Feyza DARENDELİLER, ÖNER ÖZDEMİR, Şükran POYRAZOĞLU, Sema ANAK, Ömer DEVECİOĞLU, Leyla AĞAOĞLU

Çocukluk dönemi hematolojik malign hastalıklarda tedaviye bağlı gelişen gonad işlev bozuklukları

Amaç: Kliniğimizde lösemi [akut lenfoblastik lösemi n:27, akut myeloid lösemi n:l] ve lenfoma (Hodgkin n:15, Hodgkin dışı lenfoma n:7) nedeniyle tedavi görmüş ve tedavi bitiminden sonra ortalama 5.0$pm$3.7 (1-13) yıl geçirmiş olan 50 (17 K, 33E) çocuk ve adolesanın gonad işlevleri açısından değerlendirilmesidir. Yöntem: Kemoterapi ve radyoterapi uygulanmış olan hastalarda gonad işlevleri açısından tüm hastaların tiroid hormon, prolaktin, östradiol-(kız), bazal ve gonadotropin salgılatın hormon (GnRH) uyarısı sonrası luteinizan hormon (LH), folikül stimülan hormon (FSH) düzeylerine ve erkeklerde bazal ve human korionik gonadotropin (hCG) uyarısı sonrası testosteron düzeylerine bakıldı. Tedavi sonrası lösemili 10 hastaya teslis biyopsisi yapıldı. Kızların uterus ve over boyutları ultrasonografi ile değerlendirildi. Bulgular: Yaş ortalaması 14.5$pm$4.1 (8.9-26.5) yıl olan çocukların 15'i (7K, 8E) prepübertal, 2'si gecikmiş püberteli ve 33'ü (10K, 23E) pübertal idi. Pübertal çocukların 12'sinin teslis volümü küçüktü. Kızların bir vaka hariç püberte gelişimi normaldi. Bazal östradiol ve testosteron düzeyleri normal olmasına karşın bazal ve/veya GnRH sonrası LH düzeyleri lösemili vakaların % 83'inde, lenfomalı vakaların % 78'inde yüksekti. FSH düzeyleri ise sırasıyla % 79 ve % 91 oranında artmıştı. Cinsler ve hastalık grupları arasında anlamlı fark yoktu. Küçük testisli vakaların hepsinde gonadotropinler patolojik olarak yüksekti. Prepübertal çocukların % 93.7'si, normal pübertal gelişim gösteren çocukların % 77'sinde anormal gonadotropin artışı saptandı. Prepübertal erkeklerin hepsinde ve pübertal erkeklerin % 53'ünde hCG uyarısına yetersiz testosteron yapımı ve % 66'sında oligo-azospermi vardı. Teslis biyopsisi ile % 60 oranında germ hücrelerinde etkilenme bulundu. Kızların % 33.3'ünde pelvik ultrasonda över ve/veya uterus hipoplazisi vardı. Sonuç: Primer gonadal yetmezliğin göstergesi olan hormonal bozukluk prepübertal ye normal püberteli çocukların büyük oranında mevcuttu. Infradiafragmatik radyasyon, adriamisin ve kümulatif siklofosfamid dozu gonad işlev bozukluğunu öngören en önemli parametrelerdi.

Anahtar Kelimeler:

Gonad hastalıkları, Lenfom, Gonadlar, Çocuk, Ergen, Lösemi

Gonadal dysfunction after treatment for childhood heamatological malignancy

Aim: Gonadal functions were evaluated in 50 (17F, 33M) long-term survivors of acute leukemia (acute lymphoblastic leukemia n:27, acute myeloid leukemia n:l) and lymphoma (Hodgkin's disease n:15, non-Hodgkin's lymphoma n:7) after a mean duration of 5.0±3.7 (l-13)yrs since the end of therapy. Methods: Thyroid hormones, prolactin and basal and gonadotropin-releasing hormone (GnRH) stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels, basal and human chorionic gonadotropin (hCG) stimulated testosterone (males) and estradiol (female) were measured in the patients who have received chemotherapy and radiotherapy. Testis biopsy was done in 10 leukemic patients after treatment. Ovarian and uterine volumes of girls were evaluated by ultrasonography. Results: The mean age at investigation was 14.5±4.1 yrs. Fifteen children (7F,8M) were prepübertal, 2 boys had delayed puberty and 33 (10F, 23m) were pübertal 12 of whom had small testicular volume with respect to chronological age. The girls showed normal pübertal development except for one. Basal and/or peak LH at GnRH test were abnormally elevated in 83 % of leukemia and 78 % of lymphoma group and FSH in 79 % and 91 %, respectively, in spite of normal basal estrogen and testosterone levels. There was no difference in pathological response between sexes and disease groups. All children with small testis had pathologic gonadotropin response hovewer 93.7 % of prepübertal and 77 % of cases with normal pübertal de-velopment had also elevated basal and peak LH/FSH. All prepübertal males and 53 % of normal pübertal males revealed insufficient testosteron response to hCG with abnormal spermiogram findings in 66 %. Testis biopsy sho-wed that 6 of 10 patients had germ cell damage. Pelvic ultrasound revealed ovarian and/or uterine hypoplasia in 33.5 % of girls. Conclusions: High percentage of hormonal abnormalities suggestive of primary gonadal failure were present in pre-pübertal and in spite of normal pübertal development in pübertal children. Infradiaphragmatic irradiation, adriamycin and cyclophosphamide cumulative doses were highly predictive of abnormal gonadal functions.

Keywords:

Gonadal Disorders, Lymphoma, Gonads, Child, Adolescent, Leukemia,

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