Increased leptin and tumour necrosis factor alpha per unit fat mass in hypopituitary women without growth hormone treatment

Abstract

Background: The adipocyte products, leptin and tumour necrosis factor (TNF)a, are associated with atherosclerotic diseases and may be factors contributing to the enhanced cardiovascular risk in hypopituitary patients with growth hormone (GH) deficiency. Objective: To investigate whether leptin and TNFa are increased in a group of hypopituitary women previously found to have increased cardiovascular morbidity, and to compare them with matched individuals of the same sex and age and with similar body composition. Design and Patients: Thirty-three GH-deficient women with a median age of 64 years (range 39-77 years) were investigated cross-sectionally. The patients were compared with 33 controls matched for sex, age, smoking habits, educational level and residence. Methods: Body composition was measured by bioimpedance analysis. Fasting concentrations of leptin, TNFa and insulin were analysed in patients and controls. Results: There was no significant difference in body mass index or fat mass between patients and controls (both P $ 0:4). Serum leptin did not differ significantly between patients and controls. However, when serum leptin concentrations were expressed per kilogram fat mass, the patients had significantly greater concentrations ðP ¼ 0:01Þ. Serum TNFa and TNFa per kilogram fat mass were also significantly greater in the patients (both P ¼ 0:001). In contrast, serum insulin did not differ significantly between patients and controls. In the patients, serum leptin concentrations correlated positively with kilogram fat mass (r ¼ 0:54, P ¼ 0:002). Leptin concentration per kilogram fat mass was positively correlated with insulin (r ¼ 0:40, P ¼ 0:03). Conclusions: In contrast to serum concentrations of TNFa, serum leptin did not differ from that in controls, implying that leptin is not a major contributor to the previously found increase in cardiovascular morbidity in the hypopituitary women investigated. However, the patients had increased leptin concentrations per unit fat mass, indicating an altered adipocyte secretory function in this group.

TNF-α levels in children with growth hormone deficiency and the effect of long-term growth hormone replacement therapy

“…On the other hand, there are studies supporting our findings in the literature [7,12,28]. The results of the study by Serri et al [7], were similar to our findings as they found significantly higher basal TNF-a levels in GHD patients than controls and TNF-a levels decreased significantly at the end of 3 months' rhGH treatment in GHD.…”

“…The ages of children in GHD groups in this study and our study were very similar (12.7 ± 2.5 years in treated GHD and 13.0 ± 2.6 years in untreated GHD in Lanes et al's study and 12.60 ± 2.27 years in our study). In hypopituitary women without GH treatment, higher serum TNF-a levels per unit fat mass were demonstrated according to controls [28]. GH administration had also been shown to lower serum TNF-a levels in children suffering from burns [29].…”

Stress and Body Mass Index Each Contributes Independently to Tumor Necrosis Factor-α Production in Prepubescent Latino Children

“…These results have paralleled studies of children suffering from burns (Chrysopoulo, Jeschke, Ramirez, Barrow, & Herndon, 1999) and cystic fibrosis (Hardin et al, 2001) in that GH administration resulted in a marked decrease in TNF-α levels among both patient populations. Hypopituitary women without GH treatment have also demonstrated clinically elevated TNF-α levels per unit of fat mass as compared with control subjects (Bulow, Ahren, & Erfurth, 2001). Importantly, both IGF-1 and GH have been shown to increase throughout the course of normal childhood development, peaking at approximately Tanner stages (TSs) III and IV (i.e., during puberty; Veldhuis, Roemmich, & Rogol, 2000).…”

Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency

“…With insulin resistance possibly contributing the greatest risk of premature cardiovascular disease, 12 many recent studies have now examined the role of adipocytokines, such as adiponectin 4 and tumour necrosis factor‐α (TNF‐α), 13 as other possible predictors of future cardiovascular events. Low adiponectin levels have been reported in type 2 diabetes 14 and the metabolic syndrome, 15 whereas high TNF‐α levels are reported in obese 16 and GH‐deficient adults 13 . As inflammation is also implicated in the pathogenesis of atherosclerosis, 17 surrogate markers of inflammatory activity such as C‐reactive protein (CRP) and interleukin‐6 (IL‐6) have been shown to predict the risk of cardiovascular events in healthy subjects 18 .…”