L4: Thyroid Gland Physiology Flashcards
Follicles of the Thyroid gland contain _______: an extracellular storage form of thyroid hormone
Follicles contain Colloid: an extracellular storage form of thyroid hormone (T3/T4 bound to Thyroglobulin)
__________ cells synthesize and secrete T3/T4 in response to ___________
Follicular cells synthesize and secrete thyroid hormones (T3/T4) in response to anterior pituitary TSH
Role of Parafollicular cells of the thyroid?
Secrete peptide hormone calcitonin (not considered thyroid hormone)- Calcitonin plays role in calcium homeostasis
What is required for Thyroid Hormone (T3/T4) synthesis?
Iodine
Inland areas w/ poor consumption of seafood=> thyroid gland deficiency due to lack of iodine
Steps of Thyroid Hormone Synthesis/Secretion
- Make Thyroglobulin
- Iodine Trapping: transporter on the basolateral membrane, concentrates iodide in the cell
-
T3/T4 Synthesis:
T4 (90% of output)
T3 (10% of output) - more via peripheral deiodination of T4 in liver/kidneys -
Secretion:
T3/T4 attached to thyroglobulin => colloid endocytosed back into follicular cell => T3/T4 released and thyroglobulin broken down
What regulates Thyroid Gland Function?
TSH (Anterior Pituitary)
Plasma transport protein with highest affinity for Thyroid Hormones (T3/T4)?
Thyroxine Binding globulin (TBG) -Higher affinity for T4 than T3
Plasma transport protein with intermediate affinity for Thyroid Hormones (T3/T4)?
TBPAA (Transthyretin)
Plasma transport protein with lowest affinity for Thyroid Hormones (T3/T4)?
Albumin
lowest affinity but highest abundance-readily dissociable
Which thyroid hormone do you measure to assess thyroid function?
T4
Which Thyroid Hormone is more potent?
T3 10X more potent than T4
Which thyroid hormone has a higher plasma half life?
T4»_space;> T3
Enzymes responsible for Activation/Deactivation of T3/T4? What are they dependent on?
Deiodinases are selenium dependent enzymes
- 5’ monodeiodinase converts T4 to T3 in target cells ( Removes C5 outer ring)
- 5 monodeiodinase inactivates T4 and T3 (removes C5 inner ring)
What enzyme converts T4 to T3 in target cells
MOA?
When is it less active?
5’ Monodeiodinase
Removes C5 outer ring
Enzymes less active during fasting / starvation and cortisol excess
What enzyme inactivates T4 and T3
MOA?
Consequences of Malfunction?
5 Monodeiodinase inactivates T4 and T3 (Selenium Dependent)
Removes C5 inner ring
Malfunction forms Reverse T3 (Competitive inhibitor of T3) => features of hypothyroidism
________________ hormones play a key role in regulating Basal Metabolic Rate (BMR)
Thyroid hormones play a key role in regulating Basal Metabolic Rate (BMR)
- Hyperthyroidism: HIGH BMR
- Hypothyroidism: LOW BMR
Metabolic Effects of T3
Stimulates _______ and release of ______________and ___________
Stimulates metabolism of __________ to bile acids
Facilitates removal of ________ from plasma
Generally stimulates all aspects of _________ metabolism and increases ______ turnover
Stimulates lipolysis and release of free fatty acids and glycerol
Stimulates metabolism of cholesterol to bile acids
Facilitates removal of LDL from plasma
Generally stimulates all aspects of carbohydrate metabolism and increases protein turnover
Role of Thyroid Hormones in Growth/Development?
Essential for normal growth
- increases protein synthesis, energy production and substrate availability
- Enables anabolic actions of growth hormone
Essential for CNS development: promotes nerve cell growth and myelin formation
Delayed CNS development and intellectual disability as a result of Thyroid hormone Deficiency?
Cretinism
Maternal and/or fetal hypothyroidism causes delayed CNS development and intellectual disability
Role of Thyroid Hormones on Cardiovascular Hemodynamics?
T3 Upregulates Beta Adrenergic Receptors (Enhanced sensitivity to epinephrine leading to increased: heart rate, stroke volume, cardiac output and force of cardiac contractions
Regulation of Thyroid Function?
Anterior pituitary (Thyroid Stimulating Hormone (TSH) )
Increased Thyroid Hormone synthesis
Stimulates follicular cell growth, follicle formation
Maintenance of function and growth of gland
Hypothalamus
TRH secretion from hypothalamus regulates secretion of pituitary TSH
Hypothermia is major stimulus to TRH secretion
What regulates the secretion of TSH?
Major Stimulus?
TRH secreted from hypothalamus regulates secretion of pituitary TSH
Hypothermia is major stimulus to TRH secretion
Causes of Primary Hypothyroidism?
- Iodine deficicncy
- Genetic (Receptor/enzyme mutation)
- Toxicity
- Cancer
- Hashimoto’s Thyroiditis (Autoimmune)
MOST COMMON clinical presentation of hypothyroidism resulting from autoantibodies to TSH receptor which act as TSH antagonists
Hashimoto’s Thyroiditis
Cause of Secondary Hypothyroidism?
Abnormality of Hypothalamus (TRH) or Anterior Pituitary (TSH)
Symptoms of Hypothryroidism?
- Goitre (neck swelling)
- Decreased heart rate and cardiac output
- Decreased appetite
- Lethargy/somnolence
- Decreased basal metabolism =>Cold intolerance
- Psychological disorders (depression, anxiety)
Children: Intellectual disability, dwarfism (cretinism)
Diagnosis of Hypothyroidism?
Primary Hypothyroidism (Decreased T3/T4 production)
- INCREASED TSH
- presence of anti-thyroid antibody (Hashimoto’s Thyroiditis)
Secondary Hypothyroidism: (Decreased T3/T4 production)
- DECREASED TSH
Treatment of Hypothyroidism
Levothyroxine: T3/T4 replacement therapy
Also Dietary iodine supplementation
What demographic does Hyperthyroidism most commonly affect?
Hyperthyroidism is 10x more common in women
Symptoms of Hyperthyroidism?
- Increased basal metabolic rate
- Heat intolerance
- Increased body temperature
- Increased heart rate / arrhythmias
- Nervousness, anxiety
- Goiter (Neck bulging)
- Exophthalmos (‘bulging eyes’)
Causes of Primary Hyperthyroidism?
Abnormality of thyroid itself:
- Graves Disease: autoantibodies to TSH receptors which act as TSH agonists leading to: T3/T4 hypersecretion that cannot be overridden by feedback regulation
- Thyroid adenoma
Causes of Secondary Hyperthyroidism?
Abnormality of Hypothalamus or Pituitary:
- Excess TSH (pituitary)
- Excess TRH (hypothalamus)
Disease in which autoantibodies to TSH receptor act as TSH agonists leading to T3/T4 hypersecretion stimulus that cannot be overridden by feedback regulation?
Graves Disease (Cause of Primary Hyperthyroidism)
Difference between the two autoimmune disorders affecting the Thyroid?
Hashimoto’s Thyroiditis: autoantibodies to TSH receptor which act as TSH ANTAGONIST => HYPOTHYROIDISM
Graves Disease: Autoantibodies to TSH receptor which act as TSH AGONIST => HYPERTHYROIDISM
Goiter in Hypothyroid vs. Hyperthyroid states?
Hypothyroid State:
- Low levels of T3/T4 production due to iodine deficiency leads to reduced negative feedback => Increased TSH production from anterior pituitary => hypertrophy of thyroid gland w/o increased TH production (due to lack of iodine)
- NO Feedback inhibition as no increase in T3/T4
Hyperthyroid State:
- In Graves Disease autoantibodies to TSH receptor which act as TSH AGONISTS=>T3/T4 hypersecretion => Hypertrophy of Thyroid (GOITER) as stimulus cannot be overridden by feedback regulation
- Feedback inhibition is ineffective bc TSH is not cause of thyroid stimulation
Treatment of a Thyrotoxic Crisis (Thyroid Storm)
Beta-blockers (reduce sympathetic activation and T4 to T3 conversion)
Glucocorticoids (reduce T4 to T3 conversion)
Thionamides (inhibit new hormone synthesis)
Plasma Transport of T3/T4?
______% bound to carrier proteins
__________________________ -Higher affinity for T4 than T3
_________________________- Intermediate binding affinity
_________________________- Lowest binding affinity, Highest abundance
99% bound to carrier proteins
Thyroxine Binding globulin (TBG) -Higher affinity for T4 than T3
TBPAA (Transthyretin)- Intermediate binding affinity
Albumin- Lowest binding affinity, Highest abundance
