3.1 - Hypopituitarism Flashcards
What are the hormones the anterior pituitary gland makes?
- growth hormone (somatotrophin)
- prolactin
- thyroid stimulating hormone (TSH)
- luteinising hormone (LH)
- follicle stimulating hormone (FSH)
- adrenocorticotrophic hormone (ACTH, corticotrophin)
How does the hypothalamus control the anterior pituitary?
- hypothalamus produces hypothalamic releasing or inhibitory factors which travel in hypothalamo-pituitary portal circulation to the anterior pituitary to regulate anterior pituitary hormone production
- portal system has leaky, fenestrated blood vessels
What does growth hormone release lead to?
- growth
- GHRH from hypothalamus –> GH –> IGF-1 –> growth
What does prolactin release lead to?
- milk production
- negatively regulated by dopamine
What does LH release lead to?
- acts on ovary –> oestrogen and progesterone release in women
- acts on testes –> testosterone release in men
What does FSH release lead to?
- acts on ovary –> oestrogen and progesterone release in women
- acts on testes –> testosterone and spermatogenesis in men
What does TSH release lead to?
- triiodothyronine (T3) and thyroxine (T4) from thyroid gland
- regulated by TRH
What does ACTH release lead to?
- cortisol release from adrenal gland
- regulated by CRH
What are the two types of anterior pituitary failure?
- primary disease - the gland itself fails e.g. gonads, adrenal cortex, thyroid
- secondary disease - no signals from hypothalamus or anterior pituitary
What happens in primary hypothyroidism and give an example?
- problem with thyroid gland - T3 and T4 fall, TSH increases due to no -ve feedback
- TRH would also be high but we do not measure it
- e.g. autoimmune destruction of thyroid gland
What happens in secondary hypothyroidism and give an example?
- problem with anterior pituitary or hypothalamus = TSH cannot be made
- TSH falls –> T3 and T4 fall
- e.g. pituitary tumour damaging thyrotrophs
What happens in primary hypoadrenalism and give an example?
- problem with adrenal gland - cortisol falls, ACTH increases due to no -ve feedback
- CRH would also be high but we do not measure it
- e.g. autoimmune destruction of adrenal cortex e.g. Addison’s
What happens in secondary hypoadrenalism and give an example?
- problem with anterior pituitary or hypothalamus so ACTH cannot be made
- ACTH falls –> cortisol falls
- e.g. pituitary tumour damaging corticotrophs
What happens in primary hypogonadism and give an example?
- problem with testes/ovaries - testosterone (men) or oestrogen (women) falls, LH and FSH increase due to no -ve feedback
- GnRH would also be high but we do not measure it
- e.g. destruction of testes (e.g. mumps) or ovaries (e.g. chemotherapy)
What happens in secondary hypogonadism and give an example?
- problem with anterior pituitary or hypothalamus so LH/FSH cannot be made
- LH/FSH fall –> testosterone/oestrogen fall
- e.g. pituitary tumour damaging gonadotrophs
What are the two types of causes of hypopituitarism?
Congenital and acquired
What is congenital hypopituitarism?
- pituitary gland has not developed properly in utero
- usually due to mutations of transcription factor genes needed for normal APG development
What are the features of congenital hypopituitarism?
- deficient in GH and at least one more anterior pituitary hormone
- short stature
What does an MRI show in congenital hypopituitarism?
Hypoplastic (underdeveloped) anterior pituitary gland
What are examples of acquired hypopituitarism? (8)
- tumours e.g. adenomas, metastases. cysts
- radiation (hypothalamic/pituitary damage)
- infection e.g. meningitis
- traumatic brain injury
- pituitary surgery
- inflammatory (hypophysitis)
- pituitary apoplexy - haemorrhage/less commonly infection
- peri-partum infarction (Sheehan’s syndrome)
What is the occurrence of congenital vs acquired hypopituitarism?
Congenital is rare, acquired is much more common
What does hypopituitarism usually describe?
- anterior pituitary dysfunction
- but, certain processes - especially inflammation (hypophysitis) or surgery may cause posterior pituitary dysfunction too
What is panhypopituitarism?
Total loss of anterior and posterior pituitary function
How can radiotherapy cause radiotherapy induced hypopituitarism?
- pituitary and hypothalamus are both sensitive to radiation
- radiotherapy could be direct to pituitary (e.g. to treat acromegaly)
- radiotherapy could be indirect to pituitary (e.g. to treat CNS tumour nearby) = pituitary innocent bystander
What does the extent of damage to the pituitary caused by radiation depend on?
Total dose of radiotherapy delivered to hypothalamo-pituitary axis - higher dose = higher risk of HPA axis damage
What happens to GH, gonadotrophins and prolactin due to radiotherapy induced hypopituitarism?
- GH and gonadotrophins are most sensitive to damage
- prolactin can increase after radiotherapy due to loss of hypothalamic dopamine
How long does risk to pituitary persist for after radiotherapy?
Up to 10 years, so annual assessment needed
How does hypopituitarism present for FSH/LH? (4)
- reduced libido
- secondary amenorrhoea
- erectile dysfunction
- reduced pubic hair
How does hypopituitarism present for ACTH?
- fatigue
- NB not a salt losing crises as aldosterone dependent on renin-angiotensin axis
How does hypopituitarism present for TSH? (3)
- fatigue
- maybe weight gain
- bradycardia if extreme
How does hypopituitarism present for GH?
- reduced QOL
- NB short stature only in children
How does hypopituitarism present for prolactin?
Inability to breastfeed
What is Sheehan’s syndrome?
- post-partum hypopituitarism secondary to hypotension (post-partum haemorrhage - PPH)
- PPH (blood loss) leads to pituitary infarction (loss of blood supply)
- more common in developing countries
How does Sheehan’s syndrome occur?
- at the end of pregnancy, anterior pituitary is 2x normal size but blood supply has not increased
- this is normal but any blood loss means blood supply to pituitary too low
- blood supply not low enough for organ failure/death, but enough to infarct pituitary = cells die
- (PPG not affected as downgrowth of hypothalamus so neuronal not glandular)
What are the symptoms of Sheehan’s syndrome?
- lethargy, anorexia, weight loss - TSH/ACTH/GH deficiency
- failure of lactation (cannot breastfeed) - prolactin deficiency
- failure to resume menses post-delivery
- posterior pituitary usually not affected
How is Sheehan’s disease treated?
Lifelong supply of pituitary hormones
What happens to anterior pituitary during pregnancy?
It enlarges (lactotroph hyperplasia)
What is pituitary apoplexy?
- bleeding (haemorrhage) into the pituitary
- often dramatic presentation in patients with pre-existing pituitary tumours (adenomas)
- may be first presentation of pituitary adenoma
What can the haemorrhage in pituitary apoplexy be precipitated by?
Anticoagulants
What are the features of pituitary apoplexy?
- severe sudden onset headache (due to sudden increase in intracranial pressure)
- visual field defect - compressed optic chiasm (bitemporal hemianopia)
- if blood enters cavernous sinus it could compress nearby cranial nerves causing eye movement problems: diplopia - double vision (IV, VI), ptosis (III)
What is important to keep in mind when measuring basal plasma hormone concentrations to diagnose hypopituitarism?
- cortisol - diurnal rhythm so time of day changes conc in blood
- T4 - circulating half life of 6 days so may be normal on day of presentation but low a week later
- FSH/LH - cyclical in women
- GH/ACTH - pulsatile
What is a dynamic pituitary function test for ACTH & GH?
- ACTH & GH are stress hormones so we induce stress in patients by making them hypoglycaemic (<2.2mM) using insulin
- look for GH increase and ACTH release (cortisol measured since ACTH is hard to measure)
- if high levels, normal function
What is a dynamic pituitary function test for TSH?
Could give TRH to see whether pituitary can make TSH
What is a dynamic pituitary function test for FSH and LH?
Could give GnRH to see whether pituitary can make FSH and LH
How would we make a radiological diagnosis of hypopituitarism?
- pituitary MRI - CT not so good at delineating pituitary gland
- may reveal specific pituitary pathology e.g. haemorrhage (apoplexy), adenoma
- would see an empty sella - thin rim of pituitary tissue
How do we treat GH deficiency?
- NICE guidance
- confirm GH deficiency on dynamic pituitary function test
- assess QoL using specific questionnaire
- daily injection (no oral option as peptide)
- measure response by improvement in QoL and plasma IGF-1
How do we treat prolactin deficiency?
Cannot treat
How do we treat TSH deficiency?
- replace with once daily levothyroxine
- in secondary hypothyroidism, TSH is low so you cannot use this to adjust dose as you do in primary hypothyroidism
- aim for a fT4 above the middle of the reference range
How do we treat ACTH deficiency?
- replace cortisol rather than ACTH
- difficult to mimic diurnal variation of cortisol
- two main options in the UK using synthetic glucocorticoids
What are the two main options in the UK to replace cortisol using synthetic glucocorticoids?
- Prednisolone - once daily AM e.g. 3mg
- Hydrocortisone - three times per day e.g. 10mg/5mg/5mg
Who is at risk of adrenal crisis?
Those with primary adrenal failure (Addison’s) or secondary adrenal failure (ACTH deficiency) at risk of adrenal crisis triggered by intercurrent illness
What are the features of an adrenal crisis? (5)
- dizziness
- hypotension
- vomiting
- weakness
- can result in collapse and death
What are the sick day rules for patients with ACTH deficiency? (4)
- patients who take replacement steroid e.g. prednisolone, hydrocortisone must be told sick day rules
- steroid alert pendant/bracelet
- double steroid dose (glucocorticoid not mineralocorticoid) if fever/recurrent illness
- if unable to take tablets (e.g. vomiting), inject IM hydrocortisone or come to A&E
How is FSH/LH deficiency treated in men when no fertility is required?
- replace testosterone - topical or intramuscular
- measure plasma testosterone
- replacing testosterone does not restore sperm production (FSH dependent)
How is FSH/LH deficiency treated in men when fertility is required?
- induction of spermatogenesis by gonadotrophin injections
- best response if secondary hypogonadism has developed after puberty
- measure testosterone and semen analysis
- sperm production may take 6-12 months
How is FSH/LH deficiency treated in women when no fertility is required?
- replace oestrogen
- oral or topical
- will need additional progestogen if intact uterus to prevent endometrial hyperplasia
How is FSH/LH deficiency treated in women when fertility is required?
Can induce ovulation by carefully timed gonadotrophin injections (IVF)
