Flashcards in Lecture #2 -- Thyroid Physiology Deck (120):
What nerve should be watched out for in thyroid surgery
Recurrent Laryngeal Nerve
Where are thyroid hormone receptors located?
Give an example of an endocrine, neurocrine, paracrine, and autocrine hormone.
Endocrine -- Insulin
Neurocrine -- ADH
Paracrine -- Gastrin
Autocrine -- Norepinephrine
Thyrotropin Releasing Hormone can stimulate the release of
How is thyroid hormone release regulated?
Negative Feedback from T3, T4 inhibits TSH release from the A Pit
Four structural groups of hormones
Fatty Acid Derivatives -- Eicosanoids
Amine hormones are usually derived from
Tyrosine or Tryptophan
Six examples of Amine hormones
Two other (non-tyrosine) AAs used in hormone synthesis?
Tryptophan -- Serotonin, Pineal Hormone Melatonin
Glutamic Acid -- Histamine
Peptide hormones are typically produced as....
Larger MW precursors that are proteolytically cleaved to active form
Peptide hormones are _______ soluble
Is Thyrotropin (TSH) a peptide or steroid hormone?
Is Vitamin D3 a peptide or steroid hormone?
List Five types of steroid hormones
Major glucocorticoid in mammals?
Major mineralocorticoid in humans?
Common Androgen and Estrogens?
Most commonly considered progestogen?
What is the rate limiting step of steroid hormone synthesis?
Transport of free cholesterol from cytoplasm into mitochondria.
Carried out by Steroidogenic Acute Regulatory Protein
Describe the Adenylyl Cyclase pathway
Stims Ad Cyclase -- ATP --> cAMP
cAMP activates PKA and is turned to 5' AMP
Phosphorylation of Proteins
Describe the Phospholipase C pathway
Stims Phospho C --- PIP2 --> DAG+IP3
IP3 --> Calcium release from ER/SR
DAG + Ca --> PKC activity
PKC ---> Physiologic Actions
Example of receptor tyrosine kinases and tyrosine kinase - associated receptors
RTK -- NGF Receptor, Insulin
TK-Associated -- Growth Hormone
Describe the activation pathway of a steroid hormone
Hor thru membrane
Binds to intracellular receptor
Dimerization and binding to Sequence Response Element
Transcription.......Protein--> Physiologic Action
Amine (Epinephrine) -- Class and Receptor Location
Amine (Thyroid Hormone) -- Class and Receptor Location
Peptide -- Class and Receptor Location
Steroids/Vitamin D -- Class and Receptor Location
Primary function of thyroid?
Maintenance of all metabolic pathways needed for growth, development, body maintenance, and repair
As TRH release is constant, why aren't women constantly lactating?
Dopamine inhibition of prolactin
Where does TSH come from?
Basophil cells of the anterior pituitary
How does TSH stimulate thyroid hormone production
Iodide Uptake and Incorporation into Thyroglobulin
Release of T3 and T4 from thyroglobulin
Stimulates production of Cuboidal Cells of thyroid cells
Roles of Thyroid Hormones in Development
- Development of CNS in fetus/neonate
Stim differentiation, dendrite formation, and myelination
- Stim production/maint. of enzymes responsible for
synthetic/degrative pathways in metabolism
- Increase intermediary metabolism and ox phos
- Stim tissue growth and bone development
- Increase GH gene expression
Effect of thyroid hormone on metabolism (overall)
Stimulates the formation of the intermediate pathways of carbohydrates, fat, and protein metabolism
Amplifies cell metabolic activity and heat production
How does Thyroid Hormone mediate increased metab?
Stimulates mito. proteins, Na/K ATPase
Stim Anabolic Protein Pathways, Lipolysis, and lipogenesis
Produce positive chronotropic and inotropic effects on the heart
Functional unit of the thyroid gland =
Thyroid embryology information
-Descends from foramen cecum as bilobed diverticulum in
front of pharynx
- Eventually resides over larynx with 2 lobes+isthmus
- Neural Crest gives C cells that fuse and disperse thruout
Connection that may exist between thyroid and tongue?
What is the foramen cecum
Endodermal proliferative center at root of tongue
C cells are also known as...
Where are C cells from?
Ultimobranchial body (last structure derived from branchial pouches)
BIG PICTURE -- NEURAL CREST ORIGIN
What do C cells secrete?
C cells are escalated in what disease state mentioned in class?
Medullary Thyroid Cancer
Can also be a side effect of meds
What is a pyramidal lobe?
Persistence of the Inferior Thyroglossal Duct
Attached to hyoid bone or incorpoated into a thyroglossal duct cyst
Clinical significance of thyroglossal duct cyst
Can form a sinus
Treat with "Sistrunk" Procedure (resect w/ part of hyoid)
Where should you look for an ectopic thyroid?
Can occur anywhere along the path of descent
Usually at the base of the tongue (lingual thyroid)
Molecularly, what are thyroid hormones
Double tyrosines with incorporation of 3 or 4 iodines
What do T3/T4 use for transport in the blood?
Thyroxine binding globulin
Who makes thyroglobulin?
Synth from tyrosine in the follicular cells
Then put in vesicles to the follicular lumen
Role of the Sodium-Iodide transporter
Actively transports I- into thyroid follicular cells for incorportation into thyroid hormones
What inhibits the Sodium-Iodide transporter?
Thiocyanate and Perchlorate Anions
What enzyme oxidized I to I2. Where?
Follicular Cell Membrane
What happens in organification?
I2 is combined with tyrosine on thyroglobulin
Forms MIT and DIT
Inhibitor of Peroxidase enzyme?
What is Wolff-Chaikoff?
High levels of I- inhibit organification which inhibits synthesis of Thyroid Hormone
What happens in the thyroid follicle following TSH stimulation?
Iodinated thyroglubulin is taken back into follicular cells by endocytosis
Describe the peripheral conversion of T4.
Converted to T3 by 5-iodinase
T3 is 3-4x as potent as T4
Decribe what happens after reuptake in the secretion fo T3/T4
Internalized vesicle joins with lysosome
Enzymes cleave T3/T4 from thyroglobulin
Some T4 is converted to T3
Released into extracellular space by diffusion
What happens to MIT/DIT attached to thyroglobulin after lysosome release into intracellular
Deiodinase converts them back to I-, recycled in the system
Say it all -- the steps of Thyroid Hormone Synth.
1. Thyroglobulin is synthesized in RER and Golgi
Sent to Lumen
2. Na-I cotransport
4. I2 combines with tyrosine moities
5. Coupling Rxns --> Make Colloid
6. Endocytosis upon stimulation
7. Hydrolysis of T3/4 from thy.glob. by lysosomal enzymes
8. Recycle MIT and DIT
What is rT3?
When might you expect to see it elevated in a patient?
Inactive form of T3
More shows up in patients that are especially sick
(Helps chill out metabolism)
Where does most conversation of T4->T3 take place?
Liver and Kidneys
How much thyroid hormone is bound?
What proteins bind thyroid hormone in the blood?
Thyroid Binding Globulin (75%)
Thyroid Binding Pre-Albumin (15-20%)
Very small changes in free T4 will...
Alter TSH levels
Where do people get iodine from?
Enzyme that inhibits Iodine oxidization?
Regulation of Iodinde uptake?
High Iodide levels --> Decreased Iodide uptake into Fol
Low Iodide --> Increased Uptake into Follicular
How is the Wolff-Chaikoff effect countered?
Iodide leak from the normal thyroid tissue
What may happen to patients with autoimmune thyroiditis?
Failure to adapt
Jod-Basedow effect and Wolff-Chaikoff effect have what relationship?
What does the Jod-Basedow Effect specify
Excessive Iodine Loads --> Hyperthyroidism
Seen in Graves, Toxic multinodular goiter, toxic adenoma
Jod-Basedow can lead to thyrotoxicosis if the excess iodine comes from...
Iodine containing meds
What happens with thyroid-binding globulin in pregnancy?
Increases occur secondary to estrogenic stimulation of TBG synthesis and reduce hepatic clearance
What causes the reduced hepatic clearance of thyroid-binding globulin in pregnancy?
hCG has what effect on thyrotropic activity
Increases it by directly activating TSH receptor
Timeline for hCG release
Begins shortly after conception
Peaks around gestational week 10
Declines to a nadir by approx. week 20
What happens in the TSH decline after the hCG increased it
Partial inhibition of Pit gland by cross reactivity of alpha subs
Can drop women's TSH levels to less than normal levels
How do thyroid hormones increase the basal metabolic rate?
Increasing Na-K ATPase and beta-1 adrenergic receptors
Describe the effect of thyroid hormone on protein synth/deg
Low Thyroid Hor --> Increased Protein Synth
High Thyroid Hor --> Increased Protein Degradation
Effects of thyroid hormone on the respiratory system?
Increase respiratory rate
Increase minute ventilation
Increase ventilatory response to hypercapnia/hypoxia
Effects of thyroid hormones on the renal system
Increased Blood Flow
Effects of thyroid hormone on Oxygen-Carrying Capacity
Inc. RBC Mass
Increased O2 dissociation from hemoglobin
Effects of thyroid hormones on intermediary metabolism
Increased glucose absorption
Increase carbohydrate, lipid, protein turnover
Downregulate insulin receptors
Increase substrate availability
Effects of thyroid hormones in growth and tissue development
-Increase growth/maturation of bone, tooth, epidermis, hair follicles, nails
-Increased Rate/Force of Skeletal muscle contraction
-Inhibits synthesis/Inc. degrad of mucopolysaccharides
Effects of thyroid hormones on Nervous system
- Critical for development
- Wakefulness and Alertness
- Memory and Learning
- Normal Emotional Tone
- Speed and Amplitude of Periph. Nerve Reflexes
Effects of Thyroid on Reproductive System
- Req. for follicular development and ovulation
- Req. for pregnancy maintenence
- Req. for spermatogenesis
Effects of Glucocorticoids on Thyroid?
Excess --> decreased TSH
Diminished --> Increased TSH
Effect of estrogens on Thyroid activity?
Increase TBG, TSH
Increased T4 requirement
Effects of hypothyroidism in children?
Effects of hypothyroidism in adults?
Impaired mentation, Diminished nerve velocity
Loss of Appetite
Five primary causes of hypothyroidism?
Hashimoto's (Autoantibody destruction of thyroid)
Hypothalamic/Pit Disease (low TRH/TSH)
Surgical Thyroid Removal
TH biosynthesis diseases
Relationship of hypothyroidism and goiter?
Diminished Thyroid Hormone --> Increased TSH
Increased thyroid bloodflow, stimulated FC
Increased in Colloid Production
Difference between primary and secondary hypothyroidism?
Primary -- Thyroid can't produce enough hormones
Secondary -- thyroid isn't being stimulated by pit to produce hors
Make a diagnosis...
Normal Free T4
Make a diagnosis...
Low Free T4
Make a diagnosis...
Normal Free T4
Make a diagnosis...
Low Free T4
Normal or Low TSH
TSH or TRH Deficiency
What is Hashimoto's thyroiditis?
Autoimmune destruction of the thyroid gland
Associated with HLA DR5
How do you treat hypothyroidism?
Levothyroxine (Synthetic T4)
What is Grave's Disease?
IgG locks activation of adenyl cyclase. Causes excess thyroid hormone production, assocaited with diffuse toxic goiter
Symptoms of Grave's Disease?
Nervousness, Irritability, Fatigue, Heat Intolerance, Cutaneous vasodilation, sweating, Inc. HR, Weight Loss
Common metabolic symptoms of hyperthyroidism
High sugar from increased gluconeogenesis
Decreased muscle mass
Who usually gets Grave's Disease?
How does hyperthyroidism lead to Exopthalamos and dermopathy?
Fibroblasts in orbit and overlying shin express TSH
Activation --> Glycosaminoglycan buildup, Inflam., Fibrosis,
Influence of Thyroid hormones on sympathetic system?
Inc. synthesis of beta-1 receptors
(Inc. HR, pulse pressure, CO)
What EKG should you look out for in hyperthyroid patients?
How is hyperthyroidism treated?
Effects of PTU?
1. Blocks Peroxidase mediated oxidation, organification, and coupling
2. Blocks peripheral conversion of T4 to T3
Four Drugs that Block iodine uptake
Effect of lithium on thyroid activity?
Inhibits iodination of thyroglobulin
Five classifications of thyroiditis?
Acute (Suppurative) thyroiditis
Subacute (granulomatous) thyroiditis
Silent (Painless) thyroiditis
Chronic lymphocytic (Hashimoto's) thyroiditis
Fibrous (Reidel's) thyroiditis
What tends to cause acute thyroiditis?
What tends to cause silent thyroiditis?
Most common thyroiditis?
Subacute thyroiditis key differential?
It really hurts
Three examples of subacute thyroiditis
Giant Cell Thyroiditis
Cause of Dequervain's thyroiditis?
Follows Viral Illness