Thyroid Gland

Question 1

Describe the embryology of thyroid gland

Answer 1

Begins as a midline outpouching from floor of pharynx (originates from base of tongue). Development of thyroglossal duct occurs followed by division into 2 lobes. Duct disappears leaving foramen caecum. Thyroid in its final position by week 7 of gestation and then the actual gland develops.

Question 2

How are iodothyronines formed?

Answer 2

Thyroglobulin contains tyrosine residues which undergo iodination - if a single iodine residue is added to the aromatic ring, it forms 3-monoiodotyrosine (MIT). Similarly, the addition of 2 iodine residues forms DIT. When a MIT and DIT react in a coupling reaction, they give rise to T3 with 3 iodine residues (triiodothyronine). When 2 DIT react, they form T4 (thyroxine). T3 is the bioactive hormone however, only 20% of thyroid output is T3. Mostly, T4 produced and circulated to cells. Iodination carried out by thyroperoxidase.

Question 3

Describe the deiodination of tetraiodothyronine

Answer 3

Thyroxine (T4) is the main hormone product of the thyroid gland. Once in cells it is deiodinated to triiodothyronine (T3) by deiodinase enzyme, its bioactive form. Also deiodinated in a different position to produce reverse T3 (inactive).

Question 4

How do thyroid hormones become active in cells?

Answer 4

Healthy adult thyroid gland secretes both T3 and T4. Tetraiodothyronine (Thyroxine, T4) is a prohormone converted by deiodinase enzyme into the more active metabolite triiodothyronine (T3) in peripheral tissue. T3 provides almost all the thyroid hormone activity in target cells.

Question 5

How are thyroid hormones transported in the bloodstream?

Answer 5

Mostly bound to plasma proteins. These proteins are:
a) thyroid-binding globulin: TBG (70-80%)
b) albumin (10-15%)
c) prealbumin (aka transthyretin)
Only 0.05% T4 and 0.5% T3 is unbound (bioactive components).

Question 6

What happens when T3 and T4 enter the cell?

Answer 6

T3 and T4 enter cell within target tissue through respective receptors from the bloodstream. Deiodinase acts on T4 and converts it to T3 which then diffuses into nucleus. When it binds to the thyroid receptor on the thyroid receptor response element, can enable and inhibit transcription.

Question 7

What is the role of thyroid hormone in babies and what can a lack cause?

Answer 7

Essential for fetal growth & development, in particular that of the central nervous system. Untreated congenital hypothyroidism is known as cretinism. TSH measured in newborn infant’s heel-prick test.

Question 8

What are the general effects of thyroid hormones?

Answer 8

1. Increases basal metabolic rate
2. Protein, carbohydrate & fat metabolism
3. Potentiate actions of catecholamines (e.g. tachycardia, lipolysis)
4. Effects on the GI, CNS, Reproductive systems

Question 9

What effects do thyroid hormones have on growth, the CNS and cardiovascular system?

Answer 9

Growth formation and bone maturation. Maturation of CNS. Increases cardiac output.

Question 10

How do thyroid hormones effect basal metabolic state?

Answer 10

Increase Na+/K+ ATPase activity. Therefore, O2 consumption increased. Greater heat production and hence higher BMR.

Question 11

How do thyroid hormones effect metabolism?

Answer 11

Increase glucose absorption. Increase glycogenolysis and gluconeogenesis. Increase lipolysis, protein synthesis & degradation.

Question 12

How is thyroid hormone production controlled?

Answer 12

When the hypothalamus produces thyrotrophin releasing hormone, anterior pituitary gland is activated to produce thyroid stimulating hormone. The TSH then activates the thyroid gland to produce thyroid hormones. However, T3 and T4 inhibit TRH and TSH in the hypothalamus and pituitary gland respectively. Moreover, the Wolff-Chaikoff effect occurs when an excess of iodine inhibits the formation of T3 and T4 by the thyroid gland.

Question 13

Are thyroid disorders more common in men or women?

Answer 13

More common in women by a 4:1 ratio as most thyroid disorders are a result of autoimmunity. Women are more likely to develop autoimmune conditions as pregnancy exposes one to many different antigens – hence, women’s immune systems are slightly different to cope with this and therefore, their immune system is more predisposed to autoimmunity.

Question 14

Is an overactive thyroid gland or an underactive thyroid gland more common?

Answer 14

Both are equally common.

Question 15

What occurs in primary hypothyroidism?

Answer 15

Caused by autoimmune damage to thyroid. Causes decline in thyroxine levels and TSH levels climb. Commonest forms of autoimmune thyroid disease are Hashimoto’s thyroiditis and Graves’ disease (hyperthyroidism).
Hashimoto’s is usually associated with hypothyroidism
The presence of one autoimmune disease increases risk of others.

Question 16

What are the symptoms of hypothyroidism?

Answer 16

Fatigue, memory impairment, depression.
Shaggy hair, hair loss
Swollen face, swelling of the eye sockets, rough, deep or hoarse voice
Enlarged thyroid gland
Weight gain, constipation
Slowed heart rate (Bradycardia), weakness
Dry, rough skin, paresthesia and muscle cramps
Diminished potency and fertility, low libido, cycle disorder

Mind, Hair, Face, Palpate, Weight, Heart, Skin, Sex

Question 17

How does levothyroxine work and who is it given to?

Answer 17

Levothyroxine almost identical to T4 and so acts as T3, since cells can deiodinate it in exactly the same way as T4 to form bioactive T3. Given to patients with hypothyroidism or patients with hyperthyroidism who are on a blocking and replacement regimen (carbimazole given to stop all production of natural thyroid hormone and then administer amount of levothyroxine needed for daily function.)

Question 18

What is the dosage of levothyroxine and what are possible complications?

Answer 18

100mg is the starting dose unless patient elderly or at risk of ischaemic heart disease, in which case dose reduced. Amount given adjusted based on TSH levels, where aim is to bring it within a normal range. Most commonly administered orally unless patient cannot take it and must be given intravenously. Minor complications can include weight loss or headache if too much levothyroxine administered. Major complications include myocardial infarction and tachycardia.

Question 19

Why is levothyroxine prescribed instead of liothyronine?

Answer 19

T4 given instead of T3, as there is no evidence that T3 works better. Plus, drug is expensive. Sometimes patients may blame overlapping symptoms which occur in hypothyroidism and other conditions on their thyroid.

Question 20

What is combined thyroid hormone replacement?

Answer 20

When T4 and T3 prescribed together - some patients report it helps but literature is limited. Complicated by symptoms of ‘toxicity’ – palpitations, tremor, anxiety - often combination treatment suppresses TSH.

Question 21

What occurs in hyperthyroidism?

Answer 21

Thyroid makes too much thyroxine so thyroxine levels rise and TSH levels drop. Can be caused by Graves’ disease where whole gland smoothly enlarged and whole gland overactive. Can also be caused by toxic multinodular goitre or solitary toxic nodule.

Question 22

What are the symptoms of hyperthyroidism?

Answer 22

Anxiety, Irritability, Insomnia and depression
Broken hair, hair loss
Weight loss, strong feelings of hunger, frequent bowel movements (diarrhea)
Enlarged thyroid gland
Fragile fingernails and shaking hands
Tachycardia, Arrythmia, high BP
Warm moist skin and increased body temperature - heat intolerance
Muscle cramps and muscle weakness
Irregularity of periods

Mind Hair Muscle Hand Palpate Weight Heart Skin Sex

Question 23

What is Graves’ disease?

Answer 23

Is an autoimmune condition where antibodies bind to and stimulate TSH receptor in the thyroid, forming a smooth goitre. Other antibodies bind to muscles behind the eye causing exophthalmos. This is when eyes appear protruding and patients complain of dry, gritty eyes which don’t close properly at night. Can see white of eye and the red in the cornea is known as injection. Other antibodies stimulate growth of soft tissue of shins: Pretibial myxoedema.