The SPARTACUS Trial: Controversies and Unresolved Issues

Felix Beuschlein; Paolo Mulatero; Evelyn Asbach; Silvia Monticone; Cristiana Catena; Leonardo A. Sechi; Michael Stowasser

doi:10.1055/s-0043-120524

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2017; 49(12): 936-942
DOI: 10.1055/s-0043-120524

Review

The SPARTACUS Trial: Controversies and Unresolved Issues

Felix Beuschlein

¹Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU, Munich, Germany

²Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland

,

Paolo Mulatero

³Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Torino, Torino, Italy

,

Evelyn Asbach

¹Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, LMU, Munich, Germany

,

Silvia Monticone

³Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Torino, Torino, Italy

,

Cristiana Catena

⁴Clinica Medica and Chair of Internal Medicine, Department of Medicine, University of Udine, Udine, Italy

,

Leonardo A. Sechi

⁴Clinica Medica and Chair of Internal Medicine, Department of Medicine, University of Udine, Udine, Italy

,

Michael Stowasser

⁵Endocrine Hypertension Research Centre, University of Queensland Diamantina Institute, Greenslopes and Princess Alexandra Hospitals, Brisbane, Australia

› Institutsangaben

Abstract

Adrenal vein sampling (AVS) is considered the gold standard for the differential diagnosis in patients with primary aldosteronism (PA). The distinction between unilateral and bilateral disease dictates the targeted therapeutic approach with surgery for aldosterone producing adenomas and medical therapy for patients with bilateral hyperplasia. Thereby, this diagnostic step is crucial in clinical care. As AVS is an invasive, not well standardized procedure that is restricted to few specialized centers, several attempts have been made to simplify diagnostic algorithms. In this clinical scenario, the recently published SPARTACUS trial aimed at answering the question whether AVS in fact is superior for differential diagnosis in comparison to imaging of the adrenal glands. In this multicenter study, patients were randomized to be treated according to AVS results or based on abdominal imaging only. Clinical outcome in both patient groups after one year was reported as not different. While the study results found broad interest, it also stirred considerable controversies. This review provides an overview on the different views regarding the outline of the SPARTACUS trial and the interpretation of its results.

Key words

primary aldosteronism - differential diagnosis - randomized controlled trial

Volltext

Referenzen

References
1 Hannemann A, Wallaschofski H. Prevalence of primary aldosteronism in patient's cohorts and in population-based studies – a review of the current literature. Horm Metab Res 2012; 44: 157-162
2 Mulatero P, Stowasser M, Loh KC, Fardella CE, Gordon RD, Mosso L, Gomez-Sanchez CE, Veglio F, Young Jr. WF. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab 2004; 89: 1045-1050
3 Reincke M, Beuschlein F. Progress in primary aldosteronism: translation on the move. Horm Metab Res 2015; 47: 933-934
4 Catena C, Colussi G, Nadalini E, Chiuch A, Baroselli S, Lapenna R, Sechi LA. Cardiovascular outcomes in patients with primary aldosteronism after treatment. Arch Intern Med 2008; 168: 80-85
5 Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005; 45: 1243-1248
6 Lichtenauer UD, Gerum S, Asbach E, Manolopoulou J, Fourkiotis V, Quinkler M, Bidlingmaier M, Reincke M. The clinical value of salivary aldosterone in diagnosis and follow-up of primary aldosteronism. Horm Metab Res 2016; 48: 638-643
7 Catena C, Colussi G, Brosolo G, Novello M, Sechi LA. Aldosterone and left ventricular remodeling. Horm Metab Res 2015; 47: 981-986
8 Prejbisz A, Warchol-Celinska E, Lenders JW, Januszewicz A. Cardiovascular risk in primary hyperaldosteronism. Horm Metab Res 2015; 47: 973-980
9 Remde H, Hanslik G, Rayes N, Quinkler M. Glucose metabolism in primary aldosteronism. Horm Metab Res 2015; 47: 987-993
10 Asbach E, Bekeran M, Reincke M. Parathyroid gland function in primary aldosteronism. Horm Metab Res 2015; 47: 994-999
11 Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young Jr WF. The management of primary aldosteronism: case detection, diagnosis, and treatment: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016; 101: 1889-1916
12 Sechi LA, Colussi GL, Novello M, Uzzau A, Catena C. Mineralocorticoid receptor antagonists and clinical outcomes in primary aldosteronism: As good as surgery?. Horm Metab Res 2015; 47: 1000-1006
13 Sato M, Morimoto R, Seiji K, Iwakura Y, Ono Y, Kudo M, Satoh F, Ito S, Ishibashi T, Takase K. Cost-effectiveness analysis of the diagnosis and treatment of primary aldosteronism in japan. Horm Metab Res 2015; 47: 826-832
14 Moors M, Williams TA, Deinum J, Eisenhofer G, Reincke M, Lenders JW. Steroid hormone production in patients with aldosterone producing adenomas. Horm Metab Res 2015; 47: 967-972
15 Burrello J, Monticone S, Tetti M, Rossato D, Versace K, Castellano I, Williams TA, Veglio F, Mulatero P. Subtype diagnosis of primary aldosteronism: Approach to different clinical scenarios. Horm Metab Res 2015; 47: 959-966
16 Viola A, Monticone S, Burrello J, Buffolo F, Lucchiari M, Rabbia F, Williams TA, Veglio F, Mengozzi G, Mulatero P. Renin and aldosterone measurements in the management of arterial hypertension. Horm Metab Res 2015; 47: 418-426
17 Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR, Deinum J. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med 2009; 151: 329-337
18 Stewart PM, Allolio B. Adrenal vein sampling for Primary Aldosteronism: time for a reality check. Clin Endocrinol (Oxf) 2010; 72: 146-148
19 Rossi GP, Barisa M, Allolio B, Auchus RJ, Amar L, Cohen D, Degenhart C, Deinum J, Fischer E, Gordon R, Kickuth R, Kline G, Lacroix A, Magill S, Miotto D, Naruse M, Nishikawa T, Omura M, Pimenta E, Plouin PF, Quinkler M, Reincke M, Rossi E, Rump LC, Satoh F, Schultze Kool L, Seccia TM, Stowasser M, Tanabe A, Trerotola S, Vonend O, Widimsky Jr. J, Wu KD, Wu VC, Pessina AC. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab 2012; 97: 1606-1614
20 Vonend O, Ockenfels N, Gao X, Allolio B, Lang K, Mai K, Quack I, Saleh A, Degenhart C, Seufert J, Seiler L, Beuschlein F, Quinkler M, Podrabsky P, Bidlingmaier M, Lorenz R, Reincke M, Rump LC, German Conn's R. Adrenal venous sampling: evaluation of the German Conn's registry. Hypertension 2011; 57: 990-995
21 Riester A, Fischer E, Degenhart C, Reiser MF, Bidlingmaier M, Beuschlein F, Reincke M, Quinkler M. Age below 40 or a recently proposed clinical prediction score cannot bypass adrenal venous sampling in primary aldosteronism. J Clin Endocrinol Metab 2014; 99: E1035-E1039
22 Kupers EM, Amar L, Raynaud A, Plouin PF, Steichen O. A clinical prediction score to diagnose unilateral primary aldosteronism. J Clin Endocrinol Metab 2012; 97: 3530-3537
23 Sze WC, Soh LM, Lau JH, Reznek R, Sahdev A, Matson M, Riddoch F, Carpenter R, Berney D, Grossman AB, Chew SL, Akker SA, Druce MR, Waterhouse M, Monson JP, Drake WM. Diagnosing unilateral primary aldosteronism – comparison of a clinical prediction score, computed tomography and adrenal venous sampling. Clin Endocrinol (Oxf) 2014; 81: 25-30
24 Abe T, Naruse M, Young Jr. WF, Kobashi N, Doi Y, Izawa A, Akama K, Okumura Y, Ikenaga M, Kimura H, Saji H, Mukai K, Matsumoto H. A Novel CYP11B2-Specific Imaging Agent for Detection of Unilateral Subtypes of Primary Aldosteronism. J Clin Endocrinol Metab 2016; 101: 1008-1015
25 Burton TJ, Mackenzie IS, Balan K, Koo B, Bird N, Soloviev DV, Azizan EA, Aigbirhio F, Gurnell M, Brown MJ. Evaluation of the sensitivity and specificity of (11)C-metomidate positron emission tomography (PET)-CT for lateralizing aldosterone secretion by Conn's adenomas. J Clin Endocrinol Metab 2012; 97: 100-109
26 Dekkers T, Prejbisz A, Kool LJ, Groenewoud HJ, Velema M, Spiering W, Kolodziejczyk-Kruk S, Arntz M, Kadziela J, Langenhuijsen JF, Kerstens MN, van den Meiracker AH, van den Born BJ, Sweep FC, Hermus AR, Januszewicz A, Ligthart-Naber AF, Makai P, van der Wilt GJ, Lenders JW, Deinum J. Investigators S. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: An outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol 2016; 4: 739-746
27 Monticone S, Viola A, Rossato D, Veglio F, Reincke M, Gomez-Sanchez C, Mulatero P. Adrenal vein sampling in primary aldosteronism: Towards a standardised protocol. Lancet Diabetes Endocrinol 2015; 3: 296-303
28 Rossi GP, Auchus RJ, Brown M, Lenders JW, Naruse M, Plouin PF, Satoh F, Young Jr WF. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension 2014; 63: 151-160
29 Monticone S, Satoh F, Giacchetti G, Viola A, Morimoto R, Kudo M, Iwakura Y, Ono Y, Turchi F, Paci E, Veglio F, Boscaro M, Rainey W, Ito S, Mulatero P. Effect of adrenocorticotropic hormone stimulation during adrenal vein sampling in primary aldosteronism. Hypertension 2012; 59: 840-846
30 Wolley MJ, Ahmed AH, Gordon RD, Stowasser M. Does ACTH improve the diagnostic performance of adrenal vein sampling for subtyping primary aldosteronism?. Clin Endocrinol (Oxf) 2016; 85: 703-709
31 Williams TA, JWM Lenders, Mulatero P, Burrello J, Rottenkolber M, Adolf C, Satoh F, Amar L, Quinkler M, Deinum J, Beuschlein F, Kitamoto KK, Pham U, Morimoto R, Umakoshi H, Prejbisz A, Kocjan T, Naruse M, Stowasser M, Nishikawa T, Young Jr. WF, Gomez-Sanchez CE, Funder JW, Reincke M. Primary Aldosteronism Surgery Outcome Investigators. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol 2017; 5: 689-699
32 Modolo R, de Faria AP, Ritter AM, Coca A, Moreno H. Defined daily dose (DDD) and its potential use in clinical trials of resistant hypertension. Int J Cardiol 2016; 202: 515-516
33 Monticone S, Burrello J, Tizzani D, Bertello C, Viola A, Buffolo F, Gabetti L, Mengozzi G, Williams TA, Rabbia F, Veglio F, Mulatero P. Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice. J Am Coll Cardiol 2017; 69: 1811-1820
34 Ghose RP, Hall PM, Bravo EL. Medical management of aldosterone-producing adenomas. Ann Intern Med 1999; 131: 105-108
35 Catena C, Colussi G, Lapenna R, Nadalini E, Chiuch A, Gianfagna P, Sechi LA. Long-term cardiac effects of adrenalectomy or mineralocorticoid antagonists in patients with primary aldosteronism. Hypertension 2007; 50: 911-918
36 Sukor N, Gordon RD, Ku YK, Jones M, Stowasser M. Role of unilateral adrenalectomy in bilateral primary aldosteronism: A 22-year single center experience. J Clin Endocrinol Metab 2009; 94: 2437-2445
37 Catena C, Colussi G, Di Fabio A, Valeri M, Marzano L, Uzzau A, Sechi LA. Mineralocorticoid antagonists treatment versus surgery in primary aldosteronism. Horm Metab Res 2010; 42: 440-445
38 Mulatero P, Bertello C, Sukor N, Gordon R, Rossato D, Daunt N, Leggett D, Mengozzi G, Veglio F, Stowasser M. Impact of different diagnostic criteria during adrenal vein sampling on reproducibility of subtype diagnosis in patients with primary aldosteronism. Hypertension 2010; 55: 667-673
39 Lethielleux G, Amar L, Raynaud A, Plouin PF, Steichen O. Influence of diagnostic criteria on the interpretation of adrenal vein sampling. Hypertension 2015; 65: 849-854
40 Ceral J, Solar M, Krajina A, Ballon M, Suba P, Cap J. Adrenal venous sampling in primary aldosteronism: A low dilution of adrenal venous blood is crucial for a correct interpretation of the results. Eur J Endocrinol 2010; 162: 101-107
41 Satoh F, Abe T, Tanemoto M, Nakamura M, Abe M, Uruno A, Morimoto R, Sato A, Takase K, Ishidoya S, Arai Y, Suzuki T, Sasano H, Ishibashi T, Ito S. Localization of aldosterone-producing adrenocortical adenomas: significance of adrenal venous sampling. Hypertens Res 2007; 30: 1083-1095
42 Loh KC, Koay ES, Khaw MC, Emmanuel SC, Young Jr. WF. Prevalence of primary aldosteronism among Asian hypertensive patients in Singapore. J Clin Endocrinol Metab 2000; 85: 2854-2859
43 Rossi GP, Bernini G, Caliumi C, Desideri G, Fabris B, Ferri C, Ganzaroli C, Giacchetti G, Letizia C, Maccario M, Mallamaci F, Mannelli M, Mattarello MJ, Moretti A, Palumbo G, Parenti G, Porteri E, Semplicini A, Rizzoni D, Rossi E, Boscaro M, Pessina AC, Mantero F. Investigators PS. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol 2006; 48: 2293-2300