Galactorrhoea is milky secretion from the breasts. The term usually refers to milk secretion not due to breast-feeding. It is bilateral and from multiple ducts. The milk volume may be large or small, and milk may be secreted spontaneously or expressed.
Physiology of lactation and prolactin
Lactation requires prolactin (PRL). Other hormones are involved in priming the breast prior to lactation: oestrogen, progesterone, insulin, thyroid hormones and glucocorticoids. Oxytocin is involved in milk release. Conversely, oestrogens and progesterone can also have an inhibitory effect on lactation: the fall in levels after delivery facilitates lactation, whilst an injection of oestrogen was used in the past to inhibit lactation.
There is a physiological increase in PRL levels in response to pregnancy, breast stimulation (especially sucking), stress, sleep, dehydration, sexual intercourse, seizures, exercise and food ingestion.
Causes
When galactorrhoea is accompanied by amenorrhoea, it is usually caused by hyperprolactinaemia.
Physiological
Pregnancy and post-lactation: women may lactate from the second trimester, and may continue to produce milk up to two years after stopping breast-feeding.Fluctuating hormone levels: puberty and the menopause.Neonatal: exposure to maternal hormones in utero can produce gynaecomastia and galactorrhoea in the newborn (sometimes known as ‘witch’s milk’); no action is required and it will subside rapidly and spontaneously.Nipple stimulation or suckling.
Non-physiological causes of hyperprolactinaemia
Idiopathic hyperprolactinaemia (40% of cases of hyperprolactinaemia).Prolactinomas (PRL levels are usually very high in this case as the tumour causes hypersecretion of PRL).Other causes of hypersecretion of PRL:
Addison’s disease.
Acromegaly.
Cushing’s disease.
Metastatic tumours.
Infections such as tuberculosis.
Sarcoidosis.
Histiocytosis.
Drugs (see ‘Drugs that raise PRL’, below).
Systemic disorders: Chronic kidney disease.Liver failure.Hypothyroidism.
Epileptic seizures.
Chest wall lesions or irritation: Breast surgery.Burns.Herpes zoster.
Spinal cord injury.
Trauma.
Pituitary stalk infiltration or interruption, due to: Sarcoidosis, tuberculosis, or schistosomiasis.
Multiple sclerosis.
Resection of the pituitary stalk.
Tumours: meningioma, craniopharyngioma, dysgerminoma, dermoid cyst, pineal gland tumours.
Empty sella.
Rathke’s cyst.
Irradiation.
Trauma.
Drugs that raise PRL
The following list is not comprehensive but drugs which raise PRL include:
Antipsychotics – the most common drugs to cause hyperprolactinaemia: Traditional phenothiazine antipsychotics (chlorpromazine, prochlorperazine, thioridazine, trifluoperazine) and haloperidol.
Atypical neuroleptics may also be implicated, but less frequently. Risperidone is the most likely to cause a raised PRL, also amisulpride. Olanzapine is less likely to do so.
Antidepressants, especially the selective serotonin reuptake inhibitors (SSRIs). Monoamine-oxidase inhibitors (MAOIs) and some tricyclic antidepressants (TCAs) less often.
H2 antagonists, especially cimetidine, but also ranitidine.
Antihypertensives, including beta-blockers, methyldopa and verapamil.
Contraceptives, including combined oral contraceptives and depot contraceptives.
Prokinetics: domperidone, metoclopramideIllicit drugs including cannabis, opiates and amfetamines.
Various others including digoxin, spironolactone, opiates, danazol, sumatriptan, isoniazid and valproate.
Normoprolactinaemic causes of galactorrhoea
Idiopathic galactorrhoea. When all else has been excluded, what remains is labelled as idiopathic. Female patients with galactorrhoea but normal PRL levels, normal thyroid function and regular periods can probably be observed.
Differential diagnosis
Breast disease
Mammary duct ectasia can cause nipple secretions which may be milky or discoloured in appearance. The discharge can be bilateral and from multiple ducts.Duct papilloma typically causes serous or bloodstained discharge from a single duct. Underlying malignancy is rare but needs excluding.Persistent discharge through a fistula following an abscess.
Investigations
Initial investigations
PRL levels. Very high levels suggest prolactinoma. If PRL levels are not elevated, further investigations (such as hormone levels and scans) are not required.TFTs (it is important to exclude hypothyroidism).Renal and liver function.Pregnancy test if appropriate.
Further investigations
May be needed:
Formal testing of visual fields: defects suggest optic nerve compression and merit urgent referral.MRI scan – needed, for example, if PRL levels are significantly raised and not explained by any other cause, or if there is irregular menstruation. CT scans may be used if MRI is unavailable, but MRI is the scan of choice.Other endocrine assessments (eg, for Cushing’s disease or acromegaly) may be appropriate.If the nature of breast secretions is unclear, microscopy may be used.
Management
Exclude serious pathology: investigations as above; exclude breast disease.Identify and treat the cause, if possible:Treat hypothyroidism. Management of prolactinomasReview/change any contributing drugs.If the cause cannot be addressed, consider:Dopamine agonists are thought to be more effective in reducing galactorrhoea.These dopamine agonists may also be used in those with normal PRL levels if galactorrhoea is troublesome and reassurance alone is not sufficient. This usually resolves the galactorrhoea within two months and the medication can then be stopped.Hormone treatment: testosterone for men or oestrogens for women (eg, the combined oral contraceptive pill). These help to prevent osteoporosis and may improve symptoms.
Complications and prognosis
These depend on the underlying cause. There is probably an increased risk of osteoporosis if hyperprolactinaemia is untreated.
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