Efficacy of Rapid Escalation of Cabergoline in Comparison to Conventional Dosing in Prolactin Secreting Macroadenomas.

Efficacy of Rapid Escalation of Cabergoline in Comparison to Conventional Dosing in Prolactin Secreting Macroadenomas.

To study the effects of rapid escalation of Cabergoline in comparison to conventional dosing in macroprolactinomas. Rapid escalation of cabergoline may help in earlier normalization of prolactin and shrinkage of tumor mass, and thus decrease the cumulative dose of cabergoline altogether.

The efficacy of cabergoline is dose related and determined by percentage of Dopamine 2 receptor occupancy and prolonged receptor affinity. Activation of membrane receptors and target cell responses is proportional to the degree of receptor occupancy. Greater the drug concentration, greater is the binding and receptor occupancy and greater is the efficacy of the drug. Receptor occupancy can be increased either by using high dose of cabergoline or by rapid escalation of cabergoline. The patients, who respond to increasing dosages of cabergoline, probably do so by increased receptor occupancy with higher doses.

Rapid escalation of doses of cabergoline is another approach to increase the drug concentration and increase the occupancy of the receptor. Earlier decrease in serum prolactin levels with rapid escalation may help in reducing the cumulative dose of cabergoline and total duration of treatment. Though studies with high doses of cabergoline have been performed in prolactinomas with normalization of prolactin levels in almost 100%, but systematic studies using rapid escalation of cabergoline in prolactinomas are lacking except the one by Bhansali et al. In their study, serum prolactin became normal in 93 per cent of the patients with a mean duration of 8.2 wk. The mean decrease in serum prolactin was 99 per cent by four weeks, however a similar decrease (93 to 99%) in prolactin was achieved in other studies with a time lag of 48 to 160 wk. This supports the notion that rapid hike in doses of cabergoline decreases serum prolactin levels faster and it becomes normal in the majority of patients earlier6. However it was an uncontrolled study with limited number of subjects.

Therefore present study was planned to study the efficacy of rapid escalation of Cabergoline versus conventional dosing in patients with macroprolactinomas. Rapid escalation of cabergoline dose may help in earlier normalization of prolactin and shrinkage of tumor mass, and thus decrease the cumulative dose of cabergoline altogether.

Inclusion Criteria:

Males or females presenting with

1. Prolactin secreting macroadenomas (≥10 mm maximum diameter)
2. With/without visual complaints
3. With /without parasellar or suprasellar extension
4. Treatment Naïve

Exclusion Criteria:

1. On treatment with dopamine agonists.
2. Taking other drugs influencing prolactin Levels.
3. Systemic disease like Chronic Kidney Disease, Chronic Lung Disease
4. Other secondary causes of hyperprolactinemia.
5. Prolactin secreting microadenomas
6. Pregnancy during follow up
7. Prolactinoma as part of MEN-1 Syndrome
8. History suggestive of recent apoplexy (3 months)
9. Contraindication to cabergoline therapy like pre existing psychosis.