A single measurement of serum prolactin level is usually adequate to document hyperprolactinemia. Prolactin secretion, however, is pulsatile and stress, as well as a number of physiological states such as sleep, and exercise can also mildly elevate prolactin levels. For these reasons, a test that shows a level of 25– 40 ng/ ml should be repeated before hyperprolactinemia is diagnosed. When other causes of hyperprolactinemia have been ruled out (including medication intake) on the basis of history, physical examination, and assessment of thyroid and renal function, the diagnosis of a prolactinoma can be confirmed by gadolinium- enhanced magnetic resonance imaging (MRI) (see later in this section).
In general, serum prolactin levels are correlated with tumour size. Values between upper limits of normal and 100 ng/ ml may be due to drugs or idiopathic causes, but can also be caused by microadenomas. Macroadenomas are typically associated with levels of over 250 ng/ ml, and in some cases the level exceeds 1000 ng/ ml. Care must be taken in interpreting a moderate elevation of the prolactin level (<100 ng/ ml) in the presence of a macroadenoma, as this may be due to either compression of the pituitary stalk by the tumour or these values can be artificially low due to the ‘hook effect’. The ‘hook effect’ occurs when a very high serum prolactin level saturates both the capture and signal antibodies used in immunoradiometric and chemiluminescent assays, preventing the binding of the two in a ‘sandwich’. The artefact can be avoided by repeating the assay with serial serum dilution.
The degree of prolactin elevation correlates with the severity of hypogonadism. High prolactin levels greater than 100 ng/ ml are associated with hypogonadism and low serum oestradiol levels, which result in amenorrhoea and vaginal dryness; while levels of 50 to 100 ng/ ml can be associated with both oligomenorrhea and amenorrhea, and levels of 20 to 50 ng/ ml can result in insufficient progesterone secretion and luteal phase shortening that may result in subfertility.
In PCOS, elevations in serum prolactin have been reported to occur and likely represent lactotrope stimulation by chronic oestrogen exposure rather than coexistence of a prolactinoma.
