Contribution of weight cycling to serum leptin in human obesity.

OBJECTIVE: To investigate to what extent serum leptin concentrations in obese humans are influenced by a history of weight cycling. DESIGN: Cross-sectional study on serum leptin concentrations and body composition in a cohort of obese subjects in whom a retrospective recall of weight and diet history was made. SUBJECTS: One hundred and twenty-eight obese patients (89 females and 39 males), aged 18-61 y, body mass index (BMI) 31.2-63.4 kg/m(2). MEASUREMENTS: Serum leptin; various fatness and fat distribution parameters (by anthropometry and bioelectrical impedance analysis); history of overweight at puberty; number, magnitude and timing of previous diet episodes and of consequent weight regain by interview. RESULTS: By univariate analysis, serum leptin concentrations were significantly correlated with weight, waist-hip ratio, percentage body fat, maximal percentage weight loss in a single diet episode, cumulative percentage weight loss in all diet episodes, cumulative weight regained in all diet episodes, but not with the number of diet episodes. All correlations related to anthropometric and body composition parameters were stronger for men, compared to women, although the male subgroup was smaller. On the contrary, there was a strong positive correlation between weight cycling parameters and serum leptin in women but not in men. Leptin concentrations were significantly higher in patients who were overweight at puberty than in those who were not overweight at puberty. After correction for percentage body fat, presence of overweight at puberty did not correlate any longer with leptin concentrations in either gender. In women, cumulative percentage weight loss in all diet episodes contributed an additional 5% to the variance of serum leptin in the overall model. CONCLUSION: The positive correlation between weight cycling and leptin concentration in obesity is mainly accounted for the higher percentage body fat in obese weight cyclers, although in women weight cycling per se independently contributes to the variance of serum leptin.

Scintigraphic imaging of pituitary adenomas: an in vivo evaluation of somatostatin receptors.

UNLABELLED: We have performed pituitary scintigraphy with the somatostatin (SS) analog pentetreotidean by (111In-P) in patients with GH-secreting adenoma or with "clinically non functioning" adenoma (NFA) to evaluate the presence and the functionality of SS receptors (SS-R). 111In-P pituitary accumulation was expressed as Activity Ratio (AR): the ratio between the uptake of radioactivity by the adenoma and that of the normal brain tissue. In subjects without pituitary disease, AR ranged from 1.6 to 2.2 and a value lower than 2.2 was thus arbitrarily considered as normal. In 15 out of the 17 patients with GH-secreting adenoma, an accumulation of the radioligand was shown. Median AR was 3.8 (range 1-6.9; in 14 AR were greater that 2.2) and ARs were directly correlated (r = 0.54; p < 0.05) with the suppressibility of plasma GH levels by octreotide (OC) acute administration. In two patients who repeated scintigraphy during chronic OC treatment, AR values were reduced. In all the 22 patients with NFA an accumulation of 111In-P at the pituitary level was observed and median AR was 3.0 (range 1.5-20; in 14 greater that 2.2). In vitro autoradiography of surgical specimens in 6 NFA patients revealed SS-R in 4 cases with high scintigraphic AR and negative results in two cases with low AR. Scintiscan was repeated during chronic OC treatment in 5 patients with high score: AR decreased in one patient, increased in three, and did not change in the other patient. No changes in tumor size were shown in any of these patients. A total of 8 patients (3 GH secreting and 5 NFA) had "normal" AR values. CONCLUSIONS: In acromegaly scintigraphy with 111In-P visualizes functioning pituitary SS-R coupled to intracellular events that control hormonal hypersecretion and tumor growth. In contrast, in spite of the positivity of 111In-P imaging in most patients with NFA, their receptors might have a defect in the coupling-transduction process, as they are not inhibited by OC treatment and no tumor shrinkage is observed.

Persistence of somatostatinergic tone in acromegaly.

It is a matter of debate whether hypothalamic somatostatin (SRIH) secretion in acromegaly is preserved and still regulated by the physiological feedback mechanisms of growth hormone (GH) and insulin-like growth factor I. To gather further information on this, the reproducibility of plasma GH changes induced by growth hormone-releasing hormone (GHRH) administration was evaluated in 15 acromegalic patients. There was a highly significant correlation between the peak/basal ratio (P/B) GH response in the 15 patients administered GHRH on two separate occasions (r = 0.99, p < 0.001). The test was performed also before and after the administration of drugs able to inhibit or stimulate hypothalamic SRIH release, by activating (pyridostigmine) or inhibiting (pirenzepine) cholinergic pathways, respectively. The GHRH-induced GH response (P/B = 2, range 1.1-26.1) was increased significantly by pyridostigmine pretreatment in 30 patients (P/B = 2.6, range 1.3-34.8; p = 0.0045). In nine out of 30 patients an increase of greater than 2 SD of within-subject GHRH variability was observed in response to GHRH plus pyridostigmine when compared to GHRH alone. An inverse correlation (r = -0.37, p < 0.05) was observed between GH response to GHRH alone and after pyridostigmine pretreatment. On the contrary, no change of GHRH-induced GH response was observed in 12 patients after pirenzepine pretreatment (P/B = 1.9, range 1.1-5 and P/B = 2, range 1.3-6 without and after pirenzepine pretreatment, respectively). These data suggest that in acromegaly the somatostatinergic tone does not seem to fluctuate, and that it can be inhibited often by cholinergic pathway activation but not increased further by cholinergic suppression.