Prolactinoma and Hyperprolactinaemia

Somatotroph adenomas of the pituitary secreting prolactin, and other conditions presenting with elevated serum prolactin levels. Diagnosis requires blood testing of prolactin levels, a full drug history and frequently MRI scanning.

Interfering drugs


Withdraw drug if possible 

If the hyperprolactinaemia occurs in the presence of a drug known to elevate prolactin, for example risperidone, discuss whether it is possible to withdraw this with the patient with the responsible psychiatrist.

Any interfering agents should be withdrawn for at least six weeks prior to retesting prolactin on at least two occasions.

Psychotropic agents must be withdrawn under close psychiatric supervision only whereas other agents, for example contraceptive pills, may be stopped abruptly.

If it is not possible to withdraw potentially offending drugs, latest guidelines suggest imaging the pituitary gland.


Serum levels normalise

If serum levels normalise after drug withdrawal, the patient should be reassured that no further investigation or treatment should be necessary.

If the patient requires resumption of treatment, estrogen or testosterone therapy may be considered for symptom control.

Severe symptoms, for example galactorrhoea, may necessitate switching to an alternative psychotropic agent under supervision.

Dopamine agonists should be used with extreme caution in this instance.


Prolactin remains elevated

If the prolactin does not normalise on drug withdrawal, or if the agent cannot be stopped for other reasons, proceed to MRI scan and management as below.

No offending drugs


MRI pituitary

This is performed to rule out a large non functioning pituitary tumour particularly in patients using interfering medications, or to assess the pre-treatment size of a prolactinoma.


Baseline pituitary function

Ensure that thyroid function is normal and assess whether the patient has PCOS before treating elevated prolactin.

Other abnormalities of pituitary function, for example hypopituitarism or elevation of IGF-I, will require formal assessment and treatment as appropriate.

Microprolactinoma


No symptoms

If the patient does not complain of galactorrhoea and is menstruating regularly or is post menopausal, treatment may not be necessary.


Consider dopamine agonist therapy

Cabergoline is the first line dopamine agonist, as it has the highest efficacy in terms of biochemical control and tumour shrinkage. Very low doses, for example cabergoline 0.25mg once or twice a week, should be enough to control symptoms in the majority of cases with microprolactinomas.

Warn patients of possible psychiatric, fibrotic and gastrointestinal side effects and advise them to take medication during the main meal of the day.

Aim to use the minimum dose to achieve regular menses and control galactorrhoea. Absolute normalisation of prolactin may not be necessary. 

Treatment should be started after the MRI scan is performed since tumour shrinkage may be rapid.


Consider the combined oral contraceptive pill

If the patient with a microadenoma is amenorrhoeic but has no other symptoms, the contraceptive pill may be used as an alternative to a dopamine agonist. 


Monitoring for patients on dopamine agonists

Baseline chest radiograph, electrocardiogram, echocardiogram and renal function should all be performed within three months of starting ergot derived dopamine agonists in view of recent guidance. Further monitoring tends to be on an annual basis, though should depend on the cumulative dose exposure, underlying conditions and results of previous screens.


Follow up

Clinical review after three months is mandatory to review the scans with the patient, ensure resolution of symptoms and to recheck serum prolactin.


Long term treatment

With a confirmed microadenoma, aim to withdraw treatment every two years or at the time of natural menopause if the patient is well controlled: normalised serum prolactin with no visible tumour on MRI scanning. 

Treatment should resume if the patient develops amenorrhoea, or if there was a large initial lesion on MRI scan and the prolactin rises dramatically post treatment cessation. 

Generally, there is no indication to repeat MRI scans if the initial pre-treatment MRI was normal or showed a microadenoma.

Macroprolactinoma


Visual perimetry and acuity

If visual fields are abnormal on examination, or a macroadenoma is suspected, this must be performed at baseline and repeated during treatment to confirm response. With non functioning pituitary adenomas, serum prolactin will fall but tumour shrinkage will not be observed and so surgery should be considered.


Consider starting dopamine agonist therapy immediately after the MRI scan is performed

If visual loss is confirmed or the optic chiasm compromised on the MRI scan, higher doses of dopamine agonists may be used for urgent decompression of the optic pathway.

Warn patients of possible psychiatric, fibrotic and gastrointestinal side effects and advise them to take medication during the main meal of the day.

Warn patients with very large macroadenomas of the symptoms of a cerebrospinal fluid leak, as this can occassionally occur on shrinkage of macroprolactnimoas on medical therapy.


Repeat prolactin within one week, then at one month

Serum prolactin levels are expected to fall smoothly but dramatically in response to dopamine agonist therapy.

A very rapid response, for example complete normalisation within a week, may indicate that the prolactin is elevated due to disinhibition from a non functioning tumour. In this case, there will be no visual field or MRI response and urgent surgery should in stead be considered.


Follow up

Clinical review with repeat visual fields, serum prolactin and ideally repeat MRI scanning at six weeks.

If serum prolactin levels have not responded, consider alternative dopamine agonist.

If the prolactin has responded dramatically, but there is no improvement in vision arrange a repeat MRI scan and consider urgent surgery, as this may represent disinhibition of prolactin secretion due to a nonfunctioning pituitary tumour.

If prolactin is falling, and the patient is clinically improving, continue treatment and arrange routine rescanning (timing depends on initial clinical and MRI features and clinical response).

If the prolactin has not fallen satisfactorily, switch patients on bromocriptine to cabergoline, or increase the dose of cabergoline as tolerated. 

Patients not controlled or intolerant of higher doses of dopamine agonist should be discussed at a pituitary MDT and offered surgery or radiotherapy.

Vaginal bromocryptine may also be used in patients unable to tolerate oral dopamine agonists.


Monitoring for patients on dopamine agonists

Baseline chest radiograph, electrocardiogram, echocardiogram and renal function should all be performed within three months of starting ergot derived dopamine agonists in view of recent guidance. Further monitoring depends on initial results, underlying conditions, and cumulative dose exposure, but is generally repeated on an annual basis.


Clinical review at three months

Aim to use the minimum dose necessary to restore vision and to control tumour size and symptoms, rather than aiming for a 'normal' serum prolactin.

Retest baseline pituitary function at three months.

Menses will usually be restored in female patients. However, with long standing macroprolactinomas, gonadotropin function may not return. Testosterone replacement is thus frequently required in male patients despite good control of serum prolactin.


Long term follow up

Patients with sight threatening macroadenomas should be seen at six weeks, then three, six and 12 months, then annually lifelong for monitoring of their treatment, tumour size and pituitary function.

Aim to reduce doses wherever possible while maintaining disease control.

Attempt to withdraw treatment every two years if the patient is well controlled with a normal serum prolactin and no visible remnant on MRI scanning.

Consider surgery or conventional radiotherapy if ongoing dopamine agonist requirements are high, dopamine agonists are not tolerated, or ifi the tumour is not well controlled on scanning.

Patients who are pregnant or actively seeking fertility

Cabergoline is not licensed for use in pregnancy. Therefore patients seeking fertility should be maintained on the lowest dose of bromocriptine that controls their prolactin and on which they have normal menstrual cycles. 

Patients should generally discontinue dopamine agonist therapy as soon as they are pregnant. In exceptional cases with large tumours abutting the chiasm a decision to continue therapy through pregnancy may be made.

Regular clinical review and visual field testing should be performed throughout pregnancy (at least once per trimester) though monitoring of prolactin is not recommended and MRI scanning (without gadolinem) is only indicated in pregnancy if the patient develops a new field defect or severe headache indicating possible apoplexy. 

If there is significant and symptomatic growth in pregnancy, bromocriptine should be restarted.

Patients with macroadenomas who have not acheived tumour control should be offered surgery prior to planning pregnancy.