Recent Developments in Primary Aldosteronism

E. Asbach; T. A. Williams; M. Reincke

doi:10.1055/s-0042-105278

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2016; 124(06): 335-341
DOI: 10.1055/s-0042-105278

Invited review

Recent Developments in Primary Aldosteronism

E. Asbach

¹Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München

,

T. A. Williams

¹Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München

,

M. Reincke

¹Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München

› Author Affiliations

Abstract

Primary aldosteronism (PA) is the most frequent endocrine cause of secondary arterial hypertension. Sporadic forms of PA caused mainly by an aldosterone producing adenoma (APA) or idiopathic adrenal hyperplasia (IAH) predominate; in contrast, familial forms (familial hyperaldosteronism types I, II and III) affect only a minor proportion of PA patients. Patient based registries and biobanks, international networks and next generation sequencing technologies have emerged over recent years. Somatic hot-spot mutations in the potassium channel GIRK4 (encoded by KCNJ5), in ATPases and a L-type voltage-gated calcium-channel correlate with the autonomous aldosterone production in approximately half of all APAs. The recently discovered form FH III is caused by different germline KCNJ5 mutations with variable clinical presentations and severity. Autoantibodies to the angiotensin II Type 1 receptor have been identified in patients with PA and possibly play a pathophysiological role in the development of PA. Adrenal vein sampling (AVS) represents the gold standard in differentiating unilateral and bilateral forms of PA. Recent consensus papers have tried to implement current guidelines in order to standardise the technique of AVS. New techniques like segmental AVS might allow a finer mapping of the aldosterone production within the adrenal gland. The measurement of the steroids 18-hydroxycortisol and 18-oxocortisol by liquid chromatography tandem mass spectrometry has been shown to be useful to distinguish between unilateral and bilateral forms of PA.

Key words

primary aldosteronism - aldosterone - somatic mutation - KCNJ5 - familial hyperaldosteronism - adrenal vein sampling

Full Text

References

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 et al. Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab 2004; 89: 1045-1050
3 Rossi GP, Bernini G, Caliumi C et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol 2006; 48: 2293-2300 [pii] 10.1016/j.jacc.2006.07.059
4 Funder JW, Carey RM, Fardella C et al. Case detection, diagnosis, and treatment of patients with primary aldosteronism: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 3266-3281
5 Rossi GP. A comprehensive review of the clinical aspects of primary aldosteronism. Nat Rev Endocrinol 2011; 7: 485-495
6 Stowasser M, Gordon RD. Familial hyperaldosteronism. J Steroid Biochem Mol Biol 2001; 78: 215-229 [pii]
7 Chao CT, Wu VC, Kuo CC et al. Diagnosis and management of primary aldosteronism: an updated review. Annals of medicine 2013; 45: 375-383
8 Choi M, Scholl UI, Yue P et al. K+channel mutations in adrenal aldosterone-producing adenomas and hereditary hypertension. Science 2011; 331: 768-772 [pii] 10.1126/science.1198785
9 Boulkroun S, Beuschlein F, Rossi GP et al. Prevalence, clinical, and molecular correlates of KCNJ5 mutations in primary aldosteronism. Hypertension 2012; 59: 592-598
10 Azizan EA, Murthy M, Stowasser M et al. Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas. Hypertension 2012; 59: 587-591
11 Oki K, Plonczynski MW, Luis Lam M et al. Potassium channel mutant KCNJ5 T158A expression in HAC-15 cells increases aldosterone synthesis. Endocrinology 2012; 153: 1774-1782
12 Stindl J, Tauber P, Sterner C et al. Pathogenesis of Adrenal Aldosterone-Producing Adenomas Carrying Mutations of the Na(+)/K(+)-ATPase. Endocrinology 2015; 156: 4582-4591
13 Fernandes-Rosa FL, Williams TA, Riester A et al. Genetic spectrum and clinical correlates of somatic mutations in aldosterone-producing adenoma. Hypertension 2014; 64: 354-361
14 Fischer E, Adolf C, Pallauf A et al. Aldosterone excess impairs first phase insulin secretion in primary aldosteronism. J Clin Endocrinol Metab 2013; 98: 2513-2520
15 Brown J, de Boer IH, Robinson-Cohen C et al. Aldosterone, parathyroid hormone, and the use of renin-angiotensin-aldosterone system inhibitors: the multi-ethnic study of atherosclerosis. J Clin Endocrinol Metab 2015; 100: 490-499
16 Williams TA, Monticone S, Schack VR et al. Somatic ATP1A1, ATP2B3, and KCNJ5 mutations in aldosterone-producing adenomas. Hypertension 2014; 63: 188-195
17 Petramala L, Savoriti C, Zinnamosca L et al. Primary aldosteronism with concurrent primary hyperparathyroidism in a patient with arrhythmic disorders. Intern Med 2013; 52: 2071-2075
18 Sariakjali B, Jamaspishvili E, Evran M et al. Primary hyperparathyroidism in a patient with primary aldosteronism. BMC research notes 2015; 8: 310
19 Zheng FF, Zhu LM, Nie AF et al. Clinical characteristics of somatic mutations in Chinese patients with aldosterone-producing adenoma. Hypertension 2015; 65: 622-628
20 Williams TA, Lenders JW, Burrello J et al. KCNJ5 Mutations: Sex, Salt and Selection. Horm Metab Res 2015; 47: 953-958
21 Lenzini L, Rossitto G, Maiolino G et al. A Meta-Analysis of Somatic KCNJ5 K(+) Channel Mutations In 1636 Patients With an Aldosterone-Producing Adenoma. J Clin Endocrinol Metab 2015; 100: E1089-E1095
22 Sutherland DJ, Ruse JL, Laidlaw JC. Hypertension, increased aldosterone secretion and low plasma renin activity relieved by dexamethasone. Canadian Medical Association journal 1966; 95: 1109-1119
23 Salti IS, Stiefel M, Ruse JL et al. Non-tumorous “primary” aldosteronism. I. Type relieved by glucocorticoid (glucocorticoid-remediable aldosteronism). Canadian Medical Association journal 1969; 101: 1-10
24 Lifton RP, Dluhy RG, Powers M et al. A chimaeric 11 beta-hydroxylase/aldosterone synthase gene causes glucocorticoid-remediable aldosteronism and human hypertension. Nature 1992; 355: 262-265
25 Mulatero P, Tizzani D, Viola A et al. Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study (Primary Aldosteronism in TOrino-GENetic forms). Hypertension 2011; 58: 797-803
26 Pizzolo F, Trabetti E, Guarini P et al. Glucocorticoid remediable aldosteronism (GRA) screening in hypertensive patients from a primary care setting. J Hum Hypertens 2005; 19: 325-327
27 Funder JW. Genetics of primary aldosteronism. Frontiers of hormone research 2014; 43: 70-78
28 Aglony M, Martinez-Aguayo A, Carvajal CA et al. Frequency of familial hyperaldosteronism type 1 in a hypertensive pediatric population: clinical and biochemical presentation. Hypertension 2011; 57: 1117-1121
29 Litchfield WR, Anderson BF, Weiss RJ et al. Intracranial aneurysm and hemorrhagic stroke in glucocorticoid-remediable aldosteronism. Hypertension 1998; 31: 445-450
30 Gates LJ, Benjamin N, Haites NE et al. Is random screening of value in detecting glucocorticoid-remediable aldosteronism within a hypertensive population?. J Hum Hypertens 2001; 15: 173-176
31 Funder JW, Carey RM, Mantero F et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2016; jc20154061
32 New MI, Levine LS. Hypertension of childhood with suppressed renin. Endocr Rev 1980; 1: 421-430
33 MacConnachie AA, Kelly KF, McNamara A et al. Rapid diagnosis and identification of cross-over sites in patients with glucocorticoid remediable aldosteronism. J Clin Endocrinol Metab 1998; 83: 4328-4331
34 Stowasser M, Gordon RD. Primary aldosteronism: learning from the study of familial varieties. J Hypertens 2000; 18: 1165-1176
35 Gordon RD, Stowasser M, Tunny TJ et al. Clinical and pathological diversity of primary aldosteronism, including a new familial variety. Clin Exp Pharmacol Physiol 1991; 18: 283-286
36 Lafferty AR, Torpy DJ, Stowasser M et al. A novel genetic locus for low renin hypertension: familial hyperaldosteronism type II maps to chromosome 7 (7p22). Journal of medical genetics 2000; 37: 831-835
37 So A, Duffy DL, Gordon RD et al. Familial hyperaldosteronism type II is linked to the chromosome 7p22 region but also shows predicted heterogeneity. J Hypertens 2005; 23: 1477-1484
38 Sukor N, Mulatero P, Gordon RD et al. Further evidence for linkage of familial hyperaldosteronism type II at chromosome 7p22 in Italian as well as Australian and South American families. J Hypertens 2008; 26: 1577-1582
39 Torpy DJ, Gordon RD, Lin JP et al. Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. J Clin Endocrinol Metab 1998; 83: 3214-3218
40 Pallauf A, Schirpenbach C, Zwermann O et al. The prevalence of familial hyperaldosteronism in apparently sporadic primary aldosteronism in Germany: a single center experience. Horm Metab Res 2012; 44: 215-220
41 Medeau V, Assie G, Zennaro MC et al. Familial aspect of primary hyperaldosteronism: analysis of families compatible with primary hyperaldosteronism type 2. Ann Endocrinol (Paris) 2005; 66: 240-246
42 Stowasser M. Update in primary aldosteronism. J Clin Endocrinol Metab 2009; 94: 3623-3630 [pii] 10.1210/jc.2009-1399
43 Geller DS, Zhang J, Wisgerhof MV et al. A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab 2008; 93: 3117-3123
44 Marx SJ. Hyperplasia in glands with hormone excess. Endocrine-related cancer 2016; 23: R1-R14
45 Mulatero P, Tauber P, Zennaro MC et al. KCNJ5 mutations in European families with nonglucocorticoid remediable familial hyperaldosteronism. Hypertension 2012; 59: 235-240
46 Charmandari E, Sertedaki A, Kino T et al. A novel point mutation in the KCNJ5 gene causing primary hyperaldosteronism and early-onset autosomal dominant hypertension. J Clin Endocrinol Metab 2012; 97: E1532-E1539
47 Zennaro MC, Boulkroun S, Fernandes-Rosa F. Inherited forms of mineralocorticoid hypertension. Best Pract Res Clin Endocrinol Metab 2015; 29: 633-645
48 Mulatero P, Monticone S, Rainey WE et al. Role of KCNJ5 in familial and sporadic primary aldosteronism. Nat Rev Endocrinol 2013; 9: 104-112
49 Scholl UI, Stolting G, Nelson-Williams C et al. Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism. eLife 2015; 4: e06315
50 Nishimoto K, Nakagawa K, Li D et al. Adrenocortical zonation in humans under normal and pathological conditions. J Clin Endocrinol Metab 2010; 95: 2296-2305
51 Nishimoto K, Tomlins SA, Kuick R et al. Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands. Proc Natl Acad Sci U S A 2015; 112: E4591-E4599
52 Wallukat G, Homuth V, Fischer T et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest 1999; 103: 945-952
53 Dragun D, Muller DN, Brasen JH et al. Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med 2005; 352: 558-569
54 Fu ML, Herlitz H, Schulze W et al. Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension. J Hypertens 2000; 18: 945-953
55 Rossitto G, Regolisti G, Rossi E et al. Elevation of angiotensin-II type-1-receptor autoantibodies titer in primary aldosteronism as a result of aldosterone-producing adenoma. Hypertension 2013; 61: 526-533
56 Kem DC, Li H, Velarde-Miranda C et al. Autoimmune mechanisms activating the angiotensin AT1 receptor in ‘primary’ aldosteronism. J Clin Endocrinol Metab 2014; 99: 1790-1797
57 Li H, Yu X, Cicala MV et al. Prevalence of angiotensin II type 1 receptor (AT1R)-activating autoantibodies in primary aldosteronism. Journal of the American Society of Hypertension : JASH 2015; 9: 15-20
58 Williams TA, Mulatero P, Bidlingmaier M et al. Genetic and Potential Autoimmune Triggers of Primary Aldosteronism. Hypertension 2015; 66: 248-253
59 Kempers MJ, Lenders JW, van Outheusden L et al. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med 2009; 151: 329-337 [pii]
60 Nishikawa T, Omura M, Satoh F et al. Guidelines for the diagnosis and treatment of primary aldosteronism–the Japan Endocrine Society 2009. Endocr J 2011; 58: 711-721
61 Stewart PM, Allolio B. Adrenal vein sampling for Primary Aldosteronism: time for a reality check. Clin Endocrinol (Oxf) 2010; 72: 146-148 [pii] 10.1111/j.1365-2265.2009.03714.x
62 Vonend O, Ockenfels N, Gao X et al. Adrenal Venous Sampling: Evaluation of the German Conn’s Registry. Hypertension 2011; 57: 990-995 [pii] 10.1161/HYPERTENSIONAHA.110.168484
63 Rossi GP, Barisa M, Allolio B et al. The Adrenal Vein Sampling International Study (AVIS) for identifying the major subtypes of primary aldosteronism. J Clin Endocrinol Metab 2012; 97: 1606-1614
64 Rossi GP, Auchus RJ, Brown M et al. An expert consensus statement on use of adrenal vein sampling for the subtyping of primary aldosteronism. Hypertension 2014; 63: 151-160
65 Monticone S, Viola A, Rossato D et al. Adrenal vein sampling in primary aldosteronism: towards a standardised protocol. The lancet Diabetes & endocrinology 2015; 3: 296-303
66 Auchus RJ, Wians Jr. FH, Anderson ME et al. What we still do not know about adrenal vein sampling for primary aldosteronism. Horm Metab Res 2010; 42: 411-415
67 Seccia TM, Miotto D, Battistel M et al. A stress reaction affects assessment of selectivity of adrenal venous sampling and of lateralization of aldosterone excess in primary aldosteronism. Eur J Endocrinol 2012; 166: 869-875
68 Young WF, Stanson AW, Thompson GB et al. Role for adrenal venous sampling in primary aldosteronism. Surgery 2004; 136: 1227-1235 [pii] 10.1016/j.surg.2004.06.051
69 Daunt N. Adrenal vein sampling: how to make it quick, easy, and successful. Radiographics 2005; 25 (Suppl. 01) S143-S158 [pii] 10.1148/rg.25si055514
70 Rossi GP, Pitter G, Bernante P et al. Adrenal vein sampling for primary aldosteronism: the assessment of selectivity and lateralization of aldosterone excess baseline and after adrenocorticotropic hormone (ACTH) stimulation. J Hypertens 2008; 26: 989-997 00004872-200805000-00022 [pii]
71 Seccia TM, Miotto D, De Toni R et al. Adrenocorticotropic hormone stimulation during adrenal vein sampling for identifying surgically curable subtypes of primary aldosteronism: comparison of 3 different protocols. Hypertension 2009; 53: 761-766 [pii] 10.1161/HYPERTENSIONAHA.108.128553
72 Kline GA, Harvey A, Jones C et al. Adrenal vein sampling may not be a gold-standard diagnostic test in primary aldosteronism: final diagnosis depends upon which interpretation rule is used. Variable interpretation of adrenal vein sampling. Int Urol Nephrol 2008; 40: 1035-1043
73 Monticone S, Satoh F, Viola A et al. Aldosterone suppression on contralateral adrenal during adrenal vein sampling does not predict blood pressure response after adrenalectomy. J Clin Endocrinol Metab 2014; 99: 4158-4166
74 Wolley MJ, Gordon RD, Ahmed AH et al. Does contralateral suppression at adrenal venous sampling predict outcome following unilateral adrenalectomy for primary aldosteronism? A retrospective study. J Clin Endocrinol Metab 2015; 100: 1477-1484
75 Kloos RT, Gross MD, Francis IR et al. Incidentally discovered adrenal masses. Endocr Rev 1995; 16: 460-484
76 Zhang Y, Feng B. The association of serum parathyriod hormone and calcium levels with primary aldosteronism: a meta-analysis. Minerva endocrinologica. 2016
77 Riester A, Fischer E, Degenhart C et al. 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
78 Sze WC, Soh LM, Lau JH et al. Diagnosing unilateral primary aldosteronism - comparison of a clinical prediction score, computed tomography and adrenal venous sampling. Clin Endocrinol (Oxf) 2014; 81: 25-30
79 Lim V, Guo Q, Grant CS et al. Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical cure of primary aldosteronism. J Clin Endocrinol Metab 2014; 99: 2712-2719
80 Satoh F, Morimoto R, Seiji K et al. PROGRESS IN PRIMARY ALDOSTERONISM: Is there a role for segmental adrenal venous sampling and adrenal sparing surgery in patients with primary aldosteronism?. Eur J Endocrinol 2015;
81 Nishikawa T, Matsuzawa Y, Saito J et al. Is it Possible to Extirpate Cardiovascular Events in Primary Aldosteronism After Surgical Treatment. Japanese clinical medicine 2010; 1: 21-23
82 Omura M, Saito J, Matsuzawa Y et al. Supper-selective ACTH-stimulated adrenal vein sampling is necessary for detecting precisely functional state of various lesions in unilateral and bilateral adrenal disorders, inducing primary aldosteronism with subclinical Cushing’s syndrome. Endocr J 2011; 58: 919-920
83 Satani N, Ota H, Seiji K et al. Intra-adrenal Aldosterone Secretion: Segmental Adrenal Venous Sampling for Localization. Radiology 2015; 142: 159
84 Kaye DR, Storey BB, Pacak K et al. Partial adrenalectomy: underused first line therapy for small adrenal tumors. The Journal of urology 2010; 184: 18-25
85 Wu VC, Chueh SC, Chang HW et al. Bilateral aldosterone-producing adenomas: differentiation from bilateral adrenal hyperplasia. QJM 2008; 101: 13-22 [pii] 10.1093/qjmed/hcm101
86 Satoh F, Morimoto R, Ono Y et al. Measurement of peripheral plasma 18-oxocortisol can discriminate unilateral adenoma from bilateral diseases in patients with primary aldosteronism. Hypertension 2015; 65: 1096-1102
87 Ulick S, Blumenfeld JD, Atlas SA et al. The unique steroidogenesis of the aldosteronoma in the differential diagnosis of primary aldosteronism. J Clin Endocrinol Metab 1993; 76: 873-878
88 Stowasser M, Bachmann AW, Tunny TJ et al. Production of 18-oxo-cortisol in subtypes of primary aldosteronism. Clin Exp Pharmacol Physiol 1996; 23: 591-593
89 Mosso L, Gomez-Sanchez CE, Foecking MF et al. Serum 18-hydroxycortisol in primary aldosteronism, hypertension, and normotensives. Hypertension 2001; 38: 688-691
90 Mulatero P, di Cella SM, Monticone S et al. 18-hydroxycorticosterone, 18-hydroxycortisol, and 18-oxocortisol in the diagnosis of primary aldosteronism and its subtypes. J Clin Endocrinol Metab 2012; 97: 881-889
91 Kunzel HE, Apostolopoulou K, Pallauf A et al. Quality of life in patients with primary aldosteronism: gender differences in untreated and long-term treated patients and associations with treatment and aldosterone. Journal of psychiatric research 2012; 46: 1650-1654