Hypersecretion of anterior pituitary hormones

Question 1

What can cause hyperpituitarism?

Answer 1

Usually an isolated pituitary tumour but can also be ectopic.
Often associated with visual field defects (e.g. bitemporal hemianopia - due to close proximity to optic chiasm)

Question 2

Why may hyperpituitarism cause bilateral hemianopia?

Answer 2

Both eyes may be affected by bitemporal hemianopia as the decussation of nerves is at the optic chiasm (where the pituitary is)

Question 3

What can an excess of different anterior pituitary hormones cause?

Answer 3

ACTH (corticotrophin) -> Cushing’s disease

TSH (thyrotrophin) -> Thyrotoxicosis

LH, FSH (gonadotrophins) -> Precocious puberty in children

Prolactin -> Hyperprolactinaemia

GH -> Gigantism, Acromegaly

Question 4

What are the causes of hyperprolactinaemia?

Answer 4

Physiological - pregnancy, breastfeeding

Pathological - prolactinoma

Question 5

What can high prolactin levels lead to?

Answer 5

Suppresses GnRH pulsatility

Question 6

What are the signs/symptoms of hyperprolactinaemia in men and women?

Answer 6

Women – galactorrhoea, secondary amenorrhoea/oligomenorrhoea, loss of libido, infertility

Men – galactorrhoea (UNCOMMON), erectile dysfunction, loss of libido, infertility

Question 7

What is the science behind the treatment of hyperprolactinaemia?

Answer 7

Dopamine from dopaminergic neurones binds to D2 receptors on the lactotrophs and switches off prolactin secretion

Question 8

Describe the treatment for hyperprolactinaemia

Answer 8

D2 Receptor Agonists
- These drugs deliberately inhibit prolactin release (1st line treatment)

• D2 agonists then decrease prolactin secretion and reduce the tumour size

Question 9

What are some side effects of D2 receptor agonists?

Answer 9

• nausea/emesis
• postural hypotension
• dyskinesia (loss of voluntary movement)
• depression (exhaustion of dopamine stores)
• pathological gambling

Question 10

Give examples of D2 receptor agonists

Answer 10

Bromocriptine

Cabergoline

Question 11

What is the difference between gigantism and acromegaly?

Answer 11

Childhood  =  gigantism
Adulthood  =  acromegaly.  

Gigantism is usually due to benign GH secreting pituitary adenoma

Acromegaly = Insidious (gradual but harmful) in onset. When untreated, excess GH is associated with increased morbidity and mortality. Death; CVS (60%), respiratory complications (25%) and cancer (15%).

Question 12

What are some of the features of acromegaly?

Answer 12

Growth - periosteal bone, cartilage, fibrous tissue, connective tissue, internal organs (i.e. hepatomegaly)

Clinical features - excessive sweating (hyperhidrosis), headache, supraorbital ridge enlargement, big nose, big hands and feet, thickened lips, macroglossia, prognathism (protrusion of lower jaw), carpal tunnel syndrome, barrel chest and kyphosis

Question 13

How can acromegaly be diagnosed?

Answer 13

Patients can bring old photos of themselves to help diagnose.

GH is pulsatile and so random measurement is unhelpful however after an oral glucose load, the GH should drop in a healthy person as the insulin rises but in acromegaly, there is a rise of GH. There will be an elevated level of serum IGF-1

Question 14

Describe the treatment for acromegaly

Answer 14

• Surgery is first line – trans-sphenoidal entry and remove tumour
• Somatostatin analogues (e.g. OCTREOTIDE) or dopamine agonists (e.g. CABERGOLINE)
• Radiotherapy

Question 15

How do somatostatin analogues work?

Answer 15

• Injected or administered in a monthly depot injection
• Reduces GH secretion and tumour size
• Also used as pre-treatment before surgery to shrink tumour
• Can be used post-operatively if not cured or whilst waiting for radiotherapy to take effect

Question 16

What are the side effects of somatostatin analogues?

Answer 16

GI side effects common, e.g. nausea, diarrhoea, gallstones

Question 17

How can acromegaly lead to diabetes?

Answer 17

Excess GH leads to increased glucose levels (stimulates gluconeogenesis and lipolysis) -> high insulin levels in response to glucose -> increased insulin resistance -> impaired glucose tolerance -> diabetes mellitus

Question 18

What are the complications of acromegaly?

Answer 18

Obstructive sleep apneoa – increased soft tissue growth in throat

Hypertension – effect of GH or IGF-1 on vascular tree, GH mediated Na reabsorption

Cardiomyopathy – hypertension, DM, toxic effects of GH on myocardium

Cancer – colonic polyps

Question 19

Why is prolactin often high in acromegaly and what can this lead to?

Answer 19

Prolactin is often high in acromegaly –reflects tumour secreting both GH and prolactin. The hyperprolactinaemia will cause a secondary hypogonadism.

Question 20

Name a dopamine agonist

Answer 20

Cabergoline

Question 21

Name a somatostatin analogue

Answer 21

Octreotide