Pituitary gland and regulation of the endocrine system Flashcards
Describe the pituitary gland
2 lobes:
- anterior
- posterior
Describe the anterior lobe of the pituitary gland
linked to the hypothalamus by a portal circulation system
Describe the posterior lobe of the pituitary gland
Direct extension of the cns
- axons extend down directly from the hypothalamus
What hormones are stored in the posterior pituitary gland?
- ADH
- Oxytocin
What stimulates many of the pituitary gland actions?
in response to actions in the hypothalamus
What connects the hypothalamus and the pituitary gland?
hypophyseal portal
system
What hormone released from the hypothalamus stimulates growth hormone production in the pituitary gland?
Growth hormone releasing hormone (GHRH)
What hormone released from the hypothalamus stimulates FSH/LH production in the pituitary gland?
Gonadotrophin releasing hormone (GnRH)
What hormone released from the hypothalamus stimulates ACTH production in the pituitary gland?
corticotrophic releasing hormone
What hormone released from the hypothalamus stimulates TSH production in the pituitary gland?
Thyroid releasing hormone
What hormone released from the hypothalamus inhibits prolactin hormone production in the pituitary gland?
Dopamine
How is GH secretion described?
- pulsatile
- mainly overnight
How can GH be measured in the blood?
By IGF-1, as it is longer acting
What stimulates the hypothalamus to alter its activity in relation to GH?
external/environmental factors
NOT PITUITARY
How is GH and IGF-1 regulated?
Through a negative feedback loop
What is the effect of GH?
Multiple physiological effects, mostly in childhood
- Either direct effects or via production of insulin-like
growth factor-1 (IGF-1) from liver
What is the effect of somatostatin production on GH?
- inhibits GH production by the anterior pituitary
What cells of the anterior pituitary produce growth hormone?
somatotrophs
What is the result of excess GH?
Gigantism = growth hormone excess in childhood/puberty
Growth hormone excess after puberty will not cause
people to grow taller, grow wider instead
What is the result of GH deficiency?
Dwarfism in childhood
Describe the normal lactotroph axis state
under negative hypothalamic control as dopamine inhibitsd prolactin release
How is the normal lactotroph axis state altered in pregnancy?
high oestrogenic states overcome inhibition by dopamine
=> enhances lactation
What is ADH?
vasopressin
What is oxytocin?
stimulates cervical dilatation and uterine contractions
Name disorders of the posterior pituitary
- diabetes insipidus
- syndrome of inappropriate anti-diuretic hormone (SIADH)
Name disorders that can result from pituitary tumours
overproduction/under function
- anterior pituitary excess hormones
- hypopituitarism
What is diabetes insipidus?
- lack of ADH and inability to reabsorb water
- passage of large volumes of dilute urine
What are the clinical features of diabetes insipidus?
- polyuria
- polydipsia
- nocturia
- low urine osmolality
- high plasma osmolality
(must exclude hyperglycaemia and hypercalcaemia)
What symptoms are common between diabetes insipidus and diabetes mellitus?
- polyuria
- polydipsia
Describe the action of ADH
- acts on ADH receptor (AVPR2)
- stimulates GPCR and PKA activation
= insertion of aquaporin channels
inhibition of endocytosis of channel
Where are ADH receptors found?
basolateral membrane of kidney collecting ducts
What are the two causes of diabetes insipidis?
- cranial (deficiency)
- nephrogenic (resistance)
Describe cranial diabetes insipidis
Deficiency of ADH:
- Can be idiopathic or genetic (mutation in ADH gene)
- Trauma, tumours, infections, inflammatory conditions of the posterior pituitary
- Usually patients who have had pituitary surgery
Describe nephrogenic diabetes insipidis
Resistance to ADH
- Genetic (usually AVPR2 mutation)
- secondary to drugs (e.g. lithium used to treat various forms of mental instability), metabolic upset (profound hypokalaemia or hypercalcaemia), renal disease
How is diabetes insipidus diagnosed?
water deprivation test
What is the water deprivation test?
patient to keep diary of urine production to determine genuine polyuria before testing
(may just be urinating frequently but small
amounts = not DI)
- Deprive fluid for 8h
- Measure plasma and urine osmolality every 2-4h
- Then give synthetic ADH (ddAVP) and reassess urine osmolality
- Will correct cranial DI but not nephrogenic DI (due to resistance rather than deficiency)
How is cranial diabetes insipidistreated?
Desmopressin (vasopressin/ADH analogue)
- Can be given orally/nasal spray/injection
- Monitor plasma sodium and osmolality
How is nephrogenic diabetes insipidis treated?
Treat underlying cause
- High doses of ddAVP
- Very difficult to treat
What is a non-functioning pituitary adenoma?
Pituitary tumour that does not secrete active hormones
‘incidentalomas’
What further tests should be carried out on non-functioning pituitary adenoma?
- exclude hormone function (excess/hypo)
- Ensure no effect on visual fields (Pituitary located just below optic chiasm)
Tumour can expand upwards and push on chiasm causing loss of peripheral vision (‘bitemporal hemianopia’)
- Tunnel vision
- May require urgent surgery to decompress optic nerve
What are secretory pituitary adenomas?
Pituitary tumour that secretes active hormones
What are the different types of secondary pituitary adenomas?
- prolactinomas
- somatotrophic adenomas
- corticotrophic adenomas
- gonadotrophic adenomas
- thyrotrophic adenomas
What is a prolactinoma?
- most common pituitary tumour
- secretes prolactin
What are the clinical features of prolactinomas?
Clinical features result from suppression of gonadotrophic hormones => hypogonadrotrophic
hypogonadism (negative feedback on gonadotropins)
- Galactorrhoea – milky discharge from breasts
- Menstrual disturbance and subfertility in women
(present earlier in women)
- Rare in men, but presents with reduced libido/erectile dysfunction in men
How are prolactinomas managed?
Dopamine agonists (cabergoline) – dopamine inhibits prolactin production
- Virtually always pharmacologically managed
- Surgery if large tumour with visual field effects (very unusual - normally small and
shrink with cabergoline)
What is a somatotrophic adenoma?
pituitary tumour that secretes growth hormone?
What are the effects of a somatotrophic adenoma?
increased growth hormone secretion
= acromegaly
What is acromegaly?
Excessive production of GH (and IGF-1) in adults (causes ‘gigantism’ in children)
o Growth plates have fused, and therefore cannot cause increase in height
o Cartilage, muscles and tendons can still grow
- Rare, UK annual incidence is 4/million
- Usually due to pituitary adenoma (often large - macroadenomas)
What are the symptoms of acromegaly?
Sweats, headache, tiredness, increase in ring or
shoe size, joint pains
- Impaired function of the rest of the pituitary
What are the signs of acromegaly?
Coarse facial appearance
o Enlarged tongue
o Enlarged hands and feet
o Visual field loss
What are the complications of acromegaly?
Hypertension
o diabetes or impaired glucose tolerance
o Increased risk of bowel cancer – GH is thought to be carcinogenic
o heart failure
How is acromegaly diagnosed?
- glucose tolerance test
- IGR-1 level
- pituitary MRI
How is a glucose tolerance test used to diagnose acromegaly?
glucose normally suppresses GH
o Glucose load fails to suppress GH
o May reveal underlying DM or IGT
How is an IGF-1 level used to diagnose acromegaly?
Produced by liver in response to GH
o long half-life, protein bound
o So more useful than plasma GH
o NB: because of short half-life, GH might even be normal if measured
How is an MRI used to diagnose acromegaly?
Tumour usually large (macroadenoma, > 1 cm) and often extends into surrounding structures
(cavernous sinus)
How is acromegaly managed?
- surgery (not curative but reduces tumour)
- somatostatin analogues to inhibit GH secretion
- radiotherapy to treat residual tumour, but increases risk of hypopituitarism
What is hypopituitarism?
Failure of (usually anterior) pituitary function
Can affect a single hormonal axis (FSH/LH most commonly) or all hormones (panhypopituitarism)
Leads to secondary gonadal/thyroid/adrenal failure
How is hypopituitarism treated?
Need multiple hormone replacement (give cortisol first if all axes affected)
o Lack of cortisol is life threatening
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o Controversy over need for GH in adults
What are the causes of hypopituitarism?
- tumours
- radiotherapy
- infarction
- infiltrations
- trauma/surgery
- congenital