Pituitary Gland: Non-Functioning Tumours, Prolactinoma, Acromegaly

Question 1

Hormones released by the anterior pituitary?

Answer 1

ACTH (stimulates adrenal glands)

TSH (stimulates thyroid glands)

FSH and LH (stimulate reproductive glands)

PRL (stimulates mammary glands)

STH (stimulates body parts)

Question 2

Hormones released by the posterior pituitary?

Answer 2

ADH (stimulates urine collection channels in the kidney)

Oxytocin (stimulates mammary glands and smooth muscles above the uterus)

Question 3

Method of hormone release from the anterior pituitary?

Answer 3

1. Stimulatory and inhibitory hormones are released from the body of the nerve cells in the hypothalamus
2. 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
3. Stimulatory/inhibitory hormones leave the capillaries and affected the pituitary gland in secretion of hormones
4. Hormones leave the pituitary gland through small vessels connected to the general bloodstream

Question 4

Method of hormone release from the posterior pituitary?

Answer 4

1. ADH and oxytocin are synthesised in the body of the nerve cells within the hypothalamus
2. Neuron that secretes ADH and oxytocin moves downwards from the axon and gathers at the axon tip
3. Hormones, transported with axons to the posterior lobe of the pituitary gland, enter the bloodstream from here

Question 5

Describe the thyroid axis

Answer 5

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

Question 6

Describe the hypothalamo-pituitary testicular axis

Answer 6

Hypothalamus releases GnRH, which stimulates LH and FSH release

These stimulate testosterone release

-ve feedback occurs to switch off LH and FSH production

Question 7

Describe the steroid hormone axis

Answer 7

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

Question 8

Which hormones are controlled in a stimulatory fashion?

Answer 8

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

Question 9

Which hormones are controlled in an inhibitory fashion?

Answer 9

Dopamine INHIBITS prolactin production (this is the control on the hormone)

Question 10

Which hormones are stored before exerting an effect?

Answer 10

Vasopressin and oxytocin are stored in the posterior pituitary and then exert their effects directly

Question 11

3 principle problems in endocrinology?

Answer 11

1. Too much hormone
2. Too little hormone
3. Gland is larger than usual

The pituitary gland be doing all 3 simultaneously

Question 12

Paired hormones (pituitary and peripheral)

Answer 12

ADD TABLE GREEN

Question 13

Baseline tests for checking pituitary function?

Answer 13

TSH and thyroxine (fT4)

LH/FSH and E2

GH and IGF-1

PRL

Question 14

Local compression that may occur with a pituitary tumour?

Answer 14

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)

Question 15

Basic principles of dynamic testing in the endocrinology scenarios of:

1. Too much hormone
2. Too little hormone

?

Answer 15

1. If there is too much hormone, do a test that attempts to SUPPRESS THE HORMONE
2. If there is too little hormones, do a test that attempts to STIMULATE THE HORMONE

Question 16

Examples of dynamic pituitary function tests that are stimulatory?

Answer 16

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

Question 17

Describe the synacthen test

Answer 17

Uses synthetic ACTH to stimulate cortisol, which is checked every 30 minutes

Question 18

Describe the insulin stress test

Answer 18

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

Question 19

Describe the water deprivation test

Answer 19

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

Question 20

Classifications of pituitary tumours with relation to size?

Answer 20

Microadenoma is ≤ 1cm

Macroadenoma is > 1cm

Question 21

Majority of pituitary adenomas are?

Answer 21

Benign; carcinomas are rare, as are metastases from another primary tumour

Question 22

Consequences of non-functioning pituitary adenoma?

Answer 22

• Compression on the optic chiasma
• Compression on other structures, e.g: cranial nerve 3, 4, 6
• Hypoadrenalism
• Hypothyroidism
• Hypogonadism
• Diabetes insipidus
• GH deficiency

Question 23

Eye symptoms with a pituitary gland tumour?

Answer 23

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

Question 24

Physiological causes of raised prolactin?

Answer 24

Breast feeding

Pregnancy

Stress

Sleep

Question 25

Drug causes of raised prolactin?

Answer 25

Dopamine antagonists, e.g: metoclopramide Anti-psychotics, e.g: phenothiazines To a lesser extent: • Anti-depressants, e.g: TCA and SSRIs • Oestrogens and cocaine

Question 26

Pathological causes of raised prolactin?

Answer 26

Hypothyrodism Stalk lesions (can be iatrogenic or due to a road-traffic accident) Prolactinoma

Question 27

Clinical symptoms and signs of raised prolactin in females?

Answer 27

``` EARLY presentation with: • Ammenorrhoea • Galactorrhoea (milk production from the breasts) • Menstrual irregularity • Infertility ```

Question 28

Clinical symptoms and signs of raised prolactin in males?

Answer 28

``` LATE presentation with: • Impotence (raised prolactin decreases testosterone) • Visual field abnormalities • Headache • Anterior pituitary malfunction ```

Question 29

Ix for prolactinoma?

Answer 29

Prolactin conc. MRI of the pituitary Visual field testing (for BILATERAL HEMIANOPIA) Pituitary function tests, e.g: other hormone affected

Question 30

Features to search for on an MRI of the pituitary?

Answer 30

* Microprolactinoma (<1 cm) * Macroprolactinoma (>1 cm) * Pituitary stalk * Optic chiasma

Question 31

Treatment of a prolactinoma?

Answer 31

Cebergoline (Dostinex) is given orally 2X per week; it is a DOPAMINE AGONIST It has few side effects and reduces prolactin and tumour size

Question 32

What is acromegaly?

Answer 32

There is GH excess In childhood, it is called gigantism

Question 33

Signs and symptoms of acromegaly?

Answer 33

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

Question 34

Ix for acromegaly?

Answer 34

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

Question 35

Describe the GTT

Answer 35

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

Question 36

Other tests for acromegaly?

Answer 36

Visual field

Question 37

Treatment of acromegaly?

Answer 37

Pituitary surgery (MAJORITY) External radiotherapy to the pituitary fossa

Question 38

Post-operate checks in acromegaly?

Answer 38

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

Question 39

Effects of somatostatin analogues in acromegaly?

Answer 39

Reduces GH in most patients Tumour shrinkage over 6-12 months; re-expansion occurs 6 weeks after stopping though Relieves headache in 1 hour

Question 40

Side effects of somatostatin analogues?

Answer 40

Local stinging Short-term: • Flatulence, diarrhoea and abdominal pains Long-term: • Gastritis and gallstones

Question 41

Somatostatin analogues used in acromegaly?

Answer 41

Octreotide (subcutaneous 3X/day) Sandostatin LAR (IM once/28 days) Lanreotide autogel (IM once/28 days)

Question 42

Dopamine agonists used in acromegaly?

Answer 42

Cabergoline up to (3g weekly) This works better if there is co-secretion of prolactin

Question 43

Use of pegvisomant?

Answer 43

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)

Question 44

Acromegaly follow-up?

Answer 44

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