L74: Thyroid Flashcards
Where is the thyroid gland located?
Anterior to cricoid cartilage
What supplies the thyroid gland with blood?
Superior (ext carotid) and Inferior (thyrocervical trunk) thyroid arteries
Venous plexus on surface -> superior, middle, inferior thyroid veins -> drain into internal jugular vein
What innervates the thyroid gland?
Sympathetic NS by the middle and inferior cervical ganglion
What are the cellular components of the thyroid gland?
Follicle: has lumen filled with colloid with thyroglobulin (TG) Parafollicular Cells (C Cells): produce calcitonin and maintain follicle
Epithelial cells
Fibroblasts
Lymphocytes
Adipocytes
What is the colloid?
extracellular storage site of T3/T4 and thyroglobulin found in follicle
Where are hte parafollicular cells located?
Inside the basement membrane -> do not touch the colloid
What are 2 requirements for thyroid hormones?
Thyroglobulin and Iodide
What happens to excess iodide?
Excreted in urine as iodine
How much iodide intake is needed to avoid thyroid hormone deficiency?
20ug/day
What is the Wolf-Chaikoff Effect?
Intrathyroidal response that ensures constant iodide storage with changing dietary iodiede intake
Increased intake -> decreased gland transport and hormone synthesis
Decreased intake -> increased gland transport and hormone synthesis
How can the Wolf-Chaikoff effect be used clinically?
Use very high doses of iodide to rapidly shut down thyroid hormone production in hyperthyroid patients
What is the HPT Axis?
Hypothalamus (PVN) -> TRH -> Pituitary (Thyrotropes) -> TSH -> Thyroid gland
What regulates thyroid hormone release?
Neg Feedback by T4/T3 at hypothalamus
Neg Feedback by T4 at pituitary
Tonic inhibition by somatostatin and dopamine
What is the sequence of events of hte HPT Axis?
TRH from PVN neurons bind to GPCRs on thyrotrope cells in ant. pituitary -> activate DAG/IP3 -> release TSH -> bind to receptors in basolateral side of follicular epithelial cells -> stimulate T4/T3 synthesis and release from follicle -> deiodinase peripherally -> Intracellular T3 ->neg feedback to inhibit TRH and TSH
Where are T4 molecules deiodinated to T3?
In the thyrotopes and braine by Type II deiodinase
What is the thyroid sensor?
Type II Deiodinase
How is the thyroid follicle polarized?
Apical: exposed to lumen (colloid); thyroid hormone syntehsis and iodination of TG
Basolateral: Exposed to blood; Iodine uptake/trap; Thyroid hormone release
What are the steps in thyroid hormone syntehsis?
Iodide Trapping: TSH stimulates NIS co transporter in basla membrane of follicular epithelial cell to trap iodide
Transport: I- transported to follicular lumen and oxidized by TPO to form iodine; TG transported to lumen
Iodination: Iodinate tyrosyl residues on TG
Conjugation: Conjugate iodinated tyrosines to make T4 andT3 linked TG
Endocytosis: Conjugated TG with T4/T3 enters follicular epithelial cells and packaged in endosomes
Proteolysis: TG, MIT, DIT, T4, T3 released from vesicle
Secretion: T4/T3 secreted into circulation at basal membrane
Which form of thyroid hormone has the longer half life?
T4 > T3
Which is the primary active form of thyroid hormone?
T3
Converted intracellularly from T4 and binds with high affinity to receptor
What is rT3?
Reverse triiodothyronine -> biologically inactive
How is T3 formed?
Coupleing 1 MIT and DIT residues
How is rT3 formed?
Inactive
Presence of two iodinated residues on outer ring
How is T4 formed?
Couple 2 DIT residues
What is radioactive iodide uptake scan?
Diagnostic tool to measure iodide uptake in thyroid epithelial cell using radioactive iodide and anions -> determines funciton of thyroid gland
What mediates the transport of iodide in the thyroid epithelial cell?
NIS (Sodium iodide symporter)
What is normal uptake of iodide after 24 hours?
25%
What is considered hyperthyroid/hypothyroid?
Hyperthyroid: >60% iodide uptake after 24 hours
Hypothyroid:
What is an organification defect?
When iodide cannot be incorporated into tyrosine -> Test by blockiing NIS with perchlorate and measure radioactive iodide uptake
What is Type I Deiodinase?
Outer and inner ring deiodinase -> forms T3
Found in: Liver, Kidney, Thyroid, Skeletal muscle
Primary source of T3 in circulation
What is Type II Deiodinase?
Outer ring deiodinase -> forms T3
Found in: Brain, Pituitary, Placenta, Cardiac Muscle
What is Type III Deiodinase?
Inner ring deiodinase -> forms rT3
Found in: brain, placenta, skin
Which is produced more and stored in the thyroid?
T4
Which deiodinase is the thyroid hormone sensor in the pituitary?
Type II deiodinase
What % of thyroid hormones are bound in circulation?
> 99%
TBG(70%)
Transthyretin (TTR): 10%
Albumin: 15-25%
What is TBG?
Thyroxine binding globulin-> made in liver
T4 has highest affinity for TBG
What increases TBG levels?
Estrogen, hepatitis
What decreases TBG levels?
Nephrotic syndrome
Steroids
How does a decrease in TBG change free T4/T3 levels?
No net change; Changes in TBG dont usually affect bioavailable T3-> DOES affect TOTAL T4/T3 levels
How does the thyroid hormone receptor work?
Nuclear receptor that forms heterodimers with retinoic acid receptor (RXR) -> complex binds to DNA -> recruit coregulatory proteins-> transcriptional activation
Where are thyroid hormone receptors found?
Every cell type
How does BMR change with hypo/hyperthyroid
Hypo: deceased
Hyper: increased
How does thyroid hormone affect carbohydrate metabolism?
Increase gluconeogenesis and glycogenolysis
normal glucose serum
How does thyroid hormone affect protein metabolism?
Increase protein synthesis + Inc proteolysis => muscle wasting
How does thyroid hormone affect lipid metabolism?
Inc Iipogenesis, inc lipolysis, dec serum cholesterol
How does thyroid hormone affect thermogenesis?
Hypo: Decreased -> cold intolerant
Hyper: Increased-> heat intolerant
What does T3 do in terms of cellular metabolism?
Increases cellular oxygen consumption and heat production by increasing mitochondrial activity
What are the effects on the CNS by thyroid hormone?
T3 is critical for normal brain development
Neuronal cell migration/differentiation
Myelination
Synaptic transmission
What is Cretinism?
Caused by iodine deficiency during development leading to
short stature/impaired bone formation
mental retardation
delayed motor development
What are the effects of thyroid hormone on the heart?
T3 increases cardiac output -> inc SV and HR
Hyperthyroidism can cause arrhythmias
What is a goiter and what causes it?
Enlarged thyroid
Caused by thyroid cancer and both hypothyroidism and hyperthyroidism
What is Graves Disease?
Hyperthyroid condition due to autoimmunity -> Antibodies stimulate TSH receptors -> inc T4/T3 levels
Causes goiter with hyperthyroid sx
What is noted on the histology of thyroid gland from a Graves Disease patient?
Scant colloid
Tall Columnar ACtivated Follicular cells
Infiltration of lymphocytes
What is Hashimoto’s Thyroiditis?
Hypothyroid condition due to autoimmune destruction of thyroid follicles
Antibodies target TPO and TG
Forms a diffuse goiter with hypothyroid sx
Why does hypothyroidism cause a goiter?
lack of neg feedback by T4/T3 causes increased, continuous secreiton of TSH from pituitary
What are hyperthyroid sx?
tachycardia opthalmopathy irritability/hyperactivity Heat intolerance Weight loss Muscle Wasting
What are hypothyroid sx?
lethargy/fatigue Hair loss Cold Intolerance Brittle nailes Decreased appetite Weight gain
What is a thyroid storm
Emergency life threatening sitation in which hyperthyroid is coupled with severe acute illness leading to: High fever Tachycardia AMS NVD Circulatory collapse Possibly death
What are the treatmetns for a thyroid storm?
PTU: acute treatment
Carbimazole
Beta Blockers to normalize heart function
