The thyroid gland

Question 1

Briefly, how is the thyroid gland involved in development?

Answer 1

Essential for normal development, especially CNS and bone

Question 2

Briefly, how is the thyroid gland involved in metabolic functions?

Answer 2

Essential for normal metabolism of many body tissues

Question 3

Describe the histology of the thyroid gland

Answer 3

1. protein-rich colloid
2. Surrounded by epithelial cells known as the follicular cells - synthesise and secrete thyroid hormones
3. We also have C-cells which secrete calcitonin

Question 4

What are the 2 major thyroid hormones?

Answer 4

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

Question 5

Describe the synthesise of a thyroid hormones

Answer 5

Active uptake of I- across basolateral membrane, against concentration and electrical gradient, by Na/I symporter (NIS). Stimulated by TSH.

Iodide efflux (diffusion) across apical membrane via exchanger known as pendrin (PDS).

At extracellular apical membrane iodide is oxidized to iodine and covalently bound to tyrosine residues within the thyroglobulin (TG) macromolecule. Requires thyroid peroxidase (TPO) and H2O2.

Tyrosine residues may be iodinated in one (mono-iodotyrosine, MIT) or two (DIT) positions. Coupling of iodotyrosine residues (catalysed by TPO) produces T4 (DIT-DIT) and a smaller amount of T3 (MIT-DIT).

Under the influence of TSH, colloid droplets consisting of thyroid hormones within the thyroglobulin molecules are taken back up into the follicular cells by pinocytosis.

Fusion of colloid droplets with lysosomes causes hydrolysis of thyroglobulin and release of T3 and T4.

About 10% of T4 undergoes mono- deiodination to T3 before it is secreted. The released iodide is reutilized. Several-fold more iodide is reused than is taken from the blood each day but in states of iodide excess there is loss from the thyroid.

Approximately 100 μg TH secreted per day (90% T4 and about 10% T3). Secretion probably relies on membrane transporter

Question 6

What are most thyroid hormones bound to?

Answer 6

Over 99% bound to plasma protein

Mainly thyroid-binding globulin (~70%), also transthyretin (10-20%), albumin (10-20%)

Question 7

What type of receptor to the thyroid receptors belong to?

What does it have a high affinity for?

In order for them to be activated what happens to the receptors?

What are the receptors encoded by?

Answer 7

TH receptors (TRs) 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 regulates the activity of the 2 main thyroid hormones?

Answer 8

D3 - this deactivates T4 and T3 into the inactive form

D2 - an activating enzyme that converted T4 to T3

Question 9

What are the 3 functions of thyroid hormones?

Answer 9

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 signalling
Gluconeogenesis, lipolysis

Growth and development

Question 10

How is TSH released from the Anterior pituitary gland?

Answer 10

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 11

Describe the TSH and thyroid hormones negative feedback pathway

Answer 11

On image

Question 12

What type of receptor does the TSH bind to?

Answer 12

G protein-coupled receptor – 7 transmembrane

Involved the adenyl cyclase pathway and sometimes the Phospholipase C

Question 13

What does TSH do?

Answer 13

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)

Question 14

Define Euthyroid

What is Hyperthyroidism?

Answer 14

normal thyroid function

TH excess
Primary: problem is thyroid gland itself
Secondary: problem is pituitary regulation

Question 15

What is Hypothyroidism?

Answer 15

TH deficiency

Question 16

Using the negative feedback pathways what is primary hyperthyroidism, primary hypothyroidism and secondary hyperthyroidism

Answer 16

On image

Question 17

What is graves disease?

Answer 17

Autoimmune
High circulating TH, low TSH
Weight loss, tachycardia, fatigue
Diffuse goitre (TSH receptor stimulation)
Opthalmopathy

Question 18

What is Hashimoto’s: primary hypothyroidism

Answer 18

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