Dynamic tests of prolactin secretion in hyperprolactinemic states: carbidopa-L-dopa and indirectly acting dopamine agonists

In normal subjects, similar degrees of PRL suppression have been reported after L-dopa alone and after a lower dose of L-dopa given in combination with carbidopa (CD), a peripheral inhibitor of L-dopa decarboxylase. In patients bearing PRL-secreting pituitary adenomas, CD-L-dopa induces a minimal suppression of plasma PRL, which is significantly less than after L-dopa alone. Similarly, indirectly acting dopamine (DA) agonists (IADAs), i.e. drugs which release DA and /or block DA reuptake without directly stimulating DA receptors, while capable of suppressing plasma PRL in normal subjects and subjects with puerperal hyperprolactinemia, fail to do so in patients with PRL-secreting adenomas. In the present study, to determine whether in puerperal subjects central nervous system (CNS) dopaminergic function is actually preserved and to elucidate the mechanism (s) underlying the defective CNS dopaminergic function of patients with prolactinomas, we have investigated: 1) whether, like IADA, CDL- dopa suppresses PRL levels in postpartum women; and 2) the PRL-inhibiting properties of two IAD As, viz. nomifensine (Nom) and methylphenidate (Methphen), L-dopa alone, and L-dopa with CD-L-dopa in patients bearing PRL-secreting pituitary adenomas. In 7 puerperal women, oral administration of 500 mg L-dopa alone or 125 mg after a 24-h pretreatment with CD (50 mg every 6 h) produced similar degrees of PRL suppression. In 12 women, 8 with presumptive evidence of a PRL-secreting pituitary adenoma and 4 with surgery-confirmed tumor, L-dopa alone led to PRL suppression comparable to that in puerperal subjects, but pretreatment with CD significantly blunted the PRL-inhibiting effect of L-dopa. Acute administration of Nom (200 mg, orally) or Methphen (20 mg, orally) evoked no significant suppression of plasma PRL. However, scrutiny of plasma PRL responses in individual cases showed that 5 of the 12 patients suppressed plasma PRL levels after CD-L-dopa in a manner similar to that seen after L-dopa alone. Also, in these subjects, PRL was not suppressed after Nom and Methphen treatment. These data indicate that: 1) CNS dopaminergic function, as assessed by CD-L-dopa, is preserved in postpartum women, 2) there are patients bearing PRL-secreting pituitary adenomas who are unresponsive to the PRL-inhibiting properties of IADA, but suppress baseline PRL levels after CD-L-dopa in the same way as normal and postpartum subjects; and 3) IAD As and CDL- dopa do not probe the same aspects of CNS dopaminergic function. © 1982 by The Endocrine Society