Thyroid Flashcards
They thyroid consists of two lobes that are connected by
isthmus in front of the _______.
larynx
They thyroid weights about ____g.
15-20
Blood perfusion to the thyroid is…
(5ml/g/min)
*highly perfused organ
Adrenergic & ___________
innervation that regulates the tone of blood vessels.
Cholinergic
-The lobes of Thyroid gland: aggregates of
spherical follicles
* Connection between follicular cells: tight junction
Follicle
- thick gel-like substance in the lumen of follicles
- composed primarily of thyroglobulin (10-20%)
Colloid
(thyroid globulin main component?)
Iodinating glycoprotein
- Produce thyroxine (T4) & triiodo thyronine(T3)
- Basal membrane of follicular cells are close to
capillary network
Follicular cells
What cells regulate calcitonin in the thyroid?
Parafollicular cells/ C-cells
-regulate calcitonin secretion
What are the functional cells of the thyroid?
✦ Follicular cells
What two hormones can activate Vit. D?
PTH and calcitonin (paradox effect)
What is the storage form of thyroid hormone?
the active form?
T4- thyroxine*
T3-Triiodothyronine*
T4 is most abundant in blood but weaker action
increased catecholamine effect?
Thyroid hormones
ex: norepinephrine, epinephrine
increases CNS, HR, etc.
____ iodine is removed to become T3
5 ‘
Reverse T3?
Know what it looks like
Erythrode sick syndrome
Thyroid hormone synthesis:
ER —> Apical membrane of follicular cells.
Thyroglobulin
Concentrate iodide from circulation [iodide transporter]
- maximum 25-200 times higher than circulation [via basal membrane of FC]
Follicular cells (FC)
The sodium/iodide cotransporter, also known as the sodium/iodide symporter, is a protein that in humans is encoded by the SLC5A5 gene. It is a transmembrane glycoprotein with a molecular weight of 87 kDa and 13 transmembrane domains, which transports two sodium cations for each iodide anion into the cell
How is thyroglobulin assembled?
-Iodination of thyroglobulin [thyroid peroxidase]
-Product formed: monoidotyrosine (MIT) & diiodotyrosine (DIT)
Coupling reaction of iodinated tyrosine residues
-Mediated by thyroid _______
-DIT + MIT = T3
-DIT + DIT = T4
-After iodination, the thyroglobulin molecule is stored as part of the colloid in the lumen of follicle
peroxidase
DIT + MIT =
DIT + DIT =
T3, T4
low total T3 and free T3 levels with low or normal T4 and thyroid-stimulating hormone (TSH) levels.
-thyroid is NORMAL but the pt appears sick
Euthyroid sick syndrome
Steps of thyroid hormone secretion?
-Start with pinocytosis at the apical membranes of follicular cells
-Colloid droplets migrate toward the basal region of the follicular cells
-Lysosomes fuse with the colloid droplets
Lysosomes hydrolyze the thyroglobulin to its constituent and amino
acids
-T4 and T3 and the other iodinated amino acids are released into the
cytosol
-The rest of the amino acids are either released into circulation or recycled for new protein synthesis
-The MIT and DIT residues are deiodinated and the iodine is recycled to be incorporated into new TH
True or false:
All cells in follicle all make hormone at the same time, and release at the same time.
All of cells forming follicles are are release or building and very synchronized.
But not all the follicles in the thyroid gland are synchronized
True
Less than ____% of the T4 and T3 in blood is in free form
1
Thyroid hormone secretion:
binds to what carrier (plasma) proteins?
➡ thyroid-binding globulin (TBG), transthyretin, albumin, lipoprotein
-Protein-bound form of T4 and T3 are large reservoir of performed
hormone
Protein-bound T4 and T3 are protected from…
metabolic inactivation and
excretion in the urine (long half-life)
What is the name for pre-albumin?
transthyretin
Free T4 and T3 fall in the blood stimulates anterior pituitary gland
to secrete TSH
TSH Receptor coupled with Gs protein located on the ___________
memb
Basal plasma
Adenylyl cyclase –cAMP-PKA pathway —> Mitogenic function
TSH stimulates what
-Iodide uptake by follicular cells
-iodination of tyrosine residues in the thyroglobulin
-Couples of iodinated tyrosines to form iodothyronines
-Pinocytosis of colloid by the apical memb [Greater endocytosis
of thyroglobulin and its hydrolysis]
TSH increased what type of metabolism
energy metabolism in the thyroid follicular cell
TSH promotes what to maintain size
protein synthesis in follicular cells [maintaining size and
structural integrity]
Thyroid hormone Action
Acts by binding to
T3 has blank affinity
The hormone receptor complex binds to
-Acts by binding to a specific nuclear thyroid hormone receptor (TR)
-T3 has 15 folds higher binding affinity for TRs than does T4.
-The hormone-receptor complex binds to DNA via zinc fingers and increases/decreases
the expression of a variety of different genes that code proteins that regulate cell
function
In humans, there what what genes of thyroid receptor and how are they forming and where are they located
-In humans, there are two TR genes; α and β
-By alternative splicing, each forms at least two different mRNAs and therefore two
different receptor proteins.
-TRs are located in the nuclei of target cells bound to thyroid hormone response
element (TRE) in the DNA.
-TR bound to the TRE in the absence of T3 generally act to repress gene expression.
-TR-independent action
Role of Thyroid hormones
Are essential for what two processes
-CNS development and Normal body growth
-Thyroid hormone receptors increase about 10-fold in the fetal brain at
about the time T3 and T4 begin to rise in the blood
Thyroid hormone deficiency prenatal and postnatal periods of
differentiation and maturation of the brain: Mental retardation
Thyroid hormones are able to regulate the expression of genes involved Neuron replication & Differentiation
Thyroid hormones
normal body growth
-Thyroid hormones stimulate the expression of the gene for Growth
Hormones in the somatotrophs of the anterior pituitary gland
-Thyroid hormones have direct effects on the synthesis of a variety of
structural and enzymatic proteins
Thyroid hormones regulate what type of metabolism
basal energy metabolism of the body
-Thyroid hormones regulate basal rate of oxidative phosphorylation
Thyroid hormones regulates carbohydrate metabolism
-Increase absorption of glucose
-Enhancement of glucose transfer to muscle and fat
-Facilitation of insulin-mediated glucose uptake
*Gluconeogenesis(low TH)/Glycogenolysis (high TH)
Thyroid Hormones regulate lipid metabolism
-Lipolysis
-Reduction of cholesterol
Role of Thyroid hormones
increase and enhance what
-Enhance sympathetic nervous system effects
-Increase heart rate and force of contraction
-Elevates blood pressure
-Increase cardiac output
Thyroid hormones regulate their own secretion
-T3 exerts an inhibitory effect on TSH secretion by thyrotrophs in
the anterior pituitary gland
-This action of T3 on thyrotrophs is thought to be due to changes
in gene expression in these cells
LABORATORY DIAGNOSIS OF THYROID DISEASE
Primary vs secondary condition
-Primary (1o ) thyroid disease is abnormality in the thyroid gland
-Secondary (2o ) thyroid disease is really an abnormality in pituitary
gland which causes error in amount of TSH produced
Primary (1) HYPOTHYROIDISM
Thyroid glan d secretes insufficient T3 and T4 without regard for feedback.
Involves destruction of the thyroid gland or congenital lack of development of
thyroid gland
PRIMARY (1O ) HYPOTHYROIDISM
Laboratory: decreased what and increased what
Symptoms
-Laboratory: ↓ total and free, active T3 and T 4, ↑ TSH
-Symptoms:
slowdown of metabolic processes
weight gain
cold-intolerance
Lethargy
Hashimotos Thyroiditis
Requires what treatment
-is the most common cause of primary hypothyroidism
An autoimmune disease associated with goiter.
An increase in TSH production which stimulates growth of the thyroid gland.
-Requires replacement thyroid hormone to inhi bit TSH secretion.
THYROID HORMONE EXCESS IN ADULTS
Hyperthyroidism/thyrotoxicosis
types
Graves’ disease (Autoimmune disease)
Adenomas of the thyroid gland
Graves disease
-form diffuse toxic goiter
-Synthesizes and secretes thyroid hormones at an accelerated rate
-chronic elevation of thyroid hormone in the blood
Adenomas of the thyroid gland
-Secrete thyroid hormones and excessive TSH secretion
-Due to the malfunction of hypothalamic-pituitary-thyroid axis
Hyperthyroidism
symptoms
-Nervous and emotionally irritable
-Physical weakness and fatigue
Increased basal metabolic rate [increased body heat generation]
-Increased heart rate and cardiac output
Weight loss [↑ food intake, ↑↑degradation of protein and lipid]
-All of above can be reversed with reduction in thyroid hormone secretion
or surgical removal
Primary 1 Hyperthyroidism
Thyroid gland secretes excess T3 and T4 without regard for feedback
Examples of primary: Toxic adenoma, Toxic multinodular goiter (Plummer’s disease) or
Graves’ disease
PRIMARY (1°) HYPERTHYROIDISM
Symptoms and lab results
weight loss, sweat, anxiety and tremor
Increased total T 4 and total T 3 (free and protein-bound)
↑ free T 4 and free T 3 (called FT 4 and FT 3)
↓↓ TSH (exponential decrease for modest decrease in thyroid hormones)
Graves disease
Most common cause of thyrotoxicosis
-Most common cause of thyrotoxicosis (excessive production of thyroid hormones
and the response of peripheral tissues to excess thyroid hormone)
- Graves’ disease is autoimmune production of an antibody that resembles TSH →
inappropriate stimulation of thyroid gland → uncontrolled increase in secretion of T4
& T3 → hyperthyroidism
Thyroid hormones analysis
Most useful test
serum levels of total T4 and T3 are measured by
The most useful test for assessing thyroid function is TSH
Serum total T 4 and T 3 levels are generally measured by radioimmunoassay
(RIA), chemiluminometric assay or similar immunometric technique
Because > 99.9% of thyroid hormone is bound to protein, any alteration in
Thyroid-binding proteins can frequently lead to total T4/T 3 levels out of
range
Free thyroxine index
-T4 x T3 uptake
**T3 uptake: measure of unbound TBG.
