Hypopituitarism Flashcards
General overview of structure of the pituitary?
Anterior - glandular
Posterior - neural
Sits on sella turcica
Optic chains above
Anterior blood supply through hypophyseal portal system. Hypothalamic releasing or inhibitory factors travel in this to regulate anterior pituitary production
Posterior has no blood supply
Hypothalamus hormones -> anterior pituitary-> glands
Best way to view is with MRI
What are the anterior pituitary hormones?
Growth hormone (Somatostatin, GhRH)
Prolactin (dopamine)
TSH (TRH)
LH and FSH (GnRH)
ACTH (CRH)
(Hypothalamus hormones in brackets)
What are the effects of the anterior pituitary hormones?
GH -> liver and bones, growth and IGF-1
Prolactin -> breast, milk production (oxytocin is ejection)
LH and FSH -> gonads, oestrogen, progesterone and testosterone
TSH -> thyroid, T3 and T4
ACTH -> adrenal cortex, cortisol
What are primary and secondary diseases?
Effect glands: thyroid, adrenal, gonads
Low home be levels from these can be primary or secondary
Primary: problem is with the last gland
Secondary: problem is with the anterior pituitary
Eg.
Thyroid:
1° - high TSH, low T3 and T4
2° - low TSH, low T3 and 4
Adrenal:
1° - high ACTH, low cortisol
2° - low both
Gonads:
1° - high LH and FSH, low testosterone/oestrogen/progesterone
2° - both low
What are primary and secondary hypothyroidism?
Thyroid:
1° - high TSH, low T3 and T4
May be autoimmune destruction of thyroid gland
TRH would also be high but this can’t be measured
2° - low TSH, low T3 and 4
May be pituitary tumour damaging thyrotrophs
What are primary and secondary hypoadrenalism?
NB cortisol is regulated by ACTH so this is effected. Aldosterone is not (renin-angiotensin)
Adrenal:
1° - high ACTH, low cortisol
May be auto immune destruction of adrenal cortex
2° - both low
May be pituitary tumour damaging corticosteroids
What are primary and secondary hypogonadism?
Gonads:
1° - high LH and FSH, low testosterone/oestrogen/progesterone
May be destruction of testes by mumps or ovaries by chemo
2° - both low
May be pituitary tumour damaging gonadotrophs
What are the two categories of hypopituitarism (give examples of both)?
CONGENITAL:
Rare,
Usually due to mutations of transcription factor genes needed for normal anterior pituitary development (eg. PROP1 mutation)
They will be deficient in GH and at least one other ant pit hormone
They will have a short stature
Hypoplastic pituitary gland on MRI
ACQUIRED:
More common
Tumours (adenomas, metastases, cysts)
Radiation (hypothalamic/pituitary damage)
Infection (eg. Meningitis)
Traumatic brain injury
Pituitary surgery
Inflammation (hypophysitis)
Pituitary apoplexy (haemorrhage, or less commonly infarction)
Peri-partum infarction (sheehans syndrome)
What is panhypopituitarism?
Total loss of anterior and posterior pituitary function
Hypopituitarism usually only describes anterior dysfunction, but certain processes such as inflammation (hypophysitis) and surgery can cause posterior dysfunction too.
What is radiotherapy induced hypopituitarism?
Radiotherapy , either directly to pituitary due to acromegaly eg, or indirectly to surrounding structures such as a nasopharyngeal carcinoma, causes hypopituitarism
Extent of damage depends on dose of radiotherapy
Growth hormone and gonadotrophins are most sensitive
Prolactin can increase after radiotherapy is the hypothalamus is damaged, as dopamine has an inhibitory effect on prolactin
The risk of damage persists up to 10 years after therapy, so annual assessment is needed
How does hypopituitarism present?
GH - reduced quality of life, short stature only in children
FSH and LH - reduced libido, secondary amenorrhoea, erectile dysfunction, reduced pubic hair
TSH - fatigue (may also be weight gain)
ACTH - fatigue (NB not a salt losing crisis as renin-angiotensin is not affected)
Prolactin - inability to breastfeed
What is Sheehan’s syndrome? (Including symptoms)
Post-partum hypopituitarism secondary to hypotension (due to haemorrhage - PPH). Leads to pituitary infarction
More common in developing countries
Anterior pituitary enlarges during pregnancy due to lactotroph hyperplasia
Symptoms:
Lethargy, anorexia, weight loss - TSH/ACTH deficiency
Failure of lactation - prolactin deficiency
Failure to resume menses post delivery - LH/FSH deficiency
Posterior pituitary is usually not affected coz it has no blood supply
What is pituitary apoplexy?
Intra pituitary haemorrhage or les commonly infarction
Often has a dramatic presentation in patients who already have a pituitary tumour (adenoma). It may be the first presentation of an adenoma
Can be precipitated by anticoagulants
Symptoms:
Severe sudden onset headache
Visual field defect (compressed optic chias - bitemporal hemianopia)
Involvement of the cavernous sinus (contains internal carotid arteries and cranial nerves) may lead to Diplopia (IV, VI) and ptosis (III)
How is hypopituitarism diagnosed?
Biochemically:
by measuring hormone levels. But caution must be taken
Cortisol - diurnal rhythm, high around 9am
T4 - circulating half life of 6days
FSH/LH - cyclical in women
GH/ACTH - pulsatile
Radiologically: Pituitary MRI (CT can’t delineate pituitary gland well)
This may reveal specific pituitary pathology (eg. Haemorrhage (apoplexy) or adenoma)
In an MRI you may see the haemorrhage or a tumour, or congenitally the sella may look empty as there is only a thin rim of pituitary tissue
How is dynamic pituitary function used in hypopituitarism diagnosis?
ACTH and GH are stress hormones (act when the body is stressed)
So
Insulin is injected to induce hypoglycaemia (<2.2mM). This is the stress
Insulin induced hypoglycaemia stimulates GH and ACTH (cortisol is measured) release
An increase in both of these would be normal. They would remain low in hypopituitarism
You can also inject TRH and GnRH to see if it has any effect on TSH and LH/FSH levels
How is hypopituitarism treated?
Hormone replacement
Only one you can’t fix is low prolactin, no substitute, and not really enough demand
How is the GH deficiency treated?
Confirmation of GH deficiency must be confirmed by dynamic pituitary function test
Assess quality of life using a specific questionnaire
Then daily injections
A response is measured by seeing whether there is an improvement in quality of life and plasma IGF-1
I think the injections are stopped if there is no effect
How is TSH deficiency treated?
Replace with once daily levothyroxine
The dose must be adjusted. TSH will be low, I like in primary hypothyroidism so TSH levels can’t be used to adjust dose.
Aim for T4 levels above the middle of the reference range
How is ACTH deficiency treated?
Replace cortisol rather than cortisol
It is difficult to mimic the diurnal variation of cortisol
Prednisolone- once daily (3mg)
OR
Hydrocortisone- three times daily (10mg->5mg-> 5mg)
These are both glucocorticoids
What must be taken into account with ACTH deficiency?
Sick day rules
Also patients with addisons (primary adrenal failure)
Because these people are at risk of adrenal crisis: dizziness, hypotension, vomiting, weakness.
Can result in collapse and death
Sick day rules:
Steroid alert bracelet
Double steroid dose if fever/intercurrent illness
Unable to take tablets (vomiting) inject IM or come to a and e
How is FSH/LH deficiency treated in men?
No fertility required:
Replace testosterone (topical/IM)
Measure plasma T
This does not restore sperm production - this is dependant on FSH
Fertility requires:
Induction of spermatogenesis by gonadotropin injections
Best response If secondary hypogonadism has developed after puberty
Measure T and semen analysis
Sperm production may take 6-12 months
How is FSH/LH deficiency treated in women?
No fertility required:
Replace oestrogen (oral or topical)
Will need additional progestogen (fake progesterone) if uterus is intact to prevent endometrial hyperplasia (no periods)
Fertility required:
Can induce ovulation by carefully timed gonadotropin injection
