Surgery of Subclinical Cortisol Secreting Adrenal Incidentalomas

Adrenal Incidentalomas Clinical Trial

— CHIRACIC  

Official title:

Surgery of Subclinical Cortisol Secreting Adrenal Incidentalomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02364089
• Other study ID #: CHUBX 2012/34
• Status: Completed
• Phase: N/A
• Start date: April 9, 2015
• Est. completion date: November 23, 2022

Study information

• Verified date: July 2023
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: November 23, 2022
• Est. primary completion date: March 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Adrenal Gland Neoplasms
• Adrenal Incidentalomas
• Adrenocortical Adenoma

Intervention

Procedure:
• Laparoscopic surgical removal of the adrenal tumor

Drug:
• Standardized medical treatment of hypertension by SAHR
Standardized anti-hypertensive drug regimen has been established according to international recommendations and includes the following steps: step 1: Angiotensin converting enzyme inhibitor (ACE-I) or angiotensin II receptor antagonist (ARBs) at half-dose (Ranipril 5mg or Ibesartan 150 mg ) step 2: CEI or ARA2 at full dose (Ranipril 10 mg or Ibesartan 300 mg) step 3: Add-on of Amlodipine 10 mg or Diltiazem LP 300 mg step 4: Add-on of Indapamide LP 1.5 mg step 5: Add-on of Spironolactone 25 mg step 6: Add-on of Bisoprolol 10 mg step 7: Add-on of Prazosine LP 5mg/day.

Locations

Country	Name	City	State
France	Service d'Endocrinologie, Diabétologie, Nutrition - CHU d'Amiens	Amiens	Haut De France
France	Département Endocrinologie-Diabétologie -Nutrition - CHU d'ANGERS	Angers	Pays De La Loire
France	Service d'Endocrinologie - Niveau 18 - Caen CHU Côte de Nacre	Caen	Basse-Normandie
France	Service d'Endocrinologie et des Maladies de la Reproduction- Assistance Publique - Hôpitaux de Paris - Hôpial Bicêtre	Le Kremlin Bicêtre	ILE DE France
France	Service d'Endocrinologie, Diabétologie et Métabolisme - CHRU de LILLE	Lille	Nord-Pas-de-Calais
France	Service d'Endocrinologie, Diabète et Maladies Métaboliques - Assistance publique - Hôpitaux de Marseille	Marseille	Provence-Alpes-Côte d'Azur
France	CIC Endocrinologie-Nutrition - CHU de Nantes	Nantes	Pays De La Loire
France	Assistance Publique - Hôpitaux de Paris - Hôpital COCHIN	Paris	ILE DE France
France	Service d'Hypertension et de Médecine Vasculaire - Assistance Publique - Hôpitaux de Paris - Hôpital européen Georges Pompidou	Paris	ILE DE France
France	Service Endocrinologie, Diabétologie, maladies métaboliques - CHU de Bordeaux	Pessac	Aquitaine
France	CHU de Poitiers	Poitiers
France	Endocrinologie, Diabète et Maladies Métaboliques - CHU de Rouen	Rouen	Haute-Normandie
France	Service de Médecine Interne, Endocrinologie et Nutrition - CHU de Strasbourg	Strasbourg	Alsace
France	Service d'Endocrinologie et Maladies Métabolique - CHU de Toulouse	Toulouse	Midi-Pyrénées
Germany	Endokrinologie, Diabetes und Ernährungsmedizin, Campus Mitte, Medizinische Klinik - Charité - Universitätsmedizin Berlin	Berlin
Germany	Department of Internal Medicine I, Endocrine and Diabetes Uni -University Hospital Würzburg	Würzburg
Italy	S Orsola-Malpighi Hospital	Bologna

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Countries where clinical trial is conducted

France,  Germany,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Blood pressure value and SAHR step 12 months after inclusion	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.	13 months
Secondary	Antihypertensive treatment score and daily drug dose		12 months
Secondary	Incidence of complications in the two strategies.		12 months
Secondary	Direct costs of the two strategies.		12 months
Secondary	Assessment of predictive factors for the success of surgery on BP	age, family history of hypertension, duration of hypertension, kidney function, biochemical endocrine abnormalities, urinary steroid profile	12 months
Secondary	number of patients requiring antihypertensive treatment		12 months
Secondary	24 hours ambulatory blood pressure monitoring values		At inclusion (day 0) and at 12 months
Secondary	Blood glucose and lipid lowering agents values		12 months
Secondary	Cardiovascular risk factors/markers level	Comparison of the two therapeutic strategies with regard to cardiovascular risk factors/markers: BMI, body composition evaluated by DEXA, abdominal fat evaluated on CT-scan, fasting blood glucose and insulin, HbA1C, HOMA-IR (homeostasis model of assessment of insulin resistance) and OGTT (oral glucose tolerance test), blood lipids, pro-inflammatory adipokines	12 months
Secondary	Number of patients with persistent diabetes, dyslipidemia and metabolic syndrome		12 months
Secondary	Evaluation of quality of life	Comparison of the two therapeutic strategies with regard to quality of life	At inclusion and 12 months