Thyroid Disease

Question 1

What is the histology of the thyroid gland?

Answer 1

Made up of follicles;

• Colloid (formed of thyroglobulin and iodine)
• Surrounded by parafolliciular cells

Question 2

How does iodine enter the colloid of the follicular lumen?

Answer 2

• Iodide transported from the bloodstream into follicular cell via I/Na co-transporter
• Exocytosed into the follicular lumen and oxidised to iodine by thyroid peroxidase

Question 3

How is T3 and T4 formed in the follicular lumen?

Answer 3

• Tyrosine residues on thyroglobulin are iodinated

- Mono/di-iodinated tyrosine combine to form T3/T4

Question 4

What enzyme is responsible for the iodination of thyroglobulin?

Answer 4

TPO - Thyroid Peroxidase

Question 5

What is the composition of T3 and T4?

Answer 5

T3 - MIT+DIT

T4 - 2xDIT

Question 6

How does T3 and T4 enter the circulation

Answer 6

• Endocytosed into the follicular cell
• Cleaved from thyroglobulin via lysosome
• Diffuse into circulation

Question 7

What plasma proteins to T3 and T4 bind to?

Answer 7

Thyroid-binding globulins, albumin and transthyretin

Question 8

How is biologically active free T3 formed?

Answer 8

• Most circulating thyroid hormone is T4 which is de-iodinated in the periphery by tissues which require thyroid hormone activity

Question 9

How is the secretion of thyroid hormone regulated?

Answer 9

• Hypothalamus releases Thyrotropin Releasing Hormone (TRH)
• Stimulates the anterior pituitary to release Thyroid Stimulating Hormone (TSH)
• Stimulates thyroid to produce T3 and T4, which negatively feedback

Question 10

How do thyroid hormones elicit a response in target cells?

Answer 10

Diffuse into cells and bind to nuclear receptors which act as transcription factors for certain genes.

Question 11

What is the general action of thyroid hormones?

Answer 11

Increased metabolism and glucose uptake

Question 12

What is the action of thyroid hormones on carbohydrate, lipid and protein metabolism?

Answer 12

• Increased gluconeogenesis and glycogenolysis
• Increased lipolysis
• Increased proteolysis

Question 13

What is the action of thyroid hormones on the CV/resp system?

Answer 13

Increased HR, CO and RR

Question 14

What are the common causes of hyperthyroidism?

Answer 14

• Graves disease (most common)
• Multinodular goitre
• Thyroid adenoma

Question 15

What is the pathophysiology of Graves disease?

Answer 15

Autoimmune condition, producing antibodies of the TSH receptor. Stimulates the thyroid to produce T3 and T4, negative feedback of TSH does not affect thyroid hormone production.

Question 16

What are the clinical features of hyperthyroidism (specify those specific to Graves disease)?

Answer 16

Hypermetabolism:

• Weight loss
• Diarrhoea
• Sweating

Increased CV output:

• Tachycardia
• Palapatations
• Hypertension

GRAVES

• Opthalmopathy: Bulging, dry, bloodshot eyes
• Dermopathy of shins: Scaly thickening skin

Question 17

What investigations should be ordered and what results seen in hyperthyroidism?

Answer 17

• Low TSH
• High free T4

Positive TSH receptor antibody in Graves

Question 18

What are the management options for hyperthyroidism?

Answer 18

• Thioamides - carmibazole and proplythiouracil
• Beta blockers to reduce CV symptoms
• Radioactive iodine
• Thyroidectomy (results is permanent hypothyroidism)

Question 19

What is the mechanism of action of thioamide drugs?

Answer 19

Carmibazole and propylthiouracil

• TPO (thyroid peroxidase) inhibitor
• Reduced iodination of thyroglobulin, therefore production of T3 ad T4

Question 20

What is are the risks of thioamide drugs?

Answer 20

Agranulocytosis causing infection - watch out for fever or sore throat

Question 21

What is the mechanism and risks of radioactive iodine?

Answer 21

Taken up by the thyroid and destroys the granular tissue via beta emission.

Stay away from others due to radiation risk, and results in hypothyroidism.

Question 22

What are the two types of goitre?

Answer 22

Diffuse - hypertrophy of the whole thyroid

Nodular - Formation of nodules, can be malignant

Question 23

What is the diagnosis and treatment of thyroid carcinomas?

Answer 23

Fine needle aspiration of nodules. Surgical excision and radioactive iodine therapy.

Question 24

What are the causes of hypothyroidism?

Answer 24

• Hashimotos thyroiditis
• Thyroidectomy or radio-iodine therapy
• Iodine deficiency
• Secondary hypothyroidism relating to AP/hypothalamus (rare)

Question 25

What is the pathophysiology of Hashimotos thyroiditis?

Answer 25

Autoimmune condition producing TPO (thyroid peroxidase antibodies). Causing inflammation of the thyroid and decreased T3 and T4 production due to reduced iodination of thyroglobulin by TPO.

Question 26

What is the clinical presentation of hypothyroidism?

Answer 26

• Weight gain
• Intolerance to cold
• Heavy menstruation
• Dry, thin hair
• Periorbital and peripheral oedema

Question 27

What investigation and results would give a diagnosis of hypothyroidism (Hashimotos)?

Answer 27

• High TSH
• Low free T4
• High TPO antibody

Question 28

What is the treatment of hypothyroidism?

Answer 28

Oral levothyroxinetaken daily

Question 29

What is the most common cause of congenital hypothyroidism?

Answer 29

Genetic defect to the TSH receptor

Question 30

What is Pendred syndrome?

Answer 30

Congenital hypothyroidism. Autosomal recessive genetic condition causing deficiency in Pendrin which transports iodine to the colloid.