Erken puberte açısından değerlendirilen obez ve obez olmayan kız çocuklarının klinik, laboratuvar ve radyolojik verilerinin karşılaştırılması

Yıl 2020, Cilt: 13 Sayı: 2, 487 - 494, 14.05.2020

Deniz Özalp Kızılay , Hale Ünver Tuhan

https://doi.org/10.31362/patd.664874

Öz

Amaç: Erken puberte (EP) etiyolojisinde, genetik faktörler sorumlu tutulsa da beslenme ve çevresel faktörler de suçlanmaktadır. Kızlarda EP ile obezite prevalansının artması arasında korelasyon gösterilmiştir. Fazla kilolu ve obez çocukların, genellikle büyümede ve seksüel maturasyonda hızlanma ile birlikte ileri kemik yaşına (KY) sahip olduğu bildirilmiştir. Çalışmamızda, meme gelişimi ile başvuran ve EP açısından tetkik edilen obez ve obez olmayan kız çocuklarının klinik, laboratuvar ve radyolojik bulgularını karşılaştırmayı amaçladık.
Gereç ve Yöntem: Çalışmaya 3-8 yaş aralığında, meme dokusu nedeniyle çocuk endokrin polikliniğine başvuran ve EP ayırıcı tanısı için gonadotropin salgılatıcı hormon (GnRH) uyarı testi yapılan 50 obez ve fazla kilolu, 50 normal kilolu kız olgu alındı. Olguların takvim yaşı (TY), vücut ağırlığı standart deviasyon skoru (SDS), boy SDS, KY, KY-TY farkı (ΔKY-TY), bazal ve uyarılmış folikül stimülan hormon (FSH), luteinizan hormon (LH), östradiol, pik LH/FSH oranı, pelvik ultrasonla değerlendirilen uterus uzun çapı, uterus ve over volümleri kaydedildi.
Bulgular: Obez ve fazla kilolu olguların, boy SDS ve ΔKY-TY değerleri istatistiksel olarak anlamlı yüksek (sırasıyla p=0.001 ve p=0.02), KY istatistiksel olarak anlamlıya yakın yüksek bulundu (p=0.05). Obez olmayan olgularda bazal FSH değeri anlamlı yüksek saptandı (p=0.03). GnRH test yanıtlarında, Santral EP (SEP) tanı oranı obez olmayan olgularda (%26), obez olgulara (%16) göre daha yüksek saptandı, iki grup arasında anlamlı fark yoktu.
Sonuç: Obez olgularda, Boy SDS ve ΔKY-TY değerlerini daha yüksek ancak SEP tanı oranını düşük saptadık. Obez kızlarda kompensatuar hiperinsülinemi, insülin direnci, endokrin bozucular ve androjenler gibi altta yatan mekanizmalar, KY ilerlemesine ve pubertal karakteristik değişikliklere katkıda bulunarak SEP öngörüsünde yanıltıcı olabilir.

Anahtar Kelimeler

Erken puberte, kız çocuk, obezite

Kaynakça

• Referans1- Çayır Y, Çayır A. Birinci basamakta erken puberteli çocuğa yaklaşım. Tıp Araştırmaları Dergisi 2013;11:1-4.
• Referans2- Carel JC, Léger J. Clinical practice. Precocious puberty. N Engl J Med 2008;358:2366-2377.
• Referans3- Sağsöz N, Orbak Z, Tan H. Precocious puberty in girls. T Klin J Gynecol Obst 1999;9:67-78.
• Referans4- Golub MS, Collman GW, Foster PM et al. Public health implications of altered puberty timing. Pediatrics 2008;121:218-230.
• Referans5- Burt Solorzano CM, McCartney CR. Obesity and the pubertal transition in girls and boys. Reproduction 2010;140:399-410.
• Referans6- Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 2006;1:11-25.
• Referans7- Çatlı G, Erdem P, Anık A, Abacı A, Böber E. Clinical and laboratory findings in the differential diagnosis of central precocious puberty and premature thelarche. Turk Pediatri Ars 2015;50:20-26.
• Referans8- Bratberg GH, Nilsen TI, Holmen TL, Vatten LJ. Early sexual maturation, central adiposity and subsequent overweight in late adolescence, a four-year follow-up of 1605 adolescent Norwegian boys and girls: the Young HUNT study. BMC Public Health 2007;7:54.
• Referans9- Kaplowitz PB. Link between body fat and the timing of puberty. Pediatrics 2008;121:208-217.
• Referans10- McCartney CR, Blank SK, Prendergast KA, et al. Obesity and sex steroid changes across puberty: evidence for marked hyperandrogenemia in pre and early pubertal obese girls. J Clin Endocrinol Metab 2007;92:430-436.
• Referans11- Jasik CB, Lustig RH. Adolescent obesity and puberty: the perfect storm. Ann N Y Acad Sci 2008;1135:265-279.
• Referans12- Lee JM. Insulin resistance in children and adolescents. Rev Endocr Metab Disord 2006;7:141-147.
• Referans13- Blank SK, McCartney CR, Chhabra S, et al. Modulation of gonadotropin-releasing hormone pulse generator sensitivity to progesterone inhibition in hyperandrogenic adolescent girls-implications for regulation of pubertal maturation. J Clin Endocrinol Metab 2009;94:2360-2366.
• Referans14- Yue ZHAO, Ling HOU, Hong-jie GAO, Di ZHAN, Cai ZHANG, Xiao-ping LUO. Independent Relationship between Body Mass Index and LH Peak Value of GnRH Stimulation Test in ICPP Girls: A Cross-sectional Study. J Huazhong Univ Sci Technol 2017; 37:556-562.
• Referans15- Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Childh 1969;44:291-303.
• Referans16- Bundak R, Furman A, Gunoz H, Darendeliler F, Bas F, Neyzi O. Body mass index references for Turkish children. Acta Paediatr 2006;95:194-198.
• Referans17- Neyzi O, Gunoz H, Furman A, Bundak R, Gokcay G, Darendeliler F, et al. Weight, height, head circumference and body mass index references for Turkish children. Cocuk Sağlığı ve Hastalıkları Dergisi 2008;51:1-14.
• Referans18- Greulich WW PS. Radiologic atlas of skeletal development of the hand and wrist. . 2 ed. Standford (CA): Stanford University Press 1959.
• Referans19- Lee HS, Park HK, Ko JH, Kim YJ, Hwang JS. Utility of Basal luteinizing hormone levels for detecting central precocious puberty in girls. Horm Metab Res 2012;44:851-854.
• Referans20- Carel JC, Eugster EA, Rogol A, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009;123:752-762.
• Referans21- Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics 2001;108:347-353.
• Referans22- Atay Z, Turan S, Guran T, Furman A, Bereket A. The prevalence and risk factors of premature thelarche and pubarche in 4- to 8-year-old girls. Acta Paediatr 2012;101:71-75.
• Referans23- de Leonibus C, Marcovecchio ML, Chiavaroli V, de Giorgis T, Chiarelli F, Mohn A. Timing of puberty and physical growth in obese children: a longitudinal study in boys and girls. Pediatr Obes 2014;9:292-299.
• Referans24- Sopher AB, Jean AM, Zwany SK et al. Bone age advancement in prepubertal chil¬dren with obesity and premature adrenarche: possible potenti¬ating factors. Obesity (Silver Spring) 2011;19:1259-1264.
• Referans25- De Simone M, Farello G, Palumbo M et al. Growth charts, growth velocity and bone development in childhood obesity. Int J Obes Relat Metab Disord 1995;19:851-857.
• Referans26- Shalitin S, Kiess W. Putative effects of obesity on linear growth and puberty. Horm Res Paediatr 2017;88:101-110.
• Referans27- Russell DL, Keil MF, Bonat SH et al. The relation between skeletal maturation and adiposity in African American and Caucasian children. The Journal of pediatrics 2001;139:844-848.
• Referans28- Johnson W, Stovitz SD, Choh AC et al. Patterns of linear growth and skeletal maturation from birth to 18 years of age in overweight young adults. Int J Obes (Lond) 2012;36:535-541.
• Referans29- Stovitz SD, Demerath EW, Hannan PJ, Lytle LA, Himes JH. Growing into obesity: patterns of height growth in those who become normal weight, overweight, or obese as young adults. Am J Hum Biol 2011;23:635-641.
• Referans30- Pludowski P, Litwin M, Niemirska A, et al. Accelarated skeletal maturation in children with primary hypertension. Hypertension 2009;54:1234-1239.
• Referans31- Klein KO, Newfield RS, Hassink SG. Bone maturation along the spectrum from normal weight to obesity: a complex interplay of sex, growth factors and weight gain. J Pediatr Endocrinol Metab 2015;29:311-318.
• Referans32- Vandewalle S, Taes Y, Fiers T et al. Sex steroids in relation to sexual and skeletal maturation in obese male adolescents. J Clin Endocrinol Metab 2014;99:2977-2985.
• Referans33- Reinehr T, de Sousa G, Wabitsch M. Relationships of IGF-I and androgens to skeletal maturation in obese children and adolescents. J Pediatr Endocrinol Metab 2006;19:1133-1140.
• Referans34- Lee HS, Shim YS, Jeong HR, Kwon EB, Hwang JS. The Association between bone age advancement and insulin resistance in prepubertal obese children. Exp Clin Endocrinol Diabetes 2015;123:604-607.
• Referans35- Klein KO, Larmore KA, de Lancey E, Brown JM, Considine RV, Hassink SG. Effect of obesity on estradiol level, and its relationship to leptin, bone maturation, and bone mineral density in children. J Clin Endocrinol Metab 1998;83:3469-3475.
• Referans36- Gönç N. Normal puberte gelişimi ve puberte prekoks. Hacettepe Tıp Dergisi 2009;40:164-168.
• Referans37- Ahmed ML, Ong KK, Dunger DB. Childhood obesity and the timing of puberty. Trends Endocrinol Metab 2009;20:237-242.
• Referans38- Fu JF, Liang JF, Zhou XL et al. Impact of BMI on gonadorelin-stimulated LH peak in premenarcheal girls with idiopathic central precocious puberty. Obesity 2015,23:637-643.
• Referans39- Giabicani E, Allali S, Durand A et al. Presentation of 493 consecutive girls with idiopathic central precocious puberty: a single-center study. PLoS One 2013;8:709-731
• Referans40- Bordini B, Littlejohn E, Rosenfield RL. LH Dynamics in Overweight Girls with Premature Adrenarche and Slowly Progressive Sexual Precocity. Int J Pediatr Endocrinol 2010;2010:724696
• Referans41- McCartney CR, Prendergast KA, Blank SK, Helm KD, Chhabra S, Marshall JC. Maturation of luteinizing hormone (gonadotropin-releasing hormone) secretion across puberty: evidence for altered regulation in obese peripubertal girls. J Clin Endocrinol Metab 2009;94:56-66.
• Referans42- Lee HY, Lee YJ, Ahn MB, Cho WK, Suh BK. The effect of overweight on the luteinizing hormone level after gonadorelin stimulation test in girls with idiopathic central precocious puberty. Ann Pediatr Endocrinol Metab 2018;23:215-219.
• Referans43- Lee HS, Yoon JS, Hwang JS. Luteinizing hormone secretion during gonadotropin-releasing hormone stimulation tests in obese girls with central precocious puberty. J Clin Res Pediatr Endocrinol 2016;8:392-398.
• Referans44- Roth LW, Bradshaw-Pierce EL, Allshouse AA, Lesh J, Chosich J, Bradford AP, et al. Evidence of GnRH antagonist escape in obese women. J Clin Endocrinol Metab 2014;99:871-875.
• Referans45- Leung KC, Johannsson G, Leong GM, Ho KK. Estrogen regulation of growth hormone action. Endocr Rev 2004;25:693-721.
• Referans46- Schneider J, Bradlow HL, Strain G, Levin J, Anderson K, Fishman J. Effects of obesity on estradiol metabolism: decreased formation of nonuterotropic metabolites. J Clin Endocrinol Metab 1983;56:973-978.
• Referans47- Poretsky L, Cataldo NA, Rosenwaks Z, Giudice LC. The insulin-related ovarian regulatory system in health and disease. Endocr Rev 1999;20:535-582.
• Referans48- de Ridder CM, Thijssen JH, Bruning PF, Van den Brande JL, Zonderland ML, Erich WB. Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls. J Clin Endocrinol Metab 1992;75:442-446.
• Referans49- Sliwowska JH, Fergani C, Gawałek M, Skowronska B, Fichna P, Lehman MN. Insulin: its role in the central control of reproduction. Physiol Behav 2014;133:197-206.
• Referans50- Pinkney J, Streeter A, Hosking J, Mostazir M, Jeffery A, Wilkin T. Adiposity, chronic inflammation, and the prepubertal decline of sex hormone binding globulin in children: evidence for associations with the timing of puberty (Earlybird 58). J Clin Endocrinol Metab 2014;99:3224-3232.
• Referans51- Pilia S, Casini MR, Foschini ML et al. The effect of puberty on insulin resistance in obese children. J Endocrinol Invest 2009;32:401-405.
• Referans52- Rosenfield RL, Fang VS. The effects of prolonged physiologic estradiol therapy on the maturation of hypogonadal teen-agers. J Pediatr 1974;85:830-837.
• Referans53- Wennink JM, Delemarre-van de Waal HA, Schoemaker R, Schoemaker H, Schoemaker J. Luteinizing hormone and follicle stimulating hormone secretion patterns in girls throughout puberty measured using highly sensitive immunoradiometric assays. Clin Endocrinol (Oxf) 1990;33:333-344.
• Referans54- de Groot CJ, van den Berg A, Ballieux BE et al. Determinants of advanced bone age in childhood obesity. Horm Res Paediatr 2017;87:254-263.