Thyroid Flashcards
What percentage of hormone secreted from the thyroid is T3/T4?
T3 = 7% T4 = 93%
Which cell in the thyroid secretes T3 and T4? How are these cells arranged?
Folicle cells
Arranged into lobules of 20-40 evenly distributed cells
Which receptor allows TSH to act on the thyroid, how does it do this?
Thyrotropin receptor (on thyroid epithelial cells) G-protein coupled receptor is activated when bound to TSH, converts GTP to GDP increasing cAMP levels (therefore increasing T3+T4 production)
What is the name of the lumen in each thyroid lobule?
The colloid
What is thyroglobulin?
A carbon chain consisting of many tyrosine molecules
What type of epithelium lines the colloid?
Cuboidal epithelium
What is the major constituent of the colloid?
Thyroglobulin
Thyroid follicules store enough thyroid hormone to supply to body for how long?
3-4 months
What is RT3?
Reverese T3
Where diiodotyrosine joins monoiodotyrosine (with the diidotyrosine first)
Functionally insignificant in humans
Which hormone is more potent, T3 or T4?
T3 (by around 10x)
What is the main protein which carries T4 and T3 in the blood?
Thyroxine-binding globulin
Much lesser extent also thyroxine-binding prealbumin and albumin
How do T3 and T4 travel in the blood, why must they travel this way?
Travel bound to proteins
As they are lipids so not soluble
What is the main protein which carries T4 and T3 in the blood?
Thyroxine-binding globulin (binds most of the T3)
(Much lesser extent also thyroxine-binding prealbumin and albumin)
Albumin binds majority of T4 but T4 is much less abundant than T3
What is Hashimoto’s thyroiditis?
A primary hypothyroidism disease
Autoimmune cause- TCell infiltration
(Blocks thyroperoxidase)- Anti-TPO antigen
High TSH level and low T4 level indicates what?
Hypothyroidism
Low TSH level and high T4 level indicates what?
Hyperthyroidism
In iodine deficiency what happens to the thyroid?
Low T3/T4 detected
Hypothalamus detects and releases more TRH and TSH which leads to receptor overload
This leads to a goitre
Where is calcitonin produced?
In the C-Cells which are interspersed with the columnar epithelium
What is the role of the c-cells?
They are interspersed with the follicular epithelium and produced the hormone calcitonin
(Also known as parafollicular cells)
What is the role of calcitonin?
Lowers blood calcium (counteracts PTH)
Inhibits Ca intestinal absorbtion
Inhibits osteoclasts and stimulates osteoblasts
What is graves disease?
aka toxic diffuse goiter
An autoimmune disease which affects they thyroid. It results in hyperthyroidism and goitre
Where is thyroglobulin synthesized and then processed?
Synth: Endoplasmic reticulum
Processed: Golgi apparatus
How does Iodide enter the follicle cell? Where does the energy for this come from and what is the process called?
IODIDE TRAPPING
Enters via the 2Na/I symporter
Energy comes from concentration gradient (low intracellular Na) created by Na/K ATPase pump
How is iodide moved from the folicle cell into the colloid?
Via the PENDRIN I/Cl antiporter
What converts iodide to iodine?
Peroxidase enzymes
What happens to free iodine in the colloid?
It joins with the tyrosine residues on thyroglobulin, creating either monoiodotyrosines or diodotyrosines
What is the name of the process of moving MIT/ DIT’s/T3/T4 into the follicle cells from the colloid?
Pinocytosis
How are T3 and T4 created in the colloid?
By joining of MIT’s and DIT’s
Mono/diidotyrosines
When does T3/T4 seperate from thyroglobulin and how does this occur?
When taken back into follicle cells
Done by lysosomes
How do T3 and T4 get back into the blood and what happened to them once the reach the blood?
Lipid soluble so go through basolateral membrane
Carrier mostly by carrier proteins
How does the body stabilise T3 and T4 levels?
Bind to intracellular proteins for storage over days/ weeks
How does the body stabilise T3 and T4 levels?
Bind to intracellular proteins for storage over days/ weeks (T4 binds more strongly)
T4 can be classed as a pro- form of T3, how is it converted and where does this happen?
By diodinase enzymes
Type 1- In liver, thyroid, kidney (low affinity)
Type 2- In pituitary/ brain/ brown fat/ thyroid (high affinity)
Type 3- Inactivates T3 and T4
How does T3 have its effect on the cell?
Binds to nucelic receptors (thyroid hormone receptor and retinoid X receptor)
This changes gene transcription and mRNA leaves the nucleus
What affects does increased thyroid hormone levels have on body
CNS development
Growth of skeletal muscle
Increased cardiac output/ heart rate/ resp rate
Increase O2 consumption/ gluconeogenesis/ protein synth
Where are the parathyroid glands located?
Usually 4 glands
Found behind the thyroid
What is the difference between thyrotoxicosis and hyperthyroidism?
Thyrotoxicosis- Increased levels of thyroid hormone (any cause e.g. hyperthyroidism or levothyroxine over dose)
Hyperthyroidism- Excessive production of thyroid hormone by thyroid gland
What is the lifetime risk of hyperthyroidism and what is it’s most common cause? What is the most common age of presentation?
Presents most commonly 20-50
Lifetime risk F: 2% / M: 0.2%
70% cases due to graves disease
What are the risk factors (5) for hyperthyroidism?
Family history, high iodine intake, smoking, childbirth, multinodular goitre
What are the symptoms (11) of hyperthyroidism?
Weight loss despite increased appetite (10% have weight gain) or appetite changes
Anxiety/ nervousness/ irritability
Tremor/ sweating/ palpitations/ heat intolerance
Weakness/ fatigue/ changes in menstruation
What are the signs (8) of hyperthyroidism?
Fine tremour/ tachycardia/ goitre
Warm, sweaty palms/ palmar erythema
Hair thinning/ hyperreflexia/ muscle weakness or wasting
What are the additional 3 signs and symptoms seen in graves disease?
Hyperthyroid symptoms Eye bulge (exophthalmos) Pretibial myxedema (waxy/ orange peel skin)- Rare ~3% of P
What are the signs and symptoms of thyrotoxic crisis (aka thyrotoxic storm/ hyperthyroid crisis)? How should it be treated?
Fever >38.5/ Tachycardia/ delirium/ coma/ seizures
Vomiting/ diarrhoea/ Jaundice
25% mortality (arrhythmia’s etc)
TREAT WITH propylthiouracil
What is the name of the autoantibody in Graves disease?
Thyroid-stimulating immunoglobulin
What are the three most common causes of thyrotoxicosis?
Graves
Multinodular goitre (surgery)
Solitary nodule
What are the risks associated with thyoidectomy?
2% relapse rate (take T4 post surgery)
1% vocal cord paralysis
5% permenant parathyroid damage
(very surgeon dependant)
What is the difference in what is monitored when treating with thyroxine for hypothyroidism or carbimazole for hyperthyrodism?
Titrate dose against:
Carbimazole: T4 levels
Thyroxine: TSH levels
What is myxedema?
Hypothyroidism (severe)
Also describes dermatological changes
What is goitre and what can cause diffuse goitre?
Its and enlarged thyroid
Cause (diffuse): Graves/ hashimoto hypothyroidism/ colloid goitre/ iodine deficiency/ drugs
What should you do about nodules found on the thyroid?
V.common (Increases with age)
For >1cm do ultrasound or fine needle aspiration
What is the most accurate blood test to diagnose hypo/hyperthyroidism?
TSH
What is subclinical hyperthyroidism?
Normal T3/T4
Low TSH
Which foods provide the best iodine sources?
Seaweed (like kelp)- Best
Seafoods (cod, shrimp)
Meat/ egg/ milk
What hyperthyroidism do to pulse pressure?
Increases pulse pressure
raised systolic/ decreased diastolic
What does T3 do to mitochondia levels?
Increases them and causes growth of mitochondria
Which hormone (T3/T4) is most stable in blood?
T4
What would happen to a child with hypothyroidism in relation to their growth?
FTT
What would happen to a child with hyperthyroidism in relation to their growth?
Initially grow very fast but then not reach full potential as epiphesis plates close earlier?
Which of the two types of cellular receptors (membrance/ nuclear) has a quicker response time?
Membrane
As nuclear need to use transcription to have effects which takes longer
How does TSH act on the cell to increase T3/T4?
Binds to membrane receptor and activates cAMP
Faster breakdown of thyroglobulin
Growth of thyroid cell
Increased concentration of
What % of T4 is unbound and which type of T4 is active?
T4 is only active when unbound
0.03% is ‘free’ in blood
What temperature issues do patients with hyper and hypothyroid experience?
Hyperthyroid: Heat intolerance
Hypothyroid: Cold intolerance
Why do patients with hyperthyroidism experience nervousness?
Because TSH increases sympathetic stimulation (and increased release from all endocrine glands)
What effect does thyroid hormone have on cholesterol?
Lowers serum cholesterol levels
What antibody is involved in Graves disease?
TSI- thyroid stimulating immunoglobulin
What is derbyshire neck?
Goitre caused by lack of iodine in the diet
What is the difference between PTU (propylthiouracil) and carbimazole?
Carbimazole inhibits TPO centrally but PTU does this and also inhibits conversion of T4 to T3 peripherally
Roughly how long are drugs such as carbimazole given?
18months
Which isotopes of I are used for treatment and diagnostic imaging?
Diagnosis: I(123)
Treatment: (131)
What are the similarities between the epidemiology of Graves and anxiety?
Both affects F much more than M
Around 20-50 peak age
Where would you find the TPO enzyme?
On the luminal membrane of the thyroid follicule cells
What do low T4 levels do to TSH levels?
Raise TSH
Graves disease is most like to affect what age group and gender? Whereas multinodular goitre is most likely to affect…?
Graves: F (younger age)
MG: M (older age)
What is the general mechanism of carbimazole and propylthiouracil?
Block iodine organification
Stops TPO enzyme iodinating tyrosine residue on thyroglobulin
What is the most common SE of carbimazole and propylthiouracil?
Rash and itching
Where are C-cells found and what is there role?
aka parafollicular cells
Interspersed with columnar epithelium Make calcitonin (lowers blood calcium)
What use does T3 have in diagnosing hypothyroidism?
Very little use as levels don’t drop until disease is severe
TSH is used instead
What is the unit MBq used to measure?
Megabecquerel
Disintergrations per second (radioactivity)
What causes exophthalmos in graves disease?
TSH receptor antibodies also go into the tissues of the orbital muscles and cause inflammation
What is the most common malignancy of the thyroid?
Papillary carcinoma
What is the pathophysiology of Graves disease?
Autoimmunie- antibodies produced to TSH receptor
These antibodies bind to the TSHr and chronically stimulate it
What is the role of the Na+/K+ ATPase pump?
Pumps Na+ out of cells and K+ into cells
Uses ATP as both molecules are moving against their concentration gradient
What does TSI stand for?
Thyroid stimulating immunoglobulin
All diiodinase enzymes contain which amino acid?
Selenocysteine
