Premium
The effect of pegvisomant‐induced serum IGF‐I normalization on serum leptin levels in patients with acromegaly
Author(s) -
Parkinson C.,
Whatmore A. J.,
Yates A. P.,
Drake W. M.,
Brabant G.,
Clayton P. E.,
Trainer P. J.
Publication year - 2003
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1046/j.1365-2265.2003.01795.x
Subject(s) - leptin , pegvisomant , acromegaly , medicine , endocrinology , body mass index , leptin receptor , hormone , obesity , growth hormone
Summary background In humans, serum leptin correlates positively with fat mass. GH is lipolytic and patients with active acromegaly have lowered serum leptin compared to age, sex and body mass index (BMI)‐matched controls, but a direct influence of GH on serum leptin remains unclear. In patients with acromegaly, total leptin increases following successful pituitary surgery and during somatostatin (SMS) analogue therapy (despite no change in BMI) but whether this represents changes in soluble leptin receptor, bound or free leptin is unclear. Pegvisomant, a GH receptor antagonist capable of normalizing serum IGF‐I in over 97% of patients, represents a novel treatment strategy in acromegaly and its effect on leptin has not previously been reported. patients Sixteen patients (nine male (M), seven female (F), median age 52 years, range 27–78 years) with active acromegaly (serum IGF‐I at least 30% above the upper limit of an age‐related reference range) were studied. Serum IGF‐I was normalized in all subjects with pegvisomant [mean duration 7 months (range 3–11 months), median dose 20 mg/day (range 10–40 mg/day)]. A single batch measurement of leptin, bound leptin (BL), soluble leptin receptor (SLR), insulin and glucose were performed on samples from baseline and first occurrence of serum IGF‐I normalization. results As in normal subjects, females with acromegaly had higher baseline serum leptin [median M = 6·1 (range 1·6–58·7), F = 25·9 (range 3·19–54·1) ng/ml; P = 0·04], which correlated positively with BMI ( R = 0·78, P = 0·0004). Forward step‐wise regression analysis demonstrated that BMI and gender accounted for 90% of the variance in mean serum log 10 leptin. Pegvisomant‐induced serum IGF‐I normalization was associated with a rise in serum leptin [8·9 (range 1·6–58·3) to 12·7 (range 2·3–90·8) ng/ml, P < 0·0001]. Although the absolute increase was not significantly different, mean percentage increase was greater in men (M = 66·6 ± 51%, F = 11·8 ± 16%, P = 0·017) despite similar serum IGF‐I and BMI in male and female subjects at baseline. No change in BL or SLR accompanied serum IGF‐I normalization [0·27 (range 0·15–1·26) to 0·27 (range 0·14–1·2) nmol/l, P = 0·27 and 3·2 (range 1·2–6·8) to 2·7 (range 1–7·4) nmol/l, P = 0·5, respectively]. After normalization of serum IGF‐I, a correlation between BMI and leptin remained ( R = 0·86, P < 0·0001) and together BMI and gender accounted for 87% of the variance in mean log 10 serum leptin ( P = 0·0002). conclusion Pegvisomant‐induced serum IGF‐I normalization in patients with active acromegaly is associated with a significant increase in total, and by implication, free leptin.