Overnight Dexamethasone in Primary Aldosteronism Screening in Patients on Interfering Therapy (the ODEPRASC Study)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Medical University of Gdansk
- Enrollment
- 240
- Locations
- 1
- Primary Endpoint
- Overall diagnostic accuracy of post-DXM ARR
Study Overview
Brief Summary
The goal of this observational study is to learn whether screening for primary aldosteronism can be improved among patients on chronic blood pressure-lowering medications by ordering intake of 1 mg of dexamethasone prior to hormonal examinations.
Primary aldosteronism is a condition, in which an adrenal gland steroid aldosterone is released in excessive amounts; it commonly causes hypertension but requires specific therapy different from usually prescribed in other forms of hypertension.
Dexamethasone is a synthetic steroid used for both therapeutic and diagnostic purposes. A single 1 mg dexamethasone dose taken at 11 p.m. in order to measure hormone concentrations the following morning (so called overnight 1-mg dexamethasone test) is a commonly applied test in the work-up of adrenal disorders.
The main question the project aims to answer is:
Can screening for primary aldosteronism be improved among patients receiving blood pressure-lowering medications with overnight 1-mg dexamethasone intake?
Participants will undergo changes in their chronic medication to be able to definitely rule out or confirm primary aldosteronism in blood hormonal examinations. These modifications and modifications are not part of the research project.
For this project participants will be asked to
- undergo the 1-mg dexamethasone test one to three times in order to compare hormonal concentrations before and after it,
- collect urine for 24 hours to determine aldosterone in the urine sample after medications interfering in aldosterone release are temporarily withdrawn.
Detailed Description
Background Primary aldosteronism (PA) underlies or contributes to hypertension (HT) in up to 30% of patients. In the last two decades PA has been demonstrated to encompass mild forms, which do not meet established diagnostic criteria, yet are still clinically relevant. However, PA has been shown to be vastly underdiagnosed: less than 5% of patients from at-risk populations undergo screening.
One of the main reasons for low PA screening prevalence is the recommendation of hypotensive therapy modification prior to hormonal assessment, i.e. withdrawal of medications interfering in the renin-angiotensin-aldosterone system (RAAS) (2016 Endocrine Society guideline, 2020 European Society of Hypertension consensus statement). On the other hand, in many instances, PA may be diagnosed despite treatment with RAAS-interfering drugs.
Previous research showed efficacy in the diagnostic approach toward PA can be greatly improved by incorporating adrenocorticotropic hormone (ACTH) suppression. This was achieved by determining PA screening and confirmatory thresholds following a 2-day 2-mg/day dexamethasone (DXM) test. Patients diagnosed with PA by meeting these novel diagnostic criteria responded well to mineralocorticoid receptor antagonists.
These two diagnostic approaches (work-up in patients receiving RAAS-interfering drugs along with ACTH suppression) have not been combined so far.
Aim To generate and temporally validate PA screening thresholds (aldosterone-to-renin ratio, ARR, and aldosterone, Ald) among patients with HT receiving medications interfering in the RAAS by applying overnight ACTH suppression.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Other
Eligibility Criteria
- Ages
- 40 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •suspected or diagnosed HT,
- •age between 40 and 75,
- •available aldosterone and renin result at the time of one-day clinic stay,
- •scheduled 1-mg-DXM test (indicated for possible mild autonomous cortisol secretion, MACS),
- •presence of an adrenal lesion with radiologic features of adrenocortical adenoma/hyperplasia.
Exclusion Criteria
- •baseline (pre-DXM) hyperreninemia (renin exceeding the upper limit of normal at the study site, i.e. 46.1 mIU/l, assay manufacturer: Diasorin),
- •baseline (pre-DXM) Ald<3 ng/dl,
- •overt clinical and/or biochemical features of adrenal hormone deficiency or excess other than MACS (8 a.m. cortisolemia in the 50-140 nmol/l range in the 1-mg DXM test),
- •therapy with glucocorticoids, non-steroidal anti-inflammatory drugs, hormonal replacement therapy, hormonal contraceptive therapy, and/or licorice intake,
- •established or suspected secondary HT other than due to PA,
- •comorbidities including: poorly controlled and/or other than type 2 diabetes mellitus (T2DM), present and past alcohol abuse, obesity grade 3 (i.e. body mass index of at least 40 kg/m2), severe CV disease disqualifying a patient from chronic medication modification, active malignancy, decompensated autoimmune disease as well as an autoimmune disease associated with cardiovascular and/or renal complications, estimated glomerular filtration rate (eGFR) below 45 ml/min/1.73m2, poor physical condition, lack and withdrawal of consent for participation.
Outcomes
Primary Outcomes
Overall diagnostic accuracy of post-DXM ARR
Time Frame: 24 months
percentage of correctly categorized patients with hypertension on RAAS-interfering medications as either with clear or unclear PA screening threshold base on post-DXM ARR determination
Secondary Outcomes
- Association between post-DXM ARR and 24-h urinary aldosteronuria in the oral salt loading test(24 months)