Effect of Surgical or Conservative Approach in Patients With Adrenal Incidentalomas on Cardiovascular, Metabolic, Neuropsychological and Bone Manifestations: Respective Roles of Cortisol Secretion and Glucocorticoid Sensitivity
试验速览
- 阶段
- 不适用
- 入组人数
- 61
- 主要终点
- variation of blood pressure
研究概览
简要总结
Subclinical hypercortisolism (SH) is a status of asymptomatic hypercortisolism, frequently found in patients with adrenal adenomas (estimated prevalence: 0.8-2% after 60 years of age). Although SH may lead to diabetes, hypertension and osteoporosis, the diagnostic SH criteria and those suggesting the need of adrenalectomy are debated. Indeed, beside the cortisol secretion, the individual cortisol sensitivity may play a role in determining the SH consequences.
Subjects with possible SH due to adrenal adenoma will be randomized to surgery/conservative follow up. The effects of surgery on the cardiovascular, bone, metabolic complications of SH and on neuropsychological aspects and quality of life (QoL) and the possibility to predict them by using cortisol sensitivity and secretion markers will be studied. The study may clarify how to individuate patients who can benefit from surgery. These results will help reducing the costs of both useless surgical operations and SH consequences.
详细描述
Subclinical hypercortisolism (SH) is a status of asymptomatic hypercortisolism, which is present in up to the 30% of patients with incidentally discovered adrenal adenomas (adrenal incidentalomas, AI). Since AI are present in 7-10% of individuals after 60 years of age, the estimated SH prevalence in this population is 0.8-2%. In patients with SH due to an adrenal adenoma the risk of diabetes, hypertension, cardiovascular events, osteoporosis and mortality seems to be increased, and monolateral adrenalectomy beneficial. However, no randomized studies evaluated the effects of surgery on SH consequences and established the criteria indicating the need of surgery itself. Thus, in many patients the SH diagnosis is uncertain and the best approach (surgical or conservative) unknown. These uncertainties are also due to the influence of the individual glucocorticoid (GC) sensitivity. Indeed, in the single individual the various polymorphisms of GC receptor (GR) and the different 11ß-hydroxysteroid-dehydrogenase type 2 enzyme (11HSD2) activity, regulating the tissue exposure to the active GC, may differently predispose to the consequences of GC excess. Therefore, in AI patients, beside the evaluation of the degree of the cortisol hypersecretion, the assessment of the cortisol sensitivity may be useful in establishing the individual risk of SH consequences and the possible usefulness of a surgical approach.
Specific Aim:
In AI subjects with uncertain SH the combined evaluation of the clinical features together with the parameters of cortisol secretion and sensitivity will consent to decide which patient has the greatest probability to ameliorate after surgery.
- To assess the variation of blood pressure control, lipids and glucose metabolism, vascular damage, bone mineral density (BMD), clinical and morphometric vertebral fractures, body composition, coagulation parameters, neuropsychological aspects and quality of life (QoL) in AI patients with uncertain SH after the surgical removal of the adrenal mass or after a conservative treatment.
- To assess in AI patients and uncertain hypercortisolism the effect of the surgical and conservative approach on cardiovascular, metabolic and bone manifestations, neuropsychological aspects and quality of life (QoL), in relation to the degree of cortisol secretion and sensitivity.
- To establish the best clinical-biochemical criteria for diagnosing SH, on the basis of the changes of the outcomes after the surgical or conservative approach, and therefore, for addressing the treatment of choice in the individual patient with AI.
Methods. During the enrollment period (24 months), all patients between 40 and 75 years of age referred for unilateral AI larger than 1 cm will be evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •unilateral adrenal incidentaloma larger than 1 cm
- •cortisol after 1-mg overnight dexamethasone suppression test (1mgDST) between 1.8 and 5 mcg/dl
排除标准
- •hypogonadism, thyrotoxicosis, chronic renal failure and hepatic disease, alcoholism, eating, rheumatologic or hematological disorders;
- •intake of drugs influencing cortisol and dexamethasone metabolism or cortisol secretion;
- •signs of hypercortisolism (moon facies, striae rubrae, easy bruising);
- •possible metastatic disease or radiologic features not consistent with adrenocortical adenoma at computed tomography (CT);
- •pheochromocytoma and aldosteronoma;
- •non-adrenal SH.
结局指标
主要结局
variation of blood pressure
时间窗: 6 months
To assess the variation of blood pressure ambulatory systolic and diastolic blood pressure (BP, mmHg), and antihypertensive treatment at baseline and follow-up will be assessed; BP will be considered improved or worsened if the non-hypertensive patients passed from a pre-hypertension category to another or the hypertensive patients from a hypertension grade to another in accordance to giudelines, of if if antihypertensive treatment was reduced by 50%
variation of glucose levels
时间窗: 6 months
To assess the variation of glucose levels, fasting glucose levels and glucose levels after oral glucose tolerance test will be evaluated at baseline and follow-up. Glucose levels will be considered improved or worsened if fasting glucose levels pass from a category to another, following the Adult Treatment Panel III criteria or if antidiabetic treatment was reduced by 50%
variation of lipids
时间窗: 6 months
At baseline and follow up triglyceride levels; total cholesterol levels, HDL and LDL levels (mg/dl) will be evaluated. Dyslipidemia will be diagnosed in the presence of triglyceride levels \>150 mg/dl or high-density lipoprotein (HDL) cholesterol levels \<40 or 50 mg/dl in males and females. dyslipidemia will be defined improved or worsened if cholesterol levels pass from a category to another, following the Adult Treatment Panel III criteria
variation of body weight
时间窗: 6 months
At baseline and follow up body weight (kilograms) will be evaluated. the improvement/worsening during follow-up will be defined in the presence of a \>5% BW decrease/increase
variation of bone mineral density (BMD)
时间窗: 24 months
To assess the variation of bone mineral density at baseline and follow-up a Dual-energy X-ray absorptiometry (DXA) scan will be performed
occurrence of vertebral fractures
时间窗: 24 months
A dorso-lumbar spine x-ray to evaluate the presence of morphometric fractures (presence/absence) will be performed
variation of intimal medial thickness
时间窗: 12 months
To assess the variation of vascular damage a supra-aortic trunk echo-Doppler to evaluate at baseline and follow-up variations of intimal medial thickness will be performed
variation of Relative wall thickness (RWT)
时间窗: 12 months
the variation of Relative wall thickness (RWT) will be evaluated by an echocardiography. It will be calculated from Left ventricular end diastolic dimension (LVEDD) (mm); Interventricular septal end diastole (IV Sd, mm) and Posterior wall thickness at end-diastole (PWd) parameters (mm)
variation of Sheehan Disability Scale
时间窗: 6 months
Sheehan Disability Scale will be evaluated to assess perceived stress (SDS-stress scale ranges 1-10, a higher score means higher levels of stress)
Cognitive evaluation by Brief Assessment Cognition in Schizophrenia (BACS) score
时间窗: 6 months
BACS evaluate verbal memory score (normal if \>33); working memory (normal if \>14.9); verbal fluency (normal if \>31.6), symbol coding (normal if \>40.5), tower of london (\>12.4)
次要结局
- cortisol secretion and sensitivity(24 months)
- variation of Inflammation markers and bone metabolism markers(6 months)
研究者
Iacopo Chiodini
Associate Professor of Endocrinology, MD
Istituto Auxologico Italiano