Hypopituitarism Flashcards
List the hormones released by the adenohypophysis. (5)
Adenohypophysis = anterior pituitary
Releases: - 1 mark for each
1) LH/FSH
2) GH
3) TSH
4) ACTH
5) Prolactin
What hypothalmic neurons regulate the release of: (5)
1) LH/FSH
2) GH
3) TSH
4) ACTH
5) Prolactin
1) GnRH
2) GHRH (also somatostatin)
3) TSHR
4) CRH
5) DA/TRH (thryotrophin releasing hormone)
What is the difference between primary, secondary and tertiary endocrine gland disease? (3)
https://www.google.com/search?q=primary+secondary+tertiary+endocrine+disorders&source=lnms&tbm=isch&sa=X&ved=0ahUKEwje87HqqNrgAhUtUBUIHQNNB1YQ_AUIDigB&biw=1177&bih=603#imgrc=wQSYz4QW0mUOuM:
What is the term given to decreased secretion of all anterior pituitary hormones? (1)
Panhypopituitarism
Broadly speaking what can cause panhypopituitarism? (2)
Genetic - rare (congenital)
Acquired
Why is the genetic contribution to panhypopituitarism congenital rather than acquired? (3)
- The mutations that lead to panhypopituitarism occur in TFs that are involved in development of cells of the anterior pituitary (adenohypophysis)
- For example, it could be mutation in the PROP1 gene
- Poorly developed cells in the anterior pituitary will not be able to release their hormones as effectively if at all
- On an MRI will observe a hypoplastic adenohypophysis
How can one ‘acquire’ panhypopituitarism? (3)
- Tumours e.g. craniopharyngiomas from the hypothalamus or adenomas developed from within the pituitary itself
- Inflammatory - the pituitary gland and endocrine glands are generally susceptible to autoimmune attack
- Peripartum infarction (as in the case of Sheehan’s syndrome)
- Haemorrhage (as in the case of pituitary apoplexy)
- Traumatic brain injury
- Radiation
- Infection
- Infiltrative diseases e.g. neurosarcoidosis
What are the 3 forms of panhypopituitarism? (3)
1) Simmond’s disease
2) Sheehan’s syndrome
3) Pituitary apoplexy
What are the symptoms of Simmond’s disease? (3)
- Depends on which hormones are missing (multiple or all may be missing)
- Missing GH won’t have too much effect on adults
- Missing LH/FSH = secondary hypogonadism (in females will get secondary amenorrhoea and in males will get erectile dysfunction. In both may have loss of libido)
- Missing ATCH = secondary hypoadrenalism (inability to produce cortisol - fatigue)
- Missing TSH = secondary hypothyroidism (lower metabolic rate - fatigue + weight gain )
What causes Sheehan’s syndrome? (3)
- During pregnancy lactotrophs proliferate (hyperplasia) as have increased activity
- Post-partum haemorrhage can lead to severe systemic hypotension in women because they lose so much blood
- Blood loss can lead to reflex vasoconstriction. Vasoconstrictor spasm in hypophyseal arteries can lead to ischaemia of the adenohypophysis
- Neurohypophysis largely unaffected
- Ischaemia leads to death of cells (by necrosis)
What causes pituitary apoplexy? (4)
- Pituitary apoplexy is caused by intra-pituitary haemorrhage or less commonly infarction
- Ischaemia leads to death of cells within the adenohypophysis
- This can be caused by a pituitary adenoma (symptomatically may present with double vision)
- This can be precipitated by use of anticoagulants
How does Sheehan’s syndrome present? (3)
- Prolactin deficiency means there will be a failure to lactate
- Failure to resume menses (amenorrhea)
- ACTH deficiency (and loss of cortisol) may lead to weight loss
- TSH deficiency may lead to lethargy/fatigue
Why is basal plasma concentration of pituitary (or other hormones) not a great diagnostic tool? (1)
Interpretation is limited because the hypothalamus releases its hormones in a pulsatile fashion
This means the rest of the axis is subject to the same sort of pulsatile nature so a single measurement is useless - you don’t know where in the cycle the concentrations are
How can we biochemically diagnose hypopituitarism? (3)
- Conduct a stimulation test
- The gold standard technique is to induce hypoglycaemia using insulin
- This triggers the release of ACTH (and also GH) to promote cortisol release to counteract insulin
- For the other hormones just use the standard hypothalamic releasing hormone (for LH/FSH –> GnRH and for TSH –> TRH)
How can hypopituitarism be diagnosed? (2)
- Biochemical diagnosis (stimulation tests)
- Radiological (MRI e.g. to see if there is atrophy of tissues)
With ACTH deficiency how would you treat the patient? (extra +1)
Administer hydrocortisone and then regularly check serum cortisol
With prolactin deficiency how would you treat the patient? (extra +1)
You cannot replace prolactin. For men no significant effect. For women they can’t breast feed
With TSH deficiency how would you treat the patient? (extra +1)
Administer thryoxine and check serum free T4
With LH/FSH deficiency how would you treat the patient? (extra +2)
In men give testosterone and monitor serum testosterone/check for symptom improvement
In women give HRT (E2 + progestagen) and monitor symptom improvement/withdrawal bleeds
What happens to adults and children with GH (somatotrophin) deficiency? (2)
Children: pituitary dwarfism
Adults: not that much (may have reduced sense of well-being/lower quality of life and show less muscle mass + more fat tissue + loss of bone mineral density)
Draw the GH (somatotrophin) axis. (4)
See bottom of page 4
- GHRH (1)
- Somatostatin (SS) inhibitor effect (1)
- Somatotrophin from adenohypophysis (acting on peripheral tissues + liver)
- IGFI/IGF II from liver
Other than GH deficiency what else can cause short stature? (4)
- Malnutrition or malabsorption (e.g. coeliac’s)
- Genetic diseases e.g. Down’s syndrome, Prader Willi, Turner’s
- Emotional deprivation
- A consequence of other systemic diseases like cystic fibrosis
- Endocrine disorders like Cushing’s, hypothyroidism, poorly controlled T1DM
- Skeletal dysplasias (achondroplasia/osteogenesis imperfecta)
Pituitary dwarfism causes slow growth in children. What is pituitary dwarfism caused by? (1)
It is caused by not producing enough or any growth hormone (somatotrophin) due to disease of the adenohypophysis itself
Larown dwarfism can cause slow growth in children. What is Laron dwarfism caused by? (1)
It is caused by a defect in the GH receptor so the individual does not respond to GH even if levels are sufficient
Name 2 diseases of the GH axis which can lead to short stature.(2)
Pituitary dwarfism
Laron dwarfism
Prader-Willi syndrome
How does Prader-Willi syndrome cause short stature? (1)
In PWS the hypothalamus of the individual does not sufficiently promote GH release so you get apparent GH deficiency
How is the treatment for short stature caused by Prader-Willi syndrome different to the treatment of short stature caused by Laron dwarfism? (3)
- In PWS can give GH and by-pass the hypothalamic dysfunction
- In Laron dwarfism GH treatment would not work because it is the actual GH receptor that is the problem
- In Laron dwarfism can give IGF-1 (a downstream signalling molecule of GH)
How is short stature diagnosed? (1)
Based on projected growth curves, these are based on father and mother’s height
What can cause GH deficiency in adults? (2)
- Trauma
- Pituitary tumour or pituitary surgery
- Cranial radiotherapy
How can GH deficiency in adults be diagnosed? (3)
- Generally use biochemical testing: stimulation tests
- Stimulate in a number of different ways e.g. GHRH + Arg (synergistic), glucagon, exercise (10 minute step climbing if appropriate)
- Gold standard insulin induce hypoglycaemia
What are the benefits of GH treatment in adults? (2)
Better psychological well being
Increased bone mineral density
Increased muscle mass
Less adiposity
Does GH therapy increase risk of cancer?
No - does not seem to
What disadvantages of GH therapy are there? (1)
EXPENSIVE. 42K/year of treatment
