The diagnosis of PRL adenoma requires both imaging of pituitary adenoma and laboratory analysis indicating the presence of persistent hyperprolactinemia. Normal male and female PRL levels are below 25ug/l and 20ug/l, respectively (commonly used assay, 1ug/l is equivalent to 21.2mIU/l, WHO standard 84/500). However, other test methods yield correspondingly high or low PRL values, and the range of normal values should be adjusted according to the use of the particular test method. Interfering dopamine effects usually result in moderately elevated PRL, rarely exceeding 150ug/l. Overall, serum PRL levels are positively correlated with tumor size. PRL values between the upper limit of normal and 100ug/l can be due to psychoactive medication, estrogen or functional (spontaneous), but may also be due to PRL microadenomas. The majority of patients with PRL adenomas have PRL levels above 150ug/l (5 times higher than normal). Macroadenomas usually have PRL levels above 250ug/l and in some cases above 1000ug/l. Moreover, these values are not absolute and PRL adenomas show fluctuating increases in PRL levels and may also show an uncorrelated correlation between tumor size and hormone production. Therefore, moderately elevated PRL levels in patients with pituitary macroadenomas should be interpreted with caution, since hyperprolactinemia is caused by tumor compression of the pituitary stalk and not by PRL adenomas.
Dynamic tests of PRL secretion Several dynamic tests of PRL secretion are recommended as diagnostic tools for the evaluation of hyperprolactinemia, including TRH, levodopa, amiloride isoquel, domperidone stimulation test, and insulin-induced hypoglycemia. Although several of these methods are useful in specific cases, it is now widely accepted that the diagnosis of PRL adenoma should be confirmed by analysis of basal PRL values, pituitary imaging, and exclusion of other causes.
Pituitary imaging Confirmation of the diagnosis of PRL adenoma requires not only laboratory evidence of persistent hyperprolactinemia, but also imaging evidence of pituitary adenoma. After ruling out potential secondary causes of hyperprolactinemia, such as pregnancy, an enhanced MRI scan should be completed. CT scans enhanced by venous contrast are slightly inferior to MRI in diagnosing small adenomas and in defining the extent of macroadenoma extension, but enhanced CT scans are used when MRI is not available or when MRI is contraindicated. It should be noted that 10% of the normal population has microadenomas. It is not necessary to perform routine MRI scans in the normal population to exclude microadenomas. Visual field examinations (e.g., computerized Goldman perimetry) should be performed in patients with macroadenomas whose tumors are adjacent to the optic crossing, but visual field examinations are not necessary in patients with microadenomas.
Hyperprolactinemia with concomitant MRI findings of pituitary adenoma does not always clearly suggest the diagnosis of PRL adenoma, as tumor compression of the pituitary stalk can also cause hyperprolactinemia. A definitive diagnosis requires pathological analysis, however, PRL adenomas rarely require surgical removal. As an alternative, an empirical diagnosis is obtained by continuous evaluation of serum PRL levels and tumor size over several months of treatment with medications (dopamine agonists). Three outcomes are possible after a course of treatment: normal PRL plus a significant reduction in tumor volume (75% or more) confirms the diagnosis of PRL adenoma; normal PRL with no change in tumor volume or only a mild reduction suggests pituitary adenoma rather than PRL adenoma; and no change in both serum PRL and tumor volume indicates a drug-resistant PRL adenoma.