Hypopituitarism Flashcards
What hormone inhibits the release of GH?
Somatostatin
What hormone do each of the following anterior pituitary cells release: Thyrotrophs Lactotrophs Somatotrophs Gonadotrophs Corticotrophs
TSH Prolactin GH LH and FSH ACTH
Briefly explain the hypothalamus-pituitary circulation.
Hypothalamic regulatory factors are released from hypothalamic parvocellular neurones into the primary
capillary plexus within the median eminence. Exert inhibitory or stimulatory effect on endocrine cells via the secondary capillary plexus. Regulate pituitary hormone production via portal circulation.
What will direct dysfunction of the anterior pituitary gland cause?
A downstream inhibition of hormone secretion from the target organs.
What happens to T3/T4 and to TSH levels if a patient has primary hypothyroidism?
T3 & T4 decreases, TSH increases
(TRH is unmeasurable) – there is a loss of
negative feedback exerted onto anterior
pituitary gland and hypothalamus.
What happens to the levels of T3/T4 and TSH in a patient with secondary hypothyroidism?
TSH falls
T4 and T3 fall
Does ACTH regulate aldosterone production?
NO
Aldosterone production is regulated by the renin -angiotensin system
What happens to cortisol and ACTH levels in a patient with primary hypoadrenalism?
Cortisol falls
ACTH increases
(we don’t measure CRH but that would also be high)
What happens to cortisol and ACTH levels in a patient with secondary hypoadrenalism?
Can’t make ACTH therefore ACTH falls and cortisol falls
What happens to a male patients testosterone, and LH and FSH levels if they have primary hypogonadism?
Testosterone will fall, but FSH and LH will increase (we don’t measure GnRH but that would also be high)
What type of cause of hypopituitarism is more rare?
Congenital
What is a congenital cause of hypopituitarism usually due to? (give an example)
Mutations of transcription factor genes needed for normal pituitary development. e.g. PROP1 mutation
Why would being born with hypopituitarism exhibit short stature?
Low GH + at least one more anterior pituitary hormone - therefore don’t grow.
What does hypoplastic mean?
Underdeveloped
List the acquired causes of hypopituitarism
Tumours (adenomas, metastases, cysts)
Radiation (hypothalamic/pituitary damage)
Pituitary apoplexy – haemorrhage (or less commonly, infarction).
Infection (meningitis)
Traumatic brain injury
Inflammatory (hypophysitis)
Pituitary apoplexy – haemorrhage (or less commonly, infarction).
Peri-partum infarction (Sheehan’s syndrome).
What is panhypopituitarism?
The total loss of anterior and posterior pituitary function is panhypopituitarism.
Hypopituitarism - nomenclature
May affect one axis, several or all
Often describes anterior pituitary dysfunction, but certain processes - especially inflammation (hypophysitis) or surgery - may cause posterior pituitary dysfunction too.
Radiotherapy induced hypopituitarism
Pituitary and hypothalamus are both sensitive to radiation,
- Radiotherapy direct to pituitary (acromegaly)
- Indirect – nasopharyngeal carcinoma
Extent depends on the overall dose of radiotherapy delivered to the hypothalmo-pituitary axis (Gy).
Risk persists up to 10 years after radiotherapy, so there is an annual assessment.
What 2 anterior pituitary hormones most sensitive to radiotherapy?
GH and gonadotrophin
What hormone can increase after radiotherapy?
Prolactin due to the loss of hypothalamic dopamine
Presentation of hypopituitarism for the following hormones: FSH/LH ACTH TSH GH PRL
FSH/LH: Reduced libido, secondary amenorrhoea, erectile dysfunction and reduced pubic hair.
ACTH: Fatigue, NB not a salt losing crisis (renin-angiotensin)
TSH: Fatigue
GH: Reduced quality of life, NB short stature only in children
PRL: Inability to breastfeed
What is Sheehan’s Syndrome?
Post-partum hypopituitarism secondary to hypotension (post-partum haemorrhage).
Anterior pituitary enlarges in pregnancy (lactotroph hyperplasia).
PPH leads to pituitary infarction.
In what parts of the world is Sheehan’s Syndrome most common?
Developing countries
What are the symptoms of Sheehan’s syndrome?
Lethargy, anorexia, weight loss- TSH/ACTH/GH deficiency
Failure to lactation – PRL deficiency
Failure to resume menses post-delivery
(Posterior pituitary function maintained)
What type of scan is the best way to look at the PG?
MRI
What is apoplexy?
Refers to stroke symptoms occurring SUDDENLY. Such symptoms occur due to bleeding into the brain. It can also occur by a blood clot in a brain blood vessel. Conditions such as subarachnoid hemorrhage or stroke are sometimes called apoplexy.
What is pituitary apoplexy?
An intra-pituitary haemorrhage or (less commonly infarction) associated with pituitary tumours (adenomas).
May be the first presentation of pituitary adenoma.
Can be precipitated by anti-coagulants.
How may a patient present with pituitary apoplexy?
Severe sudden onset headache
Visual field defect – compressed optic chiasm manifesting as bitemporal hemianopia
Cavernous sinus involvement may lead to diplopia (IV, VI), ptosis (III).
What should you be careful of when interpreting the basal plasma concentrations of the following hormones: Cortisol T4 FSH/LH GH/ACTH
Cortisol - highest in morning, comes down as the day goes on.
T4 - long half life therefore on the first day of pituitary apoplexy T4 levels may be normal.
FSH/LH - cyclical in women therefore depends at what time during the menstrual cycle it is measured.
GH/ACTH - pulsatile
What 2 pituitary hormones can be called as “stress” hormones?
ACTH and GH
Explain the purpose of doing a dynamic test in the diagnosis of hypopituitarism.
Insulin induced hypoglycaemia stimulates the release of GH and ACTH (cortisol response). If however the patient doesn’t respond by releasing GH and ACTH it means they have hypopituitarism.
(TRH stimulates TSH release and GnRH stimulates FSH and LH release).
Can you replace prolactin?
No
Treatment of GH deficiency
Confirm GH deficiency on dynamic pituitary function test
Assess quality of life using specific questionnaire
Daily growth hormone injection
Measure response by improvement in QoL and
plasma IGF-I
Treatment of TSH deficiency
Replace with levothyroxine
TSH will be low in the case of secondary hypothyroidism. You should therefore aim for fT4 above the middle of the reference as an indicator that the medication is working.
Treatment of ACTH deficiency
Replace CORTISOL Difficult to mimic diurnal variation of cortisol Prednisolone once daily AM (3mg) OR Hydrocortisone thrice daily 10mg/5mg/5mg
Outline the sick day rules for patients with ACTH deficiency.
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/intercurrent illness
Unable to take tablets (eg vomiting), inject IM or come straight to A&E
List adrenal crisis features.
Dizziness, hypotension, vomiting, weakness, can result in collapse and death
Treatment of FSH/LH deficiency (Male) - No fertility required
Replace testosterone – topical or intramuscular most popular
Measure plasma testosterone
Replacing testosterone does not restore sperm production (this is dependent on FSH)
Treatment of FSH/LH (Male) - Fertility 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.
Treatment of FSH/LH deficiency women - No fertility required
Replace oestrogen
Oral or topical
Will need additional progestogens if intact uterus to prevent endometrial hyperplasia
Treatment of FSH/LH deficiency women - Fertility required
Can induce ovulation by carefully timed gonadotropin injections (IVF)
