Thyroid

Question 1

Thyroid gland

Answer 1

gland at the base of the neck
releases two classes of hormones:
1. T3 and T4 thyroid hormones
2. calcitonin

Question 2

Hypothalamic pituitary axis

Answer 2

hypothalamus releases thyrotropin releasing hormone
→ stimulates the anterior pituitary to release thyroid stimulating hormone
→ stimulates thyroid to release T3 and T4
→ exert negative feedback on both upstream glands

Question 3

thyroid hormone physiological effects

Answer 3

1. increase basal metabolic rate
2. sensitization to catecholamines → increased cardiac output, heart rate, breathing rate = more energy
3. important role in growth and development = deficiency can cause stunted growth

Question 4

thyroid hormone synthesis

Answer 4

synthesized from thyroglobulin tyrosine side chains
1. tyrosine side chains are iodinated by thyroglobulin peroxidase → addition of iodide to 3 position or 3 and 5 positions of tyrosine aromatic ring
2. peroxidase will couple the iodinated tyrosine side chains → depending on if it has one or two iodine atoms, T3 or T4 will form

Question 5

thyroid hormone-producing cells

Answer 5

thyroid glands are organized into follicles: formation of cells circled around lumen (fluid-filled space)
- apical side
- intracellular
- basolateral side (bloodstream)

Question 6

synthesis of T3 and T4

Answer 6

1. synthesis of thyroglobulin by thyroid gland cell → released into the lumen of the follicle
2. iodination
3. coupling
4. endocytosis → stimulation of thyroid gland by TSH; cells endocytose modified thyroglobulin - taken up into cells and processed to cleave tyrosine side chains from thyroglobulin precursor
5. release of T3 and T4 into blood stream

Question 7

Iodide

Answer 7

the thyroid gland concentrates iodide from the bloodstream (Na+/I- co-transporter on basolateral side uses sodium electrochemical gradient)
iodide is transported into the follicle lumen and eventually added to thyroglobulin tyrosines during the iodination step

Question 8

thyroid hormone receptor

Answer 8

intracellular type receptor - bound as dimer to thyroid response element on DNA - acts as transcription factor after binding of thyroid hormone

Question 9

thyroid hormone mechanism of action

Answer 9

thyroid hormone acts on the thyroid hormone receptor (THR) and retionic acid receptor → influences the transcription of genes

Question 10

thyroid receptor - resting state

Answer 10

in absence of hormone, thyroid receptor has a ligand binding domain where the hormone will bind and the DNA binding domain where it will bind to the thyroid response element in DNA
at rest, unbound thyroid hormone receptors can associate with response elements and recruit co-repressors (prevent gene transcription)

Question 11

thyroid hormone action on receptor

Answer 11

thyroid hormone will circulate, bound to binding proteins
transmembrane protein on cell surface transports T3 and T4 into cell (not lipid soluble)
T4 is typically de-iodinated to form T3
→ migrates to nucleus + binds to receptor - alters composition of dimer - one THR is replaced by RXR = heterodimer
swaps out controllers of transcription = repressor → activator
→ recruitment of co-activator leads to enhanced transcription of target gene by recruiting necessary machinery

Question 12

thyroid disorders

Answer 12

hypothyroidism - Hashimoto’s
hyperthyroidism - Grave’s Disease

Question 13

hypothyroidism

Answer 13

deficient thyroid function - not enough release of thyroid hormone

symptoms: fatigue, weight gain, hypersensitivity to cold, bradycardia

treated by hormone replacement - synthetic T4 (levothyroxine)

Question 14

causes of hypothyroidism

Answer 14

iodine deficiency - dietary
Hashimoto’s thyroiditis - autoimmunity towards thyroid
congenital defect - abnormal development
poor hormone regulation - insufficient TSH/TRH

Question 15

Hashimoto’s thyroiditis

Answer 15

autoimmune disease- antibodies recognize other thyroid-specific proteins and damage the thyroid

follicles shrink and die

Question 16

primary hypothyroidism

Answer 16

defect in thyroid function
low T3 and T4
high TSH

Question 17

secondary hypothyroidism

Answer 17

central defect
low T3 and T4
low TSH

Question 18

hyperthyroidism

Answer 18

overactive thyroid function

symptoms: sleep difficulty, heat intolerance, tachycardia, weight loss, tremor

treatment: surgery, radioactive iodine, anti-thyroid drugs, symptomatic blockers

Question 19

causes of hyperthyroidism

Answer 19

Graves’ disease
hyperplasia of thyroid

Question 20

Grave’s disease

Answer 20

autoimmune disease - stimulatory auto-antibodies against TSH receptor that causes excess thyroid hormone release

exophthalmos (bulging eyes) - damage of muscles or fibroblasts of eye
goiter - overactivation of thyroid tissue

Question 21

hyperthyroidism treatment

Answer 21

surgery - resection of thyroid + hormone replacement
radioactive iodine treatment - destroy thyroid (no use in pregnancy)
anti-thyroid drugs - prevent synthesis steps of T3/T4
symptomatic treatment with B-blockers

Question 22

thioamides

Answer 22

ex. methimazole
prevent iodination + coupling steps mediated by thyroperoxidase enzymes
acts as irreversible inhibitors of enzyme