Pituitary Gland: Non-Functioning Tumours, Prolactinoma, Acromegaly Flashcards
Hormones released by the anterior pituitary?
ACTH (stimulates adrenal glands)
TSH (stimulates thyroid glands)
FSH and LH (stimulate reproductive glands)
PRL (stimulates mammary glands)
STH (stimulates body parts)
Hormones released by the posterior pituitary?
ADH (stimulates urine collection channels in the kidney)
Oxytocin (stimulates mammary glands and smooth muscles above the uterus)
Method of hormone release from the anterior pituitary?
- Stimulatory and inhibitory hormones are released from the body of the nerve cells in the hypothalamus
- Secretions are 1st absorbed by capillaries in the hypothalamus base and are then transported by blood vessels to the 2nd capillary network in the anterior pituitary
- Stimulatory/inhibitory hormones leave the capillaries and affected the pituitary gland in secretion of hormones
- Hormones leave the pituitary gland through small vessels connected to the general bloodstream
Method of hormone release from the posterior pituitary?
- ADH and oxytocin are synthesised in the body of the nerve cells within the hypothalamus
- Neuron that secretes ADH and oxytocin moves downwards from the axon and gathers at the axon tip
- Hormones, transported with axons to the posterior lobe of the pituitary gland, enter the bloodstream from here
Describe the thyroid axis
Cold exposure stimulates temperature receptor in the hypothalamus, resulting in production of:
• Thyrotrophin-releasing hormone
This stimulates the anterior pituitary to release:
• Thyrotrophin
This stimulates the thyroid gland, resulting in production of thyroxine; this can -vely feedback to switch off thyrotrophin production
Describe the hypothalamo-pituitary testicular axis
Hypothalamus releases GnRH, which stimulates LH and FSH release
These stimulate testosterone release
-ve feedback occurs to switch off LH and FSH production
Describe the steroid hormone axis
Hypothalamus release CRH (corticotrophin-releasing hormone), which stimulates the pituitary gland to release ACTH
This stimulates the adrenal glands to produce cortisol which: • Regulates BG levels • Increases fat in the body • Help in defence against infection • Helps response to stress
Cortisol can -vely feedback to switch off production of both ACTH and CRH
Which hormones are controlled in a stimulatory fashion?
CRH (produced by the hypothalamus) stimulates ACTH release from the pituitary, which, in turn, causes release of cortisol
TRH (hypothalamus) stimulates TSH release from the pituitary, which, in turn, causes thyroxine release
GnRH (hypothalamus) stimulates LF/FSH release from the pituitary, which, in turn, causes E2 (oestradiol) release
GHRH (hypothalamus) stimulates GH release from the pituitary
Which hormones are controlled in an inhibitory fashion?
Dopamine INHIBITS prolactin production (this is the control on the hormone)
Which hormones are stored before exerting an effect?
Vasopressin and oxytocin are stored in the posterior pituitary and then exert their effects directly
3 principle problems in endocrinology?
- Too much hormone
- Too little hormone
- Gland is larger than usual
The pituitary gland be doing all 3 simultaneously
Paired hormones (pituitary and peripheral)
ADD TABLE GREEN
Baseline tests for checking pituitary function?
TSH and thyroxine (fT4)
LH/FSH and E2
GH and IGF-1
PRL
Local compression that may occur with a pituitary tumour?
If the tumour grows upwards (most common), can compress the optic chiasma
If the tumour grows to the right and left, can compression the cavernous sinus
A tumour can wrap around the internal carotid artery (high risk surgery, e.g: stroke)
Basic principles of dynamic testing in the endocrinology scenarios of:
- Too much hormone
- Too little hormone
?
- If there is too much hormone, do a test that attempts to SUPPRESS THE HORMONE
- If there is too little hormones, do a test that attempts to STIMULATE THE HORMONE
Examples of dynamic pituitary function tests that are stimulatory?
Synacthen (synthetic ACTH) - attempts to stimulate cortisol
Insulin stress test (GOLD STANDARD) OR prolonged glucagon test - attempts to stimulate cortisol and GH
Water deprivation test - attempts to stimulate ADH
Describe the synacthen test
Uses synthetic ACTH to stimulate cortisol, which is checked every 30 minutes
Describe the insulin stress test
Hypoglycaemia is purposefully induced (<2.2 mmol/L to stimulate the pituitary gland)
Cortisol and GH response is monitored every 30 minutes for 2-3 hours:
• Normally, cortisol should rise >500
• Normally, GH should rise >7 ug/L
Describe the water deprivation test
Person is deprived of water for 8 hours; their serum and urine osmolarites are checked
Normally the urine conc. should increase and the serum conc. should remain normal
Urine : serum osmolarity ratio >2 is normal; if this is not the case, they have diabetes insipidus
Classifications of pituitary tumours with relation to size?
Microadenoma is ≤ 1cm
Macroadenoma is > 1cm
Majority of pituitary adenomas are?
Benign; carcinomas are rare, as are metastases from another primary tumour
Consequences of non-functioning pituitary adenoma?
- Compression on the optic chiasma
- Compression on other structures, e.g: cranial nerve 3, 4, 6
- Hypoadrenalism
- Hypothyroidism
- Hypogonadism
- Diabetes insipidus
- GH deficiency
Eye symptoms with a pituitary gland tumour?
Bitemporal hemianopia due to compression of the posterior aspect of the optic chiasm
Temporal sides of vision is lost with this but nasal sides remain intact
Physiological causes of raised prolactin?
Breast feeding
Pregnancy
Stress
Sleep
Drug causes of raised prolactin?
Dopamine antagonists, e.g: metoclopramide
Anti-psychotics, e.g: phenothiazines
To a lesser extent:
• Anti-depressants, e.g: TCA and SSRIs
• Oestrogens and cocaine
Pathological causes of raised prolactin?
Hypothyrodism
Stalk lesions (can be iatrogenic or due to a road-traffic accident)
Prolactinoma
Clinical symptoms and signs of raised prolactin in females?
EARLY presentation with: • Ammenorrhoea • Galactorrhoea (milk production from the breasts) • Menstrual irregularity • Infertility
Clinical symptoms and signs of raised prolactin in males?
LATE presentation with: • Impotence (raised prolactin decreases testosterone) • Visual field abnormalities • Headache • Anterior pituitary malfunction
Ix for prolactinoma?
Prolactin conc.
MRI of the pituitary
Visual field testing (for BILATERAL HEMIANOPIA)
Pituitary function tests, e.g: other hormone affected
Features to search for on an MRI of the pituitary?
- Microprolactinoma (<1 cm)
- Macroprolactinoma (>1 cm)
- Pituitary stalk
- Optic chiasma
Treatment of a prolactinoma?
Cebergoline (Dostinex) is given orally 2X per week; it is a DOPAMINE AGONIST
It has few side effects and reduces prolactin and tumour size
What is acromegaly?
There is GH excess
In childhood, it is called gigantism
Signs and symptoms of acromegaly?
Giant (before epiphyseal fusion)
Thickened soft tissues:
• Skin, large jaw, sweaty, large hands
Hypertension and cardiac failure (increased cardiac muscle)
Headaches (hyperdynamic blood supply through the brain, NOT due to compression effects of tumour)
Snoring/sleep apnoea
Diabetes mellitus
Local pituitary effects:
• Visual fields, hypopituitarism
Early CV death
Colonic polyps and colon cancer
Ix for acromegaly?
IGF-1 (should correspond to the age and sex)
Glucose Tolerance Test (a type of suppression test)
Can also do:
• Visual field testing
• CT/MRI pituitary scan
• Pituitary function tests for other hormones
Describe the GTT
75g of oral glucose is given
GH is checked at every 30 mins until 120 is reached
Normally, glucose should suppress GH to <0.4 ug/L
In acromegaly, GH is either:
• Unchanged
• Paradoxical rise
• Remain >1 ug/L after glucose
Other tests for acromegaly?
Visual field
Treatment of acromegaly?
Pituitary surgery (MAJORITY)
External radiotherapy to the pituitary fossa
Post-operate checks in acromegaly?
A GH <0.4 ug/L is satiffactory
If GH >1 ug/L, they require drug therapy with:
• Dopamine agonist, e.g: Cabergoline
• Somatostatin analogues, e.g: Octreotide
• GH antagonists, e.g: Pegvisomant
Effects of somatostatin analogues in acromegaly?
Reduces GH in most patients
Tumour shrinkage over 6-12 months; re-expansion occurs 6 weeks after stopping though
Relieves headache in 1 hour
Side effects of somatostatin analogues?
Local stinging
Short-term:
• Flatulence, diarrhoea and abdominal pains
Long-term:
• Gastritis and gallstones
Somatostatin analogues used in acromegaly?
Octreotide (subcutaneous 3X/day)
Sandostatin LAR (IM once/28 days)
Lanreotide autogel (IM once/28 days)
Dopamine agonists used in acromegaly?
Cabergoline up to (3g weekly)
This works better if there is co-secretion of prolactin
Use of pegvisomant?
Binds to GH receptor and blocks activity; tumour size does not decrease, in fact, sometimes, there is an increase
IGF-1 decreases but serum GH conc. may increase
Given as a last-line therapy (subcutaneous injection, 10-30 mg per day)
Acromegaly follow-up?
Achieve clinically safe GH levels:
• GH <0.4 ug/L (post-GTT) and <2 ug/L (random)
• IGF-1
Check other pituitary hormones, esp. thyroid
Cancer surveillance, e.g: colon and tubulovillous adenoma
CV risk factors
Sleep apnoea
