Thyroid Hormone Physiology and Pharmacology - Trachte Flashcards
(38 cards)
What are the components of the Thyroid Hormone Axis?
- Hypothalamus (TRH: thyrotropin releasing hormone)
- Anterior Pituitary (TSH: thyroid stimulating hormone)
- Thyroid gland
- T3/T4 hormone (T3: triiodothyronine/T4: thyroxine)
What are the main negative regulators of Thyroid hormones?
Block portal system => stop release of TSH
T3/T4 => negative feed back to stop release of TSH and TRH
What are some of the other negative regulators of Thyroid hormones?
Somatostatin, dopamine, and high glucocorticoids (adrenal cortex) all DECREASE TSH release
What is the function of TRH?
Tetrapeptide that stimulates release of TSH from thyrotrophs of the anterior pituitary
Why is Thyroid Hormone Axis important?
Has an important role in the regulation of energy homeostasis, feeding behavior, thermogenesis, and autonomic regulation.
TRH controls energy homeostasis mainly through stimulation of TSH and ultimately regulation of circulating thyroid hormone levels.
How does TRH stimulate the target cell?
Couples to PLC => phospholipase C-IP3
Cascade results in Ca++ release and rapid intracellular responses including release of secretory vesicles containing TSH.
TSH is similar to what other gonatotropin hormones?
LH= luteinizing hormone hCG= human chorionic gonadotropin FSH = follicle stimulating hormone
How does TSH stimulate the receptor signal transduction?
Receptors reside on plasmamembrane of thyroid follicular cells.
G(s)-coupled receptor => increase cAMP
TSH:TSH receptor binding stimulates many aspects of thyroid hormone synthesis and release.
What are the 7 steps of Thyroid Hormone synthesis?
- Iodide Uptake (via Na+ coupled symporter)
- Iodide Oxidation to Iodine (organification)
- Iodination of tyrosine-thryoglobulin
- Conjugation of MIT/DIT thyroglobulin
- Endocytosis of T3/T4-thyroglobulin
- Proteolysis to mature hormone
- Secretion of T3/T4 via exocytosis (?)
How do T3 and T4 compare?
T3 is more active than T4.
T4 is converted to T3 intracellularly.
T3 has a shorter circulating t1/2 T3~ 1 d; T4~ 6d
Both T3 and T4 bind thyroid hormone receptors but it is thought most T4 is converted into T3.
What are the transporters for thyroid hormone?
Thyroxine binding globulin (= TBG =thyroid binding globulin)
- binds 75% of T4 and 75% of T3
Transthyretin
Albumin
What three things does TSH stimulate the synthesis of in order to produce thyroid hormones?
Thyroid peroxidase synthesis
Thyroglobulin transcription
Na+/I- transport activity (increases I- availability to the follicular cell)
What are the main functions of thyroid hormone?
Promotes oxygen consumption, heat production and free radical formation
Regulation of BMR
Increased heat production
Increased glucose utilization, uptake and synthesis
Permissive sympathetic effects, ↑ heart rate, ↑ contractility (increases beta receptors)
Why do many states mandate newborn testing of thyroid function?
brain doesn’t develop/grow properly if low thyroid function
What happens if there is a congenital lack of thyroid hormone in infants?
(Cretinism) or maternal hypothyroidism:
- profound mental retardation
- short stature
- delay in motor development
- coarse hair
- protuberant abdomens
What are the physiologic effects of low thyroid hormone in adults?
Lethargy
Somnolence
Slowed intellectual functions including speech
Stiffness and aching muscle
*Cold intolerance
Delayed deep tendon reflex relaxation
Anovulation and amenorrhea common, menorrhagia less common
What are the physiologic effects of excess thyroid hormone in adults?
Increases heart rate (via funny Na+ channels)
Increase sensitivity to catecholamines via increase of number of beta adrenergic receptors in heart, skeletal muscle, adipose tissue and lymphocytes.
Amplifies catecholamine post-receptor action.
Increased O2 demand leads to increased production of erythropoietin and increases erythropoiesis.
Promotes GI motility resulting in increased defecation.
Promotes bone turnover with net bone loss and hypercalciuria.
Promotes increased protein turnover and net loss of skeletal muscle with myopathy (weakness, fatigue)
Increases hepatic gluconeogenesis and glycogenolysis and intestinal glucose absorption, therefore can worsen control of glucose levels with diabetes patients.
Increase in LDL receptor # and thereby accelerates LDL clearance.
Hyperthyroidism promotes aromatization of androgens to estrogens and increases sex hormone binding globulins which can contribute to gynecomastia in men.
What is Thyrotoxicosis?
any cause of excessive thyroid hormone concentration and its effects on organ systems
What is Thyroid Storm?
Thyroid storm represents the extreme manifestation of thyrotoxicosis
What are the potential etiologies of Hypothyroidism?
***Primary hypothyroidism (i.e., problem lies in thyroid gland): Congenital defects, Gland destruction (surgical, radioactive, external radiation), Iodine deficiency, Autoimmune (Hashimoto thyroiditis=chronic lymphocytic thyroiditis)
*Secondary/tertiary (i.e., problem lies in pituitary gland or hypothalamus, respectively) usually associated with other pituitary deficiencies
Thyroid hormone resistance syndromes (with normal hormone production): receptor resistance
What happens to TRH, TSH and TH levels in primary hypothyroidism?
TRH levels increase
TSH levels increase
TH levels decrease
What happens to TRH, TSH and TH levels in secondary hypothyroidism (i.e. pituitary deficiencies)?
TRH increase
TSH and TH decrease
What happens to TRH, TSH and TH levels in thyroid hormone resistance hypothyroidism?
ALL INCREASE
Increase TRH release (no inhibitory)
Increase TSH
Increase TH
What are the potential etiologies of Hyperthyroidism?
Hyperthyroidism that results in toxicosis in target tissues is called thyrotoxicosis.
Graves’ disease = Production of thyroid stimulating immunoglobulins (TSI)
