Prader-Willi syndrome (PWS) is a genetic disorder characterized by dysmorphic features, obesity, hypogonadism, hypotonia and mental retardation. Obesity has been linked to insulin resistance and the latter has also been associated with premature adrenarche. Since up to date a controlled study to investigate adrenarche and its hormonal regulation was lacking in PWS, our aim was to assess whether prepubertal PWS patients develop premature adrenarche and its relationship with markers of insulin sensitivity. Fourteen prepubertal children with PWS (6 M, 8 F) and 10 non-syndromal simple obese matched controls (5 M, 5 F) participated (mean age: 7.62 ± 1.84 years). A fasting blood sample was obtained for adrenal and ovarian androgens, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1, leptin, adiponectin and a lipid profile. Thereafter an oral glucose tolerance test was performed. PWS patients were smaller at birth and a higher proportion displayed premature pubarche. No differences were found in testosterone, androstenedione, sex hormone binding globulin, free androgen index, homeostatic model assessment-IR, 2-hour insulin, leptin or adiponectin levels. 17-hydroxyprogesterone and DHEAS levels however, were significantly higher in PWS. IGF-I levels were significantly lower in PWS and correlated significantly with height SDS (p < 0.05). In conclusion, a higher proportion of premature adrenarche in our PW patients was observed, which was not explained by differences in insulin sensitivity or plasma levels of adipokines and IGF-I.

Holm V, Cassidy S, Butler M, Hanchett J, Greenswag L, Whitman B, Greenberg F: Prader Willi syndrome: consensus diagnostic criteria. Pediatrics 1993;91:398–402.
Gunay-Aygun M, Schwartz S, Heeger S, O’Riordan M, Cassidy S: The changing purpose of Prader Willi syndrome clinical diagnostic criteria and proposed revisted criteria. Pediatrics 2001;108:e92.
Burd L, Vesely B, Martsolf J, Kerbeshian J: Prevalence study of Prader Willi Syndrome in North Dakota. Am J Med Genet 1990;37:97–99.
Whittington J, Holland A, Webb T, Butler J, Clarke D, Boer H: Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J Med Genet 2001;38:792–798.
Shemer R, Hershko A, Perk J, Mostoslavsky R, Tsuberi B, Cedar H, Buiting K, Razin A: The imprinting box of the Prader Willi/Angelman syndrome domain. Nat Genet 2000;26:440–443.
Goldstone A: Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab 2004;15:12–20.
Butler M, Bittel D, Kibiryeva N, Talebizadeh Z, Thompson T: Behavioral differences among subjects with Prader-Willi syndrome and type I or type II deletion and maternal disomy. Pediatrics 2004;113:565–573.
Nicholls R: Incriminating gene suspects, Prader Willi style. Nat Genet 1999;23:132–133.
Gerard M, Hernandez L, Wevrick R, Stewart C: Disruption of the mouse necdin gene results in early post-natal lethality. Nat Genet 1999;23:199–202.
Tsai T, Armstrong D, Beaudet A: Necdin-deficient mice do not show lethality or the obesity and infertility of Prader-Willi syndrome. Nat Genet 1999;22:15–16.
Burman P, Ritzen M, Lindgren C: Endocrine dysfunction in Prader Willi syndrome: a review with special reference to GH. Endocr Rev 2001;22:787–799.
Eiholzer U, Nordmann Y, l’Allemand D, Schlumpf M, Schmid S, Kromeyer-Hauschild K: Improving body composition and physical activity in Prader-Willi Syndrome. J Pediatr 2003;142:73–78.
Van Nil E, Westerterp K, Gerver W, Van Marken W, Kester A, Saris W: Body composition in Prader Willi syndrome compared with nonsyndromal obesity: relationship to physical activity and growth hormone function. J Pediatr 2001;139:708–714.
Myers S, Carrel A, Whitman B, Allen D: Sustained benefit after two years of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader Willi syndrome. J Pediatr 2000;137:42–49.
Lindgren A, Barkeling B, Hagg A, Ritzen E, Marcus C, Rossner S: Eating behavior in Prader Willi syndrome, normal weight, and obese control groups. J Pediatr 2000;137:50–55.
Zipf W: Glucose homeostasis in Prader Willi syndrome and potencial implications of growth hormone therapy. Acta Paediatr 1999;(suppl)433:115–117.
Goldstone A, Thomas E, Brynes A, Bell J, Frost G, Saeed N, Hajnal J, Howard J, Holland A, Bloom S: Visceral adipose tissue and metabolic complications of obesity are reduced in Prader Willi syndrome female adults: evidence for novel influences on body fat distribution. J Clin Endocrinol Metab 2001;86:4330–4338.
Talebizadeh Z, Butler M: Insulin resistance and obesity-related factors in Prader-Willi syndrome: comparison with obese subjects. Clin Genet 2004;67:230–239.
Iñiguez G, Soto N, Avila A, Salazar T, Ong K, Dunger D, Mericq V: Adiponectin levels in the first two years of life in a prospective cohort: relations with weight gain, leptin levels and insulin sensitivity. J Clin Endocrinol Metab 2004;89:5500–5503.
Myers S, Davis A, Whitman B, Santiago J, Landt M: Leptin concentrations in Prader-Willi syndrome before and after growth hormone replacement. Clin Endocrinol (Oxf) 2000;52:101–105.
Goldstein B, Scalia R: Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 2004;89:2563–2568.
Ibañez L, Dimartino-Nardi J, Potau N, Saenger P: Premature adrenarche-normal variant or forerunner of adult disease? Endocr Rev 2000;21:671–696.
Youlton R, Valenzuela C: Growth patterns in height and weight in children aged 0 to 17 years and cranial circumference in children aged 0 to 2 years from medium-high and high socioeconomic status in Santiago. Rev Chil Pediatr 1990;Spec:1–22.
Juez G, Lucero E, Ventura-Junca P, Gonzalez H, Tapia J, Winter A: Intrauterine growth in Chilean middle class newborn infants. Rev Chil Pediatr 1989;60:198–202.
WHO: Expert Committee on Diabetes Mellitus: second report. World Health Organ Tech Rep Ser 1980;646:1–80.
Huang T, Johnson M, Goran M: Development of a prediction equation for insulin sensitivity from anthropometry and fasting insulin in prepubertal and early pubertal children. Diabetes Care 2002;25:1203–1210.
Müller J: Hypogonadism and endocrine metabolic disorders in Prader Willi syndrome. Acta Paediatr 1997;423(suppl):58–59.
Zhang L, Rodriguez H, Ohno S, Miller W: Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome. Proc Natl Acad Sci USA 1995;92:10619–10623.
Dardis A, Saraco N, Rivarola M, Belgorosky A: Decrease in the expression of the 3beta-hydroxysteroid dehydrogenase gene in human adrenal tissue during prepuberty and early puberty: implications for the mechanism of adrenarche. Pediatr Res 1999;45:384–388.
Guercio G, Rivarola M, Chaler E, Maceiras M, Belgorosky A: Relationship between the GH/IGF-I axis, insulin sensitivity, and adrenal androgens in normal prepubertal and pubertal boys. J Clin Endocrinol Metab 2002;87:1162–1169.
Guercio G, Rivarola M, Chaler E, Maceiras M, Belgorosky A: Relationship between the growth hormone/insulin-like growth factor-I axis, insulin sensitivity, and adrenal androgens in normal prepubertal and pubertal girls. J Clin Endocrinol Metab 2003;88:1389–1393.
Ibañez L, Potau N, Marcos M, de Zegher F: Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab 1999;84:4739–4741.
Auchus R, Rainey W: Adrenarche – physiology, biochemistry and human disease. Clin Endocrinol (Oxf) 2004;60:288–296.
Silfen M, Manibo A, Ferin M, McMahon D, Levine L, Oberfield S: Elevated free IGF-I levels in prepubertal Hispanic girls with premature adrenarche: relationship with hyperandrogenism and insulinsensitivity. J Clin Endocrinol Metab 2002;87:398–403.
Denburg M, Silfen M, Manibo A, Chin D, Levine L, Ferin M, McMahon D, Go C, Oberfield S: Insulin sensitivity and the insulin-like growth factor system in prepubertal boys with premature adrenarche. J Clin Endocrinol Metab 2002;87:5604–5609.
Remer T, Manz F: Role of nutritional status in the regulation of adrenarche. J Clin Endocrinol Metab 1999;84:3936–3944.
L’Allemand D, Eiholzer U, Rousson V, Girard J, Blum W, Torresani T, Gasser T: Increased adrenal androgen levels in patients with Prader-Willi syndrome are associated with insulin, IGF-I, and leptin, but not with measures of obesity. Horm Res 2002;58:215–222.
Schuster D, Osei K, Zipf W: Characterization of alterations in glucose and insulin metabolism in Prader-Willi subjects. Metabolism 1996;45:1514–1520.
Ong K, Potau N, Petry C, Jones R, Ness A, Honour J, de Zegher F, Ibanez L, Dunger D; Avon Longitudinal Study of Parents and Children Study Team: Opposing influences of prenatal and postnatal weight gain on adrenarche in normal boys and girls. J Clin Endocrinol Metab 2004;89:2647–2651.
Cettour-Rose P, Samec S, Russell A, Summermatter S, Mainieri D, Carrillo-Theander C, Montani J, Seydoux J, Rohner-Jeanrenaud F, Dulloo A: Redistribution of glucose from skeletal muscle to adipose tissue during catch-up fat: a link between catch-up growth and later metabolic syndrome. Diabetes 2005;54:751–756.
Crescenzo R, Samec S, Antic V, Rohner-Jeanrenaud F, Seydoux J, Montani J, Dulloo A: A role for suppressed thermogenesis favoring catch-up fat in the pathophysiology of catch-up growth. Diabetes 2003;52:1090–1097.
Butler M, Meaney F: Standards for selected anthropometric measurements in Prader Willi syndrome. Pediatrics 1991;88:853–860.
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