The Thyroid Gland

Question 1

What is the thyroid gland and summarise its main functions

Answer 1

• One of the largest endocrine organs which located immediately below the larynx.
• Secretes two major metabolic hormones; thyroxine (T4) and triiodothyronine (T3).
• Secretion controlled by TSH,
• Thyroid gland secretes calcitonin.
• Thyroglobulin is secreted into follicular sacs within the gland

Question 2

Describe features of the cells and compartments of the thyroid gland

Answer 2

Cuboidal epithelial cells secrete colloid into follicles within the thyroid gland. The main compounent of colloid is thyroglobulin which contains the thyroid hormones.
C cells secrete calcitonin

Question 3

describe general features of T3 and T4 hormones

Answer 3

93% of metabolically active hormones secreted by thyroid gland it thyroxine. 7% is triiodothyronine (T3). However almost all T4 is eventually converted to T3.
Function of T3 and T4 is to increase metabolic rate

Question 4

What is the function of iodine?

Answer 4

• Iodine is required to form thyroxine

Question 5

Explain iodide trapping

Answer 5

This is the process of trapping iodide within the TG cells.
At the basolateral membrane, the thyroid cell actively pumps iodine into the cell via sodium-iodide symporter (2Na:1 iodide - uses energy of allowing 2Na ions to flow along conc gradient to pump iodide ion across). Iodine conc normally sits at 30x plasma levels but can increase to 250x.
Iodine is then transported through apical membrane into follicle by pendrin (chloride-iodide antiporter)

Question 6

Describe features of thyroglobulin and its role in the formation of T3 and T4

Answer 6

Thyroglobulin is a large glycoprotein molecule which contains 70 tyrosine amino acids. This is key because within the thyroglobulin molecule, the tyrosine combines with iodine to form T3 and T4.

Question 7

Explain the formation of iodine from iodide

Answer 7

• The iodide ions are converted to oxidised form of iodine by peroxide which is produced by enzyme peroxidase. Blockage or absence of peroxidase system stops formation of thyroid hormones.

Question 8

Describe the binding of oxidised iodine to thyroglobulin

Answer 8

The reaction will occur spontaneously but slowly and since oxidised iodine is associated with thyroid peroxidase, this speeds up the reaction.

Question 9

Describe the formation of T3 and T4 (stages of iodination and coupling)

Answer 9

• Tyrosine is iodized to monoiodotyrosine and then diiodotyrosine. The residues then become coupled with each other;
  T4 = 2x diiodotyrosine.
  T3 = Mono+diiodo-tyrosine
  Small amount of reverse T3 = Diiodo+monoiodotyrosine

Question 10

Explain the storage of the thyroid hormones

Answer 10

Once synthesis is finished, each thyroglobulin contains up to 30 T4s and a few T3s. The storage supply lasts for 2-3 months and so deficiency/pathology may not be detected for a while

Question 11

Describe the release of thyroid hormones

Answer 11

• Colloid (containing thyroglobulin with T3 and T4) is brought into cell apex via pinocytosis.
• The pinocytotic vesicles in the thyroid cell fuse with lysosomes which contain protease.
• Protease digests thyroglobulin to release T3 and T4 which then diffuse through basolateral membrane into capillaries

Question 12

Explain the transport of T3 and T4

Answer 12

Over 99% bound to plasma proteins, the main ones of which are thyroxine-binding globulin, thyroxine-binding prealbumin and albumin. The proteins have a high affinity for T3 and T4 and so they release them slowly. They then bind to intracellular proteins for storage

Question 13

Describe the onset and duration of action of thyroxine injections

Answer 13

• 2/3 day latent period with increasing activity over 10-12 days.
• Diminishes over several weeks/months.
• T3 has a more rapid response

Question 14

What are the effects of T3 and T4 on genes?

Answer 14

• Most of T4 is de-iodinated to form T3.
• T3 then interacts with the thyroid hormone receptor with in the nucleus which leads to an increase or decrease in the transcription of genes that leads to the formation of proteins

Question 15

The non-genomic cellular effects are mediated via?

Answer 15

Activation of intracellular 2nd messengers such as cAMP and protein kinase signalling cascades

Question 16

What are the major physiological effects of thyroid hormones?

Answer 16

• Increased basal metabolic rate,
• Mobilisation of carbohydrate, fat and protein stores.
• Increase in blood flow and cardiac output (increased HR and contraction strength),
• Increase in respiration,
• Increased GI motility and glucose uptake from GI,
• Excitatory effects on CNS (anxiety, worry, nervousness),
• Muscle vigor (decreases at high hormone conc due to excess protein catabolism),
• Increased rates of secretion of other hormones,
• Sexual disfunction

Question 17

Explain the physiological regulation of T3 and T4 secretion

Answer 17

• TSH from the anterior pituitary gland increases T3 and T4 secretions.
• TSH secretion is controlled by hypothalamic hormone called thyrotropin-releasing hormone.
• TRH hinds to receptors in pituitary membrane activating phospholipase second messenger system which produces phospholipase C then secondary messenger cascade which leads to TSH release.
• The cold causes excitation of hypothalamic centres for body temp, increasing TRH and TSH
• T3 and T4 send negative feedback back to the hypothalamus

Question 18

Explain pharmacological regulation of T3 and T4 secretion by thiocyanate

Answer 18

Thiocyanate ions decrease iodide trapping, as it competitively inhibits iodide transport into the cell however thyroglobulin is still formed but since it isn’t iodinated then it can’t form thyroid hormones.
- Low thyroid hormones increases secretion of TSH causing overgrowth of thyroid gland leading to goiter.

Question 19

What is goiter?

Answer 19

Enlarged thyroid gland

Question 20

Explain the pharmacological regulation of T3 and T4 secretion by propylthiouracil

Answer 20

Propylthiouracil prevents formation of thyroid hormones from iodides and tyrosine as it blocks peroxidase enzyme which is required for iodination of tyrosine.
Absence of T3 and T4 leads to feedback enhancement of TSH secretion which causes growth of glandular tissue and goiter

Question 21

Explain the pharmacological regulation of T3 and T4 secretion by iodides?

Answer 21

• When there is an increase of iodide then most activity decreases for a few weeks. It causes reduced iodide trapping, reduced iodination of tyrosine, stopping of endocytosis of colloid and shutdown of secretion of T3 and T4 into the blood.
• This causes decrease in gland size and blood flow which is useful before surgical removal of thyroid gland as it makes surgery easier and reduces bleeding

Question 22

What is the most common cause of hyperthyroidism and its features

Answer 22

• Graves disease.
• Autoimmune disease where thyroid-stimulating immunoglobulins antibodies form against TSH receptors in the thyroid gland. This causes continual activation of cAMP system which leads to hyperthyroidism. This stimulates thyroid hormone production more than TSH normally does

Question 23

What are the symptoms of Graves’ disease?

Answer 23

• Excitability,
• Intolerance to heat,
• Increased sweating,
• Weight loss,
• Diarrhoea,
• Muscle weakness,
• Nervousness or other psychic disorders,
• Extreme fatigue but inability to sleep,
• Tremor of hands,
• Exophthalmos

Question 24

What is the most common cause of hypothyroidism?

Answer 24

Hashimoto’s disease.
- Autoimmune disease that destroys that gland rather than stimulating it. Usually thyroiditis occurs leading to fibrosis and decreased size and secretion of thyroid hormone.

Question 25

What are the symptoms of hypothyroidism

Answer 25

• Fatigue,
• extreme somnolence,
• extreme muscular sluggishness,
• slowed heart rate, decreased cardiac output, decreased blood volume,
• Increased body weight and constipation,
• Mental sluggishness,
• Failure of many trophic functions,
• Development of froglike, husky voice,
• development of myxedema.
• Can lead to atherosclerosis, PVD, deafness, CAD and early death.