(endo) hypopituitarism Flashcards
what is hypopituitarism?
diminished hormone secretion by the anterior pituitary gland
what is the origin of the anterior pituitary gland?
glandular
what is the origin of the posterior pituitary gland?
neuronal
what hormones does the anterior pituitary produce?
growth hormone (somatotrophin) prolactin adrenocorticotrophic hormone (corticotrophin) FSH & LH thyroid stimulating hormone
what is growth hormone alternatively known as?
somatotrophin
what is adrenocorticotrophic hormone alternatively known as?
corticotrophin (or ACTH)
what are LH & FSH alternatively known as?
gonadotrophins
what is thyroid stimulating hormone alternatively known as?
thyrotrophin
what structure is the anterior pituitary function reliant on?
hypothalamus
how is the anterior pituitary reliant on the hypothalamus?
hypothalamus releases either releasing or inhibiting factors into the hypophyseal-pituitary portal circulation which carries them down to the blood vessels surrounding the APG endocrine cells stimulating hormone release
what is growth hormone responsible for?
growth
production of IGF-1 in the liver
what is prolactin responsible for?
lactation (milk production)
what are LH & FSH responsible for?
oestrogen, progesterone and testosterone production
what is ACTH responsible for?
cortisol production
what is TSH responsible for?
T3 and T4 production
what are the two main causes for anterior pituitary failure?
primary disease or secondary disease
differentiate between primary disease and secondary disease
primary disease = problem with the gland itself
secondary disease = no signals from hypothalamus or anterior pituitary to gland
what is primary hypothyroidism?
reduced thyroid gland function due to autoimmune damage
what would be the blood thyroid report for a patient with primary hypothyroidism?
reduced T3 & T4 levels
elevated TSH levels
why would TSH levels be elevated in primary hypothyroidism?
due to the negative feedback loop that responds to reduced T3 & T4 levels
why can’t TRH levels be measured?
it is a releasing factors produced in the hypothalamus and released into the hypophyseal-pituitary portal circulation which is not part of the systemic circulation
what is secondary hypothyroidism? (give an example of a cause)
reduced thyroid gland function due to reduced/underactive anterior pituitary gland function
e.g. pituitary adenoma affecting thyrotrophs
what would be the blood thyroid report for a patient with secondary hypothyroidism?
reduced T3 & T4 levels
reduced TSH levels
what is primary hypoadrenalism?
reduced adrenal cortex function due to destruction of the adrenal cortex (e.g. autoimmune)
what would be the blood report for a patient with primary hypoadrenalism?
reduced cortisol, elevated ACTH
why can’t CRH levels be measured?
it is a releasing factors produced in the hypothalamus and released into the hypophyseal-pituitary portal circulation which is not part of the systemic circulation
what is secondary hypoadrenalism? (give an example of a cause)
reduced adrenal cortex function due to underactive/reduced anterior pituitary function
e.g. pituitary adenoma affecting corticotrophs
what would be the blood cortisol report for a patient with secondary hypocortisolism?
reduced cortisol
reduced ACTH
what is primary hypogonadism?
reduced gonadal function due to damage to the ovaries (women) or the testes (men)
what would be the blood thyroid report for a patient with primary hypogonadism?
women - reduced oestrogen, elevated LH & FSH
men - reduced testosterone, elevated LH & FSH
what is secondary hypogonadism?
reduced gonadal function due to underactive/reduced anterior pituitary function
e.g. pituitary adenoma affecting gonadotrophs
what would be the blood thyroid report for a patient with secondary hypogonadism?
women - reduced oestrogen, reduced LH & FSH
men - reduced testosterone, reduced LH & FSH
why can’t GnRH levels be measured?
it is a releasing factors produced in the hypothalamus and released into the hypophyseal-pituitary portal circulation which is not part of the systemic circulation
what can cause destruction of the testes in primary hypogonadism?
mumps
what can cause destruction of the ovaries in primary hypogonadism?
chemotherapy
what are the congenital causes of hypopituitarism?
mutation of the genes needed for normal anterior pituitary development e.g. POP1 mutation
what would be the blood hormone levels of a patient with congenital hypopituitarism?
deficent in GH + at least one more APG hormone
what are the symptoms of congenital hypopituitarism?
short stature and hypoplastic APG on an MRI
define hypoplastic
underdeveloped
what causes of hypopituitarism are more common: congenital or acquired?
acquired
list possible acquired causes of hypopituitarism
pituitary tumours (adenoma, metastases, cysts)
radiation (causes hypothalamic/APG damage)
traumatic brain injury
infection (e.g. meningitis)
pituitary surgery (accidental lesions during surgery)
inflammation (hypophysitis)
pituitary apoplexy (haemorrhage)
peri-partum infarction (Sheehan’s syndrome)
how can tumours cause hypopituitarism?
pituitary adenomas (hyperproliferation of APG cells) or metastases forming secondary tumours from other cancers
how can radiation cause hypopituitarism?
radiation directed towards APG or nearby APG can cause damage to the hypothalamus + APG
how can traumatic brain injury cause hypopituitarism?
can cause lesion of the PG = impaired pituitary function
how can pituitary surgery cause hypopituitarism?
can cause lesion of the PG or pituitary stalk = impaired pituitary function
(during tumour resection or other pituitary surgeries)
how can infection cause hypopituitarism?
meningitis impairs pituitary function
define hypophysitis and explain how it can cause hypopituitarism
inflammation of the pituitary gland or pituitary stalk = impairs pituitary function
how can pituitary apoplexy cause hypopituitarism?
haemorrhage into pituitary gland impairs function
how can Sheehan’s syndrome cause hypopituitarism?
pituitary infarcts and dies due to ischaemia as a result of hypotension in a peri-partum haemorrhage
which axes does hypopituitarism refer to?
could be one axis or several axes
which portion of the pituitary gland is referred to in hypopituitarism?
most commonly the APG however if the cause is surgery or hypophysitis (inflammation), PPG can also be affected
define panhypopituitarism
total loss of anterior AND posterior pituitary function
how does radiotherapy-induced hypopituitarism occur?
the hypothalamo-pituitary axis is either:
- direct target of radiation (e.g. pituitary adenoma causing acromegaly)
- indirect target of radiation (e.g. nasopharyngeal carcinoma)
why does radiotherapy-induced hypopituitarism occur?
both the hypothalamus and the APG are sensitive to radiation
what determines the extent of radiotherapy-induced hypopituitarism?
the dose of radiotherapy given
which APG cells are most sensitive to radiotherapy and what is the implication of this on hormone levels?
gonadotrophs and somatotrophs (so gonadotrophins and GH most likely lost)
what happens to prolactin levels as a result of radiotherapy-induced hypopituitarism?
if only lactotrophs damaged + hypothalamus intact = prolactin decrease
if hypothalamus damaged = prolactin increase (due to dopamine decrease)
why is an annual assessment important in patients who receive radiation direct at/near the pituitary gland?
risk of radiotherapy-induced hypopituitarism persist up to 10 years after completion of radiotherapy
how does hypopituitarism present in terms of LH & FSH?
reduced libido reduced pubic hair secondary amenorrhoea (females) erectile dysfuction (males)
what is secondary amenorrhoea?
absence of three or more menses in a row in a female who has had her period in the past
what is primary amenorrhoea?
absence of menses at the age of 15 in the presence of normal growth and normal secondary sexual characteristics
how does hypopituitarism present in terms of ACTH?
fatigue
how does hypopituitarism present in terms of TSH?
fatigue
maybe changes in weight?
how does hypopituitarism present in terms of GH?
short stature (only in children) reduced quality of life (adults)
how does hypopituitarism present in terms of prolactin?
inability to breastfeed (women)
no known obvious symptoms in men
what is the best radiological way to visualise the pituitary gland?
an MRI scan
why does a deficiency in ACTH not necessarily result in an adrenal crisis?
with ACTH deficiency in anterior pituitary failure = cortisol production impaires BUT aldosterone production intact due to functional renin-angiotensin system
(nb - blood pressure controlled by both cortisol and aldosterone)
what is Sheehan’s syndrome?
a post-partum condition wherein a peri-partum haemorrhage causes hypotension which leads to an infarction of the pituitary gland causing post-partum hypopituitarism
where is Sheehan’s syndrome most commonly seen?
most common in developing countries
explain the pathophysiology of Sheehan’s syndrome
during pregnancy, APG enlarges due to imminent increase in prolactin demand (increased need to breastfeed) = lactotroph hyperplasia
enlarged APG requires a richer, more significant blood supply
during childbirth, increased blood loss (haemorrhage) causes peri-partum hypotension
episode of hypotension enables a small window of time for a pituitary infarction to take place (as enlarged pituitary gland is extremely sensitive)
pituitary infarcts and dies = impaired production of endocrine hormones = secondary domino effects
why does lactotroph hyperplasia normally occur during pregnancy?
in preparation for a huge increase in prolactin demand (for lactation)
why is the anterior pituitary affected most by the the peri-partum hypotension?
enlarged in pregnancy (lactotroph hyperplasia) and therefore, more sensitive to changes in blood pressure
what are the common symptoms of Sheehan’s syndrome?
lethargy, anorexia, weight loss, failure to lactate, failure to resume menses post-delivery
what causes lethargy, anorexia and weight loss in Sheehan’s syndrome?
deficiency of TSH/GH/ACTH
what causes failure of lactation in Sheehan’s syndrome?
deficiency of prolactin
what causes failure of menses returning post delivery?
deficiency of LH/FSH
what is pituitary apoplexy?
intra-pituitary haemorrhage (or less commonly, infarction)
i.e. uncontrolled bleeding into PG/impaired blood supply to PG
what is an infarction?
obstruction of blood supply to tissue causing local death of tissue (due to thrombus/embolus)
how does pituitary apoplexy relate to pituitary adenomas?
dramatic presentation of apoplexy in individuals with pituitary adenomas
(often first presentation of adenoma too)
what can pituitary apoplexy be precipitated by?
use of anti-coagulants or blood thinners (e.g. warfarn) = increase likelihood of haemorrhage (into pre-existing pituitary adenoma)
what are the main symptoms of pituitary apoplexy?
sudden onset headache
bitemporal hemianopia
ptosis/diplopia (problems with eye movement)
how does pituitary apoplexy cause bitemporal hemianopia?
visual field defect due to compressed optic chiasm = blocks sensory information transmission from temporal visual fields to the primary visual cortex
how does pituitary apoplexy cause problems with eye movements?
due to compression of the blood vessels and nerves passing through the cavernous sinus (e.g. impaired CN III causes ptosis OR impaired CN IV/VI causes diplopia)
what does compression of CN III in pituitary apoplexy cause?
ptosis (drooping eyelid)
what does compression of CN IV or CN VI in pituitary apoplexy cause?
diplopia (double vision)
what precautions need to be taken before interpreting basal plasma hormone concentrations?
cortisol - diurnal rhythm, peaks during AM
T4 - has a half life of six days
FSH/LH - cyclical in women
GH/ACTH - pulsatile
what precautions need to be taken before interpreting basal plasma cortisol concentrations?
diurnal rhythm, peaks during AM
what precautions need to be taken before interpreting basal plasma T4 concentrations?
circulating half life of T4 is six days
what precautions need to be taken before interpreting basal plasma FSH/LH concentrations?
cyclical in women
what precautions need to be taken before interpreting basal plasma GH/ACTH concentrations?
pulsatile rhythm
besides a blood test, how can ACTH and GH levels be measured?
using insulin-induced hypoglycaemia - DYNAMIC PITUITARY FUNCTION TEST
by injecting insulin to stimulate a blood glucose level of <2.2mM (inducing stress)
this in turn will stimulate GH and ACTH release (latter used to measure cortisol)
besides a blood test, how can TSH levels be measured?
by injecting TRH to stimulate a TSH release - DYNAMIC PITUITARY FUNCTION TEST
besides a blood test, how can FSH and LH levels be measured?
by injecting GnRH to stimulate LH and FSH release - DYNAMIC PITUITARY FUNCTION TEST
why do we not do random hormone measurements as opposed to inducing hormone release?
what is it better to do instead?
not reliable/robust enough due to diurnal/cyclical/pulsatile rhythms etc
somehow decrease hypoglycaemia
why are ACTH and GH released during insulin-induced hypoglycaemia?
in response to stress and as part of the adrenergic response
how can hypopituitarism be radiologically diagnosed?
using a pituitary MRI
how is GH deficiency treated in adults?
assess GH deficiency using a dynamic pituitary function test
assess quality of life (QoL) using a specific questionnaire
if results suggest deficiency,, then daily GH injection
why is GH deficiency a problem in adults?
growth hormone is believed to be essential for psychological wellbeing
what is a dynamic pituitary function test?
stimulating or suppressing a particular hormonal axis and observing the appropriate hormonal response
e.g. insulin-induced hypoglycaemia to measure ACTH/GH levels
how is the efficacy of daily GH injections monitored in GH deficient patients?
measure response by assessing improvement in QoL or measuring plasma IGF-1 levels
why is plasma IGF-1 measured in GH deficient patients receiving treatment?
when GH is released, it acts on liver to stimulate IGF-1 production
why is the posterior pituitary unaffected in Sheehan’s syndrome?
the PPG is neuronal in origin and so lacks a blood supply = so no haemorrhage can occur
can lactotroph hyperplasia lead to bitemporal hemianopia?
not unless there is a pre-existing pituitary adenoma that is pushed further up by lactotroph hyperplasia, causing compression of the optic chiasm
how is ACTH deficiency treated?
replace missing cortisol rather than missing ACTH
how is the diurnal variation of cortisol maintained in ACTH deficiency treatment?
difficult to maintain diurnal variation BUT either of two synthetic glucocorticoids are given:
- hydrocortisone (thrice a day in 10mg, 5mg, 5mg)
- prednisolone (once a day AM e.g. 3mg)
what are hydrocortisone and prednisolone and what are they used for?
synthetic glucocorticoids used to replace missing cortisol in ACTH deficiency
why would prednisolone be preferentially given rather than hydrocortisone in ACTH deficiency?
prednisolone (synthetic) is more potent and much longer-lasting compared to hydrocortisone
what is the hydrocortisone dose given in ACTH deficiency?
thrice a day (10mg, 5mg and 5mg)
what are patients with ACTH deficiency at a higher risk of?
greater risk of adrenal crisis
what is ACTH deficiency alternatively known as?
secondary adrenal failure
as pituitary doesn’t make enough ACTH to stimulate cortisol production in the adrenal glands - primary site
what are the features of an adrenal crisis?
hypotension, dizziness, vomiting, weakness
what can adrenal crisis lead to?
collapse and death
what must patients with ACTH deficiency that take replacement steroids be told?
‘sick day rules’
what is primary adrenal failure also known as?
Addison’s disease
what are the ‘sick day rules’ that a patient with ACTH deficiency should know?
steroid alert pendant/bracelet
double steroid dose required of glucocorticoid, not mineralocorticoid (!) if fever/intercurrent illness
if unable to take tablets (i.e. vomiting), inject IM hydrocortisone/A&E
how is FSH/LH deficiency treated in men when fertility is NOT required?
replace testosterone (orally ot topically) and then measure plasma testosterone
would replacing testosterone in LH/FSH deficient men restore sperm production and why?
no, as sperm production depends on FSH levels not testosterone
how is FSH/LH deficiency treated in men when fertility is required?
induce spermatogenesis using gonadotrophin (LH/FSH) injections and then measure testosterone and do a sperm analysis
how long may sperm production take after gonadotropin injections have been given to LH/FSH deficient men?
may be between 6-12 months
how is FSH/LH deficiency treated in women when fertility is NOT required?
replace oestrogen (orally or topically)
how is FSH/LH deficiency treated in women when fertility is required?
can induce ovulation using carefully timed LH/FSH injections (IVF)
what is the difference between progesterone and progestogen?
progesterone = pro-gestational steroid hormone
progestogen = synthetic progesterone
what must also be prescribed if oestrogen is taken to treat LH/FSH deficiency in women and why?
progestogen (only if uterus is intact) to prevent endometrial hyperplasia
