Hypopituitarism Flashcards
How is anterior pituitary hormone production regulated?
Hypothalamic releasing or inhibitory factors travel in the portal circulation to the anterior pituitary
Describe the differences you would see in a TFT for Primary vs Secondary Hypothyroidism
Primary Hypothyroidism —> thyroid gland itself cannot produce T3/4, e.g. autoimmune destruction of gland. Fall in T3/T4 but rise in TSH due to less -ve feedback to AP thyrotrophs.
Secondary Hypothyroidism —> eg. pituitary tumour damaging thyrotrophs. Fall in TSH production causing 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, e.g. autoimmune. Fall in cortisol but rise in ACTH due to less -ve feedback to the anterior pituitary corticotrophs.
Secondary Hypoadrenalism —> eg. Pituitary tumour damaging corticotrophs. Can’t make ACTH therefore cortisol low and ACTH is low.
Is aldosterone regulated by ACTH?
No, it is regulated by the renin-angiotensin system therefore patient won’t experience aldosterone deficiency related symptoms.
Describe the differences you would see in a blood test for Primary vs Secondary Hypogonadism.
Primary Hypogonadism —> Destruction of testes (e.g. mumps) or ovaries (eg. due to chemo). Fall in testosterone or oestrogen but rise in FSH/LH —> less -ve feedback to AP gonadotrophs.
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 infarction)
Peri-partum infarction (Sheehan’s syndrome)
Describe the possible congenital cause for Hypopituitarism and explain what happens to cause this?
- Rare
- 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
What are the causes of radiotherapy induced hypopituitarism?
- Pituitary and hypothalamus are both sensitive to radiation
- Direct: radiotherapy targeting pituitary (e.g. hormone producing pituitary tumour)
- Indirect: CNS tumour nearby
+ Higher the RT dose (measured in Gy), higher the risk of HPA axis damage
How long does the risk of damage to the anterior pituitary last after radiotherapy?
- Up to 10 years so patients require an annual assessment
- Radiotherapy is a slow process so effects on pituitary/hypothalamus aren’t immediately seen
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
Note: not a salt losing crisis as aldosterone is not regulated by ACTH, only 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 (difficult to measure)
Note: short stature only seen 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 (drop in BP) which leads to a pituitary infarction (tissue death - lack of blood and oxygen) in the enlarged anterior pituitary
- This leads to Post-Partum Hypopituitarism (PPH)
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, it is not. It is neural tissue not glandular (continuous with hypothalamus)
Outline the pathophysiology of pituitary apoplexy
Bleeding (haemorrhage) into the pituitary or loss of blood flow (infarction) to the pituitary
Often dramatic presentation in patients with pre-existing pituitary tumours (adenomas)
May be first presentation of a pituitary adenoma
Can be precipitated by anti-coagulants (blood thinners)
What are the symptoms of a pituitary apoplexy?
Severe sudden onset headache
Visual field defect – compressed optic chiasm, bitemporal hemianopia
Cavernous sinus involvement may lead to diplopia (IV, VI) - double vision, ptosis (III) - drooping of eyelid
What must you consider when making a biochemical diagnosis of hypopituitarism?
Cortisol – what time of day?
T4 – circulating t(1/2) - 6 days - long half life (takes time for levels to drop)
FSH/LH – cyclical in women
GH/ACTH - pulsatile
Outline how a dynamic pituitary function test works
- Insulin injected to induce hypoglycaemia (<2.2mM glucose)
- ACTH and GH are stress hormones - secreted in response to hypoglycaemia
- Measure multiple blood samples from tap - measure cortisol, not ACTH
- Measure GH, TSH, FSH/LH
However, hormone levels do fluctuate based on different factors so tests can’t be considered in isolation
What technique is used for a radiological diagnosis of hypopituitarism?
Pituitary MRI
How do you treat prolactin deficiency in hypopituitarism?
Can’t give prolactin back
However not much effect - no known prolactin deficiency syndrome
How do you confirm and treat GH deficiency in hypopituitarism?
According to NICE Guidance
Dynamic pituitary function test
Assess Quality of Life (QoL) using specific questionnaire
Daily injection
Measure response by
- improvement in QoL
- plasma IGF-1
How do you treat TSH deficiency?
Replace once daily with levothyroxine
How is TSH deficiency treated differently in secondary hypothyroidism than in primary hypothyroidism?
In SH, TSH will be low, so you can’t use this to adjust dose as you do in primary hypothyroidism, according to TSH levels
Aim for a fT4 above the middle of the reference range
How do you treat ACTH deficiency?
Replace cortisol rather than ACTH
Difficult to mimic diurnal variation of cortisol
Synthetic glucocorticoids:
Prednisolone once daily AM eg 3mg
Hydrocortisone three times per day eg 10mg/5mg/5mg
Who is at risk of an adrenal crisis and what are the symptoms?
Patients with primary adrenal failure (Addison’s) or secondary adrenal failure (ACTH deficiency) at risk
Triggered by intercurrent illness
Symptoms: dizziness, hypotension, vomiting, weakness - can result in collapse and death
What are the sick day rules?
Patients who take replacement steroid must be told sick day rules
Wear steroid alert pendant/bracelet
Double steroid dose (glucocorticoid not mineralocorticoid) if fever/intercurrent illness
Unable to take tablets (eg vomiting), inject IM or come straight to A & E
How is LH/FSH treated in men when no fertility is required?
Replace testosterone (topical or intramuscular most popular)
Measure plasma testosterone
Does replacing testosterone restore spermicide production?
No, replacing testosterone does not restore sperm production as this is dependent on FSH
How is LH/FSH deficiency treated in men when fertility is required and is sperm production instant?
Induction of spermatogenesis by gonadotropin injections
Best response if secondary hypogonadism has developed after puberty
Measure testosterone and semen analysis
No, sperm production may take 6-12 months
How is LH/FSH deficiency treated in women when no fertility is required?
Replace oestrogen
Oral or topical
Will need additional progestogen if intact uterus - prevents endometrial hyperplasia
How is LH/FSH deficiency treated in women when fertility is required?
Ovulation induced by carefully timed gonadotropin injections (IVF)
