Professor Maurice Scanlon
University of Wales

Prolactinomas are benign pituitary tumours. They occur when lactotrophs (cells located in the anterior pituitary responsible for producing Prolactin) function autonomously, dividing far more rapidly than usual. This may be the result of a post-birth point mutation of a growth-controlling gene in lactotrophs and the result is an increase in the amount of prolactin the anterior pituitary secretes into the blood (Hyperprolactinaemia). Although there is no supporting evidence for head injuries triggering the condition, the possibility cannot be ruled out entirely.

Tumours are divided into microprolactinomas (less than 10 mm in diameter) and macroprolactinomas (greater than 10 mm in diameter). Although not all microprolactinomas progress to macroprolactinomas, the larger tumours can be more aggressive and harder to control. Problems can be caused due to the pressure of the tumour on surrounding structures. For example, upward growth of the tumour puts pressure on the optic nerves eventually causing visual impairment that may become permanent if it is not dealt with early. Restricted drainage of Cerebrospinal fluid may lead to raised intercranial pressure causing headaches and vomiting. Lateral spread of the tumour may invade the cavernous sinus and damage the nerves involved with eye movement.

Both the size and the increased amount of prolactin released into the blood contribute to the problems caused by prolactinomas.

Increased prolactin levels interfere with normal cyclical brain functions, which control the ovaries in women and the testes in men. Also, high levels of prolactin reduce the action of two other pituitary hormones - Luteinising hormone (LH) and follicle stimulating hormone (FSH) - which normally stimulate the ovaries in women and the testes in men, causing Hypogonadism in both sexes. In women, ovaries reduce their production of Oestrogen and Progesterone, disrupting the menstrual cycle, ultimately stopping ovulation and leading to infertility. In men there is a reduction of Testosterone and sperm production falls. Impotence and a loss of libido are also often features of increased prolactin levels. Galactorrhoea (inappropriate secretion of milk) may be seen in men as well as women.

Low oestrogen and testosterone levels lead to thinning of the bones (Osteoporosis) and possibly damage to blood vessels if not treated over many years.

Other than a Prolactinoma, possible causes of hyperprolactinaemia include:

• Pregnancy - where increased oestrogen levels stimulate lactotrophs to increase in size and number thus increasing their production of prolactin.
• The use of some drugs - for instance drugs for nausea and vomiting and tranquillisers that work by binding to receptors, stimulating the production of prolactin.
• Other hormone imbalances - including polycystic ovary syndrome or Hypothyroidism.
• Stress - for example, elevated stress levels due to having a blood test! The result is a false positive.
• Macroprolactin - prolactin that circulates in the blood bound to IgG (an immunoglobulin). Although biologically inactive, it cross-reacts with the assay used to measure prolactin. Again the result is a false positive.
• Idiopathic hyperprolactinaemia - where prolactin levels are high, but there is no evidence of a tumour. Most probably this is an indication of a tumour smaller than 2 mm in diameter, around 15% of which may develop into a microadenoma over a five-year period.

After these have been excluded, substantially elevated prolactin levels are most likely to be due to a prolactinoma.

Prolactinomas are usually treated using medical therapy to reduce prolactin production, although transphenoidal surgery may be required for tumours that are drug resistant or in individuals who are intolerant of the drugs used.

Bromocriptine is a dopamine agonist that binds to dopamine receptors on lactotrophs. This effectively shuts down their cell activity and causes tumour shrinkage together with suppression of prolactin levels in up to 90% of individuals. Because of its short duration of activity it must be taken at regular intervals each day.

Cabergoline is a better alternative. It is also a dopamine agonist, but binds to the receptor with a greater affinity and lasts up to 60 hours in the blood. It need only be taken once or twice a week.

Both these drugs have side-effects, which are generally short lived, occurring during the early days of treatment while our bodies get used to them.

Quinagolide is another relatively new drug, which must be taken once daily.