Circadian and ultradian rhythm and leptin pulsatility in adult GH deficiency: Effects of GH replacement

Leptin contributes to the regulation of body weight in healthy individuals and is secreted by adipocytes in a diurnal pattern, with superimposed pulsa tility. The circulating leptin concentration is increased in both normally obese and untreated adult GH deficiency, a syndrome characterized by increa sed adiposity. Leptin circadian rhythm is preserved in adult GH deficiency patients; however, an ultradian rhythm and pulsatility has previously not b een reported. Alterations in plasma leptin concentration in obese individua ls and adult GH deficiency patients after GH replacement have been attribut ed to changes in body fat mass. In our present study leptin circadian and u ltradian rhythm, leptin pulsatility and its relationship with body fat mass were examined in 12 adult GH deficiency patients (6 men) before and 1 mont h after GH replacement. All subjects with adult GH deficiency had hypopitui tarism subsequent to pituitary surgery and were stabilized on conventional pituitary hormone replacement. Plasma leptin was measured over 24 h at 30-m in intervals, and changes in body composition were recorded using bioelectr ical impedance. The 24-h mean leptin concentration decreased from 2.04 +/- 0.04 nmol/liter in untreated adult GH deficiency patients to 1.64 +/- 0.03 nmol/liter after 1 month of GH replacement (P < 0.0001). Before GH replacement, patients de monstrated a significant mean leptin circadian rhythm (P < 0.001), with a m esor of 2.05 +/- 0.03 nmol/liter and a superimposed ultradian frequency of 2.0 +/- 0.1 cycles/d. After GH replacement, the circadian rhythm was preser ved (P < 0.001), but mesor decreased to 1.65 +/- 0.01 ninol/liter (P < 0.00 01), and leptin ultradian frequency increased to 16.0 +/- 0.2 cycles/d (P < 0.0001). Pulse analysis (ULTRA) revealed 3.1 +/- 0.9 pulses/24 h in untrea ted adult GH deficiency patients, which significantly increased to 9.9 +/- 2.2 pulses/24 h after 1 month of GH replacement (P < 0.001). There was no s ignificant change in body mass index or body fat mass after I month of GH r eplacement. The body fat percentage significantly reduced from 36.5 +/- 2.8 % to 35.5 +/- 2.7% after 1 month of GH replacement (P < 0.05). This change in body fat percentage was explained by a significant increase in lean body mass, from 56.2 +/- 2.8 kg at baseline to 57.4 +/- 2.7 kg after 1 month (P < 0.05). A significant correlation was observed between plasma leptin and body fat percentage at baseline and 1 month after GH replacement (both, r = 0.7; P < 0.01) in the absence of a significant correlation between leptin and body fat mass before and after GH replacement (P = 0.13 and P = 0.11, r espectively). Thus, untreated adult GH deficiency is associated with elevated 24-h leptin concentration, preserved circadian rhythm, and decreased pulsatility. The secretory pattern is restored after GH replacement, with a significant redu ction in the 24-h mean leptin concentration, maintenance of circadian rhyth m, and increased pulsatility. This GH-induced change in the leptin secretor y pattern precedes significant changes in body fat mass and may therefore b e independent of changes in adipose tissue. Restoration of leptin pulsatili ty may be of clinical benefit, and our data could lead to novel approaches for leptin manipulation in the future.