Endocrine disease

Question 1

what is endocrine system made of?

Answer 1

. endocrine is a signal system and is made up of discrete endocrine glands which secrete chemical messages inside of the body into the blood stream , chemical messengers go around the body to talk to other endocrine gland and induce hormonal response
. these hormones exert their effect and can regulate things like metabolism, blood sugar levels

Question 2

what are the endocrine glands?

Answer 2

. pituitary gland -
‘ growth/lactation/thyroid’

. pineal gland - sleep wake cycle

. thyroid- metabolism

. thymus- T cell maturation

. adrenal - stress response

. pancreas - glucose metabolism

. ovaries - ovulation

. testis - spermatogenesis

Question 3

what does the pineal gland do?

Answer 3

• pineal gland is located in the brain and it secretes melatonin that regulates circadian rhythm or sleep wake cycles

Question 4

what is the most common disease that affects pineal gland?

Answer 4

. pineal tumours - unregulated cell proliferation within the glands which has an effect on secretion of hormones
. pineal tumours are very , very rare
. little grey area , enlarged pineal gland
<1:200,000

Question 5

how common is pineal tumours within intracranial tumours?

Answer 5

. comprise <1% of intracranial tumours

Question 6

what age is the pineal tumour peak?

Answer 6

. adults 35-60 years of age peak

Question 7

what are the symptoms of pineal gland tumour?

Answer 7

. symptoms are not actually related to the hormone
. the symptoms arise due to the gland increasing in size and pushes around brain tissue around it

1. headache - due to hydrocephalus - which is build up of fluid within the brain - enlargement of pineal gland can block CSF flow
2. insomnia/sleep disturbances
3. nausea
4. blurred vision - due to increase in pressure which affects visual pathway
5. upward gaze palsy ( parinaud syndrome ) - pineal gland sits near superior colliculus, which regulates up gaze movements - enlargement of pineal gland can disturb superior colliculus
6. staggering gait
7. hearing loss

Question 8

where is pituitary gland located?

Answer 8

• lies close to the optic nerves
• sits below optic chaism
• sits in the hypophysial fossa of the sphenoid bone
• surrounded by sella turcica
• this means that pituitary gland is restricted in which direction it can grow when it gets a tumour because its surrounded by bones - only direction it can grow is up

Question 9

what are the two regions of pituitary gland?

Answer 9

. anterior lobe

. posterior lobe

Question 10

what does the pituitary gland link?

Answer 10

. pituitary gland is the main link between the nervous system and endocrine system
. lots of hormones are triggered by pituitary gland

Question 11

what is the most common cause of endocrine system ?

Answer 11

. the most common cause of endocrine disease is tumour formation - unregulated proliferation of cells

Question 12

how do pituitary tumours arise ?

Answer 12

1. end up with more cells which are secreting more hormones - the presence of pituitary hormone hyper -secretion ( i.e. tumours )
2. absence or diminution of hormone secretion caused by destruction of pituitary (i.e. caused by ischemia)

. increase in cell size causes an increase in gland size and that will have an effect on the other structures on the area , pressure is put on localised blood vessels and you can collapse down the lumen of blood vessels - this decreases blood flow

3. direction and extent of local expansion and invasion of adjacent structures
   non functioning adenoma (glandular tumour)- as these endocrine glands are increasing in size, the actual hormones being secreted are not changing - most dangerous - as you are getting an organ within your body increasing in size within the brain , invade adjacent structures

Question 13

how common is pituitary tumour?

Answer 13

. represent 10-15% of intracranial neoplasms

Question 14

what are different types of pituitary tumours you can have?

Answer 14

. when you get a pituitary tumour it can be in any one of endocrine gland cells - referred to as different tumour name

in order of prevalence

1. prolactinomas - tumour of lactotroph
2. growth hormone secreting adenoma - affects somatotrophs
3. non secreting adenomas - most deadly - can occur in any cell type
4. corticotroph adenoma (ACTH) - corticotrophs
5. TSH, FSH, LH - thyrotrophs and gonadotrophs

15% of pituitary adenomas secrete >1 hormone with prolactin + growth hormone the most common combination
. tumour can affect more than one cell type

Question 15

what is prolactinomas?

Answer 15

. prolactinomas makes up 30% of pituitary tumours
. lactotrophs become non-responsive to the prolactin inhibitory factor - loss of dopamine inhibition - over secretion of prolactin out of lactotrophs- cause secondary trauma

Question 16

what are the responses around the body due to prolactinomas ?

Answer 16

• differs between men and women , because of the tissue types available
• women:
  . amenorrhea - usually noticed - unusual lack of menstruation
  . oligomenorrhea - can cause concern - irregular menstruation
  . galactorrhea = witchs milk - starts production of milk ( yellow liquid )
• men:
  . testicular atrophy - less testosterone being secreted
  . diminished body hair
  . gynecomastia = man boobs - breast tissue increase in size
  . impotence

Question 17

what are growth hormone secreting tumours ?

Answer 17

• secreted from somatotrophs
• secrets excess growth hormone
• depending on when during development you get tumour formation has different phenotype and different expression of characteristics

Question 18

what happens if you get growth hormone secreting tumour during childhood?

Answer 18

you get gigantism - over axial elongation of the main bones in the body

e. g. in the legs and arms and fingers and toes
- growth hormone stimulates an over secretion of insulin which causes this growth

Question 19

what happens if you get growth hormone secreting tumour when you’re an adult?

Answer 19

you get acromegaly - patients report gradual enlargement and coarsening of facial feature, hands and feet
- tumour may be large at time of diagnosis as signs and symptoms are slow

Question 20

what happens when you have pituitary tumours that lead to a lack of secretion of growth hormone?

Answer 20

• if this occurs during puberty - pituitary dwarfism

Question 21

what do corticotrophin secreting adenomas lead to ?

Answer 21

• you get crushing syndrome
• Females : Males (4:1)
• truncal obesity
• abdominal striae
• moon faces
• thin skin - stretch marks
• high blood pressure
• glucose intolerance
• fatigue

Question 22

what happens if you have FSH and LH and TSH pituitary tumour?

Answer 22

. least common
. usually middle aged men and women
. can go long without being diagnosed
. you get visual field loss, headache, diplopia

• in men - decrease libido/energy
• TSH rare <1% of pituitary adenomas

Question 23

what are non secreting adenomas ?

Answer 23

• 3rd most common pituitary tumour
• as they are non-secreting you don’t see a phenotype - they secrete hormones at right level
• only know about tumour due to the large tissue size
• tumour without endocrine symptoms are large at time of diagnosis
• you get severe frontal headache ( 50% of patients )
• as the pituitary gland increases in size it can only grow upwards - pressure is put on optic chaism axons - this leads to visual field defects
• this results in visual field defect ( monocular )
• also known as bi-temporal hemianopia
• more likely to lose superior temporal view than inferior

Question 24

what happens at the optic chaism when the pituitary gland increases in size?

Answer 24

• temporal retina not crossing at the optic chaism
• nasal retina crosses midline at optic chaism
• when pituitary tumour grows , it will put pressure on the crossing axons
• nasal retina is responsible for temporal view
• loss of temporal visual field

Question 25

how is expression of thyroxine regulated?

Answer 25

- its regulated by negative feedback - there is a constant interplay between TRH and TSH - high levels of T3 and T4 inhibit secretion of thyroxine

Question 26

what is hyperthyroidism?

Answer 26

- over activity of thyroid gland - - can be cause by adenoma of thyroid - tumour - can also be caused of TSH secreting adenoma of pituitary - rare

Question 27

what is the most common cause of hyperthyroidism?

Answer 27

- hyperplasia of the thyroid follicular cells, induced by an autoimmune disease called Graves disease - accounts for 85% of the hyper-function of thyroid gland - activated plasma cells secrete antibodies , antibodies bind to thyroid follicular cells that would normally be bound by thyroid stimulating hormone - then induce an over secretion of thyroxine - if thyroid gland thinks there is more TSH in the blood , you will get an increase in T3 and T4 - T3 and T4 are still being secreted because it's that auto antibody that is binding to the receptors not the thyroid stimulating hormone - negative feedback cannot bring levels of T3 and T4

Question 28

explain the pathogenesis of Graves disease ?

Answer 28

- TSH will bind to TSH receptors on the thyroid follicular cells and induce T3 and T4 - T3 and T4 will be able to suppress the secretion of TSH to reduce T3 and T4 - this doesn't happen when you have activated B cells - plasma cells secrete antibodies which bind and stimulate receptors , mimicking TSH and inducing the secretion of T3 and T4 - this leads to an increase in metabolism around the body - you also get swelling of thyroid gland around the neck , thyroid follicular cells respond by increasing size - you also get inflammation - you get swelling in the neck referred to GOITRE

Question 29

what is ocular phenotype of graves disease ?

Answer 29

- exophthalmos / proptosis - eyes projected further out of the socket than normal - this means that you are no longer able to close eyelids properly - extra ocular muscle tissue enlarge because there is receptors which combine to auto antibodies and lead to over proliferation of cells . occurs in 60% of patients that suffer from graves disease - exophthalmometer with readings >21mm or difference between eyes of >2mm . keratoconjunctivitis sicca - due to eye not being able to close properly - elevation usually first to go ( inferior rectus restricts upgaze ) - then abduction - may have esodeviation due to tethered medial rectus - then diplopia - oblique muscles usually not invovled

Question 30

what are treatments for graves disease ?

Answer 30

graves disease is treatable in terms of thyroid complication - by removing thyroid gland - doesn't get rid of autoantibodies being produces which still target the extra ocular muscles - can have an operation to remove the bone at the back of the orbit - to allow eyes to sit further back 1. hyperthyroidism treatment - does not correlate well with improvement in Graves' ophthalmopathy 2. can get graves ophthalmopathy with no thyroid gland 3. both hyperthyroidism and graves ophthalmopathy have an underlying autoimmune aetiology that affects the thyroid, eyes and skin 4. so unless the underlying autoimmune disorder is addressed there is no reason for the eyes, skin and thyroid to recover by merely treating one tissue

Question 31

what is hypothyrodism ?

Answer 31

opposite of hyperthyroidism - under secretion of thyroxine

Question 32

what are the two main causes of hypothyroidism?

Answer 32

1. low dietary intake of iodine - essential for T4 production - hormone thyroxine is amino acid tyrosine plus added iodine - main cause of hypothyroidism worldwide 2. autoimmune disease of the thyroid - Hashimotos thyroditis - T cells destroy thyroid - main cause of hypothyroidism in countries where there is an iodine rich diet

Question 33

what Hashimotos's thyroiditis ?

Answer 33

- break down in self tolerance - autoimmune disease - no T4 secretion - due cytotoxic T cells which destroy the thyroid follicular cells - 10:1 female to men - 45-65 - you need to levothyroxine sodium tablets for life which regulate metabolism around the body

Question 34

what are the 3 mechanism of thyrocyte destruction ?

Answer 34

1. CD8+ cytotoxic T cells destroy thyrocytes . they do this by secreting perforin which creates a pore in the cell membrane and triggers necrosis within the cell -. they can bind death receptor ( CD95 ) which targets the self destruction 2. CD4+ T helper cells which secrete interferon gamma around thyrocytes - recruits and activates macrophages to phagocytose - macrophages destroy thyrocytes and follicles 3. plasma cells secrete anti-thyroid antibodies to thyroid cells - trigger are response from natural killer cell mediated cytotoxicity

Question 35

how to regluate metabolism around the body?

Answer 35

. levothyroxine - sodium tablets - replaces thyroxine

Question 36

what are the symptoms of Hashimotos thyroiditis ?

Answer 36

- fatigue, constipation, dry skin and weight gain - cold intolerance - slowed movement and loss of energy - decreased sweating - peripheral neuropathy

Question 37

what are the two types of diabetes?

Answer 37

- diabetes is an endocrine disease as it comes form pancreas - type 1 - b- cell destruction in islets of langerhans = no insulin production - no glucose uptake - type 2 - insulin resistance and B cell dysfunction