Surgery of Subclinical Cortisol Secreting Adrenal Incidentalomas
Condition: Adrenal Incidentalomas
MeSH terms: Adrenocortical Adenoma; Adrenal Gland Neoplasms
Study type: Interventional

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.
    

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.
    

Intervention name(s): Laparoscopic surgical removal of the adrenal tumor; Standardized medical treatment of hypertension by SAHR
Intervention type(s): Procedure; Drug
Intervention description(s): 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.
Intervention MeSH terms: Epinephrine; Racepinephrine; Epinephryl borate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Adrenal Incidentaloma; Subclinical Cushing's syndrome; Hypertension; Cardiovascular Risk Factors; Metabolic Syndrome; Surgery of adrenal tumor