Factors determining the remission of microprolactinomas after dopamine agonist withdrawal.

BACKGROUND: Withdrawal of dopamine agonist (DA) therapy in the management of microprolactinoma is common practice, but it is unclear which patients are likely to attain long-term remission. OBJECTIVE: To identify predictive factors for long-term remission. DESIGN: Prospective cohort study. PATIENTS: Forty subjects (39 female, aged 24-60 years) with microprolactinoma; all had been normoprolactinaemic on DA therapy for at least 2 years [mean duration of therapy 9 years (range 2-27)]. MEASUREMENTS: A pituitary magnetic resonance imaging (MRI) was performed on 36 (90%) subjects before DA withdrawal. Relapse was defined as prolactin greater than 480 mIU/l (22.8 microg/l) on two occasions. RESULTS: Nine out of 40 (22.5%) subjects were normoprolactinaemic 12 months after DA withdrawal. Amongst the relapse group, 24 of 31 subjects (79.4%) had already relapsed at 3 months. Normalization of MRI prior to DA withdrawal (P = 0.0006) and longer duration of DA treatment (P = 0.032) were significant predictors of remission. Age, pre-treatment prolactin, nadir prolactin, previous failure of DA withdrawal, pregnancy, dose and type of DA were not significant predictors of remission. The nine patients who were in remission at 12 months were then followed up for 58.0 +/- 5.8 months; all remained in remission. CONCLUSIONS: As many as 22.5% of subjects with microprolactinoma remained normoprolactinaemic 12 months after DA withdrawal and these subjects stayed in remission for up to 5 years. Significant predictive factors were normalization of MRI prior to discontinuation, and duration of DA treatment. Our findings support intermittent DA withdrawal after a period of normoprolactinaemia, particularly where MRI appearances have normalized.

Effect of spinal morphine after long-term potentiation of wide dynamic range neurones in the rat.

BACKGROUND: Studies have shown that long-term increase in the excitability of single wide dynamic range neurones in the spinal dorsal horn of rats may be induced after tetanic stimulation to the sciatic nerve. This sensory event is possibly an in vivo counterpart of long-term potentiation, described in the brain. This study investigated whether this phenomenon occurs in the halothane-anesthetized rat and whether the antinociceptive effects of spinally administered morphine are altered when tested on the enhanced activity. METHODS: Single unit extracellular recordings were made in three different groups of halothane-anesthetized rats (n = 6 in each group). In group 1, the evoked neuronal responses of wide dynamic range neurones by a single electrical stimulus to the peripheral nerve were recorded every 4 min, for 1 h before (baseline) and for 3 h after brief high-frequency conditioning stimulation of the sciatic nerve. In group 2, morphine was applied onto the spinal cord after long-term potentiation had been established. Increasing concentrations of morphine were added until the C fiber-evoked responses were abolished; this was followed by naloxone reversal. In group 3, the same protocol as in group 2 was used except a waiting period substituted for the electrical conditioning. RESULTS: The C fiber-evoked responses were significantly increased (P < 0.001) after conditioning compared with baseline and those in control animals. Further, significantly higher concentrations of morphine (P = 0.008) were needed to abolish the C fiber-evoked responses in tetanized animals than in control animals. Naloxone reversed the effects of morphine to the predrug potentiated baseline in group 2, showing that opioids do not block the maintenance of spinal long-term potentiation. CONCLUSIONS: Long-term potentiation of C fiber-evoked responses also can be induced in halothane-anesthetized rats, and morphine seems to have less potency during such conditions. These data suggest that long-term potentiation-like mechanisms may underlie some forms of hyperalgesia associated with a reduced effect of morphine.