Hypopituitarism Flashcards
What are the anterior pituitary hormones?
- Growth Hormone (somatotrophin)
- Prolactin
- TSH (thyrotrophin)
- LH + FSH
- ACTH (corticotrophin)
How do the hypothalamic releasing or inhibitory factors travel and to where?
- portal circulation to anterior pituitary
- Travel via blood supply from hypothalamic neurones down capillary plexus + pituitary stalk to anterior piuitary
What is GH responsible for?
Growth (children height and adults like lean muscle strength)
What prolactin responsible for?
Milk production
What is FSH responsible for?
- Oestrogen
- Progesterone
- Testosterone
What is LH responsible for?
- Oestrogen
- Progesterone
- Testosterone
What can fail in primary disease?
- Thyroid
- Adrenal cortex (cortisol)
3 Gonads
What is an example of primary hypothyroidism?
autoimmune destruction of thyroid gland (common)
What happens to levels in primary hypothyroidism?
- T3 + T4 fall
2 . TSH increases (we don’t measure TRH but that would also be high)
What is an example of secondary hypothyroidism?
pituitary tumour damaging thyrotrophs
What happens to levels in secondary hypothyroidism?
- Can’t make TSH
- TSH falls
- T3 + T4 fall (as no TSH)
How is cortisol regulated?
by ACTH - aldosterone is NOT (renin-angiotensin)
What is an example of primary hypoadrenalism?
destruction of adrenal cortex (eg autoimmune)
What happens to levels in primary hypoadrenalism?
- Cortisol falls
2. ACTH increases (we don’t measure CRH but that would also be high)
What is an example of secondary hypoadrenalism?
pituitary tumour damaging corticotrophs
What happens to levels in secondary hypoadrenalism?
- Can’t make ACTH
- ACTH falls
- cortisol falls
What is an example of primary hypogonadism?
destruction of testes (eg mumps) or ovaries (eg chemotherapy)
What happens to levels in primary hypogonadism?
- Testosterone (men) or oestrogen (women) fall
2. LH + FSH increase (we don’t measure GnRH but that would also be high)
What is an example of secondary hypogonadism?
pituitary tumour damaging gonadotrophs
What happens to levels in secondary hypogonadism?
- Can’t make LH/FSH
- LH/FSH fall
- Testosterone/oestrogen fall
What are some congenital causes of hypopitutarism?
- mutations of transcription factor genes needed for normal anterior pituitary development
- eg PROP1 mutation
- Rare
How would you be able to tell if someone had congential hypopituitarism?
- Deficient in GH and at least 1 more anterior pituitary hormone
- Short stature
- Hypoplastic (underdeveloped) anterior pituitary gland on MRI
What are some acquired reasons for hypopituitarism?
- Tumours eg adenomas, metastases, cysts
- Radiation (hypothalamic/pituitary damage)
- Infection eg meningitis
- Traumatic brain injury
- Pituitary surgery
- Inflammatory (hypophysitis)
- Pituitary apoplexy - haemorrhage (or less commonly infarction)
- Peri-partum infarction (Sheehan’s syndrome
What axis is affected in hypopituitarism?
one axis, several or all
Is hypopituaitrism exclusively for anterior pituitary?
- Often just anterior
- BUT certain process (inflammation (hypophysitis) or surgery) may cause posterior dysfunction too
What is panhypopituitarism?
Total loss of anterior + posterior pituitary function
Is the pituitary and hypothalamus sensitive to radiation?
yes
When might there be radiotherapy be given to pituitary?
- direct to pituitary eg. to treat acromegaly
2. indirect eg nasopharyngeal carcinoma
What does the extent of radiotherapy induced hypopituaitarism depend on? Which areas are most senstivie?
- depends on total dose of radiotherapy delivered to the hypothalamo-pituitary axis (Gy)
- GH and gonadotrophins most sensitive
What can increase after radiotherapy? Why?
PRL can increase after radiotherapy (loss of hypothalamic dopamine)
What is the presentation if FSH/LH is affected in hypopituitarism?
- Reduced libido
- Secondary amenorrhoea
- Erectile dysfunction
- Reduced pubic hair
What is the presentation if ACTH is affected in hypopituitarism?
- Fatigue (no cortisol)
2. NB Not a salt losing crisis as Addisons as still have aldosterone (renin-angiotensin)
What is the presentation if TSH is affected in hypopituitarism?
Fatigue
What is the presentation if GH is affected in hypopituitarism?
- Reduced quality of life
2. NB short stature only in children
What is the presentation if PRL is affected in hypopituitarism?
Inability to breastfeed
What is Sheehan’s syndrome?
- Post-partum hypopituitarism secondary to hypotension (post partum haemorrhage - PPH)
- Posterior pituitary usually not affected
Where is Sheehan’s syndrome more common?
Developing countries (as related to how much blood a woman looses in pregnancy)
What happens to the anterior pituitary in pregnancy?
enlarges in pregnancy (lactotroph hyperplasia) very normal
What can Post party haemorrhage lead to?
pituitary infarction, so bigger than normal anterior pituitary needs more blood as bigger then doesn’t receive enough
What happens in Sheehan’s syndrome?
- Lethargy, anorexia, weight loss – TSH/ACTH/(GH) deficiency
- Failure of lactation – PRL deficiency
- Failure to resume menses post-delivery
What is pituitary apoplexy?
Intra-pituitary haemorrhage or (less commonly) infarction
What is the presentation of pituitary apoplexy?
dramatic presentation in patients with pre-existing pituitary tumours (adenomas)
What can pituitary apoplexy be the first presentation of?
Pituitary adenoma
How can a pituitary apoplexy be precipitated?
Anti-coagulants (blood thinner)
What are happens in pituitary apolexy?
- Severe sudden onset headache
- Visual field defect – compressed optic chiasm, bitemporal hemianopia
- Cavernous sinus involvement may lead to diplopia (IV, VI), ptosis (III)
What do you need to be aware of in a biochemical diagnosis of hypopituitarism?
What time of day / when to take it
What is the pattern of the hormones cortisol, T4, FSH/LH and GH/ACTH?
- Cortisol – what time of day?
- T4 – circulating t1/2 6 days, T4 may be fine several days after complain of headache when worried about apoplexy
- FSH/LH – cyclical in women
- GH/ACTH - pulsatile
How would you measure ACTH/GH for the diagnosis of hypopituitarism?
Dynamic test: ACTH/GH are stress hormones
1. Insulin-induced (give insulin injection to stress body) which makes blood glucose very low
•Hypoglycaemia (<2.2mM) = ‘stress’
2. hypoglycaemia stimulates
-GH release
-ACTH release (cortisol measured)
How would you measure TSH for the diagnosis of hypopituitarism?
Give TRH to stimulate TSH release (dynamic test)
How would you measure FSH/LH for the diagnosis of hypopituitarism ?
Give GnRH stimulates FSH+LH release (dynamic test)
How would you conduct a radiological diagnosis of hypopituitarism?
Pituitary MRI (CT not so good at delineating pituitary gland)
What can a pituitary MRI reveal?
- May reveal specific pituitary pathology
eg haemorrhage (apoplexy), adenoma - Empty sella – thin rim of pituitary tissue
How do you treat GH deficiency?
- Confirm GH deficiency on dynamic pituitary function test
- Assess Quality of Life (QoL) using specific questionnaire
- Daily injection
How do you measure the response of GH deficiency treatment?
- improvement in QoL (questionnaire)
* plasma IGF-1
How do you treat TSH deficiency?
- Replace with once daily levothyroxine
- Don’t forget, TSH will be low, so you can’t use this to adjust dose as you do in primary hypothyroidism
- Aim for a fT4 above the middle of the reference range (in secondary)
What do you replace in ACTH deficiency?
- cortisol rather than ACTH
- Difficult to mimic diurnal variation or cortisol
What are the two synthetic glucocorticoids used to treat ACTH deficiency?
- Prednisolone once daily AM eg 3mg
* Hydrocortisone three times per day eg 10mg/5mg/5mg
Who is at risk of adrenal crisis?
Patients with ACTH deficiency (or Addison’s – primary adrenal failure)
What are the features of an adrenal crisis?
- dizziness
- hypotension
- vomiting
4 weakness - can result in collapse and death
What is a sick day rule and who has them?
- Patients who take replacement steroid eg prednisolone, hydrocortisone must be told sick day rules
- Steroid alert pendant/bracelet
- Double steroid dose if fever/intercurrent illness
- Unable to take tablets (eg vomiting), inject IM or come straight to A + E
How do you treat FSH/LH deficiency in men when no fertility is required? What do you measure?
- Replace testosterone – topical or intramuscular most popular
- Measure plasma testosterone
- Replacing testosterone does not restore sperm production (this is dependent on FSH)
How do you treat FSH/LH deficiency in men when fertility is required? What do you measure?
- Induction of spermatogenesis by gonadotropin injections
- Best response if secondary hypogonadism has developed after puberty
- Measure testosterone and semen analysis
- Sperm production may take 6-12 months
How do you treat FSH/LH deficiency in women when no fertility is required?
- Replace oestrogen
- Oral or topical
- Will need additional progestogen if intact uterus to prevent endometrial hyperplasia
How do you treat FSH/LH deficiency in women when fertility is required?
Can induce ovulation by carefully timedgonadotropin injections (IVF)
What is ACTH responsible for?
Tells adrenal cortex to make cortisol (aldosterone from adrenal cortex is not under control of ACTH)
What is primary failure?
Gland itself fails
What is secondary failure?
No signal from hypothalamus or anterior pituitary
Are the effects of radiation on the pituitary immediate?
Risk persists up to 10y after radiotherapy, so annual assessment
What is the best radiological way to visual the pituitary gland?
- MRI
- CT good macroscopic view and not great as small pituitary
Can you replace prolactin?
No
What is adrenal crisis triggered by?
Intercurrent illness
