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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Adrenal Tumor; Adrenal Incidentaloma; Hypercortisolism
• Intervention / Treatment: Procedure: Adrenalectomy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Anticipated): 68

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00161
    • Recruiting
    • Department of Experimental Medicine
    • Contact: Andrea M Isidori, MD, PhD; Phone Number: +390649970711; Email: andrea.isidori@uniroma1.it
    • Sub-Investigator: Marianna Minnetti
    • Sub-Investigator: Emilia Sbardella

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with non-functioning adrenal incidentalomas or adrenal incidentalomas associated with possible autonomous cortisol secretion (subclinical hypercortisolism)

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with non-functioning adrenal adenoma; Patients with incidentally discovered adrenal mass with 1mg-DST serum cortisol levels lower than 50 nmol/L
Patients with pACS receiving conservative management; 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; 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; Adrenalectomy accordint to 2016 ESE guidelines
Healthy controls; Patients without adrenal masses

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Investigators: Principal Investigator: Andrea M Isidori, MD, PHD, Sapienza

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2019
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): March 31, 2025

Study Registration Dates

• First Submitted: October 6, 2019
• First Submitted That Met QC Criteria: October 11, 2019
• First Posted (Actual): October 15, 2019

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Adrenal Gland Diseases; Adrenal Cortex Neoplasms; Adrenal Cortex Diseases; Cushing Syndrome; Adrenocortical Hyperfunction; Adrenal Gland Neoplasms; Adrenocortical Adenoma
• Other Study ID Numbers: ITACA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No