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目的 报告一个中国人糖皮质激素可治性醛固酮增多症 (GRA)家系 ,探讨其诊治方法和发病机制。方法 对家系中的患病者进行了醛固酮、皮质醇和肾素活性动态检测 ,并对 3名患者实施了地塞米松诊断性治疗。用长距离聚合酶链反应和DNA测序方法检测该家系中 11β 羟化酶基因和醛固酮合酶基因是否发生不等位交换。结果 家系中共有 4人发病 ,均有不同程度的高血压 ,低血钾 ,血浆醛固酮正常高限 ,血浆肾素活性降低且不被激发 (0 0 17± 0 0 15ng·ml 1·h 1vs 0 130± 0 0 80ng·ml 1·h 1)。 3名患者经 2mg地塞米松治疗 5天后 ,血浆醛固酮由(192± 9)ng/L降至 (87± 7)ng/L(P <0 0 5 ) ,2周及 2个月后分别为 (6 6± 12 )ng/L和 (89± 13)ng/L。一名患者对治疗反应较好 ,血钾治疗前为 2 5mEq/L ,用药 35天后升至 4 15mEq/L ;血压也有所下降 ,从第一周的 (14 6 3±10 7/ 94 6± 5 3)mmHg ,第 3周降至 (138 3± 3 1/ 87 3± 6 1)mmHg (P <0 0 5 )。先证者及其胞姐尽管血浆醛固酮显著下降 ,临床症状仅有轻微改善 ,加用安体舒通和氯化钾片后才达正常。在该家系的所有 4名受累者中 ,均可以扩增出长度为 3 9kb的异常条带。不等位交换的基因断裂点均位于 11β 羟化酶基因和醛固酮合酶基因的第2号内含子中
Objective To report a pedigree of glucocorticoid-refractory aldosteronism (GRA) in Chinese and discuss its diagnosis and treatment and its pathogenesis. Methods The prevalence of aldosterone, cortisol and renin activity in the pedigree was measured dynamically. Dexamethasone was diagnosed in 3 patients. Long-distance polymerase chain reaction and DNA sequencing were used to detect whether the 11β-hydroxylase gene and the aldosterone synthase gene were exchanged unequally. Results A total of 4 pedigrees were found in the pedigree, with varying degrees of hypertension, hypokalemia, normal plasma aldosterone level, decreased plasma renin activity and no stimulation (0 0 17 ± 0 0 15 ng · ml 1 · h 1vs 0 130 ± 0 0 80 ng · ml 1 · h 1). Plasma aldosterone decreased from (192 ± 9) ng / L to (87 ± 7) ng / L in 3 patients (P <0 05) after 2 mg dexamethasone treatment for 5 days (6 6 ± 12) ng / L and (89 ± 13) ng / L, respectively. One patient responded well to treatment with 25 mEq / L before treatment of potassium and 35-15 mEq / L after 35 days of treatment. Blood pressure also decreased from the first week of (14 6 3 ± 10 7/94 6 ± 5 3) mmHg and decreased to (138 3 ± 3 1/87 3 ± 6 1) mmHg in the third week (P <0 05). Although the plasma aldosterone significantly decreased, the probands and their sister cells showed only a slight improvement in clinical symptoms. The use of spironolactone and potassium chloride tablets did not reach their normal levels. In all four affected individuals in the pedigree, an abnormal band of 39 kb in length was amplified. The gene-breakpoints that are not exchanged are located in the second intron of the 11β-hydroxylase gene and the aldosterone synthase gene