Guidance Note 23 - Macroprolactin

CLINICAL BIOCHEMISTRY

Guidance note # 23

Controlled Document CI-CB-337-GN23 (macroprolactin) v2
Reviewed biennially. Last review August 2015 / Prepared by: Mr Gareth Jones, Principal Biochemist
Authorised by: Dr Anne Dawnay, Consultant Biochemist
Macroprolactin
Multiple forms of prolactin are present in the circulation / Whilst monomeric prolactin is the predominant bioactive form in the circulation, other non-active forms may be detected by routine lab methods. These include dimeric and polymeric prolactin complexes, as well as immunoglobulin-bound hormone.
These larger forms are collectively termed ‘macroprolactin’ and are not known to have any biological activity.
Macroprolactin is a benign cause of raised prolactin / Large macroprolactin complexes are less well cleared by the kidneys and hence remain in the circulation for longer. This can result in abnormally high measured prolactin levels that don’t reflect an underlying increase in prolactin secretion and do not cause symptoms.
However it is important to recognise that macroprolactin may co-exist with a genuine increase in prolactin secretion. When macroprolactin is present, the total measured prolactin will take longer to respond to treatment for hyperprolactinaemia.
UCLH screens for the presence of macroprolactin / In patients with a measured prolactin >700 mIU/L, the lab at UCLH will screen for macroprolactin if not done within the previous 12 months.
When a significant proportion of macroprolactin is detected, an estimated bioactive concentration is reported along with a comment to aid interpretation.
In macroprolactin positive patients, subsequent requests for prolactin will include an estimation of bioactive prolactin as routine.
Physiological and iatrogenic hyperprolactinaemia is common / Increased prolactin secretion occurs in pregnancy, with breast stimulation and during severe stress. Drugs reported to induce sustained hyperprolactinaemia (but usually <5000 mIU/L) include:
- Antipsychotics; typical, atypical
- Antidepressants; tricyclics, SSRI, MAO-I
- Other psychotropics; buspirone, alprazolam
- Prokinetics; metoclopramide, domperidone
- Anti-hypertensives; alpha-methyldopa, verapamil
- Opiates; morphine
- H2-Antagonists; cimetidine, ranitidine
Non-pituitary pathology can also cause hyperprolactinaemia / Primary hypothyroidism and chronic kidney disease are associated with elevations of prolactin but typically less than 2000 mIU/L.
A pituitary cause must be considered with any elevation of serum prolactin. A prolactin >5000 mIU/L is strongly suggestive of primary pituitary hyper-secretion (e.g. adenoma or pituitary stalk disruption).

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