Hypopituitarism & Anterior Pituitary dysfunction Flashcards
what are the anterior pituitary hormones
Growth Hormone
Prolactin
Thyroid stimulating hormone
Lutenising hormone/Follicle stimulating hormone
Adrenocorticotrophic hormone
where does the pituitary sit
Sella turcica of sphenoid bone
what does the anterior pituitary rely on?
the hypothalamus (to regulate function by releasing or inhibiting factors which travel via portal circulation)
what factors are released by the hypothalamus for the AP
growth hormone releasing hormone
somatostatin
thyrotrophin releasing hormone
dopamine
gonadotrophin releasing hormone
corticotrophin releasing hormone
what is a primary endocrine disease
disease where the pathology originates in the gland itself e.g thyroid, adrenal cortex (cortisol), gonads
what is a secondary endocrine disease
disease where the pathology originates in the signals from the hypothalamus/anterior pituitary
what is primary hypothyroidism
thyroid doesn’t produce thyroxine e.g. due to autoimmune destruction of thyroid gland
Hashimotos
T3&4 fall TSH high (we don’t measure TRH but that would also be high)
what is secondary hypothyroidism
eg pituitary tumour damaging thyrotrophs
Can’t make TSH
TSH falls
T3 & T4 fall (as no TSH)
what is primary hypoadrenalism
Addisons disease
adrenal cortex damaged/destroyed by autoimmune
ACTH high, cortisol low (we don’t measure CRH but that would also be high)
what is secondary hypoadrenalism
E.g. pituitary tumour damaging corticotrophs
adrenal cortex functioning,
but can’t make ACTH
ACTH falls, cortisol low
what is primary hypogonadism
eg destruction of testes (eg mumps) or ovaries (eg chemotherapy)
Testosterone (men) or oestrogen (women) fall, LH & FSH increase (we don’t measure GnRH but that would also be high)
what is secondary hypogonadism
eg pituitary tumour damaging gonadotrophs
Can’t make LH/FSH
LH/FSH fall, Testosterone/oestrogen fall
congenital causes of hypopituitarism
Rare. Usually due to mutations in transcription factor genes needed for normal anterior pituitary development e.g PROP1
what are the signs of congenital hypopituitarism
deficient in GH & at least one more hormone since birth
Short stature
Hypoplastic (underdeveloped) anterior pituitary on MRI
hypoplastic (underdeveloped) anterior pituitary
acquired causes of hypopituitarism
Tumours (adenoma, metastases, cysts)
radiation
infection (meningitis)
traumatic brain injury
pituitary surgery
inflammation (hypophysitis)/autoimmunity
pituitary apoplexy (haemorrhage, or less commonly infarction)
Peri-parturm infarction (Sheehan’s syndrome)
what is hypophysitis
inflammation of the pituitary or infundibulum
what is pituitary apoplexy
Bleeding (haemorrhage) into pituitary or loss of blood flow (infarction) to the pituitary- more commonly bleed
Often sudden dramatic presentation in patients with pre-existing pituitary adenoma
May be first presentation of a pituitary adenoma
Can be precipitated by anti-coagulants
what is the name for complete loss of pituitary function (post. and ant.)
panhypopituitarism
what are the causes of pituitary apoplexy
haemorrhage
less commonly infarction
what procedures may cause radiotherapy-induced hypopituitarism
What factor is risk of HPA damage proportional to
Radiotherapy directly to pituitary (e.g. hormone producing pituitary tumor) or indirect (e.g. CNS tumor nearby)
Higher total radiotherapy dose (Gy)= higher risk of HPA axis damage
what hormones are most sensitive to radioactivity
Growth hormone and gonadotrophins
how long does the risk of radiotherapy persist for?
up to 10yrs, so annual assessment
how does hypopituitarism affecting LH/FSH present?
reduced libido
secondary amenorrhoea
erectile dysfunction
reduced pubic hair
how does hypopituitarism affecting ACTH present?
fatigue
Not a salt losing crisis (that’s RAAS)
how does hypopituitarism affecting TSH present?
fatigue, weight gain
how does hypopituitarism affecting GH present?
reduced quality of life, short stature in children
how does hypopituitarism affecting Prolactin present?
inability to breastfeed
what is sheehan’s syndrome?
In what regions of the world is it most common?
post-partum haemorrhage—> postpartum hypotension—>pituitary infarction—> postpartum hypopituitarism
Most common in developing countries
what are the signs/ effects of sheehans syndrome
lethargy, anorexia, weight loss ((bc loss of GH, ACTH, TSH)), failure of lactation, failure to resume menses
Posterior pituitary not usually affected
what happens to the pituitary during pregnancy
enlargement (lactotroph hyperplasia)
what is the onset of pituitary apoplexy? What is it often precipitated by
dramatic and sudden
often precipitated by anti-coagulants
what are the signs of pituitary apoplexy
severe sudden onset headache
visual field defect - bitemporal hemianopia (optic chiasm compression)
Cavernous sinus involvement leads to possible diplopia (IV, VI) and ptosis (III)
what methods can be used to diagnose hypopituitarism
blood tests (biochemical diagnosis), dynamic pituitary function tests (stress test), pituitary MRI (radiology)
what hormone dysfunction cannot be treated
prolactin
what is the NICE guidance for treating hypopituitarism affecting GH?
Confirm GH deficiency on dynamic pituitary function test
Assess Quality of Life using specific questionnaire
daily injection of GHmeasure response by improvement in quality of life and plasma IGF-1
how to confirm GH treatment is working
assess quality of life and measure response/improvement to this
Measure serum IGF-1
what is the guidance for treating hypopituitarism affecting TSH
once daily levothyroxine
TSH will be low so you can’t use this to adjust dose as you would with primary hypothyroidism
Aim for fT4 above the middle of the reference range
what is the guidance for treating hypopituitarism affecting ACTH?
What is the difficulty in this?
Replace cortisol rather than ACTH:
prednisolone once daily AM (e.g. 3mg)
or
hydrocortisone 3x daily (10mg/5mg/5mg)
Difficult to mimic diurnal variation of cortisol
what is an adrenal crisis
Patients with primary adrenal failure (Addison’s) or secondary adrenal disease (ACTH deficiency) are at risk of dizziness, hypotension, vomiting, weakness triggered by intercurrent illness
can collapse and die
what should patients taking replacement steroids be advised to do?
“Sick day rules”
keep steroid alert pendant/ bracelet
double steroid dose if fever/intercurrent illness
if unable to take tablets (e.g. vomiting), inject IM or come to A&E
what are the guidelines for hypopituitarism affecting LH/FSH in men?
If no fertility is required- replace testosterone topically or IM, measure plasma testosterone. This doesn’t restore sperm production (dependent on FSH)
If fertility is required- induce spermatogenesis by gonadotropin injections
Measure testosterone and semen analysis
Sperm production may take 6-12 months
when is fertility in men best conserved?
if secondary hypogonadism developed after puberty (gonads are right size/development)
what are the guidelines for hypopituitarism affecting LH/FSH in women?
oral or topical oestrogen
addition of progesterone if uterus is intact to prevent endometrial hyperplasia- could increase risk of endometrial cancer
if fertility is required, carefully timed and gonadotrophin injections can induce ovulation (IVF)
Does the term hypopituitarism refer to anterior or posterior pituitary dysfunction
Give examples of processes that can cause both anterior and posterior pituitary dysfunction
Generally refers to anterior pituitary dysfunction
Inflammation (hypophysitis) or surgery may cause posterior pituitary dysfunction too
Why should you be cautious when interpreting basal plasma hormone concentrations?
Cortisol – what time of day?
T4 – circulating t1/2 6 days (so might take several days to have low T4 on test)
FSH/LH – cyclical in women
GH/ACTH - pulsatile
What dynamic pituitary function tests are used in the diagnosis of hypopituitarism
ACTH/GH = ‘stress’ hormones
Hypoglycaemia (<2.2mM) = ‘stress’
Insulin-induced hypoglycaemia stimulates
GH release
ACTH release (cortisol measured)
TRH stimulates TSH release
GnRH stimulates FSH & LH release
Radiological diagnosis of hypopituitarism
Pituitary MRI (CT not so good at delineating pituitary gland)
Posterior bright spot- posterior pituitary
May reveal specific pituitary pathology
eg haemorrhage (apoplexy), adenoma
Empty sella – thin rim of pituitary tissue
Radiological diagnosis of hypopituitarism
Pituitary MRI (CT not so good at delineating pituitary gland)
Posterior bright spot- posterior pituitary
May reveal specific pituitary pathology
eg haemorrhage (apoplexy), adenoma
Empty sella – thin rim of pituitary tissue
