Residual Secretion of Adrenal Steroid Hormones in Addison's Disease
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 6
- 主要终点
- The percentage of included patients with residual secretion of cortisol and aldosterone.
研究概览
简要总结
In autoimmune adrenal insufficiency, or Addison's disease (AD), the immune system attacks the adrenal cortex. As a result, the adrenal cells producing hormones such as cortisol and aldosterone are destroyed, leaving the body with insufficient levels to meet its needs. The common perception is that upon diagnosis of Addison's disease, basically all adrenal hormone production has ceased.
There have, however, been found a few individuals who preserve some residual secretion of cortisol even years after diagnosis. The objectives of this study is to find out how common it is, and to explore if residual function have impact on patient outcome. That is, do patients with and without residual function differ when it comes to quality of life, working ability, medication dosages, and risk of adrenal crisis?
详细描述
Autoimmune destruction of the adrenal cortex is the main cause of primary adrenal insufficiency (Addison's disease, AD). Autoimmune AD (AAD) becomes clinically manifest when 90 % of cortex of adrenal gland is destroyed. Current dogma says that adrenal insufficiency ultimately is complete, that is the adrenal cortex stops producing steroids altogether. However, several case reports indicate that there might be a subgroup of patients that retain some steroid production, even years after the diagnosis. This ability could be beneficial as it could protect against adrenal crises, ease medication, and leave the patient with better quality of life.
The objective of the study is to systematically assess to what extent patients with AAD have residual adrenocortical function, and to characterize this subgroup.
The study will be an open non-randomized three-stage multicenter clinical trial comprising patients from the Norwegian Registry for organ-specific autoimmune disease (ROAS), the Swedish Addison registry, and Germany. In stage 1, patients will be asked to fill out questionnaires and deliver medication-fasting samples for analyses of adrenal steroids. In addition, patients with congenital adrenal hyperplasia (CAH) and bilaterally adrenalectomized will serve as negative controls for adrenal steroids. In stage 2, AAD patients with residual steroid production will be invited to a cosyntropin stimulation test to estimate the maximum steroid output from the adrenal glands. Twenty patients with no sign of residual function will also be tested as a control group. In stage 3, AAD patients with confirmed residual function will be invited to go through a 30-hour ambulatory sampling of interstitial fluid for investigation of diurnal variation in adrenocortical hormone levels. Also, newly diagnosed AAD patients will be invited to repeated cosyntropin testing as a means of delineating the natural progression of adrenocortical failure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women with AAD, age 18-70 years old. This requires documented adrenal insufficiency and a positive test for 21-hydroxylase autoantibodies (biomarker for autoimmune cause) on at least one occasion.
- •Provided written informed consent
- •In case of concomitant endocrine/autoimmune diseases, the patients should be on stable adequate treatment at least the last 3 months prior to the study period.
- •For Norwegian AD patients: enrolled in ROAS
- •For Swedish AD patients: enrolled in the Swedish Addison registry
排除标准
- •Antihypertensive treatment, with the exception of doxazosin, verapamil, and moxonidine.
- •Active malignant disease, severe heart, kidney or liver failure.
- •Diabetes mellitus type
- •Pregnancy or breast feeding.
- •Pharmacological treatment with glucocorticoids (except their usual cortisone or hydrocortisone replacement therapy) or drugs that interfere with cortisol and catecholamine metabolism (antiepileptics, rifampicin, St. Johns wart).
- •Use of other glucocorticoid replacement medication than cortisone acetate or hydrocortisone.
- •Intake of grapefruit, grapefruit juice, or and liquorice juice the last week before or during the study period.
研究组 & 干预措施
Undetectable levels of adrenal hormones
Patients without detectable serum levels of adrenal hormones. Cosyntropin stimulation testing will not be performed.
Repeated cosyntropin testing in newly diagnosed patients
Newly diagnosed patients will be invited to go through repeated cosyntropin testing to delineate the natural progression of adrenocortical failure.
干预措施: Cosyntropin stimulation test (Diagnostic Test)
Detectable levels of adrenal hormones
Patients with detectable serum levels of adrenal hormones will go through cosyntropin stimulation testing.
干预措施: Cosyntropin stimulation test (Diagnostic Test)
Controls with undetectable hormone levels
Twenty patients without detectable serum levels of adrenal hormones will serve as controls in cosyntropin stimulation testing.
干预措施: Cosyntropin stimulation test (Diagnostic Test)
Congenital adrenal hyperplasia (CAH) control group
Mapping adrenal steroid profile in patients with congenital adrenal hyperplasia (CAH) with confirmed total deficiency of 21-hydroxylase.
干预措施: Baseline blood tests (Diagnostic Test)
Bilaterally adrenalectomized control group
Mapping adrenal steroid profile in patients who are bilaterally adrenalectomized.
干预措施: Baseline blood tests (Diagnostic Test)
Diurnal variation in residual adrenocortical hormone levels
Patients with detectable serum levels of adrenal hormones will go through a 30-hour ambulatory sampling of interstitial fluid for mapping of any diurnal variation in endogenous adrenocortical secretion.
干预措施: 30-hour ambulatory sampling of intestinal fluid (Device)
Cardiovascular and inflammatory biomarkers
Compare cardiovascular and inflammatory biomarker profiles in patients with and without residual production of adrenocortical steroids
干预措施: Blood test (Other)
结局指标
主要结局
The percentage of included patients with residual secretion of cortisol and aldosterone.
时间窗: 1 day
Percentage of included patients with detectable levels of adrenal steroid hormones.
次要结局
- Medication-fasting basal levels of cortisol(1 day)
- Medication-fasting basal levels of cortisol precursors(1 day)
- Medication-fasting ACTH-stimulated levels of aldosterone metabolites(1 day)
- In patients with and without residual function, generic health-related quality of life by the Short Form (36) Health Survey(1 day)
- Medication-fasting ACTH-stimulated levels of cortisol(1 day)
- Medication-fasting ACTH-stimulated levels of cortisol metabolites(1 day)
- In patients with and without residual function: disease-specific quality-of-life(1 day)
- Medication-fasting ACTH-stimulated levels of aldosterone precursors(1 day)
- Fludrocortisone replacement doses in patients with and without residual function.(1 day)
- Cortisol replacement doses, including stress doses in patients with and without residual function.(1 day)
- Number of adrenal crises pr. 100 patient years(1 day)
- Medication-fasting adrenocorticotropic hormone (ACTH)-stimulated levels of metanephrines(1 day)
- Cortisol stress doses in patients with and without residual function.(1 day)
- Medication-fasting ACTH-stimulated levels of cortisol precursors(1 day)
- Medication-fasting ACTH-stimulated levels of aldosterone(1 day)
- Medication-fasting basal levels of ACTH in patients with and without residual function.(1 day)
- Medication-fasting basal levels of metanephrines in patients with and without residual function(1 day)
- Medication-fasting basal levels of cortisol metabolites(1 day)
- Medication-fasting basal levels of aldosterone(1 day)
- Medication-fasting basal levels of aldosterone precursors(1 day)
- Medication-fasting basal levels of aldosterone metabolites(1 day)
- Medication-fasting basal levels of renin in patients with and without residual function.(1 day)