Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial.
Hypothalamic obesity is a devastating complication in children surviving brain tumors and/or cranial irradiation. These subjects are thought to exhibit autonomic dysregulation of the beta-cell, with insulin hypersecretion in response to oral glucose tolerance testing (OGTT). We report the results of a randomized, double-blind, placebo-controlled trial of octreotide therapy for pediatric hypothalamic obesity. Eighteen subjects [weight, 100.6 +/- 5.6 kg; body mass index (BMI), 37.1 +/- 1.3 kg/m(2)] received octreotide (5-15 microg/kg x d s.c.) or placebo for 6 months. With octreotide, Delta weight (mean +/- SEM) was +1.6 +/- 0.6 vs. +9.1 +/- 1.7 kg for placebo (P < 0.001). Delta BMI was -0.2 +/- 0.2 vs. +2.2 +/- 0.5 kg/m(2), respectively (P < 0.001). OGTT documented Delta insulin response (peak - basal) of -417 +/- 304 pM after octreotide vs. +216 +/- 215 pM after placebo (P = 0.034). Improvement in physical activity by parent report was noted with octreotide, but not placebo (P = 0.03). For the octreotide group, changes in quality of life positively correlated with changes in insulin response (P = 0.041). Complications and adverse events were mild and self-limited. These data demonstrate the beneficial effects of octreotide in pediatric hypothalamic obesity. Octreotide suppressed insulin, and stabilized weight and BMI. Improved quality of life correlated with the degree of insulin suppression. Octreotide was safe and well tolerated.
Lustig
Robert H
RH
Department of Endocrinology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. rlustig@peds.ucsf.edu
Hinds
Pamela S
PS
Ringwald-Smith
Karen
K
Christensen
Robbin K
RK
Kaste
Sue C
SC
Schreiber
Randi E
RE
Rai
Shesh N
SN
Lensing
Shelly Y
SY
Wu
Shengjie
S
Xiong
Xiaoping
X
D000293:Adolescent; D001786:Blood Glucose / Q000032:analysis; D001827:Body Height / Q000187:drug effects; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D002648:Child; D004311:Double-Blind Method; D002149:Energy Intake / Q000187:drug effects; D005260:Female; D006728:Hormones / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007027:Hypothalamic Diseases / Q000150:complications*; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D015282:Octreotide / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D011788:Quality of Life; D012449:Safety
D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D020738:Leptin; D010919:Placebos; D007334:Insulin-Like Growth Factor I; D015282:Octreotide