Overnight Dexamethasone in Primary Aldosteronism Screening

NCT06740838 | Recruiting

• 1 other identifier: NKBBN 287-76/2021
• Study Type: observational
• Target: 240
• Locations: 1 country
• Sites: 1

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hours to determine aldosterone in the urine sample after medications interfering in aldosterone release are temporarily withdrawn.

Conditions

Primary Aldosteronism; Hypertension

Keywords

primary aldosteronism; screening; renin; aldosterone; hypertension; corticotropin; dexamethasone

Outcome Measures

Primary Outcomes (1)

• Overall diagnostic accuracy of post-DXM ARR

  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

  24 months

Secondary Outcomes (1)

• Association between post-DXM ARR and 24-h urinary aldosteronuria in the oral salt loading test

  24 months

Study Arms (2)

Post-DXM ARR development cohort

Data from the first half of participants data will be used to generate post-DXM ARR (and possibly Ald) thresholds, which will be subsequently temporally validated in the confirmatory cohort.

Post-DXM ARR confirmatory cohort

Post-DXM ARR thresholds will be applied among participants of the confirmatory cohort, however, these will also undergo the medication withdrawal, OSLT, and other PA confirmatory tests if indicated.

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* patients of the one-day endocrine clinic of the Department of Endocrinology and Internal Medicine of the University Clinical Center of the Medical University of Gdansk, admitted for hormonal work-up due to an adrenal lesion, * study design is cross-sectional

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical University of Gdansk: lead

Study Sites (1)

Department of Endocrinology and Internal Medicine, University Clinical Center, Medical University of Gdansk

Gdansk, Pomeranian Voivodeship, 80214, Poland

RECRUITING

Related Publications (19)

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  PMID: 37343084 BACKGROUND

• Yozamp N, Hundemer GL, Moussa M, Underhill J, Fudim T, Sacks B, Vaidya A. Intraindividual Variability of Aldosterone Concentrations in Primary Aldosteronism: Implications for Case Detection. Hypertension. 2021 Mar 3;77(3):891-899. doi: 10.1161/HYPERTENSIONAHA.120.16429. Epub 2020 Dec 7.

  PMID: 33280409 BACKGROUND

• Markou A, Sertedaki A, Kaltsas G, Androulakis II, Marakaki C, Pappa T, Gouli A, Papanastasiou L, Fountoulakis S, Zacharoulis A, Karavidas A, Ragkou D, Charmandari E, Chrousos GP, Piaditis GP. Stress-induced Aldosterone Hyper-Secretion in a Substantial Subset of Patients With Essential Hypertension. J Clin Endocrinol Metab. 2015 Aug;100(8):2857-64. doi: 10.1210/jc.2015-1268. Epub 2015 May 14.

  PMID: 25974737 BACKGROUND

• Papanastasiou L, Markou A, Pappa T, Gouli A, Tsounas P, Fountoulakis S, Kounadi T, Tsiama V, Dasou A, Gryparis A, Samara C, Zografos G, Kaltsas G, Chrousos G, Piaditis G. Primary aldosteronism in hypertensive patients: clinical implications and target therapy. Eur J Clin Invest. 2014 Aug;44(8):697-706. doi: 10.1111/eci.12286.

  PMID: 24909545 BACKGROUND

• Gouli A, Kaltsas G, Tzonou A, Markou A, Androulakis II, Ragkou D, Vamvakidis K, Zografos G, Kontogeorgos G, Chrousos GP, Piaditis G. High prevalence of autonomous aldosterone secretion among patients with essential hypertension. Eur J Clin Invest. 2011 Nov;41(11):1227-36. doi: 10.1111/j.1365-2362.2011.02531.x. Epub 2011 May 3.

  PMID: 21534948 BACKGROUND

• Markou A, Kaltsas GA, Papanastasiou L, Gravvanis C, Voulgaris N, Kanti G, Zografos GN, Chrousos GP, Piaditis G. Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas. Eur J Endocrinol. 2022 Jan 6;186(2):265-273. doi: 10.1530/EJE-21-0625.

  PMID: 34882580 BACKGROUND

• Li X, Liang J, Hu J, Ma L, Yang J, Zhang A, Jing Y, Song Y, Yang Y, Feng Z, Du Z, Wang Y, Luo T, He W, Shu X, Yang S, Li Q; Chongqing Primary Aldosteronism Study (CONPASS) Group. Screening for primary aldosteronism on and off interfering medications. Endocrine. 2024 Jan;83(1):178-187. doi: 10.1007/s12020-023-03520-6. Epub 2023 Oct 5.

  PMID: 37796417 BACKGROUND

• Seifarth C, Trenkel S, Schobel H, Hahn EG, Hensen J. Influence of antihypertensive medication on aldosterone and renin concentration in the differential diagnosis of essential hypertension and primary aldosteronism. Clin Endocrinol (Oxf). 2002 Oct;57(4):457-65. doi: 10.1046/j.1365-2265.2002.01613.x.

  PMID: 12354127 BACKGROUND

• Browne GA, Griffin TP, O'Shea PM, Dennedy MC. beta-Blocker withdrawal is preferable for accurate interpretation of the aldosterone-renin ratio in chronically treated hypertension. Clin Endocrinol (Oxf). 2016 Mar;84(3):325-31. doi: 10.1111/cen.12882. Epub 2015 Sep 22.

  PMID: 26300226 BACKGROUND

• Brown JM, Robinson-Cohen C, Luque-Fernandez MA, Allison MA, Baudrand R, Ix JH, Kestenbaum B, de Boer IH, Vaidya A. The Spectrum of Subclinical Primary Aldosteronism and Incident Hypertension: A Cohort Study. Ann Intern Med. 2017 Nov 7;167(9):630-641. doi: 10.7326/M17-0882. Epub 2017 Oct 10.

  PMID: 29052707 BACKGROUND

• Parksook WW, Brown JM, Omata K, Tezuka Y, Ono Y, Satoh F, Tsai LC, Niebuhr Y, Milks J, Moore A, Honzel B, Liu H, Auchus RJ, Sunthornyothin S, Turcu AF, Vaidya A. The Spectrum of Dysregulated Aldosterone Production: An International Human Physiology Study. J Clin Endocrinol Metab. 2024 Aug 13;109(9):2220-2232. doi: 10.1210/clinem/dgae145.

  PMID: 38450549 BACKGROUND

• McEvoy JW, McCarthy CP, Bruno RM, Brouwers S, Canavan MD, Ceconi C, Christodorescu RM, Daskalopoulou SS, Ferro CJ, Gerdts E, Hanssen H, Harris J, Lauder L, McManus RJ, Molloy GJ, Rahimi K, Regitz-Zagrosek V, Rossi GP, Sandset EC, Scheenaerts B, Staessen JA, Uchmanowicz I, Volterrani M, Touyz RM; ESC Scientific Document Group. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024 Oct 7;45(38):3912-4018. doi: 10.1093/eurheartj/ehae178. No abstract available.

  PMID: 39210715 BACKGROUND

• Mulatero P, Sechi LA, Williams TA, Lenders JWM, Reincke M, Satoh F, Januszewicz A, Naruse M, Doumas M, Veglio F, Wu VC, Widimsky J. Subtype diagnosis, treatment, complications and outcomes of primary aldosteronism and future direction of research: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension. J Hypertens. 2020 Oct;38(10):1929-1936. doi: 10.1097/HJH.0000000000002520.

  PMID: 32890265 BACKGROUND

• Mulatero P, Monticone S, Deinum J, Amar L, Prejbisz A, Zennaro MC, Beuschlein F, Rossi GP, Nishikawa T, Morganti A, Seccia TM, Lin YH, Fallo F, Widimsky J. Genetics, prevalence, screening and confirmation of primary aldosteronism: a position statement and consensus of the Working Group on Endocrine Hypertension of The European Society of Hypertension. J Hypertens. 2020 Oct;38(10):1919-1928. doi: 10.1097/HJH.0000000000002510.

  PMID: 32890264 BACKGROUND

• Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2.

  PMID: 26934393 BACKGROUND

• Vaidya A, Carey RM. Evolution of the Primary Aldosteronism Syndrome: Updating the Approach. J Clin Endocrinol Metab. 2020 Dec 1;105(12):3771-83. doi: 10.1210/clinem/dgaa606.

  PMID: 32865201 BACKGROUND

• Brown JM, Siddiqui M, Calhoun DA, Carey RM, Hopkins PN, Williams GH, Vaidya A. The Unrecognized Prevalence of Primary Aldosteronism: A Cross-sectional Study. Ann Intern Med. 2020 Jul 7;173(1):10-20. doi: 10.7326/M20-0065. Epub 2020 May 26.

  PMID: 32449886 BACKGROUND

• Funder JW. Who and How Should We Screen for Primary Aldosteronism? Hypertension. 2023 Dec;80(12):2495-2500. doi: 10.1161/HYPERTENSIONAHA.123.20536. Epub 2023 Oct 6.

  PMID: 37800386 BACKGROUND

• Kmiec P, Okroj D, Zdrojewska M, Fiszer J, Zembrzuska S, Swiatkowska-Stodulska R. Overnight Dexamethasone in Primary Aldosteronism Screening in Patients on Interfering Therapy (ODEPRASC): A Diagnostic Interpretability Study Protocol. J Clin Hypertens (Greenwich). 2025 Nov;27(11):e70180. doi: 10.1111/jch.70180.

  PMID: 41268804 DERIVED

MeSH Terms

Conditions

Hyperaldosteronism; Hypertension

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Piotr Kmiec, MD, Ph.D.

  Department of Endocrinology and Internal Medicine, Medical University of Gdansk

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Piotr Kmiec, M.D., Ph.D.

CONTACT

0048 585844809; piotrkmiec@gumed.edu.pl

Renata Swiatkowska-Stodulska, Professor, MD, Ph.D.

CONTACT

0049 585844800; rensto@gumed.edu.pl

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2024
• First Posted: December 18, 2024
• Study Start: October 22, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: October 2, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)