MIT + DIT) T4 Thyroxine (DIT + DIT)
What happens to the iodine absorbed in the small intestine from the diet?
3/4 excreted into the urine
1/4 of the iodide is pumped into the thyroid follicular cells via iodide pump
- -60% organified into thyroid hormones
- -40% leaks back out into plasma (urine excretion)
Of the iodide circulating part of thyroid hormone (T3 & T4), 80% is de-organified in the tissues and excreted in the urine
–remainder eliminated in feces
97% of absorbed iodide is eliminated in urine
Thyroid Hormone Synthesis
- Iodide pumped into follicular cell with Na+ via NIS symporter due Na/K ATPase gradient
- Thyroglobulin (Tg) synthesized within follicular cell and secreted into colloid space
- Iodide is pumped into colloid and exchanged with chloride via PENDRIN transporter
- -converted into I2 - Peroxidase
- produces peroxide that act on I2 to make it iodinate tyrosines on the Tg molecules
- catalyzes coupling to form T3 and T4 - TSH stimulates pinocytosis of Tg in colloid
- brings Tg into intraccellular space as colloid droplets - Proteases act on colloid droplets, liberating MIT, DIT, T3, and T4 from Tg
- T4 and T3 secreted into EC space; MIT and DIT recycled
T4 half-life
T4 bound to thyroid binding globulin (TBG), transthyretin, and loosely to albumin
<0.05% circulates in free form
Very long half-life
T3 half-life
T3 does NOT bind transthyretin
–circulates a little less tightly bound to plasma proteins than T4 (also more potent than T4)
Neonatal (Congenital) Hypothyroidism
–Cretinism
What is the screening test?
Bone and Height age are very low before treatment
Mental age is very low and NOT improved by treatment
- -CNS development complete by 5
- -treatment needs to start at birth
Screening test:
Effects of Thyroid Hormone
Activate transcription and translation of new proteins
Growth
CNS Development
Metabolic effects:–increasing oxygen consumption in mitochondria leading to an increased basal metabolic rate
Cardiovascular (and Respiratory): in order to supply substrate and oxygen to the cells for increased metabolism, cardiac output and alveolar ventilation are increased
Effect of Thyroid Hormone on Blood Pressure Regulation
Thyroid hormones are sympathomimetic
- -do not directly increase sympathetic nerve activity
- -augment sensitivity to catecholamines and sympathetic input to tissues
Increased beta adrenergic receptor activity
Excess adrenergic activity = tachycardia
Control of Thyroid Function
Thyroid Stimulating Hormone (TSH) regulates Thyroid Function
Stimulates:
- iodine uptake
- TH synthesis and secretion (increases metabolism and negative feedback on pituitary)
- hypertrophy
Increased TH inhibits TSH release
Thyroid Releasing Hormone probably laters negative feedback sensitivity of pituitary
-increased TRH induces an inc in circulating TH
Primary Hypothyroidism
Hashimoto’s Thyroiditis
Low Free T4
High TSH
Autoimmune attack on the thyroid gland
–decrease in function
Loss of negative feedback
Not enough T4 to inhibit TSH release
Secondary Hypothyroidism
Hypopituitarism
Low Free T4
TSH NOT elevated
Inappropriately low TSH secretion for level of fT4
Primary Hyperthyroidism
Graves’ Disease
High fT4
Low TSH
Autoimmune disease–thyroid-stimulating immunoglobins are produced that activate TSH receptor, increasing fT4
High fT4 suppress TSH release
Why is TBG elevated in pregnant women?
Effect of Estrogen or estrogen therapy
Total T4 will be elevated because there is more binding protein
Free T4 will be normal because pituitary is normal and results in normal negative feedback of TSH (normal levels)
What would TSH be in the typical patient with hypothyroidism due to hypopituitarism?
Low fT4
Non elevated TSH due to hypopituitary function
