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...
Secondary hyperparathyroidism is common in chronic renal failure and is due to inadequate synthesis of calcitriol, the active metabolite of vitamin D. Intravenous administration of alphacalcidol, a synthetic analogue which is metabolized to calcitriol, was given during 12 weeks to 51 patients on chronic hemodialysis in doses between 1 and 4 μg/dialysis session. The treatment caused a modest rise, by 0.25 mmol/l, in serum calcium but a 60% reduction of intact serum PTH concentrations. Most patients acquired normal PTH values and hypercalcemia was easily avoided by dose adjustments. There was a significant reduction in serum PTH within the 1st week before the serum calcium concentrations were increased, but after that time the induced suppression of PTH was correlated to the induced rise in serum calcium. These observations are compatible with the view that calcitriol exerts both a direct inhibition of PTH release and increases the gland’s sensitivity to calcium. The major implication of the study is that intravenous treatment with alphacalcidol is of great clinical value since it is easy to administer and provides suppression of hypersecretion of PTH with few side effects.
It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0-I-6.8 mg/day for 12+3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 rain after oral glucose load increased from 5.05_+0.61 to 5.77+0.78 mmol/1 and from 5.61 __ 2.05 to 7.55 +_ 3.05 mmol/1, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin Ale was not observed. Bromocriptine led to a significant decrease in basal as well as glucosestimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients. Similarly to the increased growth hormone secretion after drug withdrawal in 11 patients, a rise in glucose-stimulated insulin secretion was found in all patients; hereby, the mean insulin levels at 0 and 120 min during oral glucose load rose significantly from 7.5+2.6 to 12.1 _+5.1 mU/1 (P<0.01) and from 71.3___52.1 to 101.4_ 50.7mU/1 (P<0.02), respectively. A direct relaAbbreviations: AUC = area under the curve; GH = growth hormone; PRL =prolactin * Dedicated to Prof. Dr. N. Z611ner on the occasion of his 70th birthday tionship between disturbance in glucose homeostasis and degree of hypersomatotropism was not observed. Our data confirm that the beneficial effect of bromocriptine therapy on glucose homeostasis in selected patients with acromegaly is still present after dopaminergic treatment over a mean period of 12 years. Compared with the published rates on improved glucose homeostasis under octreotide, the effect of bromocriptine seems to be more favorable.
In 31 severely ill patients of our intensive care unit an increased thyroid hormone binding inhibition detected by quantitative measurement of the effect of ether extracts of patients' sera on thyroxine tracer binding to TBG was found. As free fatty acids in serum were diminished in these patients, their postulated role as binding inhibitors in the "low T4 syndrome" of critically ill patients must be questioned. It cannot be excluded that THBI assays demonstrating this inhibition measure artefacts caused by heparine-induced in vitro lipolysis.
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