Serum leptin levels in patients with acromegaly before and after correction of hypersomatotropism by trans-sphenoidal surgery

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 l eptin levels are inconsistent. We studied leptin secretion in 20 acromegali cs before and 2 months after trans-sphenoidal surgery and in 20 gender-, ag e-, 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 c ollected hourly beginning at 2200 h until 0600 h the next morning. In a sub group of 10 acromegalics, leptin pulsatility was assessed for the same peri od of time in 10-min sampling intervals. Basal GH, insulin-like growth fact or-I (IGF-I), insulin, glucose, and lipids levels were measured. Area under the curve for insulin (AUC(ins)) during oral glucose tolerance test was ca lculated. 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 us. 7.1 +/- 1.1 mu g/L, P = 0.003; in women, 16.0 +/- 3.4 vs. 23.5 +/- 3.1 mu g/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 stepwis e 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, wherea s in control subjects gender, free fatty acids, insulin, and age accounted for 99.3% in leptin variability. After surgery, BMI did not change signific antly; and glucose (P = 0.014), GH (P < 0.001), and IGF-I (P < 0.001) level s together with AUC(ins) (P = 0.002) decreased, whereas mean leptin concent ration rose significantly and attained normal levels (4.1 +/- 0.8 mu g/L, P = 0.028) in acromegalic men and (23.6 +/- 4.7 mu g/L, P = 0.003) in acrome galic women. Correlation between leptin level and BMI was preserved after s urgery (r = 0.62, P = 0.005). In stepwise regression analysis, free fatty a cids (P = 0.04) contributed to 26.8% of the variance in corrected-leptin (f or BMI and gender). Leptin concentration peak height and interpeak nadir le vel rose significantly (P = 0.033 and P = 0.037) after surgery by Cluster a nalysis, without significant changes in leptin pulse frequency and incremen tal 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 t he cubic fit increased significantly after: surgery (P = 0.028 and P < 0.00 1). In conclusion in acromegalic patients: 1) leptin secretion maintains the pu lsatility and nocturnal rise; 2) the gender-based leptin differences are pr eserved; 3) GH-IGF-I normalization leads to a rise in leptin that is not re lated to changes in BMI; and 4) the possible role of rise in leptin levels when assessing clinical and metabolic outcome of therapy in acromegalic pat ients deserves additional studies.