Effect of bromocriptine withdrawal in acromegaly on body composition as assessed by bioelectrical impedance analysis

Abstract

To evaluate the effect of bromocriptine withdrawal after dopaminergic long-term treatment (15.0\m=+-\6.8mg/day, mean \m=+-\sd) in 12 acromegalic patients on body composition, bioelectrical impedance was measured before and at the end of two weeks of drug withdrawal. During withdrawal basal hGH and IGF-I increased from 2.5\m=+-\1.9 \g=m\g/l and 2.1\m=+-\0.8kU/l to 9.1\m=+-\11.7 \g=m\g/l and 4.9\m=+-\2.2kU/l, respectively, and the hGH secretion deteriorated significantly both after oral glucose load and in the TRH test, indicating recurrence of active acromegaly. Reactance and resistance decreased by 5\m=+-\4and 23\m=+-\19 \g=W\respectively (p<0.01), whereas body weight remained constant (+0.4\m=+-\2.1kg). Bioelectrical impedance analysis indicated evident shifts in body composition, i.e. a significant reduction of body fat (\m=-\2.0\m=+-\1.7kg) and a simultaneous increase in both lean body mass (+2.4\m=+-\2.2 kg) and total body water (+1.8\m=+-\ 1.6 1). The changes in body composition were related to a combined effect of unsuppressed hypersomatotropism and the lack of bromocriptine actions other than inhibition of hGH secretion (for example stimulation of the renin-angiotensin-aldosterone system by both the recurred hypersomatotropism and the absence of dopaminergic bromocriptine effects). We conclude that bioelectrical impedance analysis is a good additional tool to assess the pathophysiological effects of bromocriptine withdrawal in long-term treated acromegalic patients. Since 1974, when Liuzzi et al. observed the suppressive effect of bromocriptine (Parlodel™, Pravidel , Sandoz, Basle, Switzerland) on elevated hGH levels in acromegalic patients (1), this dopa¬ minergic drug has been widely used for the treat¬ ment of hypersomatotropism (2,3).Both hGH (4,5) and bromocriptine (6) have met¬ abolic effects on body composition. This study was performed to establish the effect of bromocriptine withdrawal after dopaminergic long-term treat¬ ment in acromegalic patients on body weight, total body water, lean body mass and body fat as assessed by bioelectrical impedance analysis. It was our hy¬ pothesis that this method better objectifies clinical improvement in bromocriptine-treated patients with active acromegaly than does biochemical testing (3,7,8).Tetrapolar bioelectrical impedance analysis is a method based on the conduction of an electrical current in the organism. In biological structures, application of a constant low-level alternating cur¬ rent results in a frequency-dependent impedance. Therefore, human body composition can be reli¬ ably assessed by measurement of body height, body weight and the two components of impedance, i.e.resistance and reactance (9-16). Patients and MethodsThe 4 female and 8 male acromegalic patients, participat¬ ing in this investigation after giving informed consent, were on daily bromocriptine doses of 10.0-27.5 mg (15.0±6.8, mean ±sd) divided in 4 doses for 12±3 years.They were selected among our acromegalic out-patients, had been treated for a long-term period with bromocrip¬ ti...

Gender dimorphism in body composition abnormalities in acromegaly: males are more affected than females

“…In most studies, an increase in LBM is found in active acromegaly, but again no gender differences have been reported (1,6,7,9,31). GH hypersecretion has clear anabolic effects on protein synthesis in acromegaly.…”

“…It is known that GH excess causes marked expansion of extracellular fluid volume, reduction in body FM, and increases LBM and BMD (6)(7)(8)(9)(16)(17)(18)(19)(20). In both genders, when serum GH and IGF1 decrease after treatment, body weight falls over the first weeks due to a decrease in total body water, body cell mass, and LBM (3,4,6,16).…”

“…Moreover, this modification is reversible after disease control, since successfully treated males and females attain the same FM as that of controls. The reduction in FM in acromegaly is due to an inhibition of lipogenesis and stimulation of lipolysis caused by GH excess (7,8,17). O'Sullivan et al suggested that the increased energy expenditure observed in acromegaly could be another regulatory mechanism of FM; energy expenditure was reduced and FM increased as GH and IGF1 levels decreased with treatment (19).…”

“…Dual-energy X-ray absorptiometry (DEXA), introduced more recently in the assessment of BC, has the advantage of providing a comprehensive, non-invasive estimate of each tissue compartment. BC changes in acromegaly, namely body weight, lean body mass (LBM), and bone mineral content (BMC) increase, while fat mass (FM) is reduced (3,(6)(7)(8)(9), but differences between genders have not been previously described. Increased body fat, and especially visceral fat, is associated with an increase in cardiovascular risk in normal population (10,11) and different diseases (11)(12)(13); whether a decrease in body fat is related to changes in cardiovascular risk in acromegaly is not known.…”

Alterations in body composition in acromegaly

“…Using the same method in 13 subjects with acromegaly, O'Sullivan et al [3] showed that ECW was 21% higher than in normals. Further support for the presence of volume expansion in acromegaly was shown by Rau et al [4] in 12 subjects with acromegaly. In this study, bromocriptine withdrawal for 2 weeks following long-term treatment resulted in an increase in TBW by 1.8 l as estimated by bioelectrical impedance analysis.…”