Evaluation of Adrenocortical Functions by Insulin Tolerance Test and Sodium Depletion in Women With Nonclassical Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency in Comparison With Healthy Volunteers.
试验速览
- 阶段
- 不适用
- 入组人数
- 41
- 试验地点
- 2
- 主要终点
- Maximal plasma cortisol concentration
研究概览
简要总结
The risk of adrenal insufficiency in patients with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency is not well documented. Indication of cortisol replacement therapy in situation of acute stress or at long term is thus controversial. The mineralocorticoid reserve of these patients has never been evaluated.
Hypothesis: The glucocorticoid and mineralocorticoid function of the adrenal glands in women with nonclassical 21-hydroxylase deficiency is comparable with the adrenal functions of healthy age- sexe- and BMI-matched subjects.
详细描述
The primary end-point of the study is to evaluate the glucocorticoid function of the adrenal glands in women with nonclassical 21-hydroxylase deficiency (= patients) by comparing the maximal cortisol concentrations obtained during insulin tolerance test (ITT) in the patients and in the healthy volunteers.
The secondary end-point of the study is to determine the % of patients with a maximal plasma cortisol concentration greater or equal to 18μg/dL during ITT; compare the maximal plasma ACTH and salivary cortisol concentration during ITT in the two study groups; to evaluate the mineralocorticoid function of the patients by comparing the variations (changes from baseline) of the plasma renin, aldosterone, urinary aldosterone, systolic and diastolic blood pressure and pulse wave velocity in response to sodium depletion in the patients and in the healthy volunteers.
Women with nonclassical 21-hydroxylase deficiency followed in the Endocrinology and reproduction illnesses Service of the BICETRE Hospital, LE KREMLIN-BICETRE, France and female healthy volunteers will be proposed to participate.
Before inclusion patients must be genotyped and both patients and healthy volunteers must undergo an ACTH (Synacthen 250 μg IV) test for plasma cortisol and 17-hydroxyprogesterone concentration assessments.
After inclusion:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Groupe of patients:
- •women aged 18-50 years with nonclassical 21-hydroxylase deficiency with homozygous or compound heterozygous mutations of CYP21A2 and plasma 17-hydroxyprogesterone concentration after stimulation with synacthen >= 10ng/mL
- •Groupe of healthy volunteers :
- •age matched female healthy volunteers with plasma 17-hydroxyprogesterone concentration after stimulation with synacthen < 2ng/mL
排除标准
- •treatment with oral or local glucocorticoids < 1 year
- •oral estroprogestative contraception < 3 months
- •spironolactone < 3 months
- •cyproterone acetate < 3 months
- •treatment modifying the activity of the renin - angiotensine - aldosterone system < 2 weeks
- •pregnancy and lactation
结局指标
主要结局
Maximal plasma cortisol concentration
时间窗: Before and up to two hours after Insulin injection (Insulin tolerance test)
Repeated measures 15, 30, 45, 60, 90 and 120 minutes after insulin IV injection
次要结局
- Maximal plasma ACTH concentration(Before and up to two hours after Insulin injection (Insulin tolerance test))
- Variation (change from baseline) of plasma rennin and plasma aldosterone concentration(Before and up to 24 hours after oral furosemide administration (Sodium depletion test))
- Variation (change from baseline) of the systolic, diastolic blood pressure and pulse wave velocity(Before and up to 24 hours after oral furosemide administration (Sodium depletion test))
- % of patients with maximal plasma cortisol concentration >=18microg/dl(Before and up to two hours after Insulin injection (Insulin tolerance test))
- Maximal salivary cortisol concentration(Before and up to two hours after Insulin injection (Insulin tolerance test))
- Variation (change from baseline) of urinary aldosterone concentration(Before and up to 24 hours after oral furosemide administration (Sodium depletion test))