Dynamics of the acute effects of octreotide, bromocriptine and both drugs in combination on growth hormone secretion in acromegaly

Abstract

The separate and combined GH-lowering effects of single doses of octreotide and bromocriptine were assessed in 51 acromegalic patients on 4 occasions each 2 days apart. Patients received sequentially: placebo sc (N=51), 50 \ g=m\ g octreotide sc (N=51), 2.5 mg bromocriptine po (N=40) or a combination of both drugs (N=25). With octreotide, in 28 patients (55%) GH levels were suppressed to less than 5 \g=m\g/land 39 of them (76.5%) had a 50% or greater decrease of their basal GH level from 2 to 6 h. During bromocriptine, GH values were suppressed to below 5 \g=m\g/l in 11 patients (27.5%) and reduced by 50% or more in 21 (52.5%). The combination of both drugs acutely suppressed GH levels to less than 2 \g=m\g/l in 32%, to less than 5 \g=m\g/l in 56%, and by more than 50% in 84% of patients. Octreotide produced a stronger and faster suppression of GH levels than bromocriptine in most patients. The combination of both drugs had an additive effect on the lowering of GH levels, especially between 7 and 10 h after drug administration. These results suggest that chronic therapy with a combination of both drugs may be as effective as therapy with higher doses of either compound alone. Albeit transient, octreotide caused a rapid near total suppression of insulin release in the morning, 15 to 45 min after administration. Postprandial glucose rise, between 2 and 3.5 h after breakfast was significantly higher during octreotide than on the control day.Medical therapy of acromegaly has been greatly improved in recent years following the availability of the long-acting somatostatin analogue, octreo¬ tide (Sandostatin®, SMS 201-995). Comparative studies between the acute inhibitory effects of bro¬ mocriptine (Parlodel®) and those of octreotide, on GH secretion in small numbers of acromegalic pa¬ tients indicate that the majority of these patients show a significantly higher sensitivity to octreotide than to bromocriptine (1-3).Chronic therapy with octreotide produces rapid clinical improvement in virtually all acromegalic patients, which is accompanied by a decrease in circulating GH and IGF-I levels. However, com¬ plete normalization of mean 24-h GH and IGF-I levels is reached in only approximately 50% of pa¬ tients during intermittent sc administration of 50-100 pg octreotide twice or thrice daily (2,(4)(5)(6)(7)(8)(9)(10)(11). It has been hypothesized that the absence of complete suppression of GH levels throughout the 24-h period is related to the pharmacokinetics of octreo¬ tide, which allows an increase in tumoural hor¬ mone secretion during the hours immediately preceeding the next injection (5)(6)(7)(8)(9)12). Indeed, in stud¬ ies in which octreotide was administered by 24 h sc infusion, acromegalic patients tended to show better control of GH secretion over the 24-h period, with concomitant normalization of circulat¬ ing IGF-I levels occurring more frequently (9,(11)(12)(13)).In the present study we have investigated whether octreotide and bromocriptine given in combination to acromegalic patients might result in a more ...

Octreotide

“…37,38 Overall, in comparative studies in a group of patients with acromegaly, octreotide was more effective than bromocriptine 39 ; some patients have a better response to the combination of octreotide and bromocriptine than to either drug alone. 40 The size of the tumor is reduced in about half the patients treated with octreotide. 35,37,38 The mechanism of tumor shrinkage is probably a (reversible) decrease in the size of individual tumor cells.…”

Combined therapy of somatostatin analogues and dopamine agonists in the treatment of pituitary tumours

“…Subsequent in vivo studies have confirmed that the combination of somatostatin analogues and dopamine agonists is more effective than somatostatin analogues alone in reducing GH levels in patients with GH-secreting adenomas resistant to somatostatin analogues (17,(19)(20)(21)(22)(23)(24)(25).…”

“…In 51 acromegalic patients, acute co-administration of bromocriptine (2.5 mg) and octreotide (0.05 mg) had an additive suppressive effect on GH hypersecretion (19). In particular, GH levels were !2 and 5 mg/l in 32 and 56% of acromegalic patients respectively.…”

“…In particular, GH levels were !2 and 5 mg/l in 32 and 56% of acromegalic patients respectively. GH levels decreased by more than 50% in 84% of patients (19). The combination of more potent dopamine agonists, such as cabergoline, with a depot preparation of somatostatin analogues, such as lanreotide, allowed us to achieve normalisation of IGF-I levels in five out of ten cases (23).…”

“…The use of a combined somatostatin analogue and dopamine agonist treatment schedule seems to be of particular interest in growth hormone (GH)-secreting adenomas that are known to be potentially responsive to both classes of compounds (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). More recently, nonfunctioning pituitary adenomas were shown to be sensitive to a combined treatment, whereas the response rate to somatostatin analogues or dopamine agonists alone is limited.…”