Leptin levels in relation to body composition and insulin concentration in patients with endogenous Cushing’s syndrome compared to controls matched for body mass index

Abstract

Cushing's syndrome (CS) is associated with weight gain and visceral obesity. We examined the relationship between regional fat distribution and serum levels of leptin, cortisol and insulin. Twenty-three consecutive patients with recently diagnosed CS (18 with pituitary adenoma, 5 with adrenal tumor), where compared to obese controls, matched for age, sex and Body Mass Index (BMI). Serum insulin, leptin, cortisol, C-peptide and body composition determined by DEXA were measured. Serum leptin levels were significantly increased in patients with CS (36.9+/-3.8 vs 18.9+/-2.4 ng/ml, p<0.001; women: 40.1+/-4.6 vs 21.7+/-2.9 ng/ml, p<0.01; men: 27.9+/-5.7 vs 10.9+/-2.3 ng/ml; p<0.05), the same were fasting insulin levels (178+/-30 vs 81+/-10 pmol/l; p<0.01) and C-peptide (1.51+/-0.12 vs 0.77+/-0.07 nmol/l; p<0.001). In a subgroup of 12 patients, truncal fat mass was significantly elevated when compared to obese controls (19.2 kg vs 14.7 kg, p<0.01, and 42% vs 36% in percentage of truncal body tissue, p<0.05), whereas total fat mass was insignificantly increased. Serum leptin correlated positively to total body fat (%) as in patients with CS (r=0.94, p<0.001) as in controls (r=0.68, p<0.01). The correlation to truncal body fat (%) was also significant in both groups (CS: r=0.84, p<0.001; controls: r=0.63, p<0.01). Multiple regression showed that percent total body fat was the predictor of leptin concentrations among patients with CS (r2=0.88, p<0.001) whereas insulin did not contribute significantly to the variance in leptin concentrations. In controls, both leptin and insulin (r2=0.65, p<0.001) contributed significantly to the variations in leptin levels. Controlled for the differences in total body fat, patients with endogenous CS have significantly increased serum leptin levels, compared to BMI-matched obese controls. This suggests that hyperleptinemia in CS not primarily reflects changes in body composition, but is the result of different hormonal influences on adipose tissue.

Serum Adipokine Concentrations in Dogs with Naturally Occurring Pituitary‐Dependent Hyperadrenocorticism

“…First, circulating leptin level is correlated with the body fat mass in dogs,21 so it is possible that an increased fat mass in the abdomen might lead to excessive hyperleptinemia. Second, in humans, it has been suggested that an increase in visceral fat has a relatively stronger effect on serum leptin in patients with Cushing's syndrome than it does in subjects with normal cortisolemia 22, 23, 24, 25. Therefore, it is also possible that an excess of endogenous cortisol promotes the production of leptin by adipose tissue without a change in fat mass 24.…”

Anthropometric measures and fasting insulin levels in children before and after cure of Cushing syndrome

“…Studies of adults with CS report a phenotype of higher abdominal and truncal fat percentages (as measured by dual-energy X-ray absorptiometry), intra-abdominal fat deposit (as measured by computed tomography) and reduced lean mass percentage compared with body mass index (BMI)- and age-comparable controls 1, 2 . In addition, studies with adult patients report that CS is associated with increased intra-abdominal fat stores compared to subcutaneous fat 3–5 .…”

Interleukin-1 Receptor Antagonist Is Associated with Fat Distribution in Endogenous Cushing’s Syndrome: A Longitudinal Study

“…A variety of hormones have been shown to regulate leptin production both in vitro and in vivo, including insulin and cortisol (7-10). Thus, the fat distribution associated with CS (11-14) has been linked to elevated plasma leptin levels (11,15,16), although the pathophysiological significance of leptin overproduction in these patients is, at present, unclear. Different mechanisms have been proposed for this apparent leptin resistance, including reduced efficiency of brain leptin transport and increased levels of soluble leptin receptor acting as a decoy for ligand signaling (17).…”