- Prolactin induces breast milk, promotes formation of the corpus luteum and suppresses Gonadotropin-releasing hormone (which in turn suppresses FSH and LH, and then reduces oestrogen and testosterone levels)
- Prolactin secretion is pulsatile and inhibited by dopamine
- Hyperprolactinaemia is often more evident in women, because the symptoms are more obvious. In men, prolactinomas can be quite large
Clinical features
- Amenorrhoea, galactorrhoea (minority). 70% of women with these two symptoms have hyperprolactinaemia. At increased but lower levels there may be a short luteal phase.
- Reduced libido
- Impotence and infertility in men
- In post-menopausal women, galactorrhoea only occurs if on Hormone Replacement Therapy. Osteopenia can occur
- Hirsutism and acne
- Signs of mass effect – headaches, visual field loss, cranial nerve palsies, seizures (especially with macroadenomas)
Causes
- Prolactinoma (56%)
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- 5% also secrete growth hormone
- Rarely associated with MEN type 1
- Macroprolactinomas are more common in men. Usually very high prolactin levels, ie >10,000 picomol/L (if lower and there’s a pituitary mass, it’s more likely a non-functioning adenoma)
- Can rarely present as pituitary apoplexy (haemorrhage of the pituitary adenoma). More likely if it’s a macroadenoma.
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- Macroprolactinaemia (9%)
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- An assay artefact caused by PRL-binding immunoglobulin G (present in 1% of normal individuals)
- More prevalent in SLE and antipsychotic-induced hyperprolactinaemia
- Doesn’t usually cause a very high prolactin level
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- Drug-induced (15%)
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- Levels of prolactin low to moderate (<4350 picomol/L, 100mcg/L)
- Anti-psychotics are the most common cause (nearly half of patients on these are affected)
- Highest rates associated with amisulpride and risperidone (lower rates with quetiapine and aripiprazole)
- Dose-dependent, and onset usually corresponds with commencement of drug
- Others
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- Metoclopramide, domperidone
- Tricyclics, MAO inhibiters, SSRIs, venlafaxine
- Methyldopa, opiates, cocaine, verapamil, oestrogen, excessive ETOH
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- Non-functioning pituitary adenoma (6%)
- Primary hypothyroidism (6%)
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- Mild elevation of prolactin (<2000) occurs in 8% of primary hypothyroidism. Can normalise if hypothyroidism treated
- Pituitary can look enlarged and can resemble a prolactinoma on imaging
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- Idiopathic (3%)
- Acromegaly (3%) – Around 25% of GH secreting tumours also secrete prolactin
- Malignancy – craniopharyngiomas, gliomas, metastatic disease. Occasionally paraneoplastic (ectopic prolactin release eg ovarian cancer)
- Lymphocytic hypophysitis – Usually occurs in late pregnancy or post-natal period. Often other autoimmune disease (thyroid, Addison’s, T1DM, hypoparathyroidism, AIH)
- Granulomatous hypophysitis – sarcoid, TB, syphilis, histiocytosis X
- Polyendocrine metabolic ovarian syndrome (PMOS) – prolactin levels lowish. Occurs in 20%
- Chronic kidney disease and cirrhosis – mild hyperprolactinaemia common
- Pregnancy and lactation
- Other causes – Chest wall trauma /surgery, hypoglycaemia, MI, exercise
Investigation
- Prolactin
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- 99% of patients with a non-functioning adenoma have prolactin levels < 4087 picomol/L (94 micrograms/L)
- Microprolactinomas typically result in levels 800-2000 mU/L
- Macroprolactinomas >2000 mU/L
- Non-functioning pituitary mass – typically <2000 mU/L
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- Check U&Es, TFTs, LFTs
- Pregnancy test
- Check medications
- Consider physiological causes above
- Check visual fields
- Macroprolactin levels (if asymptomatic / atypical)
- MRI pituitary if other causes excluded – though incidentalomas / false positives are common
- Pituitary hormone levels if there’s an adenoma present (in order of frequency of hormones affected – GH, LH/FSH, Thyroid, adrenal. Can also cause AVP deficiency)
- If prolactin level non-diagnostic – repeat
Management
- Treat the cause
- Sometimes anti-psychotics are switched to ones less likely to cause the problem
- Prolactinomas are generally treated with dopamine agonists
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- Cabergoline or Bromocriptine (can cause hypotension, nausea, fatigue)
- Monitor prolactin levels, repeat imaging annually
- Consider withdrawing dopamine agonists after a few years if shrinking
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- Bisphosphonates if prolactin can’t be suppressed
- Surgery is usually second line (unless there’s a non-functioning adenoma)
- Avoid oestrogens which can increase the tumour size (though the oral combined contraceptive may be safe in microadenomas)