Dr Jonathan Webster
Northern General Hospital, Sheffield

Prolactinomas are the most common functioning pituitary tumours. They are almost always benign (non cancerous). Most prolactinomas are small (10mm or less in diameter) and are called microprolactinomas. Microprolactinomas are more common in women than in men. Macroprolactinomas (larger than 10mm) are equally infrequent in both men and women.

The cause of prolactinomas is unknown and the vast majority occur randomly. A few prolactinomas occur as part of an inherited condition such as MEN-1 (Multiple Endocrine Neoplasia Type 1). Prolactinomas appear to be "monoclonal", i.e. they arise from a single abnormal cell.

Causes of a raised Prolactin

Normal (physiological) causes

Prolactin levels are raised during pregnancy and breast-feeding but they can be elevated as a result of stress (e.g. illness or just the anxiety caused by blood sampling).

Abnormal (pathological) causes

Pituitary and hypothalamic disease, some drugs (e.g. for anti-sickness, antidepressants, tranquillizers), Hypothyroidism (underactive thyroid), polycystic ovary syndrome (PCO or PCOS) and liver or kidney failure can al raise prolactin levels.

How common is a raised prolactin level?

• In a "normal" population - 1 in 250.
• In women attending a family planning clinic - 1 in 20.
• In women with adult-onset Amenorrhoea (absence of periods) - 1 in 10.
• In women with PCOS - 1 in 6.

Symptoms of a Prolactinoma

Symptoms in women include amenorrhoea or Oligomenorrhoea (infrequent periods), Galactorrhoea (milk leakage from the breasts), infertility and effects of low Oestrogen levels (e.g. vaginal dryness).

Symptoms in men include impotence, loss of libido and reduced fertility.

"Space occupying effects", found with larger prolactinomas in both sexes, include headaches, visual disturbances (caused by pressure on the optic nerves or "chiasm"), double vision and hypopituitarism (caused by pressure on the normal pituitary or pituitary stalk). The average age at diagnosis is mid-twenties for women and mid-thirties for men.

The long-term effect of a raised prolactin level is reduced bone density in women with amenorrhoea or oligomenorrhoea and in men with low Testosterone levels. Bone density tends to improve when the high prolactin level is treated and periods return to normal (or testosterone levels rise).

Treatment options

No treatment

This may be suitable when the tumour is small, symptoms are mild and the Gonads are functioning normally. Intermittent checks of prolactin and symptoms may be all that is required.

Surgery

Cure rates depend on the size of the tumour: 60-90% for microprolactinomas and 25% for larger tumours, which are more difficult to remove. A lot depends on the skill and experience of the surgeon. The most common complication of surgery is hypopituitarism.

Medical therapy

Prolactinomas are treated with dopamine agonists such as cabergoline, Bromocriptine or quinagolide. Dopamine agonists are chemicals that mimic the effect of dopamine, a hormone that switches off prolactin production by the Pituitary gland. Drug treatment is usually very effective, with prolactin levels being normalised and the tumour shrinking in 80-90% of cases. Side effects such as headaches, nausea and low blood pressure (causing dizzy spells) can occur. Cabergoline is longer acting, requiring only one or two doses per week compared with up to three doses daily for bromocriptine. It is more effective than bromocriptine and usually causes fewer side effects, although different drugs suit different patients. Quinagolide is taken once daily. Patients must make an informed choice after discussion of the treatment options.

Is treatment life-long?

If a dopamine agonist drug is stopped after short-term treatment (weeks or months) Hyperprolactinaemia generally reoccurs within weeks. However, after 5 years of treatment with bromocriptine, prolactin levels remain normal for about a year after stopping treatment in 25% of patients. After a year's treatment with cabergoline, prolactin remains normal for up to 5 years in 10% and periods remain normal for at least 4 months in the majority.

Gradual dose reduction of dopamine agonist therapy, or even stopping treatment, can be considered after 2-5 years. In such cases, it is important that prolactin levels and symptoms are monitored closely.

Prolactinomas and pregnancy

The chance of a Microprolactinoma getting larger during pregnancy is small (less than 2%). Once pregnancy is confirmed, dopamine agonist therapy should be stopped and the patient should be monitored for symptoms and have visual field checks.

The risk of macroprolactinomas expansion during pregnancy is 15-35%. In these cases treatment options include:

• {SB}Stopping bromocriptine and monitoring; re-starting treatment during pregnancy if there is evidence of tumour expansion;
• Continuous bromocriptine throughout pregnancy; or
• Pre-pregnancy treatment with surgery or Radiotherapy.