Prolactinoma

Question 1

Define prolactinoma.

Answer 1

Prolactinomas are benign lactotroph adenomas expressing and secreting prolactin.

Question 2

How common are prolactinomas?

Answer 2

Prolactinomas represent approximately 40% of all pituitary adenomas, with a female preponderance.

Question 3

What is the aetiology of prolactinoma?

Answer 3

Monoclonal in origin - arise from proliferation of a single mutated pituitary cell

• Most occur sporadically
• Small % occur in MEN type 1 or FIPA (family isolated pituitary adenoma - AIP gene mutations cause large prolactinomas in young age)

Question 4

Describe the hypothalamic-pituitary-prolactin axis.

Answer 4

NB: suckling also causes prolactin release.

Question 5

What are the effects of hyperprolactinaemia?

Answer 5

Secondary hypogonadism - effect of suppression of GRH and pituitary gonadotrophins

NB: disruption of DA secretion or transport via hypophysial portal vessels to the pituitary will also cause hyperprolactinaemia.

Question 6

What are the risk factors for a prolactinoma?

Answer 6

• Female - 20-50yrs
• Genetic predisposition - MEN1 or FIPA
• Oestrogen therapy - can cause medication induced hyperprolactinaemia (but not COCP or post-menopausal HRT)
• Male 30-60yrs - usually macroadenomas but rare

Question 7

What are the clinical features of prolactinoma?

Answer 7

Hyperprolactinaemia

Women:

• galactorrhoea
• menstrual irregularity
• infertility
• osteoporosis

Men:

• reduced libido
• impotence
• galactorrhoea

Mass effect:

• Visual disturbance
• Ophthalmoplegia
• Headaches
• Signs and symptoms of hypopituitarism

Question 8

How do you diagnose prolactinoma?

Answer 8

1st line:

Gandolinum enhanced MRI - confirms diagnosis (not CT)

Serum prolactin - usually >6000 in a prolactinoma. Normal range is <600.

Pregnancy test - exclude physiological cause of hyperprolactinaemia

Tests:

• U&Es - check for renal failure (can cause elevated prolactin)
• TFTs - normal unless hypothyroidism (can cause elevated prolactin)
• FSH/LH and estradiol/testosterone - may be low in secondary hypogonadism
• IGF1 - normal (acromegaly can cause hyperprolactinaemia)

Imaging:

• computerised visual field examination - check optic chiasm compression

Question 9

How do you manage a prolactinoma?

Answer 9

1st line: Medical:

• Observation if asymptomatic and if pregnancy not desired. OR
• Dopamine agonist - carbegoline/bromocriptine usually until tumour shrinkage
• +/- Combined oral contraceptive - for those who have menstrual irregularities and do not want to become pregnant

2nd line: Surgical: if patient fails to respond to medical or if they want to become pregnant

• Trans-sphenoidal surgery
• Sellar radiotherapy: where medical and surgical treatments have failed.

Question 10

What are the complications of prolactinomas?

Answer 10

Visual field impairment - bitemporal hemianopia

Anterior pituitary failure/diabetes insipidus

Hypopituitarism from radiotherapy -

Carbegoline associated valvular insufficiency - in high doses e.g. Parkinson’s can cause valvular regurgitation

Pituitary apoplexy - severe headache, vomiting, visual impairment, ocular palsy, or death, due to acute haemorrhage

Cerebrospinal fluid leakage - rhinorrhoea; presenting sign of large invasive macroprolactinomas or during medical treatment with high-dose dopamine agonist for these tumours

Question 11

What defines a macroadenoma vs microadenoma?

Answer 11

macroadenoma = >10mm

microadenoma = <10mm

Question 12

What are the other causes of a raised prolactin?

Answer 12

Question 13

List 5 drug causes of a raised prolactin.

Answer 13