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Serum Leptin Levels in Patients with Acromegaly before and after Correction of Hypersomatotropism by Trans-Sphenoidal Surgery

Svetozar S. Damjanovi, Milan S. Petakov, Sanja Raievi, Dragan Mici, Jelena Marinkovi, Carlos Dieguez, Felipe F. Casanueva and Vera Popovi

Institute of Endocrinology, Diabetes, and Diseases of Metabolism (S.S.D., M.S.P., S.R., D.M., V.P.) and Institute of Social Medicine and Statistics (J.M.), School of Medicine, University Clinical Center, Beograd, SR Yugoslavia; and Departments of Physiology (C.D.) and Medicine (F.F.C.), School of Medicine and Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela University, Santiago de Compostela, Spain

Address correspondence and requests for reprints to: F. F. Casanueva, M.D., Ph.D., Department of Medicine, Endocrine Unit, San Francisco Street, P.O. Box 563, E-15780, Santiago de Compostela, Spain. E-mail: melage{at}uscmail.usc.es

It has been shown that GH excess is associated with decreased leptin levels and decreased body fat mass. Reports regarding the effect of GH on serum leptin levels are inconsistent. We studied leptin secretion in 20 acromegalics before and 2 months after trans-sphenoidal surgery and in 20 gender-, age-, and body mass index (BMI)-matched control subjects. The mean 8-h leptin concentration for each subject was measured from a pool formed of samples collected hourly beginning at 2200 h until 0600 h the next morning. In a subgroup of 10 acromegalics, leptin pulsatility was assessed for the same period of time in 10-min sampling intervals. Basal GH, insulin-like growth factor-I (IGF-I), insulin, glucose, and lipids levels were measured. Area under the curve for insulin (AUC_ins) during oral glucose tolerance test was calculated.

Control subjects and acromegalics had similar BMI, but patients with active acromegaly had significantly lower mean leptin level (mean ± SEM; in men, 2.6 ± 0.4 vs. 7.1 ± 1.1 µg/L, P = 0.003; in women, 16.0 ± 3.4 vs. 23.5 ± 3.1 µg/L; P = 0.036). Mean 8-h leptin correlated with BMI (r = 0.57, P = 0.007, in controls; r = 0.70, P = 0.001, in patients). In stepwise regression analysis with mean 8-h leptin as a dependent variable, BMI (P < 0.001) and gender (P = 0.01) in acromegalics entered the equation, whereas in control subjects gender, free fatty acids, insulin, and age accounted for 99.3% in leptin variability. After surgery, BMI did not change significantly; and glucose (P = 0.014), GH (P < 0.001), and IGF-I (P < 0.001) levels together with AUC_ins (P = 0.002) decreased, whereas mean leptin concentration rose significantly and attained normal levels (4.1 ± 0.8 µg/L, P = 0.028) in acromegalic men and (23.6 ± 4.7 µg/L, P = 0.003) in acromegalic women. Correlation between leptin level and BMI was preserved after surgery (r = 0.62, P = 0.005). In stepwise regression analysis, free fatty acids (P = 0.04) contributed to 26.8% of the variance in corrected-leptin (for BMI and gender). Leptin concentration peak height and interpeak nadir level rose significantly (P = 0.033 and P = 0.037) after surgery by Cluster analysis, without significant changes in leptin pulse frequency and incremental peak amplitude. Nocturnal rise of leptin (mathematically described by a cubic curve) was characterized by an acrophase just after midnight, before and after surgery. The amplitude and the average leptin concentration of the cubic fit increased significantly after surgery (P = 0.028 and P < 0.001).

In conclusion in acromegalic patients: 1) leptin secretion maintains the pulsatility and nocturnal rise; 2) the gender-based leptin differences are preserved; 3) GH-IGF-I normalization leads to a rise in leptin that is not related to changes in BMI; and 4) the possible role of rise in leptin levels when assessing clinical and metabolic outcome of therapy in acromegalic patients deserves additional studies.

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