Endoscopic Ultrasound-guided Radiofrequency Ablation as a Novel Treatment Option Compared With Adrenalectomy in Left-sided Primary Aldosteronism
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 60
- Locations
- 2
- Primary Endpoint
- Biochemical outcome in PA after EUS-RFA
Study Overview
Brief Summary
In this study, the investigators will perform endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) treatment of left-sided adrenal tumours in patients with primary aldosteronism (PA) and in patients with mild autonomous cortisol secretion (MACS). Four different study groups will all receive EUS-RFA of left-sided adrenal tumours. Clinical and biochemical outcome as well as procedural safety will be evaluated. In study patients with verified lateralised aldosterone or cortisol overproduction to the left adrenal, outcome will be compared with control groups performing conventional unilateral adrenalectomy.
Study group 1: PA patients with AVS-verified left sided lateralisation and a EUS-detectable tumour in the left adrenal for EUS-RFA treatment.
Study group 2: PA patient with suspected left-sided overweight of aldosterone production and a EUS-detectable tumour but without strict lateralisation of their aldosterone overproduction, for EUS-RFA treatment as an aldosterone "debulking" procedure.
Study group 3: patients with MACS with AVS-verified lateralisation of cortisol overproduction to the left adrenal and EUS-detectable tumour for EUS-RFA treatment Study group 4: patients with MACS with bilateral adrenal tumours and verified bilateral overproduction of cortisol for EUS-RFA treatment as a cortisol "debulking" procedure.
Detailed Description
Primary aldosteronism (PA) is the most common cause of secondary hypertension, and is associated with worse cardiovascular outcome than primary hypertension. Early diagnosis and treatment is paramount to avoid excess morbidity and death. The two main forms of PA are unilateral PA, often caused by an aldosterone-producing adenoma (APA), and bilateral PA. Differentiation between unilateral and bilateral disease determines treatment options. Adrenal vein sampling (AVS) is the recommended procedure to determine PA subtype, unilateral or bilateral. For unilateral PA surgery with unilateral adrenalectomy is recommended treatment. For PA without fulfilling lateralisation criteria, life-long medical treatment is recommended.
Mild autonomous cortisol production (MACS) is present in 20-30% of all adrenal incidentalomas, and is associated with the metabolic syndrome (hypertension, diabetes, obesity and osteoporosis). Therefore these patients carry increased risk of developing cardiovascular disease. Optimal treatment is debated, and based on the degree of MACS, degree of metabolic complications, and the patient's own opinion. Unilateral adrenalectomy is an option if the overproduction is unilateral, but in 15 % of cases, the overproduction is bilateral, and treatment strategy even more troublesome.
The left adrenal is situated in near proximity to the stomach and is easily reached by endoscopic ultrasound (EUS), and may be targeted for RFA, treating an aldosterone- or cortisol-producing tumour only, and spearing the remaining adrenal. In this study we introduce EUS-RFA as a new treatment option in the following patient groups:
Study group 1: PA patients with AVS-verified left sided lateralisation and a EUS-detectable tumour in the left adrenal for EUS-RFA treatment.
Study group 2: PA patient with suspected left-sided overweight of aldosterone production and a EUS-detectable tumour but without strict lateralisation of their aldosterone overproduction, for EUS-RFA treatment as an aldosterone "debulking" procedure.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Signed written informed consent
- •If CT scan shows an adrenal nodule to the same adrenal as AVS lateralisation result: nodule size < 4 cm and enhancement criteria for adrenal adenoma (native hounsfield units < 10 or relative wash-out > 40% or absolute wash-out > 60%)
- •PA unilateral group inclusion criteria:
- •Age 18 to 60 years
- •PA diagnosis confirmed according to Endocrine Society PA Guideline criteria
- •AVS lateralisation to left adrenal (lateralisation index ≥ 4,0)
- •PA "debulking" group inclusion criteria:
- •Age 18 to 70 years
- •PA diagnosis confirmed according to Endocrine Society PA Guideline criteria
- •MACS unilateral and debulking group inclusion criteria:
- •Age 18 to 80 years
- •MACS diagnosis confirmed according to ENSAT/ECE Guideline criteria
- •AVS lateralisation to the left adrenal, and visible left adrenal tumor on CT scan OR bilateral overproduction of cortisol on AVS, and bilateral tumors/hyperplasia on CT scan (debulking)
Exclusion Criteria
- •all groups:
- •CT scan suspicion of adrenal malignancy
- •Patient refusal to undergo either EUS-RFA or adrenalectomy
Arms & Interventions
EUS-RFA of PA with AVS-verified left lateralisation
PA patients with AVS-confirmed lateralisation to the left adrenal and signed study consent will be included in this study group. EUS will be performed. If EUS identifies an adrenal nodule in the left adrenal, EUS-guided fine needle tissue sampling of the adenoma will be performed, before a subsequent EUS-RFA treatment procedure will be performed. Follow-up after 2 weeks, 3 months and 12 months for evaluation of clinical and biochemical outcome, and procedural complications.
Intervention: EUS-RFA of left adrenal tumour in PA with AVS-verified left lateralisation (Procedure)
EUS-RFA of PA without verified left lateralisation, for aldosterone "debulking"
PA patients with suspicion of aldosterone overproduction in their left adrenal, but without fulfilling the strict AVS lateralization criteria, either due to a non-representative AVS, or a representative AVS but without significant left-sided lateralization (LI < 4), and where the study investigators consider EUS-RFA treatment as an aldosterone-reducing procedure to be of high potential clinical and biochemical benefit for the patient, will be included in this study group after signed consent. EUS will be performed. If EUS identifies an adrenal nodule in the left adrenal, an EUS-guided fine needle tissue sampling of the adenoma will be performed, before a subsequent EUS-RFA treatment procedure. Follow-up after 2 weeks, 3 months and 12 months for evaluation of clinical and biochemical outcome, and procedural complications.
Intervention: EUS-RFA of left adrenal tumour in PA, "debulking group" (Procedure)
EUS-RFA of MACS with left lateralisation and left adrenal tumour
MACS patients with AVS-confirmed lateralisation the left adrenal gland and CT showing left-sided tumour will be included in this study group after signed consent. EUS will be performed, and a EUS-guided fine needle tissue sampling of the adenoma will be performed, before a subsequent EUS-RFA treatment procedure. Follow-up after 2 weeks, 3 months and 12 months for evaluation of clinical and biochemical outcome, and procedural complications.
Intervention: EUS-RFA of left adrenal tumour in MACS with AVS-verified left lateralisation (Procedure)
EUS-RFA of MACS with bilateral cortisol overproduction and bilateral tumours
MACS patients with AVS-confirmed bilateral cortisol overproduction and bilateral tumours will be included in this study group after signed study consent. EUS will be performed, and EUS-guided fine needle tissue sampling of the adenoma will be performed, before a subsequent EUS-RFA treatment procedure. Follow-up after 2 weeks, 3 months and 12 months for evaluation of clinical and biochemical outcome, and procedural complications.
Intervention: EUS-RFA of left adrenal tumour in MACS with bilateral overproduction, "debulking group (Procedure)
Outcomes
Primary Outcomes
Biochemical outcome in PA after EUS-RFA
Time Frame: 1 year
Biochemical outcome will be evaluated by international standardised "Primary aldosteronism surgery outcome" (PASO) criteria at follow-up visits after 3 and 1 year
Clinical outcome in PA after EUS-RFA
Time Frame: 1 year
Clinical outcome will be evaluated by international standardised PASO criteria at follow-up visits after 1 year
Biochemical outcome in MACS after EUS-RFA
Time Frame: 1 year
Biochemical outcome will be evaluated at follow-up visits after 3 and 1 year, evaluated by the international European Network for Study of Adrenal Tumour (ENSAT) /European Society of Endocrinology (ESE) criteria
Clinical outcome in MACS after EUS-RFA
Time Frame: 1 year
Clinical outcome will be evaluated at follow-up visits after 3 and 1 year, evaluated by the international ENSAT/ESE criteria
Secondary Outcomes
- Change from baseline in health-related quality of life at 1 year(1 year)
- Number of participants with procedural complications of EUS-RFA compared with unilateral adrenalectomy(3 months)
- Number of participants with postoperative hypoaldosteronism(3 months)
- Number of participants with postoperative hypocortisolism(6 weeks)
- Length of hospital stay after EUS-RFA compared with after adrenalectomy(3 months)