Hyperaldosteronism; Primary, Primary Aldosteronism Due to Aldosterone Producing Adenoma
Conditions
Keywords
Hybrid hormone, Subtyping, adrenalectomy, adrenal vein sampling, biomarkers, steroid profiling
Brief summary
The goal of this project is to improve the diagnostic pathway for patients with primary aldosteronism, by validating non-invasive biomarkers coupled with routine computed tomography imaging. The aim is to reduce reliance on invasive procedures, shorten diagnostic timelines, and enhance accessibility to definitive diagnosis and treatment globally.
Detailed description
Primary Aldosteronism is a common but under-diagnosed condition, despite being a curable cause of secondary hypertension with significant long-term health consequences if left untreated. Once the diagnosis of primary aldosteronism is confirmed, subtype tests are required to demonstrate unilateral primary aldosteronism before curative surgery. Most patients need to undergo adrenal vein sampling, an invasive procedure performed under radiological guidance. However, this procedure is technically-challenging, with failure to cannulate both adrenal veins frequently leading to inconclusive results. Many patients worldwide may be offered surgery based on computed tomography imaging alone because of a lack of adrenal vein sampling expertise or a failed adrenal vein sampling result. High hybrid hormones indicate a functional KCNJ5-mutant aldosterone-producing adenoma and, when coupled with computed tomography imaging, may provide a non-invasive alternative to adrenal vein sampling for identifying unilateral primary aldosteronism. Ultimately, this trial aims to reduce the number of patients that will require an invasive adrenal vein sampling in future clinical diagnostics. This will improve access, and allow more patients to receive timely and curative treatment.
Interventions
DIAGNOSTIC_TESTHybrid hormones
Participants will have a baseline blood sample taken so the investigators can measure the adrenal steroid biomarkers 18-oxocortisol, 18-hydroxylcortisol and other steroids. The collected plasma or serum will then be analyzed in the laboratory using validated methods, such as liquid chromatography-tandem mass spectrometry (LC-MS/MS), to determine the levels of these biomarkers.
Sponsors
Singapore General Hospital
Sengkang General Hospital
National University Hospital, Singapore
Changi General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
The investigators will prospectively recruit participants with primary aldosteronism who are keen for surgery if unilateral disease is diagnosed. Participants will undergo both routine subtyping (adrenal vein sampling and/or molecular imaging) and research subtyping (blood tests for hybrid hormone coupled with computed tomography). All results will be reviewed at a multi-disciplinary meeting, with computed tomography discussed first (radiologist will be masked to results of hybrid hormones and adrenal vein sampling), then hybrid hormones, then adrenal vein sampling. Participants with either adrenal vein sampling lateralization, or elevated hybrid hormones with a unilateral adrenal nodule and normal contralateral gland on computed tomography will be offered surgery. All participants will be re-evaluated post-surgery for biochemical cure of primary aldosteronism (co-primary outcome). Genetic sequencing will be performed on resected adrenals for KCNJ5 mutation (co-primary outcome).
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of primary aldosteronism according to the Endocrine Society guideline 2025. * Willing to undergo subtype testing with adrenal vein sampling and/or molecular imaging (Positron Emission Tomography/Computed Tomography, PET/CT). * Keen for surgical treatment if shown to have unilateral primary aldosteronism.
Exclusion criteria
* Inability to provide written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with complete biochemical success after unilateral adrenalectomy for unilateral primary aldosteronism using Primary Aldosteronism Surgical Outcome (PASO) measured at least six months post-adrenalectomy. | 6 months | Proportion of participants with correction of hypokalaemia and normalisation of aldosterone-renin-ratio following unilateral adrenalectomy, as per PASO criteria. |
| Proportion of participants with KCNJ5-mutant aldosterone producing adenoma/nodule | 6 months | Proportion of participants with histopathology and genetic confirmation of KCNJ5-mutant aldosterone producing adenoma/nodule in resected adrenals. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants with complete clinical success after unilateral adrenalectomy for unilateral primary aldosteronism using Primary Aldosteronism Surgical Outcome (PASO) measured at least six months post-adrenalectomy. | 6 months | Proportion of participants with reduction in blood pressure and reduction anti-hypertensive medication following unilateral adrenalectomy, as per PASO criteria. |
| Cost-effectiveness of using hybrid hormones coupled with computed tomography imaging versus other subtyping tests including adrenal vein sampling and/or molecular imaging in diagnosing participants with unilateral primary aldosteronism | 6 months | Cost-effectiveness of the diagnostic course will be calculated by using calculated costs per quality-adjusted life years (QALYs) |
| Diagnostic criteria using hybrid hormones/ steroid profiling coupled with computed tomography imaging | 6 months | The criteria of hybrid hormones/ steroid profiling coupled with computed tomography imaging which offer the best sensitivity and specificity for lateralization of aldosterone-producing adenoma. |
Countries
Singapore
Contacts
Primary ContactTroy H Puar, FRCP, PhD
Outcome results
None listed