Download PDF
CC BY-NC-ND 4.0 · Horm Metab Res 2020; 52(06): 404-411
DOI: 10.1055/a-1164-1944
Endocrine Research

The Impact of Glucocorticoid Co-Secretion in Primary Aldosteronism on Thyroid Autoantibody Titers During the Course of Disease

Laura Handgriff
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Christian Adolf
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Daniel A. Heinrich 
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Leah Braun
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Nina Nirschl
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Lisa Sturm
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Roland Ladurner
2   Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Klinikum der Universität München, Munich, Germany
,
Jens Ricke
3   Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
,
Max Seidensticker
3   Klinik und Poliklinik für Radiologie, Klinikum der Universität München, Munich, Germany
,
Martin Bidlingmaier
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
,
Martin Reincke
1   Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Excess aldosterone is associated with the increased risk of cardio-/cerebrovascular events as well as metabolic comorbidities not only due to its hypertensive effect but also due to its proinflammatory action. Autonomous cortisol secretion (ACS) in the setting of primary aldosteronism (PA) is known to worsen cardiovascular outcome and potentially exhibit immunosuppressive effects. The aim of this study was to determine the impact of ACS status in patients with PA on kinetics of thyroid autoantibodies (anti-TPO, anti-TG) pre and post therapy initiation. Ninety-seven PA patients (43 unilateral, 54 with bilateral PA) from the database of the German Conn’s Registry were included. Anti-TPO and anti-TG levels were measured pre and 6–12 months post therapeutic intervention. Patients were assessed for ACS according to their 24- hour urinary cortisol excretion, late night salivary cortisol and low-dose dexamethasone suppression test. Abnormal test results in line with ACS were identified in 74.2% of patients with PA. Following adrenalectomy, significant increases in anti-TPO levels were observed in patients with at least one abnormal test (p = 0.049), adrenalectomized patients with at least two pathological ACS tests (p = 0.015) and adrenalectomized patients with pathologic dexamethasone suppression tests (p = 0.018). No antibody increases were observed in unilateral PA patients without ACS and in patients with bilateral PA receiving mineralocorticoid antagonist therapy (MRA). Our data are in line with an immunosuppressive effect of mild glucocorticoid excess in PA on thyroid autoantibody titers. This effect is uncovered by adrenalectomy, but not by MRA treatment.

Key words

primary aldosteronism - auto-immune disease - adrenalectomy - thyroid - cortisol secretion - auto-antibodies


Publication History

Received: 20 December 2019

Accepted: 20 April 2020

Article published online:
13 May 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Rossi GP, Bernini G, Caliumi C. et al. A prospective study of the prevalence of primary aldosteronism in 1125 hypertensive patients. J Am Coll Cardiol 2006; 48: 2293-2300
    Google Scholar
  • 2 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; 101: 1889-1916
    Google Scholar
  • 3 Born-Frontsberg E, Reincke M, Rump LC. et al. Cardiovascular and cerebrovascular comorbidities of hypokalemic and normokalemic primary aldosteronism: Results of the German Conn’s Registry. J Clin Endocrinol Metab 2009; 94: 1125-1130
    Google Scholar
  • 4 Milliez P, Girerd X, Plouin PF. et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol 2005; 45: 1243-1248
    Google Scholar
  • 5 Quinkler M, Born-Frontsberg E, Fourkiotis VG. Comorbidities in primary aldosteronism. Horm Metab Res 2010; 42: 429-434
    Google Scholar
  • 6 Pitt B. Effect of aldosterone blockade in patients with systolic left ventricular dysfunction: Implications of the RALES and EPHESUS studies. Mol Cell Endocrinol 2004; 217: 53-58
    Google Scholar
  • 7 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
    Google Scholar
  • 8 Colussi G, Catena C, Lapenna R. et al. Insulin resistance and hyperinsulinemia are related to plasma aldosterone levels in hypertensive patients. Diabetes Care 2007; 30: 2349-2354
    Google Scholar
  • 9 Ahokas RA, Warrington KJ, Gerling IC. et al. Aldosteronism and peripheral blood mononuclear cell activation: A neuroendocrine-immune interface. Circ Res 2003; 93: e124-e135
    Google Scholar
  • 10 Caturegli P, Kimura H, Rocchi R. et al. Autoimmune thyroid diseases. Curr Opin Rheumatol 2007; 19: 44-48
    Google Scholar
  • 11 Lorini R, Gastaldi R, Traggiai C. et al. Hashimoto’s Thyroiditis. Pediatr Endocrinol Rev 2003; 1 (Suppl. 02) 205-211 discussion 211.
    Google Scholar
  • 12 Schirpenbach C, Segmiller F, Diederich S. et al. The diagnosis and treatment of primary hyperaldosteronism in Germany: Results on 555 patients from the German Conn Registry. Dtsch Arztebl Int 2009; 106: 305-311
    Google Scholar
  • 13 Schilbach K, Junnila RK, Bidlingmaier M. Aldosterone to renin ratio as screening tool in primary aldosteronism. Exp Clin Endocrinol Diabetes 2019; 127: 84-92
    Google Scholar
  • 14 Betz MJ, Degenhart C, Fischer E. et al. Adrenal vein sampling using rapid cortisol assays in primary aldosteronism is useful in centers with low success rates. Eur J Endocrinol 2011; 165: 301-306
    Google Scholar
  • 15 Ladurner R, Sommerey S, Buechner S. et al. Accuracy of adrenal imaging and adrenal venous sampling in diagnosing unilateral primary aldosteronism. Eur J Clin Invest 2017; 47: 372-377
    Google Scholar
  • 16 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
    Google Scholar
  • 17 Heinrich DA, Adolf C, Holler F. et al. Adrenal insufficiency after unilateral adrenalectomy in primary aldosteronism: Long-term outcome and clinical impact. J Clin Endocrinol Metab 2019; 104: 5658-5664
    Google Scholar
  • 18 Herrada AA, Contreras FJ, Marini NP. et al. Aldosterone promotes autoimmune damage by enhancing Th17-mediated immunity. J Immunol 2010; 184: 191-202
    Google Scholar
  • 19 Herrada AA, Campino C, Amador CA. et al. Aldosterone as a modulator of immunity: Implications in the organ damage. J Hypertens 2011; 29: 1684-1692
    Google Scholar
  • 20 Shi Y, Wang H, Su Z. et al. Differentiation imbalance of Th1/Th17 in peripheral blood mononuclear cells might contribute to pathogenesis of Hashimotoʼs thyroiditis. Scand J Immunol 2010; 72: 250-255
    Google Scholar
  • 21 Yoshimoto T, Hirata Y. Aldosterone as a cardiovascular risk hormone. Endocr J 2007; 54: 359-370
    Google Scholar
  • 22 Bendtzen K, Hansen PR, Rieneck K. et al. Spironolactone inhibits production of proinflammatory cytokines, including tumour necrosis factor-alpha and interferon-gamma, and has potential in the treatment of arthritis. Clin Exp Immunol 2003; 134: 151-158
    Google Scholar
  • 23 Munro Neville A. MJOH. Hyperaldosteronism and Related Syndromes of Mineralocorticoid Excess. Springer; London: 1982: 202-241
    Google Scholar
  • 24 Biglieri EG, Schambelan M, Slaton PE. et al. The intercurrent hypertension of primary aldosteronism. Circ Res 1970; 27: 195-202
    Google Scholar
  • 25 Enberg U, Volpe C, Hoog A. et al. Postoperative differentiation between unilateral adrenal adenoma and bilateral adrenal hyperplasia in primary aldosteronism by mRNA expression of the gene CYP11B2. Eur J Endocrinol 2004; 151: 73-85
    Google Scholar
  • 26 Nakamura Y, Felizola SJ, Satoh F. et al. Dissecting the molecular pathways of primary aldosteronism. Pathol Int 2014; 64: 482-489
    Google Scholar
  • 27 Omata K, Satoh F, Morimoto R. et al. Cellular and genetic causes of idiopathic hyperaldosteronism. Hypertension 2018; 72: 874-880
    Google Scholar
  • 28 Davis WW, Newsome HH, Wright LD. et al. Bilateral adrenal hyperplasia as a cause of primary aldosteronism with hypertension, hypokalemia and suppressed renin activity. Am J Med 1967; 42: 642-647
    Google Scholar
  • 29 Doorenbos H, Elings HS, Van Buchem FS. Primary aldosteronism due to adrenocortical hyperplasia. Lancet 1956; 271: 335-337
    Google Scholar
  • 30 Ganguly A. Primary aldosteronism. N Engl J Med 1998; 339: 1828-1834
    Google Scholar
  • 31 Katz FH. Primary aldosteronism with suppressed plasma renin activity due to bilateral nodular adrenocortical hyperplasia. Ann Intern Med 1967; 67: 1035-1042
    Google Scholar
  • 32 Ledingham JG, Laragh JH, Sommers SC. Secondary aldosteronism and reduced plasma renin in hypertensive disease. Trans Assoc Am Physicians 1967; 80: 168-182
    Google Scholar
  • 33 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
    Google Scholar
  • 34 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
    Google Scholar
  • 35 Li H, Yu X, Cicala MV. et al. Prevalence of angiotensin II type 1 receptor (AT1R)-activating autoantibodies in primary aldosteronism. J Am Soc Hypertens 2015; 9: 15-20
    Google Scholar
  • 36 Stowasser M. Update in primary aldosteronism. J Clin Endocrinol Metab 2015; 100: 1-10
    Google Scholar
  • 37 Er LK, Chen L, Tsai YC. et al. Risk of new-onset autoimmune diseases in primary aldosteronism: A nation-wide population-based study. J Hypertens 2019; 38: 745-754
    Google Scholar
  • 38 Piazza M, Seccia TM, Caroccia B. et al. AT1AA (Angiotensin II Type-1 Receptor Autoantibodies): Cause or consequence of human primary aldosteronism?. Hypertension 2019; 74: 793-799
    Google Scholar
  • 39 Turchi F, Ronconi V, di Tizio V. et al. Blood pressure, thyroid-stimulating hormone, and thyroid disease prevalence in primary aldosteronism and essential hypertension. Am J Hypertens 2011; 24: 1274-1279
    Google Scholar
  • 40 Armanini D, Nacamulli D, Scaroni C. et al. High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism. Endocrine 2003; 22: 155-160
    Google Scholar
  • 41 Cioni K, Pantaleoni M, Toschi E. et al. Exacerbation of autoimmune hypothyroidism after hemi-hypophysectomy in a patient with Cushing's disease. Minerva Endocrinol 1993; 18: 139-141
    Google Scholar
  • 42 Colombo P, Passini E, Re T. et al. Autoimmune thyroid disease after successful treatment of Cushing’s syndrome. J Endocrinol Invest 1994; 17: 289-290
    Google Scholar
  • 43 Takasu N, Komiya I, Nagasawa Y. et al. Exacerbation of autoimmune thyroid dysfunction after unilateral adrenalectomy in patients with Cushing’s syndrome due to an adrenocortical adenoma. N Engl J Med 1990; 322: 1708-1712
    Google Scholar
  • 44 Yamakita N, Sakata S, Hayashi H. et al. Case report: Silent thyroiditis after adrenalectomy in a patient with Cushing’s syndrome. Am J Med Sci 1993; 305: 304-306
    Google Scholar
  • 45 Uthman I, Senecal JL. Onset of rheumatoid arthritis after surgical treatment of Cushing’s disease. J Rheumatol 1995; 22: 1964-1966
    Google Scholar
  • 46 Yakushiji F, Kita M, Hiroi N. et al. Exacerbation of rheumatoid arthritis after removal of adrenal adenoma in Cushing’s syndrome. Endocr J 1995; 42: 219-223
    Google Scholar
  • 47 Noguchi Y, Tamai H, Fujisawa K. et al. Systemic lupus erythematosus after pituitary adenomectomy in a patient with Cushing’s disease. Clin Endocrinol (Oxf) 1998; 48: 670-672
    Google Scholar
  • 48 McGregor AM. Immunoendocrine interactions and autoimmunity. N Engl J Med 1990; 322: 1739-1741
    Google Scholar
  • 49 Murray IP. The effect of prednisolone on Hashimoto’s thyroiditis. Scott Med J 1958; 3: 341-345
    Google Scholar
  • 50 Niepomniszcze H, Pitoia F, Katz SB. et al. Primary thyroid disorders in endogenous Cushing's syndrome. Eur J Endocrinol 2002; 147: 305-311
    Google Scholar
  • 51 Colao A, Pivonello R, Faggiano A. et al. Increased prevalence of thyroid autoimmunity in patients successfully treated for Cushing's disease. Clin Endocrinol (Oxf) 2000; 53: 13-19
    Google Scholar