Hyposecretion of anterior pituitary hormones:

Question 1

define the 2 separate pituitary parts:

Answer 1

1) anterior pituitary- adenohypophysis
2) posterior pituitary- neurohypophysis (neuronal in origin)

both are very different in function and embryological origin

Question 2

what are the 5 anterior pituitary hormones?

Answer 2

1) LH/FSH- gonadotrophins
2) ACTH- adenocorticotrophin- to stimulate adrenal cortex to form cortisol
3) TSH- thyrotrophin
4) prolactin
5) Growth hormone

Question 3

Describe how T4 is released from thyroid gland?

Answer 3

Hypothalamus produces TRH, which stimulates TSH release from anterior pituitary. TSH travels in the blood to thyroid gland where T4 is then released.

Question 4

what 2 types of hormones does hypothalamus produce?

Answer 4

hypothalamus can either produce releasing hormone or inhibiting hormone.

Question 5

what is primary hypothyroidism?

primary endocrine gland disease

Answer 5

The thyroid gland is not working properly to produce adequate T4.
So TSH levels rise, as more produced by anterior pituitary to increase levels of T4.

high TSH and low T4

Question 6

what is secondary hypothyroidism

secondary endocrine gland disease

Answer 6

The anterior pituitary is not working to produce TSH. therefore thyroid gland is not receiving stimulus to produce T4. This is quite uncommon.

Low TSH (or low end of normal) and low T4

Question 7

what is panhypopituitarism and hypopituitarism?

Answer 7

panhypopituitarism- decreased production of all anterior pituitary hormones because anterior pituitary is not working properly.

hypopituitarism- decreased production of specific hormones is not working properly.

They can be both congenital or acquired.

Question 8

what are the characteristics of congenital panhypopituitarism

Answer 8

Possibly due to mutations in transcription factor genes which are needed for the normal development of anterior pituitary in vitro. e.g. PROP1 mutation

deficiency in GH and 1 other anterior pituitary hormone.

short stature- due to poor growth because of GH deficiency.

Upon MRI scan- gland looks underdeveloped- hypoplastic.

Question 9

what are the characteristics of acquired panhypopituitarism

Answer 9

1) tumour: pituitary tumour (benign tumour- adenoma, metastases, cyst within gland can squash it), hypothalamic tumour
2) radiation: radiation for other cancers or within pituitary can damage hypothalamus/pituitary. GH is most vulnerable to damage. TSH is quite resistant. As adults- less consequence of GH being vulnerable as compared to child.
3) infection (meningitis)
4) Traumatic brain injury
5) infiltrative diseases- inflammatory diseases (often involves pituitary stalk- neurosarcoidosis
6) autoimmune damage to endocrine gland- endocrine system is very vulnerable to this. (hypophysistis- autoimmune inflammatory damage to pituitary)
7) pituitary apoplexy- bleed i.. haemorrhage or less commonly infarction
8) peri partum infarction- pituitary gets very big during pregnancy and then not enough blood supply to it.

Question 10

what are the presentation of panhypopituitarism

Answer 10

also known as Simmond’s disease:

FSH/LH deficiency- secondary hypogonadism, reduced libido, secondary amenorrhoea, erectile dysfunction

ACTH deficiency- secondary hypoadrenalism (cortisol deficiency, fatigue

TSH deficiency: secondary hypothyroidism, fatigue

GH tends to not present so much in adults as a symptom because you stop growing when you’re an adult.

Question 11

Describe Sheehan’s syndrome:

Answer 11

Specifically describes post-partum hypopituitarism.
secondary to hypotension in pregnancy

Anterior pituitary enlarges in pregnancy due to lactrotroph enlargement (hyperplasia). Enlarged anterior pituitary is hanging from stalk with blood vessels around it. Hypotension and gland is deprived off blood supply. maybe transiently = but enough to make it not work
or infarction- complete blood supply cut off then it dies.

Posterior pituitary gland is fine.

Question 12

Presentation of Sheehans syndrome

Answer 12

lethargy, anorexia, weight loss (TSH/ACTH- cortisol deficient , GH deficiency)
failure of lactation- prolactin deficiency
failure to resume menstruation post delivery- LH/FSH deficiency.

most symptoms are quite similar to that of post pregnancy so difficult to identify.

Main indicator- stopping of lactation.

Question 13

What is pituitary apoplexy?

Answer 13

intra pituitary haemorrhage or less commonly infarction

can be precipitated with anti-coagulants.

this is often a presentation in patients with pre-existing pituitary adenomas/tumours or could be:
first presentation of pituitary adenoma.

Question 14

What are the presentations of pituitary apoplexy and why?

Answer 14

pituitary gland hangs off the pituitary stalk which is directly below the optic chiasm. The pituitary gland has the cavernous sinuses on both sides. In an apoplexy the whole gland is enlarged and compresses the optic chiasm and cavernous sinuses.

1) severe sudden onset headaches
2) double vision- diplopia. due to compression of cavernous sinus affecting cranial nerves (4 and 6)
3) droopy eyelids-Ptosis- due to compression of cavernous sinus affecting cranial nerve 3
4) bitemporal hemianopia (visual field defect, missing vision in the outer half of left and right vision) - due to squashing of optic chiasm

Question 15

what are the biochemical diagnoses for hypopituitarism?

Answer 15

1) basal (random blood supply) plasma concentrations of pituitary or target endocrine gland hormones

2) stimulated dynamic pituitary function tests (brain does not like hypoglycaemia. GH and ACTH- produces cortisol which increases blood glucose- they are stress hormones. Making someone hypoglycaemia with injection of insulin, (insulin induced hypoglycaemia) will mean with a normal pituitary response you would expect lots of ACTH and GH activity to increase blood glucose. ACTH is difficult to measure because broken down easily so cortisol is measured (surrogate for ACTH). GH is measured easily.
Also given injections of TRH to tell TSH to work which can be measured. Cortisol, GH and TSH are measured. Sometimes third injection of GnRH to stimulate LH and FSH release which can then be easily measured.

Question 16

Disadvantages of measuring basal plasma concentration of pituitary or target endocrine gland hormones?

Answer 16

LH and FSH-released in cycles due to menstruation
ACTH and GH released in pulses than constantly.
Cortisol/ACTH levels vary at night and morning.
T4- circulation half life of 6 days- long half life so may not be picked up in early days.

Hence random samples are not telling you much, as it depends on day of cycle for LH and FSH levels, time of day for cortisol etc.

Question 17

What is radiological diagnosis of hypopituitarism?

Answer 17

radiological diagnosis: pituitary MRI
may reveal specific pituitary pathologies like adenomas, haemorrhage (apoplexy).

empty sella- thin rim of pituitary tissue, no pituitary gland.

Question 18

hormone replacement therapy in hypopituitarism?

Answer 18

prolactin cannot be replaced and so if low on prolactin then cannot breastfeed.

ACTH deficiency for long period of time =death. Hydrocortisone is given and serum cortisol is measured rather than ACTH and looking for levels equivalent to that in normal healthy people.

Women need to be given back oestogen till age of 50. if they also have a uterus they need to be given oestrogen and progesterone because oestrogen alone will cause endometrial hyperplasia. Check through symptom improvements and withdrawal bleeds.

testosterone is injected into men. Check through symptom improvement and serum testosterone.

GH is replaced by giving GH. GH from anterior pituitary causes liver to produce somatomedin which is IGF1 largely, and also briefly IGF2. IGF1 can be measured to check for improvement and also check growth chart in children (harder in adults)

TSH is replaced by giving Thyroxine and measure serum free T4 to check.

Question 19

what is the other name for Growth Hormone

Answer 19

somatotrophin

Question 20

what does GH deficiency cause in adults and children?

Answer 20

adults: effects less clear
children: short stature

Question 21

What are the causes of short stature?

Answer 21

1) Genetic: Downs syndrome, Turners syndrome, Prader Willi syndrome
2) emotional deprivation
3) malabsorption: coeliac disease
4) malnutrition: not eating enough calories
5) systematic disease: cystic fibrosis, rheumatoid arthritis
6) endocrine disorders: Cushings syndrome, hypothyroidism (thyroid hormone needed for growth), GH deficiency, poorly controlled Type 1 diabetes
7) skeletal dysplasias: achondroplasia, osteogenesis imperfecta

Question 22

Describe the growth axis:

Answer 22

Hypothalamus produces GHRH which stimulates the anterior pituitary to release GH (somatotrophin). somatotrophin tells liver to make IGF1 or IGF2. IGF 1 is main somatomedin in adults and IGF2 in foetus. IGF1 and IGF2 then acts on target tissues. Somatotrophin can directly act on target tissues too.

Hypothalamus also releases somatostatin (stop growth) but less dominant effect compared to GNRH.

Question 23

Causes of short stature in children (growth axis)

Answer 23

1) Prader Willi syndrome: problems with hypothalamus.
2) Pituitary dwarfism: GH deficiency. cannot make GH if problem with anterior pituitary. Short stature because n o GH from childhood
3) Laron Dwarfism: problem with receptor on liver. Cannot tell liver to make any IGF1 for growth.

Question 24

What is Prader Willi syndrome

Answer 24

GH deficiency which is secondary to hypothalamic dysfunction.
Associated with obesity and learning difficulties.
can be treated with GH and bypass problem to allow normal growth of child.

Question 25

What is achondroplasia?

Answer 25

mutation in fibroblast growth factor receptor 3 FGF3

there is an abnormality in growth plate chrondocytes (cartilaginous cells in growth plates) - impaired linear growth. people have average (normal) size trunk but short arms and legs.

Question 26

What is pituitary dwarfism?

Answer 26

anterior pituitary does not produce enough GH. Childhood GH deficiency.

pituitary gland does not develop properly because of damage or genetic mutation during development.

Question 27

Laron Dwarfism:

Answer 27

Receptors on liver do not function properly due to mutation of GH receptor and do not produce IGF1 in response to GH produced in anterior pituitary.

IGF1 treatment in childhood can increase height.

Question 28

how do you diagnose short stature?

Answer 28

mid parental height.

a predicted adult height based on fathers and mothers height.

Question 29

What are the causes of acquired GH deficiency in adults?

Answer 29

1) Trauma
2) pituitary tumour
3) pituitary surgery
4) cranial radiotherapy

in adults growth is completed, more vulnerable to this damage to this axis by head injury, radiotherapy or tumour of the gland.

Question 30

diagnosis of GH deficiency?

Answer 30

GH deficiency occurs in the context of pituitary disease. It is unlikely to present with GH deficiency in isolation as an adult.

random GH measurements are of little use because GH is released in pulsatile.

1) Need to do insulin induced hypoglycaemia test to measure serum GH. Give IV insulin. If deficient then not much increase in GH.

2) GHRH + arginine given as IV. better in combination than alone. Arginine stimulates GH release by inhibiting somatostatin release
3) glucagon- intramuscular. injection of glucagon causes vomiting, stress of vomiting = GH release.
4) exercise (e.g. 10 min exercise)- for children, should release GH

after all these tests measure plasma GH at specific time points (before and after)

Question 31

What is growth hormone therapy?

Answer 31

Daily subcutaneous injection of human recombinant GH.

Monitor how people feel energy wise, and adjust dose according to IGF1 level. IGF1 is what is made by liver in response to GH.

Question 32

Signs and symptoms of GH deficiency in adults:

Answer 32

1) reduced lean mass (mass of bones - fat)
2) increased central adiposity so increased waist: hip ratio
3) reduced muscle strength and bulk- reduced exercise performance
4) decrease plasma HDL- cholesterol and raised LDL cholesterol. (not great lipid profile)
5) impaired psychological well being and reduced quality of life - only proven fact

limited data so all unknown facts.

Question 33

Risks of GH therapy in adults?

Answer 33

1) could cause cancer (not proven)

2) expensive- strict criteria to prescribe it.