Effectiveness of adding dopamine agonist therapy to long-acting somatostatin analogues in the management of acromegaly

Abstract

Background: The excess mortality and morbidity associated with acromegaly are secondary to prolonged elevation of GH and IGF-I. Vigorous control of these biochemical parameters results in improved morbidity and mortality. Somatostatin analogues (SAs) allow adequate control of GH and IGF-I in approximately 65% of subjects, leaving a significant cohort uncontrolled. Dopamine agonists (DAs), a cheap alternative to SAs, allow control of GH and IGF-I in less than 20% of patients with acromegaly. Aims: To assess the effectiveness of adding DA therapy to SA in the biochemical control of acromegaly. Subjects: One hundred and twenty cases from the Sheffield Acromegaly Register were reviewed; 24 (20%) did not require medical treatment following pituitary surgery alone; 16 (13%) had safe GH levels following surgery and radiotherapy; and 58 (48%) required medical treatment despite having had surgery, radiotherapy or both. The remaining 22 (18%) received only medical treatment. Methods: In nine subjects a DA (three bromocriptine, six cabergoline) was added to an SA to control active disease. GH day curves and IGF-I levels were compared before and after the addition of a DA to existing SA treatment. All were on stable maximum-dose treatment with an SA, with inadequate biochemical control prior to addition of DA therapy. Mean duration of treatment on a DA before biochemical assessments were made was 10.3 months. Six subjects had previously been treated with either transsphenoidal surgery, radiotherapy or both. In three subjects SA was the primary therapy. Results: All subjects exhibited a fall in median GH and IGF-I levels. Introduction of a DA resulted in a 36.1% reduction in median GH levels (8.3 vs 5.3 mIU/l; P ¼ 0.008) on a GH day curve and a 35.2% reduction in IGF-I levels (387.2 vs 251.0 mg/l; P ¼ 0.018). Only four subjects had elevated prolactin levels prior to the addition of a DA (. 368 mIU/l). Conclusion: Addition of DAs to SAs is of benefit in the biochemical control of acromegaly and should be considered in those inadequately controlled. Furthermore, the beneficial effects of DAs occur even when pre-treatment prolactin levels are within the normal range.

Cabergoline treatment in acromegaly: cons

“…Therefore, the addition of CAB to the treatment of these patients has been proposed and has been reported in eight studies ( Table 1); none of these studies was a randomized or placebo-controlled trial [6,[22][23][24][25][26][27][28]. The maximal duration of follow-up was 24 months.…”

An update on the treatment of acromegaly

“…Studies have reported a 35% reduction in GH and IGF-1 levels with combination dopamine agonist and somatostatin analog therapy, resulting in normalization of IGF-1 in 37% of patients, particularly in a subgroup with elevated baseline prolactin levels. 87,88 A recent metaanalysis of 15 studies of 227 patients concluded that the addition of dopamine agonists reduced IGF-1 by 22%, leading to normalized IGF-1 in 50% of previously uncontrolled patients. In this analysis, the baseline prolactin level did not correlate closely with the biochemical response, although the degree of tumor shrinkage correlated with a higher serum prolactin level.…”

Acromegaly and Gigantism

“…Patients with hyperprolactinemia and minimal GH elevation might benefit most from dopamine agonist treatment. Main usages of DAs are; when the patient prefers oral medication, after surgery in selected patients, such as those with markedly elevated prolactin and/or modestly elevated GH and IGF-I levels (Melmed et al, 2009) as additive therapy to SRL therapy in patients partially responsive to a maximum SRL dose (Wagenaar et al, 1990;Sadoul et al, 1992;Cremonini et al, 1992;Marzullo et al, 1999;Cozzi et al, 2004;Selvarajah et al, 2005). Side effects of DAs include gastrointestinal discomfort, transient nausea and vomiting, nasal congestion, dizziness, postural hypotension, headache, and mood disorders (Colao et al, 1997).…”