Bumin DÜNDAR, Ece BÖBER, Atilla BÜYÜKGEBİZ

Dokuz Eylül Üniversitesi Tıp Fakültesi pediatrik endokrinoloji bilim dalında 12 yıllık dönemde uygulanan büyüme hormonu tedavisi sonuçları

Amaç: Çalışmada Dokuz Eylül Üniversitesi Tıp Fakültesi Pediatrik Endokrinoloji Bilim Dalı'nda 1990-2002 yılları arasında büyüme hormonu (BH) tedavisi alan hastaların tamsal ve demografik özelliklerinin belirlenmesi ve tedaviye yanıtı etkileyen faktörlerin araştırılması amaçlanmıştır. Hastalar ve yöntem: Rekombinant BH tedavisi alan 77 olgu çalışmaya alındı. Dosya kayıtlarından her olgunun özgeçmişi, ebeveyn boylan, puberte evresi, tedavi süresi, tedavi öncesi ve sonrası takvim yaşı (TY), kemik yaşı (KY), oksolojik verileri ve uzama hızları belirlenerek kaydedildi. Hedef boy ile tedavi öncesi ve sonrasında TY/KY oranı, tahmini erişkin boy (TEB) standart deviasyori skoru (SDS) ve boy SDS hesaplandı. Olgular tanılarına ve puberte evrelerine göre sınıflandırılarak tedavi sonuçları karşılaştırıldı. Bulgular: Elli dokuz olgu (%76,6) izole BH eksikliği (İBHE), 8 olgu (%10,4) kombine BH eksikliği (KBHE), 7 olgu (%9,1) Turner sendromu tanısı almıştı. Geri kalan üç olgu (%3,9) intrauterin büyüme geriliği (İUBG), kronik böbrek yetmezliği (KBY) ve XY gonadal disgenezi tanısı ile BH tedavisi almıştı. Tüm hastaların ortalama tedaviye başlama yaşları 11,2 ± 2,9 yıl ve ortalama tedavi süreleri 3,8 + 2,6 yıl olarak bulundu. Tedavinin ilk yılındaki uzama hızı üçüncü yıldakinden anlamlı olarak yüksekti (fi < 0,05). Tedavi öncesi en düşük boy SDS (p < 0,05) ve tedaviyle en çok boy SDS kazanımı KBHE'li grupta bulundu (fi < 0,05). Tedavinin ilk yılında en yüksek uzama hızı yine KBHE'li grupta saptanırken (p < 0,05), ikinci yıl en düşük uzama hızı Turner Sendromu grubunda saptandı (p < 0,05). Olgular tedavi başlangıcındaki pubertal durumlarına göre değerlendirildiğinde prepubertal olguların tedavi öncesi TY/KY oranları ile (p < 0,05) tedaviyle kazanılan TEB SDS'leri (fi < 0,05) ve tedavinin üçüncü yılındaki uzama hızları diğerlerinden yüksek bulundu (fi < 0,05). Sonuç: BH tedavisiyle sağlanan boy uzama hızındaki artış, tedavinin ilk yılında daha belirgin olup, izleyen yıllarda kademeli olarak azalmaktadır. Tedaviye yanıt KBHE olan gurupta İBHE ve Turner sendromuna göre daha iyi bulunmuştur. Yaş, pubertal durum, tedavi öncesi boy SDS ve TY/KY oram BH tedavisine yanıtı belirleyen önemli faktörlerdir.

Anahtar Kelimeler:

Büyüme hormonu, Vücut boyu, Pediatri, Turner sendromu

Results of growth hormone treatment applied during twelve years period in Dokuz Eylül University, School of Medicine, Department of Pediatric Endocrinology

Objective: We aimed to determine diagnostic and demographic characteristics of patients who had been treated with biosynthetic Growth Hormone (Gri) in Pediatric Endocrinology Department between 1990 and 2002, and to investigate factors affecting response to GH therapy. Patients and method: Seventy seven children treated with recombinant GH (rGH) have been studied. The past medical history; heights of parents; pubertal stage; chronological age (CA), bone age (BA) and auxological data before and after treatment; duration of therapy; height velocity (HV) and height standard deviation score (SDS) before and during the first three years of therapy have been recorded for each patient. Midparental height and Predicted Adult Height (PAH) were calculated. Patients were classified according to their diagnoses and pubertal stages and compared the results of treatment. Results: Fifty nine children (76.6%) had Isolated GH Deficiency (IGHD), 8 children (10.4%) had Multiple Pituitary Hormone Deficiency (MPHD) and 7 girls (9.1%) were diagnosed as Turner Syndrome. Remaining 3 (3.9%) children treated with rGH because of intrauterine growth retardation, chronic renal failure and XY gonadal dysgenesis. The mean age at the start of treatment was 11.2 i 2.9 year; the median duration of treatment was 3.8 ± 2.6 year. HV during the first year of therapy was found higher than third years (p < 0.05).Height SDS before the treatment was lower (p < 0.05) and gained height SDS after the treatment was significantly higher in MPHD group (p < 0.05). HV was significantly higher in MPHD patients at the first year (p < 0.05) and significantly lower in Turner group at the second year of therapy (p < 0.05). When the patients divided into two groups based on pubertal status at the start of therapy; CA/BA was found significantly higher in pre-pubertal group (p<0.05). After treatment, PAH SDS, gained PAH SDS and HV in the third year were also significantly higher in pre-pubertal group (p<0.05). " Conclusion: This study showed that increases in HV after rGH treatments are more pronounced during first year of treatment and than reduce gradually. Response to rGH treatment is better in MPHD group than patients with IGHD and Turner Syndrome. Age, pubertal status, height SDS and CA/BA at the start of treatment seems to be important predictors of response to rGH therapy.

Keywords:

Growth Hormone, Body Height, Pediatrics, Turner Syndrome,

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1. Frasier SD. Human pituitary growth hormone (hGH) therapy in growth hormone deficiency. Endocr Rev 1983; 4:155-170.
2. Koch TK, Berg BO, De Armond SJ, Gravina RF. Creutzfeldt-Jakob disease in a young adult with idio-pathic hypopituitarism. Possible relation to the admi-nistration of cadaveric human growth hormone. N Engl J Med 1985; 313:731-733.
3. Kaplan SL, Underwood LE, August GP et al. Clinical studies with recombinant- DNA-derived methionyl human growth hormone in growth hormone deficient children. Lancet 1986; 1:697-700.
4. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age revised for use with the Greulich-Pyle hand standarts. J Pediatr 1952; 40:432- 441.
5. Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist, (2nd ed). Stanford, Stanford University Press, 1959.
6. Guyda HJ. Four decades of growth hormone therapy for short children: what have we achieved? J Clin Endocrinol Metab 1999; 84:4307-4316.
7. Chatelain P. Trends in the diagnosis and treatment of short stature as revealed by KIGS. In: Ranke MB and Wilton P editors: Growth Hormone Therapy in KIGS-10 Years’ Experience. Heidelberg: Leipzig: Barth J&J; 1999. p.11-20.
8. Wilton P. Adverse events during GH treatment: 10 years’ experience in KIGS, a pharmacoepidemiological survey. In: Ranke MB and Wilton P editors: Growth Hormone Therapy in KIGS-10 Years’ Experience. Heidelberg: Leipzig: Barth J&J; 1999. p.349-364.
9. Ogilvy-Stuart AL, Ryder WDJ, Battamaneni HR, Clayton PE, Shalet SM. Growth hormone and tumour recurrence. BMJ 1992; 304:1601-1605.
10. SatoT, Suzuki Y, Taketani T. Enhanced peripheral conversion of thyroxin to triiodothyronine during hGH therapy in GH deficient children. J Clin Endocrinol Metab 1977; 45: 324-329.
11. Reiter EO, Rosenfeld RG. Normal and aberrant growth. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR editors: Williams Text Book of Endocrinology. 9th ed. Philadelphia: WB Saunders Company; 1998. p.1427-1507.
12. Bundak R, Hindmarsh PC, Smith PC, Brook CGD. Long-term auxologic effects of human growth hor-mone. J Pediatr 1988; 112:875-879.
13. Hopwood NJ, Hintz RL, Gertner JM et al. Growth response of children with non-growth-hormone defi-ciency and marked short stature during three years of growth hormone therapy. J Pediatr 1993; 123:215-222.
14. Zadik Z, Chalew S, Zung A et al. Effect of long-term growth hormone therapy on bone age and pubertal maturation in boys with and without classic growth hormone deficiency. J Pediatr 1994; 125:189-195.
15. Bettendorf M, Graf K, Nelle M, Heinrich UE, Troger J. Metacarpal index in short stature before and during growth hormone treatment. Arch Dis Child 1998; 79:165-168.
16. Radetti G, Buzi F, Paganini C, Martelli C, Adami S. A four year dose-response study of recombinant human growth hormone treatment of growth hormone deficient children: effects on growth, bone growth and bone mineralization. Eur J Endocrinol 2000; 142:42-46.
17. Raisz GL, Kream BE, Lorenzo JA. Metabolic bone disease. In: Wilson JD, Foster DW, Kronenberg HM, Larsen PR editors: Williams Text Book of Endocrino-logy. 9th ed. Philadelphia: WB Saunders Company; 1998. p.1211-1239.
18. Smith EP, Boyd J, Frank GR et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994; 331:1056-1061.
19. Ranke MB, Price DA, Albertsson- Wikland K, Maes M, Lindberg A. Factors determining pubertal growth and final height in growth hormone treatment of idiopathic growth hormone deficiency. Analysis of 195 Patients of the Kabi Pharmacia International Growth Study. Horm Res 1997;48:62-71.
20. Coste J, Letrait M, Carel JC et al. Longterm results of growth hormone treatment in France in children of short stature: population, register based study. BMJ 1997; 315:708-713.
21. Tanner JM, Whitehouse RH, Marubini E, Resele LF. The adolescent growth spurt of boys and girls of the Harpenden growth study. Ann Hum Biol 1976;3:109- 126.
22. Ohlsson C, Isgaadr J, Tornell J, Nilsson A, Isalsson OGP, Lindahl A. Endocrine regulation of longitudinal bone growth. Acta Pediatr (Suppl) 1993; 391: 33-40.
23. Escamilla RF, Hutchings JJ, Deamer WC, Li CH. Clinical experiences with human growth hormone (LI) In pituitary infantilism and in gonadal dysgenesis. Acta Endocrinol Suppl (Copenh) 1960;51:253A.
24. Ranke MB. Growth hormone therapy in Turner synd-rome. Analysis of long-term results. Horm Res 1995; 44:35-41.
25. Van den Broeck J, Massa GG, Attanasio A et al. Final height after long-term growth hormone treatment in Turner syndrome. European Study Group. J Pediatr 1995; 127:729-735.
26. Donaldson MD. Growth hormone therapy in Turner syndrome--current uncertainties and future strategies. Horm Res 1997;48:35-44.
27. Carel JC, Mathivon L, Gendrel C, Chaussain JL. Growth hormone therapy for Turner syndrome: evidence for benefit. Horm Res 1997; 48:31-34.
28. Ranke MB, Lindberg A, Chatelain P et al. Turner syndrome; Demography, auxology and growth during growth hormone treatment. In: Ranke MB and Wilton P editors: Growth Hormone Therapy in KIGS-10 Years’ Experience. Heidelberg: Leipzig: Barth J&J; 1999. p.11-20.