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 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 increase in intrasellar pressure due to an enlarging mass 2.
Similarly, dopamine antagonists (such as the antipsychotic 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), can cause hyperprolactinemia 1.
The highest levels of circulating prolactin are, however, encountered in the setting of prolactin secretion 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 (pre-menopausal women having the highest normal levels). A typical upper level of normal is ~40ng/ml.
Unfortunately, no single value can be used as a definite "cut-off" between secreting prolactinoma and stalk-effect. Having said that it is worth considering three tiers:
- not secreting: <2 times normal (e.g. <96ng/ml 3)
- indeterminate (may be stalk effect or low-level secretion): 96-200ng/ml
- secreting: >200ng 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 generalised pituitary insufficiency 2.
In contrast, very high levels of prolactin are indicative of a prolactin-secreting adenoma. In fact, extraordinarily high levels (e.g. over 2,000ng/ml) may actually be suggestive of cavernous sinus invasion 4.
- 1. Torre DL, Falorni A. Pharmacological causes of hyperprolactinemia. Therapeutics and clinical risk management. 3 (5): 929-51. Pubmed
- 2. Bergsneider M, Mirsadraei L, Yong WH, Salamon N, Linetsky M, Wang MB, McArthur DL, Heaney AP. The pituitary stalk effect: is it a passing phenomenon?. Journal of neuro-oncology. 117 (3): 477-84. doi:10.1007/s11060-014-1386-5 - Pubmed
- 3. Kawaguchi T, Ogawa Y, Tominaga T. Diagnostic pitfalls of hyperprolactinemia: the importance of sequential pituitary imaging. BMC research notes. 7: 555. doi:10.1186/1756-0500-7-555 - Pubmed
- 4. Shucart WA. Implications of very high serum prolactin levels associated with pituitary tumors. Journal of neurosurgery. 52 (2): 226-8. doi:10.3171/jns.1980.52.2.0226 - Pubmed