Elevated prolactin (differential)
Elevated prolactin can be due to a number of causes, including elevated production/secretion as well as reduced inhibition.
Prolactin is controlled by numerous homeostatic mechanisms, with tonic secretion of prolactin inhibitory hormone (dopamine) by the hypothalamus having a dominant effect 1-3.
Mechanical interruption of the portal transport of dopamine from the hypothalamus to the anterior pituitary gland (known as the stalk-effect) will reduce inhibition and thus result in minor elevation of prolactin. This can be due to impingement or interruption of portal circulation directly (i.e. at the level of the stalk) or due to increased intrasellar pressure due to an enlarging mass or due to a congenital ectopic posterior pituitary gland/pituitary stalk interruption syndrome 2,5.
When due to dysfunction of the normal infundibular portal circulation, hyperprolactinemia may be associated with other endocrinological abnormalities (e.g. hypothyroidism - Pickardt syndrome)
Similarly, dopamine antagonists (such as the antipsychotics haloperidol and chlorpromazine) as well as a long list of other drugs (including selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAO-I) and some tricyclic antidepressants(TCA)), can cause hyperprolactinemia 1.
The highest levels of circulating prolactin are, however, encountered in the setting of prolactin-secreting pituitary macroadenomas, especially those that are large and invading the cavernous sinus.
Being familiar with normal prolactin levels, and obtaining actual levels from referrers (rather than merely "elevated prolactin") is helpful when interpreting pituitary studies. Normal range and levels will vary somewhat between institutions and will vary depending on the gender of the patient and whether or not they are menopausal (premenopausal women having the highest normal levels). A typical upper level of normal is ~40 ng/mL (equivalent to ~850 mIU/L).
Unfortunately, no single value can be used as a definite "cut-off" to distinguish secreting prolactinomas from the stalk-effect. Having said that it is worth considering three tiers:
- not secreting: <2 times normal (i.e. <96 ng/mL, <2000 mIU/L 3)
- indeterminate (may be stalk effect or low-level secretion): 96-200 ng/mL
- secreting: >200 ng/mL, >4250 mIU/L 3
This is particularly important if prolactin is only slightly elevated, as peripheral slightly delayed, but normal, enhancement of the pituitary gland on dynamic scans can be misinterpreted as representing a prolactin-secreting microadenoma.
Similarly, slight elevation of prolactin in the setting of a pituitary region mass should not suggest necessarily that the mass is a prolactin-secreting macroadenoma, as other masses may result in the so-called "stalk-effect". It is worth noting that in most cases of non-functioning macroadenomas, prolactin levels are near-normal rather than elevated. This is believed to be due to chronic mass-effect leading to a generalized pituitary insufficiency 2.
In contrast, very high levels of prolactin are indicative of a prolactin-secreting adenoma. In fact, extraordinarily high levels (e.g. >2,000 ng/mL) may actually be suggestive of cavernous sinus invasion 4.
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