Surgery of Subclinical Cortisol Secreting Adrenal Incidentalomas

Condition(s) targeted: Adrenal Incidentalomas

Intervention: Laparoscopic surgical removal of the adrenal tumor (Procedure); Standardized medical treatment of hypertension by SAHR (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: University Hospital, Bordeaux

Official(s) and/or principal investigator(s):
Paul PEREZ, Doctor, Study Chair, Affiliation: University Hospital, Bordeaux

Overall contact:
Antoine TABARIN, Professor, Phone: +33 5 57 65 64 33, Email: antoine.tabarin@chu-bordeaux.fr

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.

Official title: Surgery of Subclinical Cortisol Secreting Adrenal Incidentalomas

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Blood pressure value and SAHR step 12 months after inclusion

Secondary outcome:

Antihypertensive treatment score and daily drug dose

Incidence of complications in the two strategies.

Direct costs of the two strategies.

Assessment of predictive factors for the success of surgery on BP

number of patients requiring antihypertensive treatment

24 hours ambulatory blood pressure monitoring values

Blood glucose and lipid lowering agents values

Cardiovascular risk factors/markers level

Number of patients with persistent diabetes, dyslipidemia and metabolic syndrome

Evaluation of quality of life

Detailed 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.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Age ≤ 80 years.

- Incidentally discovered unilateral SCSI:

- Adrenocortical tumor on CT (spontaneous density < 20 HU and/or relative wash-out

> 40%, absolute wash-out > 60% ) and > 2 cm in size.

- Impaired DST (cortisol > 138 nmol/L or 5 µg/dL)

OR • Impaired DST (cortisol > 50 83 nmol/L or 1,8 3 µg/dL) AND one biological abnormality of the corticotropic axis at study entry:

- 8 a. m. plasma ACTH < 2. 2 pmol/L (10 pg/ml),

- In case of ACTH at 8 a. m. between 10 and 20 pg/mL (2. 2 and 4. 4 pmol/L), peak of ACTH

< 30 pg/mL (6. 6 pmol/L) after a CRH test

- midnight cortisol > 150 nmol/L (5. 4 µg/dL)

- elevated late-evening salivary cortisol according to the range of the assay

- increased 24-hour free urinary cortisol but <2. 0-fold the laboratory upper normal

limit.

- Systolic or diastolic hypertension treated

OR

- Systolic or diastolic hypertension (> 135/85 mmHg) not treated assessed on standard

blood pressure self-measurement device.

- Written informed consent signed by patient and investigator

Exclusion Criteria:

- Age > 80 years.

- Bilateral incidentaloma.

- Incidentally adrenocortical tumor < 2 cm

- History of myocardial infarction, pulmonary edema or stroke during the previous year

- Malignant hypertension (> 175-115 mm Hg on self-measurement)

- Beta-blocker treatment that cannot be suspended.

- Free urinary cortisol > 2. 0-fold upper normal limit

- 08h00 plasma ACTH concentration > 4. 4 pmol/L (20 pg/ml)

- Chronic renal insufficiency (clearance < 30 mL/min)

- Exogenous corticosteroid treatment by general or local route (inhaled, eye or ear

drops , ophthalmic ointment, topical skin application, ear infiltration) during the 6 months before the trial OR • Need for Corticosteroid treatment OR • Medication interfering with dexamethasone metabolism.(54)

- Pregnancy

- Life-threatening pathology (in the short term)

- Contra-indications to surgery

- Lack of control of blood pressure at the end of the Run-In period

- Dissipation of the biological endocrine criteria for SCSI at the end of the Run-In

period

Antoine TABARIN, Professor, Phone: +33 5 57 65 64 33, Email: antoine.tabarin@chu-bordeaux.fr

Service de Médecine Interne, Endocrinologie et Nutrition - CHU de Strasbourg, Strasbourg, Alsace 67000, France; Not yet recruiting
Bernard GOICHOT, Professor, Phone: +33 3 88 12 75 93, Email: Bernard.Goichot@chru-strasbourg.fr

Service Endocrinologie, Diabétologie, maladies métaboliques - CHU de Bordeaux, Pessac, Aquitaine 33600, France; Recruiting
Antoine TABARIN, Professor, Phone: +33 5 57 65 64 33, Email: antoine.tabarin@chu-bordeaux.fr
Sarah CAZENAVE, Phone: +33 5 57 65 62 77, Email: sarah.cazenave@chu-bordeaux.fr

Service d'Endocrinologie - Niveau 18 - Caen CHU Côte de Nacre, Caen, Basse-Normandie 14000, France; Not yet recruiting
Yves REZNIK, Professor, Phone: +33 2 31 06 45 86, Email: reznik-y@chu-caen.fr

Service d'Endocrinologie -Diabète-Nutrition - CHU de REIMS, Reims, Champagne-Ardenne 51000, France; Not yet recruiting
Brigitte DELEMER, Doctor, Phone: +33 3 26 78 81 01, Email: bdelemer@chu-reims.fr

Endocrinologie, Diabète et Maladies Métaboliques - CHU de Rouen, Rouen, Haute-Normandie 76000, France; Not yet recruiting
Hervé LEFEBVRE, Professor, Phone: +33 2 32 88 90 81, Email: Herve.Lefebvre@chu-rouen.fr

Service d'Endocrinologie et des Maladies de la Reproduction- Assistance Publique - Hôpitaux de Paris - Hôpial Bicêtre, Le Kremlin Bicêtre, Ile de France 94275, France; Not yet recruiting
Jacques YOUNG, Email: jacques.young@bct.ap-hop-paris.fr

Assistance Publique - Hôpitaux de Paris - Hôpital COCHIN, Paris, Ile de France 75014, France; Not yet recruiting
Jérôme BERTHERAT, Professor, Phone: +33 1 58 41 18 95, Email: jerome.bertherat@ch.aphp.fr

Service d'Endocrinologie et Gynécologie - Assistance Publique - Hôpitaux de Paris - Pitié-Salpêtrière, Paris, Ile de France 75651, France; Not yet recruiting
Philippe TOURAINE, Professor, Phone: +33 1 42 16 02 54, Email: philippe.touraine@psl.aphp.fr

Service d'Hypertension et de Médecine Vasculaire - Assistance Publique - Hôpitaux de Paris - Hôpital européen Georges Pompidou, Paris, Ile de France 75908, France; Not yet recruiting
Pierre-François PLOUIN, Professor, Phone: +33 1 56 09 37 71, Email: pierre-francois.plouin@egp.aphp.fr

Service d'Endocrinologie - CHU de Nancy, Nancy, Lorraine 54000, France; Not yet recruiting
Georges WERYHA, Professor, Phone: +33 3 83 15 35 05, Email: g.weryha@chu-nancy.fr

Service d'Endocrinologie et Maladies Métabolique - CHU de Toulouse, Toulouse, Midi-Pyrénées 31000, France; Not yet recruiting
Philippe CARON, Professor, Phone: +33 5 67 77 17 01, Email: caron.p@chu-toulouse.fr

Service d'Endocrinologie, Diabétologie et Métabolisme - CHRU de LILLE, Lille, Nord-Pas-de-Calais 59000, France; Not yet recruiting
Marie-Christine VANTYGHEM, Professor, Phone: +33 3 20 44 45 35, Email: mc-vantyghem@chru-lille.fr

Département Endocrinologie-Diabétologie -Nutrition - CHU d'ANGERS, Angers, Pays de la Loire 49000, France; Not yet recruiting
Sandrine LABOUREAU-SOARES, Doctor, Phone: +33 2 41 35 45 93, Email: sasoares@chu-angers.fr

CIC Endocrinologie-Nutrition - CHU de Nantes, Nantes, Pays de la Loire 44000, France; Not yet recruiting
Bertrand CARIOU, Professor, Phone: +33 2 53 48 27 07, Email: bertrand.cariou@univ-nantes.fr

Service d'Endocrinologie, Diabète et Maladies Métaboliques - Assistance publique - Hôpitaux de Marseille, Marseille, Provence-Alpes-Côte d'Azur 13000, France; Not yet recruiting
Thierry BRUE, Professor, Phone: +33 4 91 38 65 97, Email: Thierry.BRUE@ap-hm.fr

Service Endocrinologie - CHU de Saint-Etienne, Saint-Etienne, Rhône-Alpes 42000, France; Not yet recruiting
Natacha GERMAIN-ZITO, Professor, Phone: +33 4 77 12 77 27, Email: natacha.germain@chu-st-etienne.fr

Starting date: January 2015
Last updated: February 13, 2015