8. Pituitary disorders

Question 1

What is the most common cause of pituitary malfunction?

Answer 1

benign tumour (adenoma)

Question 2

Are pituitary tumours usually ‘functional’ or ‘non-functioning’? What is the difference?

Answer 2

• most are non-functioning: don’t produce hormone themselves but can cause hypopituitarism (underproduction) due to physical pressure from growing tumour on glandular tissue
• functional tumours are rarer: can cause hyperpituitarism (overproduction)

Question 3

What are the symptoms of pituitary adenomas? Explain why these occur.

Answer 3

pressure on surrounding structures causes:

1. headache
2. visual problems
3. eye mov. probs.
4. vomiting and nausea
5. symptoms associated with either underproduction (non-functioning) or overproduction (functional) of pituitary hormones

Question 4

Which 3 investigations are performed when a pituitary tumour is suspected?

Answer 4

i. MRI scan: delineation of anatomy, size and topographical location of pituitary or parapituitary mass
ii. assessment of visual field defects

iii. assessment of endocrine function to determine any hormonal excess/deficiency:
- measuring hormone levels in blood
- staining sections from a biopsy of the tumour with antibodies for the relevant hormone

Question 5

Which symptoms indicate lateral or superior growth of tumour?

Answer 5

lateral growth:

• headaches (compression of nerves Va and Vb)
• eye mov. probs. (compression of nerves III, IV or VI)

superior growth:
- visual probs. (compression of optic nerve)

Question 6

What are the possible causes of hypopituitarism? Which is most common?

Answer 6

Most common:
1. pituitary adenoma (mass effects)

Rarer causes:

2. radiation therapy
3. inflammatory disease
4. head injury

Question 7

Which hormones are lost first in hypopituitarism?

Answer 7

typically a progressive loss of AP function with GH and FSH/LH 1st to be affected

Question 8

Which term is used to describe deficiency of all AP hormones?

Answer 8

panhypopituitarism

Question 9

In which cases would secretion of ADH and oxytocin from PP be affected?

Answer 9

1. if tumour affects hypothalamic function

2. if inflammatory process is involved

Question 10

What are the typical causes of GH deficiency in adults or children?

Answer 10

adults: mass effects from pituitary adenoma
children: usually idiopathic but can involve specific gene mutations and autoimmune inflammation

Question 11

What are the symptoms of GH deficiency in adults?

Answer 11

often quite subtle:

1. decreased exercise tolerance
2. decreased muscle strength
3. increased body fat
4. reduced sense of “well-being”

Question 12

What are the effects of prenatal GH deficiency?

Answer 12

usually has little effect on foetal growth

if severe can cause hypoglycaemia and jaundice

Question 13

What are the effects of GH deficiency in childhood?

Answer 13

poor growth and short stature

Question 14

What is the treatment for GH deficiency?

Answer 14

recombinant GH

Question 15

What are the symptoms of gonadotropin deficiency from a pituitary adenoma?

Answer 15

women:

• lack of libido
• infertility
• oligoamenorrhea/amenorrhea

men:

• lack of libido
• impotence

Question 16

What is diabetes insipidus?

Answer 16

ADH deficiency

Question 17

What are the possible causes of ADH deficiency?

Answer 17

1. hypothalamic tumour
2. pituitary tumour that has extended into hypothalamus
3. cranial radiotherapy
4. pituitary surgery
5. autoimmune infiltration
6. infections such as meningitis

Question 18

What are the 2 main effects of ADH deficiency?

Answer 18

1. excess secretion of dilute urine… dehydration

2. increased sensation of thirst (polydipsia)

Question 19

What are the 3 main conditions caused by a hypersecreting pituitary adenoma?

Answer 19

1. prolactin excess
2. GH excess: gigantism or acromegaly
3. ACTH excess: Cushing’s syndrome

Question 20

How is prolactin secretion by AP lactotropes regulated?

Answer 20

i) PRH stimulates secretion

ii) PIH (dopamine) inhibits secretion - dominates

Question 21

What are the symptoms of hyperprolactinaemia?

Answer 21

1. galactorrhea (unexplained milk production, rare in men)
2. gynecomastia (hard breast tissue)
3. hypogonadism (diminished activity of testes/ovaries)
4. amenorrhea
5. erectile dysfunction

Question 22

Why is hypogonadism a symptom of hyperprolactinaemia?

Answer 22

increased plasma prolactin… increased dopamine due to neg. feedback… decreased GnRH… decreased FSH/LH

Question 23

Name 4 possible causes for hyperprolactinaemia.

Answer 23

1. hypersecreting pituitary adenoma (prolactinoma) - most common cause
2. non-functioning pituitary adenoma (‘stalk effect’)
3. physiological causes: pregnancy, suckling, stress and exercise
4. dopamine antagonist drugs, inc. antipsychotics (e.g. haloperidol) and antidepressants (e.g. clomipramine)

Question 24

How can one differentiate between a prolactinoma and a non-functioning pituitary adenoma?

Answer 24

• hypersecreting prolactinoma: prolactin >5000 mU/L

- non-functioning adenoma: prolactin <5000 mU/L

Question 25

What is the treatment for prolactinoma and a non-functioning pituitary adenoma?

Answer 25

- prolactinoma: dopamine R agonists, e.g. cabergoline | - non-functioning pituitary adenoma: trans-phenoidal surgery (or radiotherapy)

Question 26

What is acromegaly and which is diagnosis often late?

Answer 26

- GH excess caused by hypersecreting pituitary adenoma (typically large so also associated with local mass effects) - effects of increased GH and IGF-1 receptor activation often take several years to manifest as change in physical appearance

Question 27

What are the symptoms of acromegaly?

Answer 27

gradual change in physical features: 1. broad nose, coarse facial features, thick lips and prominent supraorbital ridge 2. enlargement of hands and feet 3. excessive sweating and greasy skin local mass effects: 4. headaches 5. visual field defects 6. other cranial nerve palsies

Question 28

Which condition is caused by excess GH secretion in childhood?

Answer 28

gigantism

Question 29

What are the long-term complications of GH excess if untreated?

Answer 29

1. diabetes mellitus and hypertension (as GH antagonises the actions of insulin) 2. some forms of cancer, e.g. colon or thyroid (due to increased IGF-1) 3. irreversible body changes 4. premature cardiovascular death

Question 30

Which biochemical tests are used to diagnose acromegaly?

Answer 30

1. oral glucose tolerance test: failure to suppress GH <1ug/L 2. elevated IGF-1 level 3. GH day curve: elevated mean GH

Question 31

What are the treatment options for agromegaly?

Answer 31

1. trans-sphenoidal surgery 2. radiotherapy: external beam (multiple short bursts over several wks) or gamma knife (high conc. over single time) 3. drug therapy

Question 32

Which drugs can be used to treat acromegaly?

Answer 32

1. GH R antagonists, eg pegvisomant 2. dopamine R agonists, eg cabergoline - some efficacy in decreasing GH (but much higher dose than for prolactinoma) 3. synthetic somatostatin analogs, eg octerotide