thyroid gland

Question 1

what are the main functions of the thyroid hormone ?

Answer 1

Developmental
* Essential for normal development, especially CNS and bone

Metabolic
* Essential for normal metabolism of many body tissues

Increase metabolic rate
* Number and size of mitochondria, enzymes in metabolic chain, Na/K ATPase activity
* Positive inotropic and chronotropic effects on heart
* Synergizes with sympathetic nervous system

Energy metabolism
* Partially antagonizes insulin signaling
* Gluconeogenesis, lipolysis

Growth and development

Question 2

describe the blood supply of the thyroid gland

Answer 2

• Rich blood supply: More blood per unit weight than kidney
• Inferior thyroid artery from subclavian
• Superior thyroid artery from carotid

Question 3

what are the thyroid hormones ?

Answer 3

• T4: major form released to blood, less active (prohormone)
• T3: active form, converted in target cells

derived from 2 iodinated tyrosine molecules

Question 4

describe the histology of the thyroid gland

Answer 4

• Red arrows: follicular cells
• Blue arrows: colloid (mainly thyroblobulin)
• Yellow arrow: c-cell (parafollicular cell)
• Follicular cells synthesize and secrete TH
• C-cells secrete calcitonin (not considered here)

Question 5

what are the steps involved in thyroid hormone synthesis ?

Answer 5

1. Iodide Uptake: Iodide (I-) is actively transported across the basolateral membrane into thyroid cells via the Na/I symporter (NIS), driven by the concentration and electrical gradients. This process is stimulated by TSH.
2. Iodide Efflux: Iodide moves across the apical membrane of thyroid cells through an exchanger called pendrin (PDS), which allows iodide to diffuse out.
3. Iodide Oxidation: At the apical membrane, iodide is oxidized by H2O2 to form iodine (I2), a reaction catalyzed by thyroid peroxidase (TPO).
4. Iodination of Tyrosine Residues: The iodine is covalently bound to tyrosine residues on the thyroglobulin (TG) protein. Iodination can occur at one (forming mono-iodotyrosine, MIT) or two (forming di-iodotyrosine, DIT) positions on tyrosine.
5. Coupling of Iodotyrosines: The iodinated tyrosines (MIT and DIT) are coupled, again catalyzed by TPO, to form thyroid hormones

Question 6

what are the steps involved in thyroid hormone release ?

Answer 6

1. Pinocytosis of Colloid Droplets: Under the influence of TSH, colloid droplets containing thyroid hormones within thyroglobulin are reabsorbed into follicular cells by pinocytosis.
2. Hydrolysis in Lysosomes: These colloid droplets fuse with lysosomes, where thyroglobulin is hydrolyzed, releasing T3 and T4.
3. Deiodination of T4 to T3: About 10% of T4 undergoes mono-deiodination to form T3 before being secreted.
4. Iodide Reutilization: The iodide released during hydrolysis is reutilized. More iodide is reused in the thyroid than taken up from the blood each day. In states of iodide excess, excess iodide is lost from the thyroid.
5. Thyroid Hormone Secretion: Approximately 100 μg of thyroid hormone is secreted per day, with 90% as T4 and 10% as T3. This secretion depends on membrane transporters.

Question 7

describe TH receptors

Answer 7

• belong to the nuclear receptor superfamily
• Ligand-activated transcription factors
• High affinity for T3
• Activation requires dimerization with another TR or retinoid X receptor (RXR)
• TRs encoded by two genes: TR alpha and TR beta

Question 8

What is the role of iodothyronine selenodeiodinases (D1-D3) and inactive metabolites in thyroid hormone regulation?

Answer 8

Iodothyronine Selenodeiodinases (D1-D3):
* Convert T4 and T3 into active or inactive forms.
* Require selenium to function.

Tissue-Specific Expression:
* D2 activates T4 to T3 in brain/muscle.
* D3 inactivates T4/T3 to rT3 or T2 in tissues like placenta/skin.

Regulation of T3 Availability:
* Controls how much active T3 binds to receptors, affecting metabolism (growth, thermogenesis, heart rate).

Inactive Metabolites (T2 and rT3):
* rT3 inhibits T3 action at receptors.
* T2 has minimal receptor effect.

Question 9

what is the hypothalamic-pituitary-thyroid axis ?

Answer 9

• Negative feedback control of thyroid hormone synthesis and secretion, via the hypothalamo-pituitary axis
• Hypothalamic neurosecretory cells release thyrotrophin-releasing hormone (TRH) into the portal capillaries
• TRH stimulates thyrotrophs of anterior pituitary to secrete thyroid stimulating hormone (TSH)

Question 10

describe the Negative feedback control of TH synthesis and secretion

Answer 10

Question 11

describe the TSH receptor

Answer 11

• GPCR
• moderated by adenylate cyclase system
• stimulates growth and development of TG

Question 12

what are the actions of TSH ?

Answer 12

• Increases iodine uptake
• Stimulates other reactions involved in TH synthesis (e.g., TPO)
• Stimulates uptake of colloid
• Induces growth of thyroid gland (which can lead to goitre - swelling in neck due to enlarged thyroid gland)

Question 13

describe hyper and hypothyroidism

Answer 13

• Euthyroid: normal thyroid function
• Hyperthyroidism: TH excess
• Primary: problem is thyroid gland itself
• Secondary: problem is pituitary regulation
• Hypothyroidism: TH deficiency

Question 14

what is Graves disease ?

Answer 14

primary hyperthyroidism
Autoimmune
High circulating TH, low TSH
Weight loss, tachycardia, fatigue
Diffuse goitre (TSH receptor stimulation)
Opthalmopathy - bulging eyes

Question 15

what is Hashimoto’s syndrome ?

Answer 15

primary hypothyroidism
Autoimmune
Low circulating TH, high TSH
Lethargy, intolerance to cold
Lack of growth and development
Diffuse goitre