Thyroid Physiology Flashcards
How was the thyroid gland discovered to be the first endocrine organ of which its secretion are vital for health?
46 year old women with low thyroid hormones was given sheep thyroid extract (1891) causing her to live for another 28 years
What is the thyroid gland?
A gland at the front of the neck in front of the trachea near the 3rd tracheal ring with 2 lateral lobes + an isthmus
What are the arteries that supply the thyroid gland?
- Super thyroid artery (branch of external carotid)
- Inferior thyroid artery (branch of thyrocervical trunk)
- Thyroid ima (sometimes)
What are the veins that supply the thyroid gland?
- Superior thyroid
- Middle thyroid
- Inferior thyroid
Branch of the brachiocephalic vein + then internal jugular vein
What are the 3 hormone secreted by the thyroid gland and what are their main functions?
- Thyroxine (T4)
- Tri-iodothyronine (T3)
- Calcitonin
T4 + T3 for basal metabolic rate
Calcitonin for Ca2+ homeostasis
What are T4 and T3 derivatives of?
Iodinated derivatives of tyrosine with T4 containing 4 iodine molecules + T3 containing 3 iodine molecules
Why is the microstructure of the thyroid gland?
Made up of follicles with colloids surrounded by follicular cells + parafollicular (C) cells allowing it to store large amount of thyroid hormone ready to secrete
What are the 6 steps of thyroid hormone synthesis?
- Thyroglobulin (tyrosine containing) synthesis
- Uptake + concentration of iodide (I-)
- Oxidation of iodine (I-) to iodine (I) by thyroid peroxidase (TPO) on luminal membrane of follicular cell
- Iodination of thyroglobulin tyrosine residue
- Coupling of 2 iodinated tyrosine molecules to form MIT + DIT (T4 or T3)
- Secretion
What do the follicles within the thyroid do?
Actively accumulate iodine, in the form of iodide (I-) from the blood + secrete it into the colloid (can be seen on a thyroid scan 24 hours after intake of radioactive iodine)
How is iodide (I-) trapped within the follicular cells?
I- enters cell by a Na/I- symporter located on basolateral side of cell
Na+/K+ ATPase functions at the same time on the basolateral membrane to supply energy for the process
Why is iodide (I-) trapped?
Because it is rare
How much iodine should adults intake?
150μg/day
What are the dietary sources of iodine?
Milk + dairy Seawater: seafood + seasalt Fruit + veg (depends on soil/imports) Some foods chelate iodine e.g. sauerkraut Supplemented foods (salt)
How much of a problem is iodine deficiency?
Worlds most prevalent cause of brain damage
Most important nutritional deficiency
What is the advantage of population supplementation of iodine?
Cheap
Safe
Acceptable to all
Widely used throughout the year
What effect has population supplementation of iodine had?
90% of salt is supplemented with iodine which has decreased iodine deficiency from 30% to <15%
Why are women living in rural India and tribal areas more likely to get iodine deficiency? What can be done about this?
Usually do not consume iodised salt + cannot afford nutrient supplements
“Bindi” worn on forehead is a significant ornamental object of Indian women + iodine can be absorbed through the skin via this (150μg per 8 hours)
What conjugates form T3 and T4?
Mono-iodotyrosine (MIT) + Di-iodotyrosine (DIT)
MIT + DIT = T3
DIT + DIT = T4
How are thyroid hormones secreted?
- Microvilli of follicle cell engulf T3 + T4, MIT + DIT all still attached to thyroglobulin
- Taken up into the cell forming a vesicle containing some colloid
- Attaches to a lysosome
- Protease breaks down the molecules to release T3 + T4 separately from MIT, DIT + thyroglobulin
- T3 + T4 secreted into blood
- MIT, DIT + thyroglobulin recycled + transported back into the colloid via pendrin
Describe the hypothalamus-pituitary-thyroid (HPT) axis.
- Hypothalamus releases TRH (produced by paraventricular nucleus)
- Anterior pituitary stimulated to produce TSH
- Thyroid produces T3 + T4
- T3 + T4 can negatively feedback to the pituitary or the hypothalamus
What is Thyroid Stimulating Hormone (TSH)?
Glycoprotein released from the anterior pituitary
How is Thyroid Stimulating Hormone (TSH) similar to Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH)?
All have α + β chains with identical α chains but protein-specific β chains
Made independently
Disease can cause increase or decrease of either or both
How does Thyroid Stimulating Hormone (TSH) increase thyroid hormone synthesis?
By binding its receptor, activating cAMP + activate protein kinases causing phosphorylations
Stimulates every step of thyroid hormone production + secretion so has a dramatic effect
How do thyroid hormones travel in the blood?
Lipophilic so need to associate with proteins:
- 70% bound to Thyroxin (Thyroid) Binding Globulin (TBG)
- 30% bound to albumin
What blood protein has a higher affinity for T4 than T3?
Thyroxin (Thyroid) Binding Globulin (TBG)
How does thyroid hormone have its action?
- T3/T4 enter cell via diffusion + transporter MCT8
- T4 must be converted to T3 by deiodinases
- T3 binds receptor T3R on nucleus
- T3 binds to DNA + changes proteins synthesis
What do deiodinases do?
3 different types that Interconvert T3, T4 + rT3 variably
What is rT3?
Inactive form of T3 incapable of metabolic activity carried out by T3
Thought to be produced by body from T4 in times of severe illness or starvation to preserve energy
How do peripheral tissues regulate T3 levels?
By upregulating or downregulating deiodinases
Where are type 1 deiodinases found? What do they do?
Cell surface of most cells esp. liver, kidney, thyroid + brain
Inner + outer ring deiodination activating T4 -> T3
Where are type 2 deiodinases found? What do they do?
IC raises T3 in CNS, brown fat, placenta, skeletal + cardiac muscle
Outer ring deiodination activating T4 -> T3
Where are type 3 deiodinases found? What do they do?
Remove iodine from T4 to make rT3 especially in placenta + CNS (perhaps to protect foetus)
Inner ring deiodination inactivating T4 -> rT3; T3 -> T2
What are the physiological effects of thyroid hormone?
- Metabolism: affects all metabolic pathways (anabolic + catabolic) affecting BMR
- Maturation + differentiation in bone/lungs/brain etc.
- Neurological functions: synapse formation, myelinogenesis + neuronal outgrowth
- Growth: regulated by GH but T3/T4 needed too
What are thyroid hormones main functions in development?
Skeletal muscle growth
CNS development
What week of development does the thyroid gland start secreting thyroid hormone? Why?
By week 12 of gestation this process is occurring under control of foetal hypothalamus + pituitary as after 1st trimester not enough TSH or T3/T4 can cross the placenta
What is cretinism?
Impaired physical + neurological development due to iodine deficiency during foetal or postnatal development
Why is TSH testing in a heel prick test done in babies?
Because after the 1st 2 years of life, the effects of cretinism cannot be reversed so screening is done in the USA, UK etc.
How does thyroid hormone affect metabolism?
T3/T3R increases/decreases mRNA/proteins having an effect on:
- Na/K ATPase on cell membranes
- Mitochondria respiratory enzymes
- Other nuclear enzymes
- Cells esp. neonatal (growth + maturation)
= increased O2 consumption + metabolic rate
How do thyroid hormones match an increase in metabolic rate?
Decrease:
Muscle mass
Adipose tissue
Increase: CO2 Ventilation Urea Renal function Thermogenesis leading to; increased sweating, ventilation + surface blood flow
What happens in the cell when there is 40% basal energy?
ATP increases O2 consumption
How much oxygen is consumed by cells at rest, with no T3 or with excess T3?
Rest: 225-250ml/min
No T3: 150ml/min
Excess T3: 400ml/min
What does T3 need to do to match the increased oxygen requirements of a cell?
Increase ventilation via increased respiratory
Increased HR, blood flow + myocardial activity increasing CO - to deliver the O2
Increase food intake + protein/lipid/carbohydration metabolism - O2 use needs substrates for oxidation
How common are thyroid gland disorders?
2nd most common endocrine disorder after diabetes
What can be effected to cause a thyroid gland dysfunction?
Gland formation/function Iodine supply (deficiency) Signalling pathways (TSH, TRH) Congenital or acquired
What can cause a problem in the body’s response to thyroid hormones?
Thyroid hormone resistance i.e. T3R defect
What are the Thyroid Function Tests (TFTs)?
TSH
Free T4
Free T3
Total T4/T3 in rare circumstances
What other thyroid blood tests might you carry out? Why?
Thyroid Abs: cause of thyroid disorder?
Thyroglobulin + calcitonin: long-term follow up of people treated with thyroid cancer
What happens to the thyroid hormones in thyroid hormone resistance?
T4 is high
TSH is normal
A high T4 should normally reduce TSH but tissues do not recognise T3
What happens to the thyroid hormones in primary hypothyroidism?
Low T4 High TSH (slightly raised = subclinical/mild/borderline)
High TSH should normally increase T4
What happens to the thyroid hormones in primary hyperthyroidism?
High T4
Low TSH
Low T4 should stimulate TSH normally
What happens to the thyroid hormones in secondary (pituitary)hypothyroidism?
Low T4
Low TSH
Low T4 should stimulate TSH normally
What symptoms occur as a result of hyperthyroidism?
Heat intolerance, sweating, warm, moist hands Weight loss despite increased appetite Diarrhoea Palpitations/rapid pulse Tiredness + weak muscles Nervousness, irritability, mood swings + shakiness Thirst + polyuria Itchiness Goitre
What is the most common kind of hyperthyroidism? What symptom is specific to this disease?
Graves disease caused by autoantibody Thyroid Stimulating Immunoglobulin (TSI) which binds to the TSH receptor
Exopthalmos
What happens to the thyroid hormones in secondary (pituitary) hyperthyroidism?
Increased T4
Increased TSH
Increased T4 should normally decrease TSH
What symptoms occur in hypothyroidism?
Fatigue + tiredness Sensitivity to the cold Constipation Dry skin + hair (alopecia) Low mood + mental slowness Goitre Overweight/obese Heavy periods + fertility problems
What are the most common causes of hypothyroidism?
Hashimotos thyroiditis (auto-immune destruction)
Iodine deficiency
What is a goitre?
Enlarged thyroid gland but this is NOT an indication of thyroid gland activity
What are the 3 causes of a goitre?
- Iodine deficiency: low T4 induces TSH secretion
- Graves disease: high T4 due to autoimmunity producing TSI which acts as TSH
- Tumours (benign or cancer)
How can both low and high T4 induce a goitre?
Iodine deficiency (hypo): low I decreased T4 secretion decreases TSH inhibition so increased TSH action on gland increases growth
Graves (hyper): TSI mimics TSH so increased action on gland by this increases T4 + gland growth
What is the treatment for hyperthyroidism?
- Drugs that inhibit production e.g. carbimazole or propylthiouracil
- Radioactive I131 which destroys gland
- Surgery
What problems can occur in thyroid surgery?
General surgery issues
Vocal chord nerve damage
Bleeding
Parathyroid gland damage
What are the treatments for hypothyroidism?
Replacement hormones:
Levothyroxine (synthetic T4) - drug of choice for maintenance due to long T1/2 (1/day) + activated in body
Iiothyronine (synthetic T3) - limited use but rapid (transient) action (spikes)
How often must blood tests be done when a patient is on levothyroxine? What are you looking for?
~ 8 weeks
Aiming for a normal TSH - if its not normal, dose can be titrated up until it is
