1B hypopituitarism Flashcards
What are the hormones the anterior pituitary makes?
- Growth hormone (somatotrophin)
- Prolactin
- Thyroid stimulating hormone/thyrotrophin (TSH)
- Gonadotrophins- Luteinising hormone (LH) and follicle stimulating hormone (FSH)
- Adrenocorticotrophic hormone (ACTH, corticotrophin)
How does the hypothalamus control the anterior pituitary?
Hypothalamus produces releasing or inhibitory factors which travel in hypothalamo-pituitary portal system to anterior pituitary to regulate anterior pituitary hormone production
Portal system has leaky, fenestrated blood vessels: very rare- capillaries on both ends and doesn’t end at the heart
What are the 2 types of anterior pituitary failure?
- Primary disease- where the gland itself fails e.g. gonads, adrenal cortex, thyroid
- Secondary disease- no signals from hypothalamus or anterior pituitary
What happens in primary hypothyroidism?
- Problem with thyroid gland- T3 and T4 fall, TSH increases because no -ve feedback
- TRH would also be high but we don’t measure it
What is an example of primary hypothyroidism?
Hashimoto: autoimmune destruction of thyroid gland
What happens in secondary hypothyroidism?
- Problem with anterior pituitary or hypothalamus so TSH can’t be made
- TSH falls → T3 and T4 fall
What is an example of secondary hypothyroidism?
Pituitary tumour damaging thyrotrophs
What happens in primary hypoadrenalism?
- Problem with adrenal gland- cortisol falls, ACTH increases because no -ve feedback
- CRH would also be high but we don’t measure it
What is an example of primary hypoadrenalism?
Autoimmune destruction of adrenal cortex e.g. Addison’s
What happens in secondary hypoadrenalism?
- Problem with anterior pituitary or hypothalamus so ACTH can’t be made
- ACTH falls → cortisol falls
What happens in secondary hypogonadism?
- Problem with anterior pituitary or hypothalamus so LH/FSH can’t be made
- LH/FSH fall → Testosterone/oestrogen fall
Give an example of primary hypogonadism
Destruction of testes (e.g. mumps) or ovaries (e.g. chemotherapy)
Give an example of secondary hypogonadism
Pituitary tumour damaging gonadotrophs
Which is more common out of acquired and congenital hypopituitarism?
Acquired hypopituitarism is much more common
What is congenital hypopituitarism?
- Pituitary gland hasn’t developed properly in utero
- Usually due to mutations of transcription factor genes needed for normal anterior pituitary development
What is an example of a gene mutation in congenital hypopituitarism?
PROP1 mutation
- Deficient in GH and at least 1 more anterior pituitary hormone
- Short stature
- Hypoplastic (underdeveloped) anterior pituitary gland on MRI
What does hypopituitarism usually describe?
Anterior pituitary dysfunction
But, certain processes (esp inflammation- hypophysitis, or surgery) may cause posterior pituitary dysfunction too
What is panhypopituitarism?
Total loss of anterior and posterior pituitary function
What are examples of acquired hypopituitarism?
- Traumatic brain injury
- Pituitary surgery
- Tumours e.g. adenomas, metastases, cysts : ischaemic when squeezed against the sella turcica bone
- Radiation (hypothalamic/pituitary damage)
- Infection e.g. meningitis
- Inflammatory (hypophysitis) (women: loss of periods; men: more difficult- loss of libido)
- Pituitary apoplexy- haemorrhage (or less commonly infarction)
- Peri-partum infarction (Sheehan’s syndrome)
How can radiotherapy cause hypopituitarism?
- Pituitary and hypothalamus are both sensitive to radiation
- Radiotherapy could be direct to pituitary e.g. to treat acromegaly
- Radiotherapy could be indirect to pituitary e.g. to treat nasopharyngeal carcinoma- so pituitary is innocent bystander
What happens to GH, gonadotrophins and PRL in radiotherapy-induced hypopituitarism?
- GH and gonadotrophins are most sensitive to damage; first to go
- PRL can increase after radiotherapy due to loss of hypothalamic dopamine
What does the extent of damage from radiotherapy depend on?
Total dose of radiotherapy delivered to hypothalamo-pituitary axis
How long does risk persist for after radiotherapy?
10 years, so annual assessment needed
How does hypopituitarism present for FSH/LH?
- Reduced libido; often not mentioned due to embarrassment
- Secondary amenorrhoea —> ask abt libido
- Erectile dysfunction —> ask abt libido
- Reduced pubic hair
How does hypopituitarism present for ACTH?
- Fatigue
N.B. not a salt losing crisis (renin-angiotensin)
How does hypopituitarism present for TSH?
- Fatigue
- Maybe weight gain
How does hypopituitarism present for GH?
- Reduced quality of life
N.B. short stature only in children
How does hypopituitarism present for PRL?
Inability to breastfeed
What is Sheehan’s syndrome?
- Post-partum hypopituitarism secondary to hypotension (post-partum haemorrhage- PPH)
- Anterior pituitary enlarges in pregnancy (lactotroph hyperplasia)
- PPH leads to pituitary infarction
What are the symptoms of Sheehan’s syndrome?
- Lethargy, anorexia, weight loss- TSH/ACTH/GH deficiency
- Failure of lactation- PRL deficiency
- Failure to resume menses post-delivery
- Posterior pituitary usually not affected
What happens to anterior pituitary during pregnancy?
It enlarges (lactotroph hyperplasia)
What is pituitary apoplexy?
- Intrapituitary haemorrhage or (less commonly) infarction
- Often dramatic presentation in patients with pre-existing pituitary adenomas (tumours)
- May be the first presentation of a pituitary adenoma
What can the haemorrhage in pituitary apoplexy be precipitated by?
Anti-coagulants
Describe this photo
- White ball in middle is haemorrhage
- C shaped grey thing on white ball is pituitary adenoma
- Black/grey stripe thing on top of white ball and adenoma is optic chiasm
What are the symptoms of pituitary apoplexy?
- Severe sudden onset headache
- Visual field defect- compressed optic chiasm (bitemporal hemianopia)
- If blood enters cavernous sinus it could compress nearby cranial nerves causing eye movement problems:
- Diplopia (double vision)- IV, VI
- Ptosis- III
What is important to keep in mind when measuring basal plasma hormone concs to diagnose hypopituitarism?
- Cortisol- diurnal rhythm so time of day changes how much in blood
- T4- has circulating half life of 6 days so might be normal on day of presentation but low a week later
- FSH/LH- cyclical in women
- GH/ACTH- pulsatile
What is a dynamic pituitary function test?
- Dynamic- taking a series of hormone measurements over a series of time points
- ACTH & GH are stress hormones so we induce stress in patients by making them hypoglycaemic (<2.2mM) using insulin- look for:
- GH increase
- ACTH release (cortisol measured since ACTH is hard to measure)
- Could give TRH to see whether anterior pituitary can make TSH
- Could give GnRH to see if anterior pituitary can make LH/FSH
How would we make a radiological diagnosis of hypopituitarism?
- Pituitary MRI (CT not so good at delineating pituitary gland)
- May reveal specific pituitary pathology e.g. haemorrhage (apoplexy), adenoma
- Would see an empty sella- thin rim of pituitary tissue (empty sella syndrome: normal and functional)
Left pic shows anterior pituitary (grey) and posterior (white sliver) but right pic has empty sella
How do we treat GH deficiency?
- NICE Guidance for GH treatment
- Confirm GH deficiency on dynamic pituitary function test
- Assess quality of life (QoL) using specific questionnaire- GH role in adults is unclear but thought to be needed for psychological wellbeing
- Daily injection
- Measure response by improvement in QoL and plasma IGF-1
How do we treat prolactin deficiency?
Not treatable
How do we treat TSH deficiency?
- Straightforward
- Replace with once daily levothyroxine
- In secondary hypothyroidism, TSH will be low so you can’t use this to adjust dose as you do in primary hypothyroidism
- Aim for a fT4 (free T4) above the middle of the reference range
How do we treat ACTH deficiency?
- Replace cortisol rather than ACTH
- Difficult to mimic diurnal variation of cortisol
- 2 main options in the UK using synthetic glucocorticoids
- Prednisolone once daily AM e.g. 3mg
- Hydrocortisone three times per day e.g. 10mg then 5mg then 5mg
What are the sick day rules for patients with ACTH deficiency?
Those with ACTH deficiency or Addison’s (primary adrenal failure) are at risk of adrenal crisis triggered by intercurrent illness e.g. UTI/chest infection
Patients taking replacement steroids e.g. prednisolone, hydrocortisone must be told sick day rules:
- Steroid alert pendant
- Double steroid dose (glucocorticoid not mineralocorticoid) if fever/intercurrent illness
- If unable to take tablets (e.g. vomiting), inject IM hydrocortisone or come straight to A&E
Adrenal crisis features?
- Dizziness
- Hypotension
- Vomiting
- Weakness
- Can result in collapse and death
How is FSH/LH deficiency treated in men when no fertility is required?
- Replace testosterone either topically or intramuscular
- Measure plasma testosterone
- Replacing testosterone doesn’t restore sperm production (this is FSH-dependent)
How is FSH/LH deficiency treated in men when fertility is required?
- Induction of spermatogenesis by gonadotrophin injections
- Best response if secondary hypogonadism developed after puberty
- Measure testosterone and semen analysis
- Sperm production may take 6-12 months
How is FSH/LH deficiency treated in women when no fertility is required?
- Replace oestrogen
- Oral or topical
- Will need additional progestogen if uterus is intact to prevent endometrial hyperplasia
How is FSH/LH deficiency treated in women when fertility is required?
Can induce ovulation by carefully timed gonadotrophin injections (IVF)
