Thyroid hormones and disease

Question 1

Describe the surface anatomy and structure of the thyroid gland

Answer 1

The thyroid gland sits on the anterior surface of the trachea, in the neck.
The isthmus sits on the 3rd tracheal cartilage, with its lobes extending to the right and left.
Smooth and symmetrical.
Elevated upon swallowing

Question 2

Describe the histology of the thyroid gland

Answer 2

The thyroid gland is formed from spheres of follicles, formed from follicular and parafollicular cells, with a central colloid.
The colloid contains TGB, which stores thyroid hormone precursors ready for TH synthesis in the colloid.
Follicular cells produce thyroid hormone
Parafollicular cells produce calcitonin.

Question 3

Describe the functions of the thyroid hormone

Answer 3

UPTAKE OF IODINE FOR THYROID HORMONE SYNTHESIS (T3 AND T4)
The thyroid hormone acts as a large store of thyroid hormone and iodine.
- Able to sequester iodide from the blood (for the synthesis of thyroid hormones)
- Secretes T3 and T4

Question 4

Name the 4 hormones produced by the thyroid hormone

Answer 4

T4
T3 active form
Reverse T3 (inactive) 
(above are phenylalanine derivative hormones - synthesised from tyrosine)
Calcitonin

Question 5

Relationship between T4 and T3

Answer 5

T4 is much more abundant than T3.

T4 is converted to T3 active form in peripheral tissues, the brain and the thyroid gland.

Question 6

Describe the functions of thyroid hormones

Answer 6

Metabolic: Increases carbohydrate metabolism (gluconeogenesis, glycolysis and glycogenolysis) and increases lipolysis and fatty acid oxidation
Cardiovascular: Increases rate, contractility force and CO. ↑ vasodilation
Growth: Essential for growth
Reproductive system: Behaviours and physiology is dependent on thyroid hormone

Question 7

Describe the functions of T3

: Cell membrane, mitochondria, nucleus, neonatal cells

Answer 7

Cell membrane –> Increases Na/K ATPase pump expression –> Increased demand for metabolites e.g. glucose
Mitochondria –> Stimulates growth, replication and activity. Increases basal metabolic rate –> Increased heat production, oxygen demand, HR and SV
Nucleus –> Increases the production of energy producing genes –> ↑ lipolysis, FA oxidation, gluconeogenesis, glycolysis
Neonatal cells –> cell division and maturation –> essential for the development of the CNS and skeleton

Question 8

HPT axis regulation and control - Positive feedback

Answer 8

Positive feedback: Oestrogen acts on the pituitary gland.

Cold and stress acts on the hypothalamus

Question 9

HPT axis regulation and control - Negative feedback

Answer 9

Hypothalamus: T3, T4 and TSH
Pituitary gland: Somatostatin, dopaminergic molecules, glucocorticoids, cytokines
β-blockers and corticosteroids inhibit conversion of T4 to T3.
Lithium and carbimazole inhibits T3 and T4 production

Question 10

Transport of thyroid hormones

Answer 10

Transported in the blood bound to a carrier protein

Question 11

Sequence of thyroid hormone synthesis, storage and release

Answer 11

1. Iodide trapping by Na/K ATPase (Rate-limiting AND energy dependent). Iodide taken into follicular cells.
2. Synthesis of thyroglobulin (TGB) in follicular cells and release into the colloid by exocytosis. TGB vesicles have TPO (thyroid peroxidase) within them
3. Pendrin channel transports iodine at the apical membrane
4. TPO oxidises iodide 2I –> I2
5. TPO iodinates the TGB tyrosine molecules, generates T1 and then T2
6. TPO conjugates/couples T1 and T2 to synthesis T3 and T4
7. TGB is taken up into follicle cells. Undergoes lysosomal digestion to release T3 and T4
8. T3 & T4 are secreted into the blood. Primary binding molecule is TBG

Question 12

Symptoms of hyperthyroidism

Answer 12

Weight loss, tachycardia, heat intolerance, increased appetite, goitre, exophthalmos, anxiety and tremor

Question 13

Symptoms of hypothyroidism

Answer 13

Weight gain, bradycardia, cold intolerance, goitre, dry hair and skin, fatigue and depression

Question 14

Causes of hyperthyroidism

Answer 14

Grave’s disease: An autoimmune disorder in which autoantibodies are produced. The TSH like autoantibodies act on the TSH receptor, promoting thyroid hormone synthesis.
Single toxic nodule
Multinodular goitre (iodine deficiency)
Thyroiditis (causes release of stored TH - no increase in synthesis)
Drug induced thyrotoxicosis Pregnancy
Iatrogenic

Question 15

Causes of hypothyroidism

Answer 15

Hashimoto's disease: Autoimmune hypothyroidism
Post surgical
Iodine deficiency/excess
Drugs
TSH deficiency 
Thyroid hormone resistance 
Maternal IgG
Congenital diseases
Thyroid cancer

Question 16

Treatment of hyperthyroidism

Answer 16

Block T4 production
TPO inhibitor: E.g. carbimazole. Delayed effects due to large stores of TGB, 4-6 weeks until changes observed
Corticosteroids and beta-blockers to decrease T4 –> T3 conversion
Beta-blockers also decrease tachycardia - act immediately

Question 17

Names of T3 and T4

Answer 17

T4 - Thyroxin

T3 - triiodothyronine

Question 18

Treatment of hypothyroidism

Answer 18

Administration of T4 (oral, cheap and easy to produce)