Surgery of Subclinical Cortisol Secreting Adrenal Incidentalomas
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 78
- 试验地点
- 17
- 主要终点
- Blood pressure value and SAHR step 12 months after inclusion
研究概览
简要总结
The general objective is to evaluate the consequences of surgical removal of SCSI on hypertension and cardiovascular risk factors in order to determine on an evidence-based basis if surgical excision of SCSI is preferable to an intensive medical regimen in patients with hypertension.
详细描述
Adrenal incidentalomas are unsuspected adrenal masses found during abdominal imaging. With the widespread use of computed tomography and MRI, adrenal incidentalomas are found in approximately 2% of patients. In an endocrinology setting, the majority of these masses are benign adenomas of the adrenal cortex. Approximately 10% of these adenomas display little excess of cortisol secretion associated to some degree of secretory autonomy but that are insufficient to generate overt Cushing's syndrome ("Subclinical Secreting Cortisol incidentalomas" or SCSI). However, hypertension and to a lesser degree obesity and impaired glucose tolerance are very frequent amongst patients with SCSI. The hypothesis that the mild hypercortisolism associated with SCSI is responsible for these clinical consequences is substantiated by few studies describing improvement after resection of SCSI. However, these studies were retrospective, uncontrolled and suffered from imprecision and numerous methodological bias. Thus, whether surgery is more beneficial than medical treatment is currently unknown and there is no consensus on the appropriate treatment for SCSI.
Patient selection Run-In period. Discontinuation of previous antihypertensive treatments and prescription of a standardized anti-hypertensive drug regimen (SAHR). Monthly Blood Pressure (BP) measurement using home BP monitoring. The duration of the Run-In periods will be ≤ 6 months and will end when BP will be controlled with the SAHR at two consecutive visits.
End of RI Second endocrine assessment for eligibility Randomization (Ra): 24h Ambulatory BP measurement, anthropometric and metabolic evaluation. Quality of life and cognition questionnaires. Randomization in 2 groups : Gr 1 Treatment group : Surgery followed by intensive medical care ; Gr 2 : Control Group : intensive medical care only.
Ra + 1Mo: Surgery in Group 1 Ra + 2.5 Mo to Ra + 13 Mo: 6 weeks interval follow-up Evaluation of home BP monitoring and adaptation of the SAHR. A step by step reduction of the SAHR will be attempted in the two patient groups at Ra+2.5Mo. A second attempt will systematically be performed in both groups at Ra+8.5 Medical evaluation of associated metabolic conditions (obesity, diabetes, dyslipidemia) and adaptation of treatments Record of medical events and side effects of treatments Ra + 13Mo: Final evaluation. Endocrine assessment. 24h Ambulatory BP measurement, anthropometric and metabolic evaluation. Quality of life and cognition questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≤ 80 years.
- •Unilateral SCSI:
- •Incidentally discovered adrenal tumor with attenuation < 20 UH and/or relative wash-out (> 40%) or absolute wash-out (> 60%) of contrast media and size ≥ 2 cm. Tumors that do not fulfil these criteria might be included if their size is ≤ 4 cm, do not exhibit signs of malignancy (necrosis areas, large and irregular rims) and are stable in size after ≥ 6 months of follow-up.
- •Impaired 1 mg dexamethasone suppression (Cortisol > 138 nmol/L or 5 µg/dL), OR Impaired 1 mg dexamethasone suppression (Cortisol > 50 nmol/L or 1.8 µg/dL) AND one biochemical abnormalities among:
- •08h00 plasma ACTH < 2.2 pmol/L or plasma ACTH following CRH injection ≤ 6.6 pmol/L,
- •midnight plasma cortisol > 150 nmol/L,
- •increased late evening salivary cortisol,
- •UFC between 1 and 2.0 x N.
- •Treated BP (and confirmed using an automated home BP monitoring) OR increased BP (≥ 135/85 mmHg) none treated, using an automated home BP monitoring.
排除标准
- •Age > 80 y,
- •Bilateral SCSI, Warning: Contralateral nodular formations < 10 mm are considered as negligible,
- •Incidentally discovered adrenal tumor size < 2 cm,
- •Malignant hypertension, stroke, pulmonary oedema or myocardial infarction during the previous year,
- •Malignant hypertension during the Run-in period,
- •Obligatory beta blocker treatment. Patients receiving betablocker treatment for other purpose than hypertension can be included. However, to be included, patients should need at least an extrastep of hypertensive treatment in order to allow the SAHR decrease following randomisation. The dose of betablocker has to stay the same during all the study.
- •UFC > ULN x 2.0 N,
- •8h00 plasma ACTH > 20 pg/ml (4.4 pmol/L),
- •Chronic renal insufficiency (clearance < 30 mL/min)
- •Dissipation of the biological endocrine criteria for SCSI at the end of the Run-In period,
- •Intake of exogenous corticoids or drugs that interfere with dexamethasone metabolism,
- •Pregnancy,
- •Childbearing woman with no contraceptive effective method (HAS criteria - 77),
- •Adverse pathological conditions responsible for reduced life expectancy.
- •Exclusion criteria after the Run-In period:
- •Spontaneous resolution of biological features of SCSI
- •Hypertension not confirmed with standard blood pressure self-measurement device
- •Hypertension not controlled (≥ 135/85 mmHg) at the end of the Run-In period
- •Malignant hypertension (> 175/115 mmHg)
- •Patient receiving betablocker and not receiving at least an extrastep of hypertensive treatment of the SAHR
研究组 & 干预措施
Surgery followed by intensive medical care
Laparoscopic surgical removal of the adrenal tumor
干预措施: Laparoscopic surgical removal of the adrenal tumor (Procedure)
Intensive medical treatment only
Standardized medical treatment of hypertension by SAHR.
干预措施: Standardized medical treatment of hypertension by SAHR (Drug)
结局指标
主要结局
Blood pressure value and SAHR step 12 months after inclusion
时间窗: 13 months
Treatment response will defined as a reduction of at least 1 step of SAHR at the end of the study, with BP maintained within the study objectives (\<135 mm Hg systolic and \<85 mm Hg diastolic) according to self-measurement at home.
次要结局
- Antihypertensive treatment score and daily drug dose(12 months)
- Evaluation of quality of life(At inclusion and 12 months)
- Cardiovascular risk factors/markers level(12 months)
- Incidence of complications in the two strategies.(12 months)
- Number of patients with persistent diabetes, dyslipidemia and metabolic syndrome(12 months)
- Assessment of predictive factors for the success of surgery on BP(12 months)
- 24 hours ambulatory blood pressure monitoring values(At inclusion (day 0) and at 12 months)
- Blood glucose and lipid lowering agents values(12 months)
- Direct costs of the two strategies.(12 months)
- number of patients requiring antihypertensive treatment(12 months)