目的分析生长激素缺乏症(GHD)和特发性矮小症(ISS)患者生长激素激发试验结果,及其与重组人生长激素(rhGH)治疗反应之间的关系。方法回顾性分析36例GHD和24例ISS左旋多巴和胰岛素低血糖生长激素激发试验结果,rhGH治疗后身高增长情况,进...目的分析生长激素缺乏症(GHD)和特发性矮小症(ISS)患者生长激素激发试验结果,及其与重组人生长激素(rhGH)治疗反应之间的关系。方法回顾性分析36例GHD和24例ISS左旋多巴和胰岛素低血糖生长激素激发试验结果,rhGH治疗后身高增长情况,进行相关性分析。结果GHD组两种激发试验峰值、曲线下面积(area under curve,AUC)与身高标准差比值(SDS)呈正相关(P<0.001),校正性别、年龄、骨龄、体质量SDS后,左旋多巴激发试验峰值及AUC与身高SDS仍呈正相关(r=0.471和0.427,P<0.05);ISS组并无此相关性。两组治疗前身高SDS无差异,治疗第2年GHD组身高SDS显著高于ISS组(P<0.05)。两组治疗后GV均明显增加,但治疗第2年GV较第1年有所下降。GHD组治疗第1年GV与治疗前两种激发试验峰值、AUC呈负相关,而ISS组并无相关性。结论rhGH可显著改善GHD和ISS患儿身高,但随着治疗的延长GV有下降趋势;治疗前GH激发试验可一定程度预测GHD患儿rhGH治疗效果,但不能预测ISS患儿rhGH治疗效果。展开更多
Background Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. This syndrome is partially caus...Background Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. This syndrome is partially caused by mutations in human glucocorticoid receptor （hGR） gene. The clinical spectrum of generalized glucocorticoid resistance is broad, ranging from fatigue or no symptoms to severe hypertension with hypokalemic alkalosis. The purpose of this study was to explore the genetic disorder of glucocorticoid resistance syndrome.Methods We identified a 56-year-old male patient diagnosed with generalized glucocorticoid resistance syndrome accompanied with an adrenocortical adenoma. This asymptomatic patient referred to Peking Union Medical College Hospital for treatment of his adrenal incidentaloma. Endocrinological evaluation consistently revealed his elevated serum cortisol level. Total RNA was extracted from the patient＇s peripheral blood mononuclear leukocytes （PBMLs） and entire coding region of hGR alpha was amplified by reverse transcription （RT）-PCR. To confirm the possible mutation identified by sequencing RT-PCR products, genomic DNA sequence of hGR gene from the patient and 50 healthy controls was analyzed by PCR and directly sequencing.Results A heterozygotic （C→T） substitution at nucleotide position of 1667 （exon 5） in GR alpha gene was found in this patient by sequencing of RT-PCR products of hGR gene. This substitution was also identified at genomic DNA level and it was absent in 100 chromosomes from 50 unrelated health controls. This substitution resulted in a threonine to isoleucine substitution （ACT→ATT） at amino acid 556 in the ligand-binding domain of GR alpha. Conclusion Generalized glucocorticoid resistance in this patient might be caused by a novel heterozygotic mutation in the ligand-binding domain of the GR alpha.展开更多
文摘目的分析生长激素缺乏症(GHD)和特发性矮小症(ISS)患者生长激素激发试验结果,及其与重组人生长激素(rhGH)治疗反应之间的关系。方法回顾性分析36例GHD和24例ISS左旋多巴和胰岛素低血糖生长激素激发试验结果,rhGH治疗后身高增长情况,进行相关性分析。结果GHD组两种激发试验峰值、曲线下面积(area under curve,AUC)与身高标准差比值(SDS)呈正相关(P<0.001),校正性别、年龄、骨龄、体质量SDS后,左旋多巴激发试验峰值及AUC与身高SDS仍呈正相关(r=0.471和0.427,P<0.05);ISS组并无此相关性。两组治疗前身高SDS无差异,治疗第2年GHD组身高SDS显著高于ISS组(P<0.05)。两组治疗后GV均明显增加,但治疗第2年GV较第1年有所下降。GHD组治疗第1年GV与治疗前两种激发试验峰值、AUC呈负相关,而ISS组并无相关性。结论rhGH可显著改善GHD和ISS患儿身高,但随着治疗的延长GV有下降趋势;治疗前GH激发试验可一定程度预测GHD患儿rhGH治疗效果,但不能预测ISS患儿rhGH治疗效果。
文摘Background Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. This syndrome is partially caused by mutations in human glucocorticoid receptor （hGR） gene. The clinical spectrum of generalized glucocorticoid resistance is broad, ranging from fatigue or no symptoms to severe hypertension with hypokalemic alkalosis. The purpose of this study was to explore the genetic disorder of glucocorticoid resistance syndrome.Methods We identified a 56-year-old male patient diagnosed with generalized glucocorticoid resistance syndrome accompanied with an adrenocortical adenoma. This asymptomatic patient referred to Peking Union Medical College Hospital for treatment of his adrenal incidentaloma. Endocrinological evaluation consistently revealed his elevated serum cortisol level. Total RNA was extracted from the patient＇s peripheral blood mononuclear leukocytes （PBMLs） and entire coding region of hGR alpha was amplified by reverse transcription （RT）-PCR. To confirm the possible mutation identified by sequencing RT-PCR products, genomic DNA sequence of hGR gene from the patient and 50 healthy controls was analyzed by PCR and directly sequencing.Results A heterozygotic （C→T） substitution at nucleotide position of 1667 （exon 5） in GR alpha gene was found in this patient by sequencing of RT-PCR products of hGR gene. This substitution was also identified at genomic DNA level and it was absent in 100 chromosomes from 50 unrelated health controls. This substitution resulted in a threonine to isoleucine substitution （ACT→ATT） at amino acid 556 in the ligand-binding domain of GR alpha. Conclusion Generalized glucocorticoid resistance in this patient might be caused by a novel heterozygotic mutation in the ligand-binding domain of the GR alpha.
