Impact of Adrenal IncidenTalomas and Possible Autonomous Cortisol Secretion on Cardiovascular and Metabolic Alterations

Study Overview
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Brief Summary
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The investigators hypothesize that cardiovascular and metabolic alterations can occur in patients with adrenal adenomas and possible Autonomous Cortisol Secretion (pACS). Investigators hypothesize that adrenalectomy in selected patients, following the 2016 ECE guidelines, can improve metabolic parameters and cardiovascular risks and features.

Detailed Description
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Adrenal incidentalomas are clinically silent masses discovered inadvertently during diagnostic imaging procedures performed for unrelated reasons. Depending on the criteria applied, up to 50% of patients with adrenal incidentalomas may have biochemical evidence of cortisol excess. Possible autonomous cortisol secretion (pACS), as defined in the 2016 European Society of Endocrinology Guidelines, is characterized by a partial, incomplete suppression of the hypothalamic-pituitary-adrenal (HPA) axis without the typical signs of overt cortisol hypersecretion. Investigators will perform a prospective longitudinal study in patients with adrenal incidentalomas associated with possible autonomous cortisol secretion, aiming to assess the effect of surgical and conservative management on cardiovascular and metabolic features. Data will be detected at baseline, at 1 and at 5 years follow-up to quantitatively identify the different cardiovascular and metabolic alterations in: (1) patients with non-functioning adrenal adenoma; (2) patients with possible autonomous cortisol secretion receiving conservative management; (3) patients with possible autonomous cortisol secretion receiving adrenalectomy according to the 2016 European Society of Endocrinology guidelines; (4) patients without adrenal masses.

Official Title
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Impact of Adrenal IncidenTalomas and Possible Autonomous Cortisol Secretion on Cardiovascular and Metabolic Alterations (ITACA Study)

Conditions
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Adrenal Tumor, Adrenal Incidentaloma, Hypercortisolism

Intervention / Treatment
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* Procedure: Adrenalectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Incidentally detected adrenal mass Exclusion Criteria: Patients with overt Cushing's syndrome, pheocromocytoma, Conn syndrome, adrenocortical carcinoma, late-onset congenital adrenal hyperplasia, adrenal metastasis and adrenal hemorrhage Patients taking medications influencing glucocorticoid production or metabolism Patients with psychiatric diseases or alcohol abuse Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with non-functioning adrenal adenoma<br>Patients with incidentally discovered adrenal mass with 1mg-DST serum cortisol levels lower than 50 nmol/L | |
| Patients with pACS receiving conservative management<br>Patients with incidentally discovered adrenal mass with 1mg-DST serum cortisol levels greater than 50 nmol/L receiving conservative management | |
| Patients with pACS receiving adrenalectomy<br>Patients with incidentally discovered adrenal mass with 1mg-DST serum cortisol levels greater than 50 nmol/L receiving adrenalectomy according to the 2016 European Society of Endocrinology guidelines | Procedure: Adrenalectomy<br>* Adrenalectomy accordint to 2016 ESE guidelines<br>|
| Healthy controls<br>Patients without adrenal masses | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Echocardiographic Change of Left Ventricular Hypertrophy | Change of Left Ventricular Hypertrophy will be evaluated by transtoracic echocardiography. Patients will be examined in the left lateral decubitus position according to the American Society of Echocardiography guidelines. | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of arterial stiffness and blood pressure using brachial oscillometric blood pressure waves for a noninvasive estimation. | Perform non-invasive measurement of arterial stiffness | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Change of blood pressure using ambulatory blood pressure monitoring blood pressure waves for a noninvasive estimation. | Perform twenty-four-hour systolic and diastolic ambulatory blood pressure monitoring | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Change in blood Coagulation Tests | Perform blood sampling for coagulative function | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Change in Dual X-Ray Absorptiometry T-score | Bone mineral density change in spine and femur | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Radiological evaluation of adrenal mass | Perform adrenal chemical shift MRI or adrenal CT scan (if MRI is contraindicated) | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Evaluation of sleep disturbances using questionnaire (PSQI) | Perform the Pittsburgh Sleep Quality Index (PSQI). Sleep disturbances will be evaluated by The Pittsburgh Sleep Quality Index (PSQI). This questionnaire contains 19 self-related questions which are combined to create 7 component scores with a range of 0-3 points (0:no difficulty, 3: severe difficulty). Global score is the result to the addition of all component scores with a range of 0-21 points (0:no difficulty, 21: severe difficulty). | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Infectious diseases frequency and severity with modified German Diseases Questionnaire | Frequencies and severity of infectious diseases will be evaluated by modified Infectious Diseases Questionnaire (GNC). This questionnaire includes questions on infectious diseases of upper and lower respiratory tract, gastrointestinal tract, skin and urogenital tract and flu contracted during the previous 12 months. Questions investigate on the number and duration of infections, necessity of antibiotic or antifungal therapy, hospital stay and days of absence from work. Final score represents the frequency of infections. | Baseline (T0), after 1 year (t1) and 5 years (t2) | 
| Quality of life: SF-36-Item Health Survey questionnaire | Quality of life will be evaluated by the Physical Component score and the Mental Component score of the self-administered questionnaire SF-36-Item Health Survey questionnaire. This questionnaire measures eight scales: physical functioning, role physical, bodily pain, general health (physical component) and vitality, social functioning, role emotional, mental health (mental component). Interpretation of the score will be the following: at each item of the questionnaire corresponds a percentage value (from 0% to 100%). The average of the single items constitutes the scale total percentage (from 0% to 100%); missing data are not considered during calculation. High score defines a more favorable health state. | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Psychometric Evaluation: Beck Depression Inventory questionnaire | Psychometric evaluation will be assessed by the score of Beck depression Index: a 21-item measure of depressive symptoms. Each answer is scored on a scale value (from 0 to 3 points). The global score is obtained adding all single scores, with a range of 0-63. Higher score constitutes worse burden of symptoms (0-13: minimal depression, 14-19: mild depression, 20-28: moderate depression, 29-63: severe depression). | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Evaluation of sexual dysfunction using FSFI questionnaire in woman | Perform the Female Sexual Function Index (FSFI) questionnaire. This is a 19-item questionnaire that covers six domains: desire, arousal, lubrication, and orgasm, satisfaction, and pain. The ranges of the domain scores are as follows: for desire 1.2 - 6.0, for arousal, lubrication, orgasm and pain 0 - 6.0 and for satisfaction 0.8 - 6.0. The higher scores of the six domains indicate better sexual functioning about that domain. The overall FSFI score is obtained by summing the six domain scores. The overall FSFI scores range from 2.0 to 36.0, with higher scores indicating better sexual functioning. | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Evaluation of sexual dysfunction using IIEF questionnaire in man | Perform the International Index of Erectile Function (IIEF) questionnaire in man. The IIEF is an internationally validated test. It is used to assign a score of erectile dysfunction: severe score 1 to 10; moderate score 11 to 16; low to moderate score 17 to 21; Low score 22 to 25; no erectile dysfunction score 26 to 30 | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Change in insuline resistance calculated with HOMA index | Measurement of HOMA index calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Change in measurement of weight | Measurement of body weight (kg) | at Baseline (T0) and after 1 year (t1) and 5 years (t2) | 
| Change in blood lipid profile | Measurement of Total Cholesterol, LDL cholesterol, HDL cholesterol, Triglyceredes | at Baseline (T0) and after 1 year (t1) and 5 years (t2) |