Hormone Levels and Tumour Size Response to Quinagolide and Cabergoline in Patients with Prolactin-secreting and Clinically Non-functioning Pituitary Adenomas: Predictive Value of Pituitary Scintigraphy with 123I-methoxybenzamide

Background: Dopamine agonists are indicated as primary therapy for PRL-secreting pituitary adenomas, while controversial results have been reported in nonfunctioning adenomas (NFA).

Objective: To evaluate whether the in vivo visualization of dopamine D2 receptor expression detected by pituitary scintigraphy using 123I-methoxybenzamide (123I-IBZM) was correlated with the response to chronic treatment with quinagolide or cabergoline.

Patients: 10 patients affected with NFA (5 men and 5 women, age ranging between 25 and 50 years), and 10 with PRL-secreting naive macroadenomas (3 men and 7 women, age ranging between 22 and 59 years), serving as control.

Study Design: All patients underwent an acute test with quinagolide: at 3-day intervals and in random order all patients received the drug (0.075 mg at 0800 h), or placebo. Blood samples were taken 15 and 5 minutes before and every 30 minutes for 6 h after drug or placebo administration. The test was considered positive when PRL and/or alpha-subunit levels decreased >/=50% as compared to baseline levels. After 6 months of treatment, 10 patients were randomised to continue the treatment with quinagolide and the remaining 10 received cabergoline for the remaining 6 months. The doses of quinagolide and cabergoline ranged from 0.075 to 0.6 mg/day and from 0.5 to 3 mg/week, respectively. At study entry, a magnetic resonance imaging (MR) study of the pituitary region and 123I-IBZM pituitary scintigraphy were performed. MR was repeated after 12 months of treatment to evaluate tumour shrinkage: reduction of tumour volume = 80% in prolactinomas and = 50% in NFA was considered significant. Basal PRL levels were 9495.0 +/- 1131.6 mU/l in prolactinomas and 602.4 +/- 50.5 mU/l in NFA.

Results: The scintigraphy was negative in 6 out of 10 patients with NFA. Moderate uptake was observed in 3 patients with prolactinoma and 2 patients with NFA whereas intense uptake was observed in the remaining 7 patients with prolactinoma and 2 patients with NFA. Among the 8 patients with NFA and high circulating alpha-subunit levels, the acute test was negative in 5 while it was positive in the remaining 3 patients. The acute test was positive in all 10 patients with prolactinoma. After 12 months of treatment with quinagolide and cabergoline, circulating PRL levels were decreased in all 10 patients with prolactinoma (571.8 +/- 255.9 mU/l), being normalized in 7 patients. Suppression of PRL levels was found in all 10 patients with NFA (89.5 +/- 2.3 mU/l). A significant reduction of alpha-subunit levels was obtained in 9 out of 10 patients with NFA: in 4 out of 8 patients alpha-subunit levels were normalized. Significant adenoma shrinkage was recorded in 4 patients with prolactinoma among the 7 with intense pituitary uptake of 123I-IBZM. Significant adenoma shrinkage was recorded only in the 2 out of 10 patients with NFA with intense pituitary uptake of 123I-IBZM. A significant positive correlation was found between the degree of uptake (considered as score) and the response to quinagolide or cabergoline treatment (considered as percent hormone suppression) either in patients affected with PRL-secreting adenoma (r = 0.856, P < 0.005) or in those affected with NFA (r = 0.787, P < 0.05).

Conclusions: An intense 123I-IBZM uptake in patients with non-functioning adenomas was predictive of a good response to a chronic treatment with quinagolide and cabergoline. This result suggests that a pituitary 123I-IBZM scintigraphy could be considered in selected patients with non-functioning adenomas before starting medical treatment with dopamine agonists.