Hypothalamus, pituitary and thyroid function

Question 1

Describe the anatomy of the hypothalamus, the posterior pituitary and the anterior pituitary

Answer 1

The hypothalamus sends neurones from the hypothalamus to form a posterior pituitary, which releases nueropeptides like oxytocin and ADH. The anterior pituitary is very close but not apart of the brain.

Question 2

Describe the process of the transmission of a hormone from the hypothalamus to the anterior pituitary.

Answer 2

The neurones in the hypothalamus send axons to the median eminence. Therre is no BBB there,, so the hormones enter the portal vessels. They then bind to their complementary receptors.

Question 3

State the 5 hormones released from the hypothalamus

Answer 3

TRH (Thyrotropin releasing hormone)
Prolactin
CRF (Corticotrophin releasing factor)
GnRH (Gonadotrophin releasing hormone)
GHRH (Growth hormone releasing hormone)

Question 4

State the 6 hormones released from the anterior pituitary

Answer 4

TSH (Thyroid stimulating hormone)
ACTH (Adrenocorticotrophin Hormone)
LH (Luteinising Hormone)
FSH (Follice Stimulating Hormone)
GH( Growth Hormone )

Question 5

Name 2 inhibitory molecules that affect the release of hormones and state the systems they target

Answer 5

Somatostatin halts GH/TRH

Dopamine halts Prolactin release

Question 6

Starting at the hypothalamus, describe how LH and FSH are released

Answer 6

Hypothalamus - Releases GnRH via median eminence and portal vessels to the anterior pituitary. The anterior pituitary releases LH and FSH via gonadotrophs.

Question 7

Describe the complications that arise in children that lack FSH or LH and suggest how this can be solved.

Answer 7

These children will not be able to undergo puberty and may lose their reproductive function. GnRH, FSH and LH can be used to manipulate reproductive function, as they are even used in IVF.

Question 8

Starting at the hypothalamus, describe how GH is released

Answer 8

Hypothalamus - Releases GHRH via median eminence and portal vessels to the anterior pituitary. The anterior pituitary releases GH via somatrophs.

Question 9

State what happens if individials have a lack of GH

Answer 9

These individuals tend to have short statures. This can be treated by GH treatment.

Question 10

State what happens if individials have excess GH

Answer 10

Too much growth hormone may result in giantism.

Question 11

What is acromegaly?

Answer 11

Too much growth hormone in adults- usually do to a pituitary adenoma (a type of cancer). Somatotrophs produce extra GH resulting in the ones in the face, fusing together.

Question 12

Starting at the anterior pituitary, describe how prolactin is released

Answer 12

The anterior pituitary releases prolactin via mammotrophs. Too much prolactin in males can result in gynaecomastia.

Question 13

Starting at the hypothalamus, describe how TSH is released

Answer 13

Hypothalamus - Releases TRH via median eminence and portal vessels to the anterior pituitary. The anterior pituitary releases TSH via thyrotrophs.

Question 14

Describe the histology of the thyroid

Answer 14

The thyroid is composed of smaller components known as thyroid follicles. These are balls of epithelial cells that surround proteinaceous (non-cellular) colloid where the thyroid hormones are sent.

Question 15

How much more potent is T3 than T4?

Answer 15

10x

Question 16

Describe the synthesis of thyroid hormones

Answer 16

TSH binds to target receptor –> opens Na+/i- symporter in the follicular cells.I- (AKA chloride trapping). Throglobulin is synthesised in the thyroid follicle cell. I- oxidised by throif peroxidase to make iodous ions. Thyroglobulin and iodous ions move to the throid follice and T3/T4 are bound to thyroglobulin. The thyroglobulin is endocytosed in to the thyroid follicle cell. Lysosomes catalyse the breakdown of thyroglobulin to form T3/T4.

Question 17

Where in the blood is T3/T4 found? Relation of T3 to T4?

Answer 17

Bound to plasmas serum proteins including thyroid binding globulin. T4 thought to be a prohormone of T3.

Question 18

What is the MOA of T3/T4?

Answer 18

Free T3 an T4 bind to to target receptors in the cell nucleus and are of the super family of nuclear receptors. They act as transcription factors. The T3 binds to the thyroid hormone receptor and in the presence of 9-cis retinoic acid and the RXR receptor, both hormone-receptor complexes dimerise and act as transciription factors ——-> regulation of protiens.

Question 19

Name 4 roles of the thyroid hormone

Answer 19

Increases 02 consumption
Increases catecholamine sensitivity in the CVS
Increases nervous system excitability
The thryoid system has permissive effects on growth and development

Question 20

How is the negative feedback system controlled?

Answer 20

The free t3 and T4 turn off more TRH and TSH release

Question 21

Name 4 causes of hypothryoidism

Answer 21

Lack of iodide in diet
Congenital reasons
Hashimoto’s throiditis
Circulating antibodies against Throid peroxidase

Question 22

Name 5 symptoms of hypothyroidism

Answer 22

Cold sensitivity
Depression
Bradycardia
Weight gain
Throid Goitres

Question 23

Why do throid goitres arise?

Answer 23

They arise due to the excess release of TSH and not enough T3/T4 stopping the release of TSH

Question 24

Name 2 causes of hypethryoidism

Answer 24

Excess iodide in diet

Grave’s Disease

Question 25

Name 6 symptoms of hyperthyroidism

Answer 25

``` Heat sensitivity Axiety Tachycardia Weight loss Toixc Goitres Exophthalmos ```

Question 26

Describe the treatment and management for hypothyroidism

Answer 26

Levothyroxine (T4) and Lio-thyronine (T3) - should be cautioned in the elderly as they can increase the heart rate in the elderly Levthryoxine dose 50-100mcg a day life long. Monthly tests until euthyroid and then once established, test every 6 months. Take t4 on an empty stomach. Take into account skiiny patients.

Question 27

What are the side effects associated with hypothyroid treatment ?

Answer 27

Patients may experience thyrotoxicosis -symptoms of hyperthroidism.

Question 28

What drug- drug interactions need to be monitored?

Answer 28

PPIs, calcium containing drugs, multivitamins and iron will lower T4 absorption. Carbamazepine, phenytoin and rifampicin can increase the clearence of t4

Question 29

Describe the treatment for hyperthyroidism and note any major side effects

Answer 29

Carbimazole or propylthiouracil or radioactive iodine 13 and Beta blockers. Carbimazole - prodrug which is metabolised to methimazole. Methimazole prevents coupling of iodine on tyrosine residues.These actions lower the production of thyroid hormones. SE: burising without provocation or sore thorats, mouth ulcers and fever. Agranulocytosis is dangerous. Propylthiouracil- inhibiting the enzyme- thyoid peroxidase, lowering the productionof thyroid hormone production. SE: Hepatic impairment- noticedd from jaundice, itchiness and dark urine. I-131 - destroys the overactive throid cells Beta blocker- lowers the sympathetic side effects of hyperthyoidism

Question 30

Describe the management for hyperthyroidism

Answer 30

The treatment will last for 18 months. It can take 2 months for the patient to become euthyroid. Once euthyroid, titrate the dose or supplement with levothyroxine. Pateints may become lethargic and may gain weight due to treatment, Patients should have regualr TFTs (Thryoid function tests).

Question 31

Describe the cause of Grave's disease

Answer 31

Antbody stimulating the TSH receptor without TSH stimulating the recepors on the thyroid follicle- results in excess thyroid production.

Question 32

How does amiodarone cause hyperthyroidism?

Answer 32

Amiodarone - Class 3 anti-arrhythmic drug. Similar sturcture to T3. Normal ioidine daily intake is 6-12 mg/day. If on amiodarone, it is redued to 0.15-0.30mg/kg if the patient is on amiodarone.It can cause Amindoarone induced thyrotoxicosis (AIT) as excess iodine builds up.

Question 33

How does amiodarone cause hyperthyroidism?

Answer 33

Amiodarone - Class 3 anti-arrhythmic drug. Similar sturcture to T3. It can cause less iodine being taken up by the thyroid follicle and reduces T4 ----> T3 convesion.

Question 34

How can lithium cause hypothyroidism?

Answer 34

Lithium is thought to lower the concentrating capacity of iodine. Lithium may inhibit the secretion of thyroid hormones by stabilising the follicular cell microtubule.