C. Maraschini

Impaired prolactin secretion in obese patients

To investigate a possible hypothalamic alteration in obesity, we have studied the pattern of PRL secretion in response to insulin hypoglycemia, arginine infusion and TRH injection in 12 grossly obese patients and in 12 normal-weight controls. In the obese patients, PRL secretion was significantly lower than in normal subjects in response to insulin hypoglycemia and arginine infusion, while it was not significantly different from that in controls in response to TRH. The mean ± SE values of the areas subtended by the PRL curves in the 3 above tests were 54.7 ± 155.81 vs 3677.3 ± 520.30 ng/2h,p<0,01, 210.3 ± 148.93 vs 1034.8 ± 203.15 ng/2h, p<0.05 and 1476.8 ±275.13 vs 2148.6 ± 682.06 ng/2h, NS, respectively, in the obese and in controls. These results are compatible with the concept of impaired hypothalamic control of PRL secretion in obesity, although it is still unclear what role this may play in the pathogenesis of this disorder.

Comparison between a Slow-Release Oral Preparation of Bromocriptine and Regular Bromocriptine in Patients with Hyperprolactinemia: A Double Blind, Double Dummy Study

The efficacy and tolerability of a slow-release preparation of bromocriptine (Parlodel SRO) were compared to those of conventional bromocriptine (Parlodel R) in a double blind, double dummy study of 12 hyperprolactinemic women (plasma PRL 81.3 +/- 4.73, ng/ml mean +/- SEM). For 2 weeks, the patients received 2.5 mg b.i.d. Parlodel R or 5 mg once daily Parlodel SRO; for the following 2 weeks, the dose of the drugs was doubled. The patients were then treated, in an open study, with 2.5-10 mg daily Parlodel SRO for 6 months. Both preparations caused a prompt and sharp PRL fall. Hormone levels remained inhibited over the whole month of observation with both preparations. Daily PRL profiles were very close with either drug although morning PRl levels were slightly higher during Parlodel SRO than during Parlodel R administration. Doubling the doses of the two drugs did not result in further significant lowering of PRL values. During the 6-month study with Parlodel SRO, plasma PRL further decreased and normalized in 11 of 12 patients. Clinical improvement occurred in the majority of cases. Tolerability of Parlodel SRO appeared to be better, though without statistically significant differences, than that of Parlodel R. Side effects were less important with the former compound in their number, severity and duration. In conclusion, thanks to its favourable pharmacological profile, Parlodel SRO appears to be a valuable alternative to regular bromocriptine in the management of hyperprolactinemia.

Inhibition by phospholipid liposomes of the prolactin and cortisol response to insulin hypoglycemia in man

This study was designed to further investigate the purported dopaminergic activity of phospholipid liposomes (PL) prepared from bovine cerebral extracts, and to obtain further indications about their pituitary or suprapituitary site of action. In eight normal subjects, we have studied the effects of PL administration (250 mg as IV bolus plus additional 250 mg infused IV over a 60-min period), compared to placebo, on the prolactin (PRL), cortisol and growth hormone (GH) response to an insulin tolerance test (ITT). In eight additional subjects, the effects of PL on the PRL and TSH response to TRH were evaluated. PL medication blunted the PRL and cortisol response in the ITT: significant differences, with respect to placebo administration, were observed between mean peak PRL values (51.9±13.63 SEM vs 83.4±26.35 ng/ml, P<0.05) and mean cortisol values at 120 min time (20.9±0.67 vs 26.7±2.46 μg/dl, P<0.05). In contrast, PL administration did not modify the ITT-related GH rise or the PRL and TSH release in response to TRH. These findings favour the view that PL are endowed with intrinsic biological activity which is dopamine-mediated, and point to the hypothalamus as their primary site of action.

Chronic Treatment With Parlodel LAR® of Patients With Prolactin-Secreting Tumours: Different Responsiveness of Micro-and Macroprolactinomas

UNLABELLED Forty-one patients with prolactinoma (25 micro-, 16 macroprolactinomas) were treated with a long-acting injectable preparation of bromocriptine (Parlodel LAR, Sandoz), 25-100 mg (mostly 50 mg) in every 4-8 weeks for as long as 43 months (median 19 months). The first injection caused a prompt fall of plasma PRL which reached its nadir value after 3 days. Thereafter, hormone levels remained well below initial values for 4 weeks or longer, though with the tendency, more pronounced in microprolactinoma patients, to rise again toward baseline. The prevalence of PRL normalization was greater in the macro- than in the microprolactinoma group. By repeated injections plasma PRL could be kept close to or within the normal limits in most of the patients. However, the extent of PRL inhibition was significantly greater in macro- than in microprolactinoma patients (p less than 0.01). Clinical improvement occurred in the majority of the patients, shrinkage of the tumour in 50% of them. Adverse reactions were generally mild or of moderate severity and subsided spontaneously in 24 h. They were less frequent (NS) and less severe (p less than 0.05) in macro- than in microprolactinoma patients. IN CONCLUSION a. injectable bromocriptine (Parlodel LAR) is a highly effective preparation particularly suitable for the long-term treatment of tumourous hyperprolactinemia; b. patients with macroprolactinoma exhibit, compared with microprolactinoma patients, better responsiveness and better tolerability to injectable bromocriptine.