Prolactinomas and hyperprolactinaemia

JRE Davis
Department of Endocrinology, Manchester Royal Infirmary, Manchester

Endocrine Nurses Training Course 2005, John MacIntyre Centre, The University of Edinburgh, 18 Holyrood Park Road, Edinburgh EH16 5AY, UK
30 August - 1 September 2005

Hyperprolactinaemia is a common clinical problem in women, whose main effects are irregularity or cessation of periods and breast milk secretion. In men it is rarer, and lactation is unusual. Various causes of hyperprolactinaemia should be considered before assuming that it is due to pituitary disease, including pregnancy, hypothyroidism, dopamine antagonist drug therapy, and sometimes short-term stress (such as venepuncture). Prolactin-secreting microadenomas and idiopathic hyperprolactinaemia are the commonest causes attributable to pituitary disease, but pituitary stalk disruption by adjacent hypothalamic or pituitary tumours can lead to ‘disconnection’ hyperprolactinaemia.

Evaluation should include a careful drug history, exclusion of pregnancy, thyroid function testing, and consideration of polycystic ovary syndrome, before investigation of pituitary function. Clinical examination should then include an assessment of visual fields, as the optic chiasm may be damaged by local mass lesions. Pituitary imaging is undertaken by MR or CT scanning. MR imaging is usually preferred, as modern scanners have excellent resolution and can clearly show key structures such as the optic chiasm and carotid arteries. It also avoids X-ray exposure of the eyes when repeat scanning is often necessary. However it is important to note that small pituitary adenomas are detectable by scan in about 20% of the normal population, and not in themselves pathologically significant.

The aim of treatment is to reduce prolactin secretion and hence restore ovarian function and suppress abnormal lactation. In patients with definite prolactinomas, tumour shrinkage and eventual remission may also be important goals. Prolactinomas are unusual among pituitary tumours in that most patients respond dramatically to medical treatment using dopamine agonist drugs such as bromocriptine, cabergoline and quinagolide, with normalisation of prolactin levels and significant tumour shrinkage in 80-90%. The main problem with dopamine agonists is the high frequency of significant side-effects, with up to 10% of patients having to discontinue treatment as a result. Surgical treatment of prolactinomas by transphenoidal excision can give a long-term cure and avoid prolonged medication, but most series have reported poor long-term endocrine results, so that surgery now plays a limited role in many centres, unless there is excellent local surgical expertise, or unless there are resistant mass lesions that require debulking.

Women starting treatment with dopamine agonist drugs should be warned to expect restoration of ovulatory menstrual cycles, normally within weeks. Patients who do not wish to become pregnant should be advised to take contraceptive precautions, as it may not be immediately apparent to them that fertility has been restored. A small number of women with modest elevations of serum prolactin may retain normal ovarian function and have few symptoms, and such women may not require any specific treatment at all.

Long-term follow-up studies of untreated patients have shown that most prolactinomas are very indolent, with little evidence of progression over many years. In addition, follow-up studies of patients treated with dopamine agonists have revealed that some patients who had stopped treatment appeared to have gone into remission, without recurrent hyperprolactinaemia. This possibility of permanent remission of the pituitary disease should therefore now prompt a trial cessation of therapy in most patients who have achieved a period of satisfactory endocrine and radiological control.

Slides

Revised: 30-Oct-2006