Incidence: Most Common Secreting Adenoma
More Common in Women - Macroprolactinomas More Common in Men

Hyperprolactinaemia

Prolactin levels are normally high during pregnancy and lactation. Abnormally high levels of prolactin at other times may be caused by a prolactin-secreting Pituitary tumour or by a non-secreting pituitary tumour that prevents dopamine (prolactin release-inhibiting hormone) from the Hypothalamus reaching normal prolactin-producing cells (lactotrophs). Raised prolactin levels are also sometimes found in Cushing's syndrome, Hypothyroidism and polycystic ovarian disease.  A number of drugs increase prolactin levels by blocking the action of dopamine, e.g., metoclopramide, domperidone, some anti-depressants and the phenothiazines.   Stress raises prolactin levels so the very act of venepuncture can result in high levels. 

The behaviour of prolactin-secreting tumours is defined by their size at presentation. Microprolactinomas (less than 10mm in diameter) rarely expand to become macroprolactinomas. In men, prolactinomas tend to present late, because reduced potency and loss of libido - the hormonal effects of raised prolactin levels - are subtle and develop slowly. In women, absent periods and/or inappropriate production of breast milk allow the diagnosis to be made early.

There should be a low threshold for referral for any patient with anysuspicion of hyperprolactinaemia as the greatest challenge in the diagnosis of hyperprolactinaemia is thinking of the disease.  Once suspected biochemical confirmation or exclusion of the disease is usually straightforward.  See 'Who and When to Refer' (factsheet 14).

Presenting symptoms

• Galactorrhoea (discharge from breasts)
• Oligomenorrhoea or Amenorrhoea
• reduced libido
• erectile dysfunction
• pressure effects (e.g., headache and visual disturbance) with macroadenoma

Investigations

Useful GP screening tests include basal prolactin, thyroid function tests, a careful drug history and exclusion of pregnancy. A prolactin level (normal range <400 mU/l) is mildly elevated (400 - 1000 mU/l) it should be repeated before referral.

Dynamic prolactin stimulation tests such as the TRH test, have no part in the investigation of hyperprolactinaemia.  Measurement of serum prolactin on three separate occasions (at least 2 hours after rising and when patient rested) provides all the information necessary.

A prolactin level of >5000 mU/l usually indicates a true Prolactinoma rather than a functionless tumour causing a raised prolactin.  Specialist tests include pituitary imaging (preferably MRI) and visual field testing if indicated (macroadenomas) and assessment of pituitary function.

Macroprolactin is a biologically inactive form of prolactin that causes no clinical problem, other than being detected in prolactin assays resulting in spurious elevation of serum prolactin levels.  Macroprolactin should be suspected in any patient with an elevated prolactin but no associated signs or symptoms.  Most laboratories can test for macroprolactin.  Please see 'Who and When to Refer' (factsheet 14).

Treatment objectives and possibilities

Osteoporosis is a concern in any patient with Hypogonadism - manifest clinically as amenorrhoea or erectile dysfunction.  In any patient with one year of hypogonadism a bone density scan should be performed and a major goal in the treatment of hyperprolactinaemia is the prevention of osteoporosis.

In addition treatment should stop galactorrhoea and restore Oestrogen levels, and hence menstruation, fertility, libido and vaginal lubrication to normal.

For macroprolactinomas, an additional objective is to shrink the tumour in order to reduce any pressure effects.

Patient management

Most patients are treated medically with the dopamine agonists cabergoline, or Bromocriptine, both of which reduce prolactin levels, allow oestrogen levels to rise and greatly reduce the size of the tumour.  Surgery to reduce tumour size, and Radiotherapy to reduce the chance of recurrence, are rarely required.

Medical treatment with cabergoline, quinagolide, or bromocriptine controls prolactin and symptoms in the majority of patients, but needs to be continued in the long term. These drugs can be associated with some dizziness and nausea. This can be limited by taking the medicine in the middle of meals or last thing at night and by starting at low dose.

Cabergoline is the most widely prescribed as it is more potent and associated with fewer side-effects and need only be taken twice weekly.

Pregnancy and prolactinomas

Patients should be followed during pregnancy by an Endocrinologist.  Ideally it is advisable for patients to have discussed pregnancy with their endocrinologist prior to conception.

Most women are advised to cease taking dopamine agonists for the duration of pregnancy and during lactation.  However, many thousands of babies have been born to mothers taking bromocriptine and there is no evidence of an increased incidence of malformation or miscarriage.  Cabergoline treatment appears to be safe during pregnancy.  During pregnancy, there is a slight risk of tumour enlargement, particularly in patients with macroadenomas.  Any patient who experiences severe headaches or visual disturbances should be seen urgently by their specialist.

Watchpoints

Urgent - refer to hospital

• Deterioration of vision

Non-urgent (but still very important)

• Remember that successful treatment usually results in restoration of fertility (particularly in microprolactinomas)
• Patients may be predisposed to problems related to osteoporosis
• Ask about erectile function. Reassure that it is part of the disease and that it can be treated

Resources for patients

Please go to the Resource Library of this website to access resources for patients.  Our library includes literuature, newsletters and articles available from The Pituitary Foundation as well as the contact information for other organisations who provide support and information.  All of our patient leaflets are available to read as well as downloadable in PDF format from this website. 

Resources for GPs

Endotext.org 'Your Endocrine Source'
www.endotext.org  (www.endotext.org/neuroendo/index.htm)

Oxford Handbook of Endocrinology OUP (2002) JAH Wass & H Turner (Eds).

Management of Pituitary Tumors: The Clinician's Practical Guide (2003) (Second Edition), Editors and authors Michael P. Powell, Stafford L. Lightman and Edward R. Laws. Humana Press, Totowa, New Jersey

Pituitary Tumours. Recommendations for service provision and guidelines for management of patients. Consensus statement of a working party (1997) RN
Clayton & JAH Wass (Eds) London: Royal College of Physicians

The Diagnosis and Treatment of Pituitary Insufficiency (1997) Lamberts SWJ (Ed) Bristol, UK: BioScientifica

Endocrinology (1997) Levy A & Lightman SL New York: Oxford University Press

The Epidemiology, Pathogenesis and Management of Pituitary Tumours (1998) Webb SM (Ed) Bristol, UK: BioScientifica