터너증후군에서 성장호르몬과 성호르몬 치료에 따른 인슐린 저항성의 변화
Changes in the Levels of Insulin Resistance after Growth Hormone Therapy and/or Sex Steroid Replacement in Turner Syndrome
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목 적: 터너증후군에서 인슐린 민감도의 감소, 내당능장애, 당뇨 등의 유병률이 높게 보고되고 있으며, 이는 심혈관 질환 발생의 위험도를 증가시킨다. 본 연구에서는 터너증후군 환자에서 성장호르몬과 여성호르몬이 당대사에 미치는 영향을 알아보고자 하였다. 방 법: 터너증후군으로 세브란스 어린이병원에서 추적관찰 중인 소아 및 성인 환자 중 경구 당부하 검사 또는 공복 혈당 및 인슐린 농도를 측정한 61명의 기록을 후향적으로 고찰하여 성장호르몬, 에스트로겐 및 프로게스테론 보충요법에 따른 인슐린 저항성 변화를 분석하였다. 인슐린 저항성은 homeostasis model assessment (HOMA-IR)와 qunatitative insulin sensitivity check index (QUICKI)를 이용하였다. 결과는 중간값과 범위로 표시하였다. 결 과: HOMA-IR은 호르몬 치료를 전혀 하지 않은 상태(1.18, 0.31-3.75)에 비해서 성장호르몬 투여 중(2.48, 0.32- 5.19)에 더 증가하였으며(n=21, P=0.035), QUICKI는 호르몬 치료 전(0.37, 0.31-0.47)에 비해서 성장호르몬 투여 중(0.33, 0.30-0.47)에 더 감소하였다(n=21, P=0.035). 성장호르몬만 사용하던 중과 비교하여 여성호르몬을 추가하였을 때 HOMA -IR은 감소하는 양상을 보였고(n=13; 각각 2.61, 0.30-4.82; 1.36, 0.36-3.81; P=0.055), QUICKI는 증가하였다(n=13; 각각 0.34, 0.30-0.48; 0.37, 0.31-0.46; P=0.046). 성장호르몬과 에스트로겐을 치료할 때와 여성호르몬 주기적 보충요법을 시행할 때를 비교하였을 때, 인슐린 저항성과 민감도의 차이는 보이지 않았다. 치료 전에 비하여 성장호르몬을 치료하는 중에 인슐린 저항성이 증가하고 민감도가 감소하는 경향을 보였으나 에스트로겐을 추가하면서 이러한 경향은 치료 전과 비슷하게 회복되었고 성장호르몬을 중단하고 여성호르몬 주기적 보충요법을 시행하는 중에도 유지되었다. 결 론: 터너증후군 환자에서 성장호르몬 치료는 내당능장애나 2형 당뇨병을 증가시키지는 않으나 치료 기간 중 인슐린 저항성을 증가시키므로, 성장호르몬 치료 전후에 당대사에 대한 주의 깊은 관찰이 필요하며, 성장이 거의 종료된 터너증후군 환자에서 성장호르몬 치료에 여성호르몬을 추가하는 것이 인슐린 저항성 악화를 예방할 수 있을 것으로 생각된다.
Abstract
Purpose: The aim of this study was to investigate the effects of growth hormone (GH) therapy and sex steroid replacement on glucose metabolism in Turner syndrome (TS). Methods: We analyzed the clinical and laboratory data of 61 children and adults with TS. The results of oral glucose tolerance test or fasting glucose with insulin levels were obtained, and the changes in insulin resistance index determined using the homeostasis model of assessment (HOMA-IR) and insulin sensitivity (quantitative insulin sensitivity check index, QUICKI) were analyzed. Data were presented in median and range. Results: With GH treatment (n=21; median duration, 38 months; range, 5-96 months), the HOMA-IR increased to levels higher than that before treatment (2.48 vs. 1.18, P=0.035), and QUICKI was decreased (0.33 vs. 0.37, P=0.035). After estrogen was added (n=13, median duration 11 months, range 2 to 55 months) to the therapy, the decrease in HOMA-IR tended to be greater and QUICKI tended to be higher (0.34 vs. 0.37, P=0.046) than that during GH treatment alone (2.16 vs. 1.36, P=0.055). However, there were no significant differences between GH with estrogen treatment and sex hormone cyclic replacement therapy (n=7) in terms of changes in the HOMA-IR and QUICKI. With GH treatment, insulin resistance tended to increase and the insulin sensitivity was tended to decrease to a level lower than that before treatment, but recovered when estrogen was added to the treatment regimenon and maintained after GH therapy was discontinued and during cyclic treatment with sex steroids. Conclusion: The incidence of glucose intolerance or the levels of type 2 diabetes mellitus did not increased during or after GH treatment in patients with TS, but insulin resistance increased transiently; therefore, close monitoring of changes in glucose metabolism is essential during GH treatment. Early replacement of estrogen in addition to GH therapy when growth is nearly accomplished might prevent the aggravation of insulin resistance in TS patients.
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