L19 - The Thyroid Gland

Question 1

Describe in detail where the thyroid gland lies anatomically

Answer 1

Anterior to the cricoid cartilage, inferior to the thyroid cartilage (adams apple) around the front on the larynx

Question 2

The thyroid gland is made up of two lobes joined by an isthmus, it is the first endocrine to develop embryologically. Explain how it develops briefly

Answer 2

Develops as an epithelial proliferation at the base of the tongue and descends down the thyroglossal duct to its final position

Question 3

Follicular cells are arranged in spheres called thyroid follicles, they make and secrete thyroglobulin which is stored in an extracellular protein called?

Answer 3

Colloid

Question 4

Thyroglobulin is an iodide dependent hormone, what do parafollucular cells secrete?

Answer 4

Calcitonin

Question 5

Which cells are the small, purple cells surrounding the colloid and which cells are the clear ones interspersed between these

Answer 5

Small purple - follicular

Clear - parafollicular

Question 6

The thyroid hormones are T3 and T4 which can be distinguished by the three of four attached iodine atoms. Thyroglobulin acts as a scaffold protein for the formation of thyroid hormones from its tyrosine residues (so it is sort of a precursor). What two processes are required to turn the residues into the hormones?

Answer 6

Iodination and coupling

Question 7

What are the three processes whcih thyroid peroxidase regulates in Vivo?

Answer 7

Oxidation of iodide to iodine (from the diet)
Addition of iodine to the tyrosine residues on the thyroglobulin
Coupling of the MIT or DIT to generate the thyroid hormones

Question 8

As we have seen dietary iodine is essential for thyroid hormone synthesis because it can’t be made in vivo. It is taken up from the bloodstream via the ‘iodine trap’ which is a sodium iodide . What percent of the bodies iodine does the thyroid gland contain?

Answer 8

95%

Question 9

Although 90% of thyroid hormone secreted is T4 why are there still relatively high levels of T3?

Answer 9

Because most of T4 is converted to T3 by the liver and the kidneys. T3 is far more biologically active

Question 10

Thyroid hormones are steroid hormones. How are they transported in the blood?

Answer 10

Bound to thyroxine binding globulin

Question 11

What two/three processes do thyroid hormones have the most effect on?

Answer 11

metabolic stimulation (including increasing BMR)
Heat production
sympathimometic effects (by increasing receptor number of the catecholamines)

Note - so when thinking about problems with the hormone think about these processes

Question 12

Specifically what kind of hormone is TSH?

Answer 12

A glycoproteins hormone

Question 13

What is the trigger for thyroid hormone release explain the intracellular pathways involved

Answer 13

TSH binding to its GPCR (Gq or Gs) on follicular cells this stimulating release via pinocytosis

Gq pathway - PLC -> cleaves pip2 to IP3 and DAG. IP3 is a calcium channel so calcium release and PKC activation

Gs pathway - activation of adenyl cyclase which actives cAMP which activities protein kinase A

Question 14

Describe the five major actions of thyroid hormone

Answer 14

1) Increase in basal metabolic rate
2) Stimulation of lipid and carbohydrate metabolism
3) sympathomimetic effects (increases number of catecholamine receptors)
4) increased cardiac output (Cos of 3)
5) essential for CNS development and function

Question 15

Like other intracellular hormones thyroid bonds it’s receptor which removes it from the HRE thus stopping its repression of gene transcription. Are the normal circulating thyroid hormones in the nanomolar, picomolar or molar concentrations?

Answer 15

Picomolar

Question 16

Goitre is enlargement of the thyroid gland due to overstimulation. This can happen in hyper or hypothyroidism. But most commonly occurs as what kind of hypothyroidism?

Answer 16

Iodine deficient hypothyroidism

Question 17

Describe 4 general symptoms and 3 general signs of hypothyroidism in adults and children

Answer 17

Symptoms - lethargy/dry skin/alopecia/hoarse voice/constipation/slow reflexes/weight gain/bradycardia

Signs Adult - thick puffy skin/muscle weakness/slow speech/mental deterioration/intolerance to cold temperature
Myxedema is a general term to describe skin, hair and puffy face/goitre

Signs infant - cretinism which is dwarfed stature, mental retardation, poor bone development, bradycardia, muscle weakness and GI disturbances

Question 18

Hashimotos disease is an autoimmune destruction of thyroid follicles leading to hypothyroidism. What would the classical appearance of their thyroid blood tests be?

Answer 18

T3 and T4 - low

TSH - high

Question 19

What are some general symptoms and signs of hyperthyroidism?

Answer 19

bulging eyes/Weight loss/irritability/heat intolerance/sweaty/tachycardia/weakness/increased appetite/possible tremor/breathlessness/loss of libido/goitre/tachycardia

Question 20

What are the classical thyroid blood tests seen in Graves’ disease?

Answer 20

T3 and T4- high

TSH - low

Question 21

Why is thyroid still being made in Graves’ disease despite almost no TSH?

Answer 21

Autoantibodies are stimulating. The thyroid gland outside of the negative feedback loop

Question 22

What is thyroid sctinigraphy?

Answer 22

The injection of a radioactive isotope to image the thyroid gland

Question 23

Anti thyroid drugs are used to treat hyperthyroidism. What is the main drug and how does it work?

Answer 23

Carbimazole - this is a pro-drug which is converted in the body to another substance which prevents thyroid peroxidase from coupling and iodintating tyrosine on thyroglobulin