L4 - Thyroid Hormones Flashcards
What cell types can be found within the thyroid gland?
Follicular (epithelial) cells, parafollicular C cells, endothelial cells, fibroblasts, lymphocytes, and adipocytes
Why are fibroblasts, lymphocytes, and adipocytes relevant to thyroid physiology?
In certain diseases these cells can be the source of thyroid pathophysiology
What is the secretory unit of the thyroid gland? What is its structure?
Thyroid follicles; Consist of thyroid epithelium arranged around a large central cavity filled with colloid
What is the predominant protein found in colloid?
Thyroglobulin
What hypophysiotropic neuropeptide controls the release of thyroid hormones? To what kind of receptor does it bind?
Thyrotropin-releasing hormone binds to a GqPCR
What compounds can directly inhibit the release of TSH from the anterior pituitary?
T3, dopamine, somatostatin, and glucocorticoids
How is negative feedback inhibition involved in the regulation of thyroid hormone release?
Circulating levels of T3 can inhibit the release of TSH directly and indirectly by inhibiting release of TRH
To what structural family of hormones do thyroid hormones belong?
Tyrosine-derivatives
In what cells is thyroglobulin produced?
Thyroid follicular epithelial cells
What are the steps and intermediates of thyroid hormone synthesis? What enzyme catalyzes this step?
Tyrosine residues of thyroglobulin undergo organification in which either one or two iodine molecules are added to tyr to form monoiodotyrosine or diiodotyrosine (MIT, DIT). 2 DIT or 1 MIT and 1 DIT are coupled to form T4 and T3, respectively; thyroid peroxidase
What maintains the concentration of iodine in the thyroid follicular epithelial cells?
A Na+/I+ symporter
True or False: the transport of iodine into thyroid follicular epithelial cells is under TSH regulation?
True
What is the driving force that allows iodine entry into the cell? What is the net movement of molecules through the Na+/I+ symporter?
The low intracellular concentration of sodium, maintained by Na/K pump; 2 Na+ and 1 I+ in
Where does organification and coupling take place?
Within the colloid in the thyroid follicle lumen
How is the Na+/I+ symporter manipulated for medical use? What other compounds can be transported via the symporter?
Radiolabeled pertechnetate can be used for imaging of the thyroid gland and it can transport in radioactive iodine for treatment; perchlorate, nitrate, and thiocyanate
What surface of the thyroid follicular epithelial cells faces the colloid?
Apical
What is the process by which thyroid hormones are released into circulation? Which hormone is released in the highest quantity?
Thyroglobulin is transported into the follicular epithelial cell via endocytotic vesicles that fuse with phagolysosomes. The thyroglobulin undergoes proteolytic digestion and cleavage, yielding T3 and T4; T4 is released more than T3
To what kind of receptor does TSH bind? In what tissues are the receptors found?
GsPCR; Thyroid and adipocytes and fibroblasts of the orbit connective tissue
What is the effect of TSH binding to thyroid tissue?
An increase in all steps of thyroid hormone synthesis and secretion
How does thyroid hormone circulate?
Bound to protein
What is the half life of T3 and T4?
T3- a little less than a day; T4- about 7 days
How are thyroid hormones metabolized in the periphery?
T4 undergoes deiodonation, loosing the outer ring iodine to become T3 or loosing the inner ring iodine to become reverse T3.. T3 and rT3 are deiodonized further to inactive T2 and T1
In which tissues are TH receptors expressed? Where in the cell are they located?
Ubiquitous expression; nuclear receptors
Why is T3 more biologically more active than T4?
It has a higher affinity for TH receptors
How does TH binding to its receptor affect physiologic change?
The receptor acts as a transcription factor and affects gene transcription
What are the metabolic effects of thyroid hormone? What is the purpose?
Stimulation of Na+/K+ ATPase expression, increased oxygen consumption, increased ATP hydrolysis, increased thermogenesis, increased basal metabolic rate, increased lipolysis and FA oxidation, increased insulin-dependent glucose utilization, increased gluconeogeneis and glycogenolysis; all maintains glucose homeostasis
What are the effects of thyroid hormone on growth and development?
Increased protein turnover, increased osteoblast and osteoclast activity, stimulate axonal growth and development and T3 controls the gene expression of myelination, cell differentiation, migration, and signaling
True or False: Normal TH function is necessary for normal reproductive behavior and physiology.
True
What are the effects of thyroid hormone on the cardiovacular system?
Increased cardiac protein synthesis (myosin, adrenergic receptors, reg. proteins), increases HR, contractility, and cardiac output, and decreases vascular resistance
What is the number one preventable cause of intellectual disability? What is the basis of the pathology?
Cretinism- iodine deficiency
What are the two general types of hypothyroidism? What is each? Which is more common?
Primary (thyroid problems) and secondary (anterior pituitary or hypothalamic problems); Primary is way more common
What are the causes of primary hypothyroidism?
Na+/I- symporter mutation; decrease in thyroid tissue, or goiter (iodine deficiency or inflammation)
What is the most common form of hyperthyroidism? What is its pathologic basis?
Graves disease; Agonistic TSH receptor autoantibodies
What is the cause of Graves’ Ophthalmopathy?
Fibroblasts and adipocytes in the paraorbital areas have TSH receptors that are stimulated by the antibodies, which stimulates their growth; there are also cytokine inflammatory things happening
What is the characteristic triad of Graves disease?
Hyperthyroidism, goiter, and exopthalamus
How does hypothyroidism clinically manifest?
Low energy levels, weight gain, low appetite, cold intolerance, abnormal menses, brittle nails, and dry course skin, delayed muscle reflexes
How does hyperthyroidism manifest clinically?
Hyper emotional state, high energy levels, high HR, weight loss, high appetite, increased bowel movements/ day
Elevation of which thyroid hormone is the most sensitive indicator for hyperthyroidism?
T3
In which cases would an increase in rT3 be seen?
Starvation or critical illness
What is the effect of excess glucocorticoid production on thyroid horomone production?
Inhbition of TRH and TSH release
What is the full name of T3? T4?
Triiodothyronine; thyroxine
(L4 - Thyroid) A patient with Graves Disease is likely to be present with:
a) decreased heart rate
b) increased metabolic rate
c) hyperglycemia
d) increased fatigue
b) increased metabolic rate
Graves disease - hyperthyroidism
(L4 - Thyroid) A patient with hypothyroidism would present which of the following:
a) hyperactivity
b) weight loss
c) decreased thermoregulation
d) muscle hyperreflexia
c) decreased thermoregulation
sluggish - hypothyroidism
(L4) TRUE/FALSE
In a patient that underwent resection of a malignant thyroid tumor, you aim for high TSH levels.
FALSE;
TSH stimulates growth, don’t want growth of a tumor
(L4)
Based on the following lab values, which of the following combinations of symptoms are most likely to find in this patient?
TSH 0.01 ulU/mL ([0.04-4.7]
T4: 12 ug/dl [4.8-11.2]
T3: 150 ng/dL [45-137 ng/dL]
a) decreased appetite
b) weight gain
c) bradycardia
d) decreased tolerance to cold
e) diarrhea
e) diarrhea
very low TSH => meaning lots of negative feedback from T4, T3
-lots of T3, T4 => lots of energy
