Lab Spotlight Endocrine Hypertension Group

Lab Spotlight: Endocrine Hypertension Group

Unmasking Hidden Hypertension: Innovating Detection, Diagnosis, and Treatment of Primary Aldosteronism

Hypertension Australia is proud to spotlight the groundbreaking work of the Endocrine Hypertension Group at Hudson Institute of Medical Research, led by Dr. Jun Yang. This dedicated team, including Prof Peter Fuller, Dr. Elisabeth Ng, Dr. Sonali Shah, Dr. Josie McCarthy, Dr. Renata Libianto, Dr Sharmin Jahan (based in Bangladesh), Dr Jimmy Shen, Dr StellaMay Gwini, Ms Catherine He, Mr James Morgan, Ms Shanshan Lu-Shirzad, Dr Michelle Kouspou, Dr Linghan Jia and Dr Muhammad Akram , is revolutionising the diagnosis and management of primary aldosteronism (PA), a common but often overlooked cause of hypertension. Their multifaceted approach encompasses innovative detection methods, optimised diagnostic techniques, and advanced treatment strategies. By collaborating with consumers, clinicians, and researchers across various disciplines, the group aims to improve health outcomes and reduce the burden of hypertension-related complications. Their tagline, “Unmasking Hidden Hypertension,” aptly captures their mission to bring PA to the forefront of hypertension research and clinical practice.

What is your team's vision?

Our vision is to:
a) revolutionise the diagnosis and management of hypertensive patients with primary aldosteronism so that all affected individuals may receive a timely diagnosis and benefit from targeted treatment;
b) improve health outcomes by reducing the burden of hypertension and chronic diseases associated with untreated primary aldosteronism;
c) build enduring research, training and clinical capacity; and
d) consolidate Australia’s research leadership in addressing the public health challenges associated with primary aldosteronism.

Tell us about your lab's research or initiatives focused on preventing, detecting, and managing high blood pressure and its complications.

My lab’s main research focus is on primary aldosteronism (PA), a common, potentially curable but grossly under-diagnosed cause of hypertension.

By collaborating with consumers with lived experience of PA, clinicians across Australia and internationally, cardiovascular researchers, implementation scientists, and health economists, my lab aims to:
1. increase PA detection across health systems and medical disciplines through scalable interventions and guideline/policy changes;
2. optimise diagnostic methods for PA with novel tests and simplified algorithms;
3. advance treatment strategies for PA with clinical trials of novel agents;
4. interrogate large cohort studies to better understand the origins and natural history of PA to identify opportunities for early intervention and prevention of complications.

What is your team currently working on?

We are actively working on all of the above themes.
1. Increase PA detection across health systems and medical disciplines
– CONSEP randomised clinical trial to test if electronic clinical decision support can increase PA diagnosis in primary care (funded)
– PARADOX study to codesign a robust screening strategy to improve PA detection in specialist clinics across Australia (seeking funding)
– TOPPA study to better understand PA in First Nations peoples (seeking funding)
– Prospective study to evaluate the prevalence of PA in people admitted with stroke (led by Josie McCarthy)
2. Optimise diagnostic methods for PA with novel tests and simplified algorithms
– Testing algorithms to bypass hospital-based tests to simplify diagnosis and reduce cost (led by Elisabeth Ng, funded by EQUIPPA)
– Novel radioactive tracer to detect aldosterone producing adrenal nodules that may be cured by surgery (led by Elisabeth Ng, funded by EQUIPPA)
– Evaluating the gut microbiome in people with PA (led by Renata Libianto)
3. Advance treatment strategies for PA with clinical trials
– REMASTER trial of targeted treatment vs standard antihypertensive therapy for people with low renin hypertension, which may lie on the same spectrum as PA (led by Sonali Shah)
4. Interrogate large cohort studies to better understand the origins and natural history of PA to identify opportunities for early intervention and prevention of complications
– Collaboration with the Raine Study to evaluate the association between markers of PA and a range of cardiovascular/renal/metabolic markers in 35-year-old study participants and their parents (funded)
– Collaboration with the Aboriginal Birth Cohort study to evaluate the associations between markers of PA and blood pressure, pulse wave velocity, renal function

What is your team planning on working on next?

All the projects for which funding is being sought will be worked on next. We are also planning more clinical trials of emerging aldosterone blockers and aldosterone synthesis inhibitors to expand the repertoire of treatment options for people with primary aldosteronism.

Has your lab received any awards, grants, or publications for your work related to Hypertension?

AWARDS AND GRANTS

2024

  • AstraZeneca (Australia) Industry funding: A Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Effect of Baxdrostat on Ambulatory Blood Pressure in Participants with Resistant Hypertension (Bax24)
  • Western Australian Cohort Studies-Research Support Program (WACS-RSP) – Identifying primary aldosteronism: a common cause of hypertension and cardiovascular disease.

2023

  • NHMRC Centre of Research Excellence – Primary Aldosteronism Centre of Excellence (PACE): optimising the diagnosis and management of a common, curable but neglected cause of hypertension
  • MRFF Clinical Trials Activity Initiative
  • The CONSEP trial: Implementing screening for a hidden cause of hypertension

2022

  • MRFF Clinician Researchers: Applied Research in Health grant – EQUIPping tertiary care for the optimal diagnosis of Primary Aldosteronism (EQUIPPA)


2021

  • George Clinical Pty Ltd Industry funding “Efficacy and safety of GMRx2 (a single pill combination containing telmisartan/amlodipine/indapamide) compared to placebo for the treatment of hypertension: An international, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial”
  • George Clinical Pty Ltd Industry funding “Efficacy and safety of GMRx2 (a single pill combination containing telmisartan/amlodipine/indapamide) compared to dual combinations for the treatment of hypertension: An international, multi-centre, randomized, double-blind, active-controlled, parallel-group trial”

2020

  • NHMRC Ideas Grant (APP1184927, CIA, 2020-2023, $571,199)
  • CASS Foundation Grant (REF 9261, CIB, $58,000)

2019

  • Heart Foundation Vanguard Grant ($75,000, CIB and primary grant writer)
  • Rebecca Cooper Foundation Project Grant ($100,000, CI) PG2019444

PUBLICATIONS

1. Shah SS, Fuller PJ, Young MJ, Yang J. Update on Low-Renin Hypertension: Current Understanding and Future Direction. Hypertension. 2024 Aug 13. doi: 10.1161/HYPERTENSIONAHA.124.23385.
2. Constantinescu G, Gruber S, Fuld S, Peitzsch M, Schulze M, Remde H, Kürzinger L, Yang J, Yen T, Williams TA, Müller L, Reincke M, Lenders JWM, Beuschlein F, Pamporaki C, Eisenhofer G. Steroidomics-Based Screening for Primary Aldosteronism: Impact of antihypertensive Drugs. Hypertension. 2024 Jul 31. doi: 10.1161/HYPERTENSIONAHA.124.23029.
3. Shah SS, Gwini SM, Stowasser M, Reid CM, Young MJ, Fuller PJ, Yang J. A Randomized trial assessing Efficacy and safety of Mineralocorticoid receptor Antagonist therapy compared to Standard antihypertensive Therapy in hypErtension with low Renin (REMASTER): rationale and study design. J Hum Hypertens. 2024 Jul 18. doi: 10.1038/s41371-024-00931-4.
4. Shah SS, Libianto R, Gwini SM, Rusell G, Young MJ, Fuller PJ, Yang J. Prevalence and Characteristics of Low-renin Hypertension in a Primary Care Population. J Endocr Soc. 2024 Jun 5;8(8):bvae113. doi: 10.1210/jendso/bvae113. PMID: 38957654
5. Tsan K, Yang J, Nainani, A, Libianto R, Russell, G. Screening for primary aldosteronism in primary care: a scoping review. Family Practice 2024 Jun 24:cmae033. doi: 10.1093/fampra/cmae033. Epub ahead of print. PMID: 38912620.
6. Yang J, McCarthy J, Shah SS, Ng E, Shen J, Libianto J Fuller PJ. Challenges in diagnosing and managing the spectrum of primary aldosteronism, Journal of the Endocrine Society, 2024; bvae109, https://doi.org/10.1210/jendso/ (invited manuscript)
7. Shen H, Luo W, Hu J, Yang J, Song Y, Chen X, Yang Y, Ma L, Cheng Q, Wang Z, Li Q, Yang S; Chongqing Primary Aldosteronism Study (CONPASS) Group. Comparison of four confirmatory tests for the diagnosis of primary aldosteronism: Bayesian analysis in the absence of a gold standard. Endocrine. 2024 Jul 15. doi: 10.1007/s12020-024-03885-2. Epub ahead of print. PMID: 39009922.
8. Schutte AE, Bennett B, Chow CK, Cloud GC, Doyle K, Girdis Z, Golledge J, Goodman A, Hespe CM, Hsu MP, James S, Jennings G, Khan T, Lee A, Murphy L, Nelson MR, Nicholls SJ, Raffoul N, Robson B, Rodgers A, Sanders A, Shang C, Sharman JE, Stocks NP, Usherwood T, Webster R, Yang J, Schlaich M. National Hypertension Taskforce of Australia: a roadmap to achieve 70% blood pressure control in Australia by 2030. Med J Aust. 2024 Jul 11. doi: 10.5694/mja2.52373. Epub ahead of print. PMID: 38990122.
9. McCarthy J, Munnings M, Clissold B, Fuller PJ, Yang J*, Phan TG*. Prevalence of primary aldosteronism in acute stroke or transient ischemic attack: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2024 Mar 7;15:1355398. doi: 10.3389/fendo.2024.1355398. PMID: 38516414; PMCID: PMC10956081.
10. Pintus G, Seccia TM, Amar L, Azizi M, Riester A, Reincke M, Widimský J, Naruse M, Kocjan T, Negro A, Kline G, Tanabe A, Satoh F, Rump LC, Vonend O, Fuller PJ, Yang J, Chee NYN, Magill SB, Shafigullina Z, Quinkler M, Oliveras A, Lee BC, Chang CC, Wu VC, Krátká Z, Battistel M, Bagordo D, Caroccia B, Ceolotto G, Rossitto G, Rossi GP. Subtype Identification of Surgically Curable Primary Aldosteronism During Treatment With Mineralocorticoid Receptor Blockade. Hypertension. 2024 Mar 25. doi: 10.1161/HYPERTENSIONAHA.124.22721. PMID: 38525605.
11. Fuld S, Constantinescu G, Pamporaki C, Peitzsch M, Schulze M, Yang J, Müller L, Prejbisz A, Januszewicz A, Remde H, Kürzinger L, Dischinger U, Ernst M, Gruber S, Reincke M, Beuschlein F, Lenders JWM, Eisenhofer G. Screening for Primary Aldosteronism by Mass Spectrometry Versus Immunoassay Measurements of Aldosterone: A Prospective Within-Patient Study. J Appl Lab Med. 2024, 9(4):752-766. doi: 10.1093/jalm/jfae017. PMID: 38532521.
12. He C, Li R, Yang J, Shen H, Wang Y, Chen X, Luo W, Zeng Q, Ma L, Song Y, Cheng Q, Wang Z, Wu FF, Li Q, Yang S, Hu J. Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study. Clin Exp Hypertens. 2024 Dec 31;46(1):2301571. doi: 10.1080/10641963.2023.2301571. Epub 2024 Jan 25. PMID: 38270079.
13. Jahan S, Yang J, Hu J, Li Q, Fuller PJ. Captopril challenge test: an underutilized test in the diagnosis of primary aldosteronism. Endocrine Connections. 2024 Jan 1:EC-23-0445. doi: 10.1530/EC-23-0445. Epub ahead of print. PMID: 38180077.
14. Turcu AF, Tezuka Y, Lim JS, Salman Z, Sehgal K, Liu H, Larose S, Parksook WW, Williams TA, Cohen DL, Wachtel H, Zhang J, Dorwal P, Satoh F, Yang J, Lacroix A, Reincke M, Giordano TJ, Udager AM, Vaidya A, Rainey WE. Multifocal, Asymmetric Bilateral Primary Aldosteronism Cannot be Excluded by Strong Adrenal Vein Sampling Lateralization: An International Retrospective Cohort Study. Hypertension. 2024 Mar;81(3):604-613. doi: 10.1161/HYPERTENSIONAHA.123.21910. Epub 2024 Jan 4. PMID: 38174562; PMCID: PMC10922262.
15. Ananda RA, Gwini SM, Long KM, Lai JH, Chen G, Russell GM, Stowasser M, Fuller PJ, Yang J. Diagnostic Delay and Disease Burden in Primary Aldosteronism: An International Patient Survey. Hypertension. 2024 Feb;81(2):348-360. doi: 10.1161/HYPERTENSIONAHA.123.21965. Epub 2023 Dec 14. PMID: 38095087.
16. Zhang X, Shu X, Wu F, Yang J, Cheng Q, Du Z, Song Y, Yang Y, Hu J, Wang Y, Li Q, Yang S; Chongqing Primary Aldosteronism Study (CONPASS) Group. Treatment decision based on unilateral index from non-adrenocorticotropic hormone-stimulated and adrenocorticotropic hormone-stimulated adrenal vein sampling in primary aldosteronism. J Hypertens. 2023 Nov 2. doi: 10.1097/HJH.0000000000003612. Epub ahead of print. PMID: 37937517.
17. Carroll RW, Corley B, Feltham J, Whitfield P, Park W, Howard R, Yssel M, Phillips I, Harper S, Yang J. The value of plasma metanephrine measurements during adrenal vein sampling. Endocrine Connections. 2024 Jan 12;13(2):e230300. doi: 10.1530/EC-23-0300. PMID: 38055778; PMCID: PMC10831578.
18. Yang S, Du Z, Zhang X, Zhen Q, Shu X, Yang J, Song Y, Yang Y, Li Q, Hu J; Chongqing Primary Aldosteronism Study (CONPASS) Group. Corticotropin Stimulation in Adrenal Venous Sampling for Patients With Primary Aldosteronism: The ADOPA Randomized Clinical Trial. JAMA Network Open. 2023 Oct 2;6(10):e2338209.
19. Graven RD, Lee I, Ren J, Yang J, Egerton-Warburton D.. (2023) “Hypertension in the emergency department: a missed opportunity to screen for primary aldosteronism?”. Academic Emergency Medicine. 2023 Oct 28. doi: 10.1111/acem.14830. Epub ahead of print. PMID: 37897111.
20. Holloway-Kew KL, Anderson KB, Rufus-Membere P, Tembo MC, Sui SX, Hyde NK, Kotowicz MA, Gwini SM, Yang J, Diez-Perez A, Henneberg M, Liao WH, Pasco JA. (2023) Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men. Calcified Tissue International. 2023 Nov;113(5):496-510.
21. 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. 2023 Oct 5. doi: 10.1007/s12020-023-03520-6. Epub ahead of print. PMID: 37796417.
22. Fuller PJ, Young MJ, Yang J, Cole TJ. Structure-function relationships of the aldosterone receptor. Vitam Horm. 2023;123:285-312. doi: 10.1016/bs.vh.2022.12.007. Epub 2023 Jan 10. PMID: 37717989.
23. Ng E, Chong W, Lau KK, Gwini SM, Carroll RW, Doery JCG, Fuller PJ, Yang J. (2023) The Where, Who and How of Adrenal Vein Sampling in Australia and New Zealand. Journal of Medical Imaging and Radiation Oncology 2024 Feb;68(1):87-93. doi: 10.1111/1754-9485.13573. Epub 2023 Sep 11. PMID: 37694592.
24. Ng E, Gwini SM, Winston Z, Fuller PJ, Yang J (2023) Predicting bilateral subtypes of primary aldosteronism without adrenal vein sampling: a systematic review and meta-analysis, Journal of Clinical Endocrinology and Metabolism 2024 Jan 18;109(2):e837-e855. doi: 10.1210/clinem/dgad451. PMID: 37531636.
25. Feng GS*, Kent JR*, Fuller PJ, Hoi AY, Kitching AR, Yang J*, Vincent FB* (2023) Primary Aldosteronism: An Unsuspected Culprit of Hypertension in Systemic Lupus Erythematosus? Clinical and Experimental Rheumatology. 2023 Nov;41(11):2312-2322. doi: 10.55563/clinexprheumatol/h58aqe. Epub 2023 Aug 29. PMID: 37650287.
26. Yang J, Young M, Cole T, Fuller PJ (2023), Mineralocorticoid receptor signalling in primary aldosteronism, Journal of Endocrinology 2023 Aug 28;259(1):e220249. doi: 10.1530/JOE-22-0249. PMID: 37486000.
27. Woode M, Wong K, Reid CM, Stowasser M, Russell G, Gwini SM, Young MJ, Fuller PJ, Yang J*, Chen G* (2023) Cost-Effectiveness of Screening for Primary Aldosteronism in Hypertensive Patients in Australia: A Markov Modelling Analysis, J of Hypertension 2023 Oct 1;41(10):1615-1625.
28. Ng E, Gwini SM, Stowasser M, Young MJ, Fuller PJ, Singh G, Yang J (2023) Aldosterone, renin and blood pressure in Indigenous and matched non-Indigenous Australian cohorts, Medical Journal of Australia 2023 Sep 18;219(6):263-269. doi: 10.5694/mja2.52062
29. Hu J, Chen X, Luo Y, Yang J, Zeng Q, Luo W, Shu X, Cheng Q, Gong L, Wang Z, Li Q, Yang S. (2023) Renin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses. Metabolism. 2023 May 24:155593. doi: 10.1016/j.metabol.2023.155593. Epub ahead of print. PMID: 37236301.
30. Rossi GP, Bagordo D, Amar L, Azizi M, Riester A, Reincke M, Degenhart C, Widimský J, Naruse M, Deinum J, Kocjan T, Negro A, Rossi E, Kline G, Tanabe A, Satoh F, Rump LC, Vonend O, Willenberg HS, Fuller PJ, Yang J, Chee NYN, Magill SB, Shafigullina Z, Quinkler M, Oliveras A, Lee BC, Chang CC, Wu VC, Krátká Z, Battistel M, Rossitto G, Seccia TM. Unilaterally Selective Adrenal Vein Sampling for Identification of Surgically Curable Primary Aldosteronism. Hypertension. 2023 Oct;80(10):2003-2013. doi: 10.1161/HYPERTENSIONAHA.123.21247. Epub 2023 Jun 15. PMID: 37317838.
31. Libianto R, Stowasser, M, Russell, G, Fuller, PJ, Yang, J (2023) Improving Detection Rates for Primary Aldosteronism. Experimental and Clinical Endocrinology and Diabetes, 2023 May; DOI10.1055/a-2048-6213
32. Carnagarin R, Nolde JM, Yang J, Marques FZ, Picone DS, Lambert GW, Beaney T, Poulter NR, Schutte AE, Reid CM, Brockman D, Schlaich MP. Stagnating rates of blood pressure control in Australia: insights from opportunistic screening of 10 046 participants of the May Measurement Month campaigns. J Hypertens. 2023 Apr 1;41(4):632-637. Epub 2023 Jan 30. PMID: 36723455.
33. Sawyer N, Glendenning P, Vasikaran SD, Page MM, van Schie G, Wong SL, Yang J, Schlaich MP, Bell DA. The adrenal vein sampling outcomes study (AVOS): success rates following adrenalectomy for unilateral primary aldosteronism. Pathology. 2023 Mar 22:S0031-3025(23)00086-7. doi: 10.1016/j.pathol.2023.02.002. Epub ahead of print. PMID: 37062662.
34. Hu J, Xu T, Shen H, Song Y, Yang J, Zhang A, Ding H, Xing N, Li Z, Qiu L, Ma L, Yang Y, Feng Z, Du Z, He W, Sun Y, Cai J, Li Q, Chen Y, Yang S. (2023) Accuracy of Gallium-68 Pentixafor Positron Emission Tomography–Computed Tomography for Subtyping Diagnosis of Primary Aldosteronism. JAMA Network Open. 2023;6(2):e2255609. doi:10.1001/jamanetworkopen.2022.55609
35. Ma L, Yang S, Yang Y, Chen X, Yang J, He Y, Cheng Q, Li J, Kang B, Tang S, Zhang A, Shu X, Li X, Shen H, Jing Y, Song Y, Li Q, Hu J. (2023), Phosphoproteomics Reveals the Wolframin-Calcium Axis as a Key Pathogenic Signaling Node in Primary Aldosteronism, Hypertension. 2023 Feb 24. doi: 10.1161/HYPERTENSIONAHA.122.20515. Epub ahead of print. PMID: 36825503.
36. Yang J, Gwini SM, Beilin LJ, Schlaich M, Stowasser M, Young MJ, Fuller PJ, Mori TA. (2023) Effect of oral contraception on screening tests for primary aldosteronism: a 10-year longitudinal study. J Clin Endocrinol Metab. 2023 Jan 12:dgad010. doi: 10.1210/clinem/dgad010.
37. Hashimura H, Hu J, Kobayashi H, Gwini SM, Shen J, Chee NYN, Doery JCG, Chong W, Fuller PJ, Abe M, Li Q, Yang J. (2023) Saline suppression to distinguish the primary aldosteronism subtype: a diagnostic study. Eur J Endocrinol. 2023 Jan 10;188(1):lvac003. doi: 10.1093/ejendo/lvac003. PMID: 36651157.
38. Ng E, Gwini SM, Libianto R, Choy KW, Lu ZX, Shen J, Doery JCG, Fuller PJ, Yang J. (2023) Aldosterone, Renin, and Aldosterone-to-Renin Ratio Variability in Screening for Primary Aldosteronism. J Clin Endocrinol Metab. 2022 Dec 17;108(1):33-41. doi: 10.1210/clinem/dgac568. Erratum in: J Clin Endocrinol Metab. 2023 Jan 19;: PMID: 36179243.

Has your lab achieved any results from your work related to Hypertension?

My lab’s research outcomes have transformed clinical practice by developing a focused expertise in the area of PA and establishing a streamlined, evidence-based pathway for its care. At Monash Health, the number of patients diagnosed with PA has increased 40-fold over 10 years (from 5/year to 200+/year); the success rate of adrenal vein sampling (a technically challenging step in PA diagnosis) has increased from 40% in 2010 to >95% in 2024; and targeted treatment has led to reduced medication burden with improved BP in all diagnosed patients (Lim et al, 2018 and 2020).

There has been wide dissemination of PA-related knowledge in print (Australian Financial Review, 28/3/2022), radio (ABC Health Report with Norman Swan, 28/3/2022), television (Channel 7 4PM News and 6PM News, 4/5/2022); websites (Endocrine Hypertension Group webpage with FAQ for doctors and patients), but a lot more work is needed to get the message out to the masses.

We recently established the Primary Aldosteronism Centre of Excellence, NHMRC Funded, to develop a program of education, translational research and capacity development to tackle this public health challenge.

Where can we find out more about your work with Hypertension?