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    The effect of pegvisomant-induced serum IGF-I normalization on serum leptin levels in patients with acromegaly.

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    Authors
    Parkinson, Craig
    Whatmore, Andrew J
    Yates, A P
    Drake, William M
    Brabant, Georg E
    Clayton, Peter E
    Trainer, Peter J
    Affiliation
    Department of Diabetes and Endocrinology, The Ipswich Hospital, Suffolk, UK. craig.parkinson@ipsh-tr.anglox.nhs.uk
    Issue Date
    2003-08
    
    Metadata
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    Abstract
    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 log10 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 log10 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.
    Citation
    The effect of pegvisomant-induced serum IGF-I normalization on serum leptin levels in patients with acromegaly. 2003, 59 (2):168-74 Clin. Endocrinol.
    Journal
    Clinical Endocrinology
    URI
    http://hdl.handle.net/10541/78876
    DOI
    10.1046/j.1365-2265.2003.01795.x
    PubMed ID
    12864793
    Type
    Article
    Language
    en
    ISSN
    0300-0664
    ae974a485f413a2113503eed53cd6c53
    10.1046/j.1365-2265.2003.01795.x
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