Hypopituitarism Flashcards
Endocrinology
Describe the differences you would see in a TFT for Primary vs Secondary Hypothyroidism.
Primary Hypothyroidism —> thyroid gland itself cannot produce T3/4 eg. autoimmune destruction of gland. Hence fall in T3/T4 but less -ve feedback to AP thyrotrophs occurs so you have a rise in TSH
Secondary Hypothyroidism —> eg. pituitary tumour damaging thyrotrophs . Therefore you have a fall in TSH production leading to a fall in T3/4
Describe the differences you would see in a blood test for Primary vs Secondary Hypoadrenalism.
Primary Hypoadrenalism —> Destruction of adrenal cortex eg. autoimmune. This would lead to less cortisol being produced and hence less -ve feedback to the anterior pituitary corticotrophs leading to more ACTH being produced.
Secondary Hypoadrenalism —> eg. Pituitary tumour damaging corticotrophs. Can’t make ACTH therefore cortisol low.
Describe the differences you would see in a blood test for Primary vs Secondary Hypogonadism.
Primary Hypogonadism —> Destruction of testes ( due to mumps) or ovaries ( eg. due to chemo). Leads to a fall in T or O —> less -ve feedback to AP gonadotrophs and hence more FSH/LH.
Secondary Hypogonadism —> eg. pituitary tumour damaging gonadrotrophs. Can’t make LH/FSH —> fall in LH/FSH and a consequent fall in T and O
Describe the possible acquired causes for Hypopituitarism and explain what happens to cause this?
Tumours e.g. adenomas, metastases, cysts
Radiation (hypothalamic/pituitary damage)
Infection e.g. meningitis
Traumatic brain injury
Pituitary surgery
Inflammatory (hypophysitis)
Pituitary apoplexy - haemorrhage (or less commonly infaction)
Peri-partum infarction (Sheehan’s syndrome)
Describe the possible congenital cause for Hypopituitarism and explain what happens to cause this?
Usually due to mutations of transcription factor genes needed for normal anterior pituitary development such as PROP1 mutation
Deficient in GH and at least 1 more anterior pituitary hormone therefore they are short in stature
Hypoplastic (underdeveloped) anterior pituitary gland on MRI
What is loss of both anterior and posterior pituitary function referred to as?
Panhypopituitarism
If you are going to lose anterior pituitary function because of radiotherapy then which hormones are lost first as a result of this?
GH and gonadotrophins are most sensitive
If you are going to increase activity of a hormone because of radiotherapy then which hormone is affected?
Dopamine release reduced leading to an increase in the amount of prolactin due to decreased hypothalamic dopamine inhibition
How long does the risk of damage to the anterior pituitary last after radiotherapy?
10 Years
What are the presentations of hypopituitarism due to a lack of FSH/LH?
Reduced libido
Secondary amenorrhoea
Erectile dysfunction
Reduced pubic hair
How does the lack of ACTH present itself in hypopituitarism?
Fatigue
NB not a salt losing crisis (renin-angiotensin) as aldosterone is not regulated by ACTH, just cortisol is
What effect does the lack of TSH have in hypopituitarism?
Fatigue - body’s energy production requires a certain amount of thyroid hormones
What effect does the lack of GH have in hypopituitarism?
Reduced quality of life
NB short stature only in children
How does the effect on prolactin in hypopituitarism present itself?
Inability to breastfeed
Briefly describe the pathophysiology behind Sheehan’s syndrome
Anterior pituitary enlarges in pregnancy due to lactotroph hyperplasia
Post-partum haemorrhage leads to hypotension which leads to a pituitary infarction in the enlarged anterior pituitary
This leads to Post-Partum Hypopituitarism
What are some of the symptoms of Sheehan’s syndrome?
Lethargy, anorexia and weight loss are due to a TSH, ACTH and GH deficiency
Failure to lactate - prolactin deficiency
Failure to resume menses post-delivery
Is the posterior pituitary usually affected in Sheehan’s syndrome and if so, how?
No
What is the best radiological way to visualise the pituitary gland?
MRI
What is pituitary apoplexy?
Intra-pituitary haemorrhage or (less commonly) infarction
How may the presentation differ in severity if the patient has a pre-existing adenoma?
Often dramatic presentation in patients with pre-existing adneomas and may be the first presentation of a pituitary adenoma
This is because the haemorrhage can be into the adenoma itself
How might a pituitary apoplexy be precipitated?
Can be precipitated by anti-coagulants - warfarin
What are some of the symptoms of a pituitary apoplexy?
Severe sudden onset headache
Visual field defect - compressed optic chiasm, bitemporal hemianopia due to pituitary adenoma
Cavernous sinus involvement may lead to diplopia (IV, VI), ptosis (III)
What do you need to be careful about when diagnosing hypopituitarism?
Caution in interpreting basal plasma hormone concentrations:
Cortisol - What time of day?
T4 - Circulating T(1/2) 6 days
FSH/LH - Cyclical in women
GH/ACTH - pulsatile
How do you use dynamic pituitary function in the diagnosis of hypopituitarsim by measuring concentrations of GH, ACTH, FSH, LH and TSH?
Insulin-induced hypoglycaemia (<2.2mM) to stimulate GH and ACTH release - These should be increased in healthy patients
TRH stimulates TSH release - This should be increased in healthy patients
GnRH stimulates FSH and LH release - This should be increased in healthy patients
Describe how you would radiologically diagnose hypopituitarism?
Pituitary MRI (CT not so good at delineating pituitary gland)
May reveal specific pituitary pathology such as apoplexy or haemorrhage
Empty sella - thin rim of pituitary tissue
Which hormone affected can you not treat?
Prolactin hormone deficiency
How would you treat a GH deficiency?
NICE guidance
Confirm GH deficiency on dynamic pituitary function test
Assess QoL using specific questionnaire
Daily injection
Measure response by:
Improvement in QoL
Plasma IGF-1
How would you treat a TSH deficiency?
Replace with once daily levothyroxine and TSH will be low so you cannot use this to adjust dose as you do in primary hypothyroidism
Aim for fT4 of above the middle of the reference range
What treatments should be given in the case of an ACTH deficiency?
Replace cortisol rather than ACTH
Difficult to mimic diurnal variation of cortisol
Two main options in UK using synthetic glucocorticoids:
Prednisolone once daily AM e.g. 3mg
Hydrocortisone 3 times per day e.g. 10mg/5mg/5mg
What triggers the adrenal crisis in Addison’s or Secondary adrenal failure?
Urinary Tract Infections or a Chest infection etc.
What are features of an Adrenal crisis?
Dizziness, hypotension, vomiting, weakness —> can result in collapse and death
How would you know if you had to check someone against the sick day rules?
Steroid alert pendant or bracelet worn
What are the sick day rules for such patients?
Double steroid dose (glucocorticoid not mineralocroticoid) if fever/intercurrent illness
Unable to take tablets (vomiting), inject IM or come straight to A&E
How would you treat an FSH/LH deficiency in men where fertility is not required?
Replace testosterone - topical or intramuscular most popular
Measure plasma testosterone
Replacing testosterone does not restore sperm production (this is dependent on FSH)
How would you treat an FSH/LH deficiency in men where fertility is required?
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 would you treat an FSH/LH deficiency in women where fertility is not required?
Replace oestrogen
Oral or Topical
Will need additional progestogen if intact uterus to prevent endometrial hyperplasia
This stops bleeding
How would you treat an FSH/LH deficiency in women where fertility is required?
Can induce ovulation by carefully timed gonadotropin injections (IVF)
