Hypersecretion of Anterior Pituitary Hormones

Question 1

What is bitemporal hemianopia?

Answer 1

Partial blindness at the temporal visual field

Question 2

What visual field defects might suprasellar tumours cause and how?

Answer 2

• Bitemporal hemianopia
• Suprasellar tumours compress the optic chiasm, in particular the fibres running along from the nasal retinae and these fibres cross over at the optic chiasm to be presented at the temporal field in the vision, therefore causing bitemporal hemianopia

Question 3

In hyperpituitarism, what does an excess in the following hormones result in?

1) ACTH
2) TSH
3) Gonadotrophins (FSH / LH)
4) Prolactin
5) GH

Answer 3

1) Cushing’s
2) Thyrotoxicosis
3) Precocious puberty
4) Hyperprolactinaemia
5) Gigantism (children), Acromegaly (adults)

Question 4

What is the difference between Cushing’s syndrome and Cushing’s disease and what are they?

Answer 4

• Cushing’s syndrome = umbrella term for XS cortisol
• Cushing’s disease = ACTH producing pituitary adenoma causing XS cortisol production from the adrenal cortex

Question 5

What causes high prolactin physiologically?

Answer 5

• Pregnancy / breastfeeding

Question 6

What is the most common cause of hyperprolactinaemia?

Answer 6

• Prolactinomas - mostly microadenomas (< 10mm)

Question 7

How does prolactin impact the gonadal axis?

Answer 7

High prolactin supresses GnRH pulsatility, thereby impacting the gonadal axis

Question 8

List the signs and symptoms of hyperprolactinaemia due to pituitary adenoma in…

1) Men
2) Women

Answer 8

1)

• Infertility
• Loss of libido
• Erectile dysfunction
• Galactorrhoea but uncommon due to lack of oestrogen priming

2)

• Galactorrhoea (milk production outside of normal lactation)
• Secondary amenorrhoea or oligomenorrhoea
• Loss of libido
• Infertility

Question 9

Why will hyperprolactinaemia cause gonadal symptoms?

Answer 9

• Because prolactin suppresses GnRH pulsatility

Question 10

Why is galactorrhoea rare in men, even with hyperprolactinaemia?

Answer 10

• The breast tissue needs to be ‘primed’ by oestrogen, men lack this background so despite the high prolactin levels, they often don’t lactate unless they have this

Question 11

Outline the prolactin axis

Answer 11

• Hypothalamus secretes both dopamine and TRH which are the inhibiting and releasing factors for prolactin secretion respectively
• Dopamine dominates
• Anterior pituitary lactotrophs secrete prolactin
• This acts on target tissue

Question 12

How is prolactin release regulated by the hypothalamus?

Answer 12

• Dopamine dominates, it is secreted by the hypothalamus
• Dopamine acts on D2 receptors on lactotrophs in the anterior pituitary and inhibits prolactin secretion
• The hypothalamus also secretes TRH as a releasing factor to promote prolactin secretion in the anterior pituitary but dopamine dominates

Question 13

1) How is hyperprolactinaemia treated and give 2 example drugs?
2) Give some side effects of these drugs

Answer 13

1)

• Dopamine receptor agonists e.g….

1. Bromocriptine
2. Cabergoline

2)

• Dyskinesia
• Depression
• Nausea and vomiting
• Pathological gambling
• Postural hypotension
• Psychotic episodes

Question 14

What does XS GH in childhood and adulthood result in?

Answer 14

• Children - gigantism
• Adults - acromegaly

Question 15

What grows in acromegaly (note - you don’t have to do list all of them just suggest some)?

Answer 15

• Periosteal bone
• Cartilage
• Fibrous tissue
• Connective tissue
• Internal organs (cardiomegaly, splenomegaly, hepatomegaly etc)

Question 16

What is the usual cause of XS GH?

Answer 16

• Benign pituitary adenoma

Question 17

What are the clinical features of acromegaly - excluding complications?

Answer 17

• Metabolic effects - diabetes
• Hyperhidrosis (XS sweating
• Carpal tunnel syndrome (median nerve compression)
• Kyphosis
• Barrel chest
• Macroglossia
• Prognathism
• Enlarged supraorbital ridges, lips, nose, hands and feet

Question 18

What is the main metabolic effect of acromegaly and describe the pathophysiology of this?

Answer 18

• Diabetes
• GH causes increased endogenous glucose production and decreased muscle glucose uptake
• There is thus an increase in insulin production
• This leads to insulin resistance and therefore diabetes

Question 19

Give 4 possible complications of acromegaly and explain how they occur?

Answer 19

1. Obstructive sleep apnoea - bone and soft tissue surrounding the airways leads to narrowing and collapse during sleep
2. HTN - direct effects of GH and / or IGF-1 on vascular tree and GH mediated renal sodium reabsorption (mineralocorticoid-like effects)
3. Cardiomyopathy - HTN, DM, direct toxic effects of XS GH on myocardium
4. Increased risk of cancer - colonic polyps

Question 20

Why is hyperprolactinaemia associated with XS GH in acromegaly and what else will this cause?

Answer 20

• The pituitary adenoma may be co-secreting GH and prolactin

Question 21

How to diagnose high GH in acromegaly (what is the test used)?

Answer 21

• Failed suppression test with oral glucose load - paradoxical rise
• Normally when you give glucose GH falls in a homeostatic response to prevent XS blood glucose levels
• In acromegaly, the GH will have a paradoxical rise in response to giving an oral glucose load

Question 22

1) Why can’t you measure [GH] diagnostically for acromegaly?
2) Apart from GH, what else is elevated in acromegaly?

Answer 22

1)

• GH secretion is pulsatile

2)

• IGF-1

Question 23

Describe treatment options for acromegaly, starting with the first-line treatment option

Answer 23

• Transphenoidal hypophysectomy - 1st line
• Somatostatin analogues e.g. octreocide
• Dopamine agonists (because GH secreting pituitary tumours frequently express D2 receptors) e.g. Cabergoline
• Radiotherapy

Question 24

What is octreocide and what does it do?

Answer 24

• Somatostatin analogue
• Therefore used to treat acromegaly
• Reduces GH secretion and tumour size - pre-treatment before surgery may make resection easier or post-operatively and whilst awaiting effects of radiotherapy