Horm Metab Res 2017; 49(11): 847-853
DOI: 10.1055/s-0043-119878
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Evaluation of Cortisol Production in Aldosterone-Producing Adenoma

Kosuke Inoue
1   Endocrinology and Diabetes Center, Yokohama Rosai Hospital, Yokohama, Japan
,
Yuto Yamazaki
2   Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
,
Yuya Tsurutani
1   Endocrinology and Diabetes Center, Yokohama Rosai Hospital, Yokohama, Japan
,
Sachiko Suematsu
1   Endocrinology and Diabetes Center, Yokohama Rosai Hospital, Yokohama, Japan
,
Chiho Sugisawa
1   Endocrinology and Diabetes Center, Yokohama Rosai Hospital, Yokohama, Japan
,
Jun Saito
1   Endocrinology and Diabetes Center, Yokohama Rosai Hospital, Yokohama, Japan
,
Masao Omura
1   Endocrinology and Diabetes Center, Yokohama Rosai Hospital, Yokohama, Japan
,
Hironobu Sasano
2   Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
,
Tetsuo Nishikawa
1   Endocrinology and Diabetes Center, Yokohama Rosai Hospital, Yokohama, Japan
› Author Affiliations
Further Information

Publication History

received 27 May 2017

accepted 11 September 2017

Publication Date:
25 October 2017 (online)

Abstract

Aldosterone-producing adenoma (APA) is sometimes accompanied with subclinical hypercortisolism. We investigated the ability of cortisol production in APA, both clinically and pathologically. A retrospective cohort study was conducted at Yokohama Rosai Hospital from 2009 to 2016. Thirty patients with APA and serum cortisol levels during the 1 mg dexamethasone suppression test (F-DST)<3.0 μg/dl were included. We evaluated the 1) difference between pre-adrenalectomy F-DST (pre-F-DST) and post-adrenalectomy F-DST (ΔF-DST), 2) correlation between ∆F-DST and pre-F-DST, tumour size determined by CT, and type of adrenalectomy (total or partial), and 3) relationship between the ratio of F-DST divided by tumour size (ΔF-DST/pre-F-DST/mm) and immunoreactivity of CYP17A1, CYP11B1, and CYP11B2. The median [interquartile range] age was 48 [38–58] years. We found a significant decrease in F-DST after adrenalectomy [before: 1.4 (1.1–1.8); after: 0.9 (0.6–1.2); p<0.001]. Additionally, a significant correlation was found for ΔF-DST and both pre-F-DST (Spearman, ρ=–0.68, p<0.001) and tumour size (ρ=–0.51, p 0.005). No significant difference was found in ΔF-DST between total and partial adrenalectomy. CYP17A1 and CYP11B1 were positive in 21 (100%) and 17 (81%) adenomas, respectively. CYP17A1 immunoreactivity in the tumour was significantly related with ΔF-DST/pre-F-DST/mm (p 0.049). F-DST significantly decreased after adrenalectomy, and most of the adenomas were immunohistochemically positive for CYP17A1 and CYP11B1 as well as CYP11B2. We should consider the possibility of autonomous cortisol production as well as hyperaldosteronism in the evaluation and treatment of APA patients.

Supplementary Material

 
  • References

  • 1 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
  • 2 Spath M, Korovkin S, Antke C, Anlauf M, Willenberg HS. Aldosterone- and cortisol-co-secreting adrenal tumors: the lost subtype of primary aldosteronism. Eur J Endocrinol 2011; 164: 447-455
  • 3 Fujimoto K, Honjo S, Tatsuoka H, Hamamoto Y, Kawasaki Y, Matsuoka A, Ikeda H, Wada Y, Sasano H, Koshiyama H. Primary aldosteronism associated with subclinical Cushing syndrome. J Endocrinol Invest 2013; 36: 564-567
  • 4 Nakamura Y, Maekawa T, Felizola SJ, Satoh F, Qi X, Velarde-Miranda C, Plonczynski MW, Ise K, Kikuchi K, Rainey WE. Adrenal CYP11B1/2 expression in primary aldosteronism: immunohistochemical analysis using novel monoclonal antibodies. Mol Cell Endocrinol 2014; 392: 73-79
  • 5 Nishimoto K, Nakagawa K, Li D, Kosaka T, Oya M, Mikami S, Shibata H, Itoh H, Mitani F, Yamazaki T, Ogishima T, Suematsu M, Mukai K. Adrenocortical zonation in humans under normal and pathological conditions. J Clin Endocrinol Metab 2010; 95: 2296-2305
  • 6 Arlt W, Lang K, Sitch AJ, Dietz AS, Rhayem Y, Bancos I, Feuchtinger A, Chortis V, Gilligan LC, Ludwig P, Riester A, Asbach E, Hughes BA, O'Neil DM, Bidlingmaier M, Tomlinson JW, Hassan-Smith ZK, Rees DA, Adolf C, Hahner S, Quinkler M, Dekkers T, Deinum J, Biehl M, Keevil BG, Shackleton CHL, Deeks JJ, Walch AK, Beuschlein F, Reincke M. Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. JCI Insight 2017; 2 pii: 93136 doi:10.1172/jci.insight.93136 [Epub ahead of print]
  • 7 Goupil R, Wolley M, Ahmed AH, Gordon RD, Stowasser M. Does concomitant autonomous adrenal cortisol overproduction have the potential to confound the interpretation of adrenal venous sampling in primary aldosteronism?. Clin Endocrinol 2015; 83: 456-461
  • 8 Di Dalmazi G, Pasquali R, Beuschlein F, Reincke M. Subclinical hypercortisolism: a state, a syndrome, or a disease?. Eur J Endocrinol 2015; 173: M61-M71
  • 9 Nishikawa T, Omura M, Satoh F, Shibata H, Takahashi K, Tamura N, Tanabe A. Guidelines for the diagnosis and treatment of primary aldosteronism-The Japan Endocrine Society. 2009; Endocr J 2011; 58: 711-721
  • 10 Satoh F, Morimoto R, Ono Y, Iwakura Y, Omata K, Kudo M, Takase K, Seiji K, Sasamoto H, Honma S, Okuyama M, Yamashita K, Gomez-Sanchez CE, Rainey WE, Arai Y, Sasano H, Nakamura Y, Ito S. Measurement of peripheral plasma 18-oxocortisol can discriminate unilateral adenoma from bilateral diseases in patients with primary aldosteronism. Hypertension 2015; 65: 1096-1102
  • 11 Omura M, Sasano H, Saito J, Yamaguchi K, Kakuta Y, Nishikawa T. Clinical characteristics of aldosterone-producing microadenoma, macroadenoma, and idiopathic hyperaldosteronism in 93 patients with primary aldosteronism. Hypertens Res 2006; 29: 883
  • 12 Inoue K, Omura M, Sugisawa C, Tsurutani Y, Saito J, Nishikawa T. clinical utility of the adrenocorticotropin stimulation test with/without dexamethasone suppression for definitive and subtype diagnosis of primary aldosteronism. Int J Mol Sci 2017; 18: 948
  • 13 Kitamoto T, Suematsu S, Yamazaki Y, Nakamura Y, Sasano H, Matsuzawa Y, Saito J, Omura M, Nishikawa T. Clinical and steroidogenic characteristics of aldosterone-producing adenomas with ATPase or CACNA1D gene mutations. J Clin Endocrinol Metab 2015; 101: 494-503
  • 14 Satoh F, Morimoto R, Seiji K, Satani N, Ota H, Iwakura Y, Ono Y, Kudo M, Nezu M, Omata K, Tezuka Y, Kawasaki Y, Ishidoya S, Arai Y, Takase K, Nakamura Y, McNamara K, Sasano H, Ito S. Is there a role for segmental adrenal venous sampling and adrenal sparing surgery in patients with primary aldosteronism?. Eur J Endocrinol 2015; 173: 465-477
  • 15 Weiss LM. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumors. Am J Surg Pathol 1984; 8: 163-170
  • 16 Gomez-Sanchez CE, Qi X, Velarde-Miranda C, Plonczynski MW, Parker CR, Rainey W, Satoh F, Maekawa T, Nakamura Y, Sasano H, Gomez-Sanchez EP. Development of monoclonal antibodies against human CYP11B1 and CYP11B2. Mol Cell Endocrinol 2014; 383: 111-117
  • 17 Budwit-Novotny DA, McCarty KS, Cox EB, Soper JT, Mutch DG, Creasman WT, Flowers JL. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res 1986; 46: 5419-5425
  • 18 Chiodini I. Diagnosis and treatment of subclinical hypercortisolism. J Clin Endocrinol Metab 2011; 96: 1223-1236
  • 19 Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO, Tabarin A. Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 100: 2807-2831
  • 20 Ono Y, Nakamura Y, Maekawa T, Felizola SJ, Morimoto R, Iwakura Y, Kudo M, Seiji K, Takase K, Arai Y, Gomez-Sanchez CE, Ito S, Sasano H, Satoh F. Different expression of 11beta-hydroxylase and aldosterone synthase between aldosterone-producing microadenomas and macroadenomas. Hypertension 2014; 64: 438-444
  • 21 White PC. Disorders of aldosterone biosynthesis and action. N Engl J Med 1994; 331: 250-258
  • 22 Fallo F, Veglio F, Bertello C, Sonino N, Della Mea P, Ermani M, Rabbia F, Federspil G, Mulatero P. Prevalence and characteristics of the metabolic syndrome in primary aldosteronism. J Clin Endocrinol Metab 2006; 91: 454-459
  • 23 Hanslik G, Wallaschofski H, Dietz A, Riester A, Reincke M, Allolio B, Lang K, Quack I, Rump LC, Willenberg HS, Beuschlein F, Quinkler M, Hannemann A. Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn's Registry. Eur J Endocrinol 2015; 173: 665-675
  • 24 Salcuni AS, Palmieri S, Carnevale V, Morelli V, Battista C, Guarnieri V, Guglielmi G, Desina G, Eller-Vainicher C, Beck-Peccoz P, Scillitani A, Chiodini I. Bone involvement in aldosteronism. J Bone Miner Res 2012; 27: 2217-2222
  • 25 Di Dalmazi G, Vicennati V, Garelli S, Casadio E, Rinaldi E, Giampalma E, Mosconi C, Golfieri R, Paccapelo A, Pagotto U, Pasquali R. Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: a 15-year retrospective study. Lancet Diabetes Endocrinol 2014; 2: 396-405
  • 26 Mitchell IC, Auchus RJ, Juneja K, Chang AY, Holt SA, Snyder 3rd WH, Nwariaku FE. "Subclinical Cushing's syndrome" is not subclinical: improvement after adrenalectomy in 9 patients. Surgery 2007; 142: 900-905 discussion 905.e901
  • 27 de La Villéon B, Bonnet S, Gouya H, Groussin L, Tenenbaum F, Gaujoux S, Dousset B. Long-term outcome after adrenalectomy for incidentally diagnosed subclinical cortisol-secreting adenomas. Surgery 2016; 160: 397-404
  • 28 Reincke M, Nieke J, Krestin GP, Saeger W, Allolio B, Winkelmann W. Preclinical Cushing's syndrome in adrenal" incidentalomas": comparison with adrenal Cushing's syndrome. J Clin Endocrinol Metab 1992; 75: 826-832
  • 29 Morelli V, Masserini B, Salcuni AS, Eller-Vainicher C, Savoca C, Viti R, Coletti F, Guglielmi G, Battista C, Iorio L, Beck-Peccoz P, Ambrosi B, Arosio M, Scillitani A, Chiodini I. Subclinical hypercortisolism: correlation between biochemical diagnostic criteria and clinical aspects. Clin Endocrinol 2010; 73: 161-166
  • 30 Chiodini I, Morelli V, Salcuni AS, Eller-Vainicher C, Torlontano M, Coletti F, Iorio L, Cuttitta A, Ambrosio A, Vicentini L. Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism. J Clin Endocrinol Metab 2010; 95: 2736-2745
  • 31 Ahmed AH, Gordon RD, Taylor PJ, Ward G, Pimenta E, Stowasser M. Effect of contraceptives on aldosterone/renin ratio may vary according to the components of contraceptive, renin assay method, and possibly route of administration. J Clin Endocrinol Metab 2011; 96: 1797-1804
  • 32 Williams TA, Peitzsch M, Dietz AS, Dekkers T, Bidlingmaier M, Riester A, Treitl M, Rhayem Y, Beuschlein F, Lenders JW, Deinum J, Eisenhofer G, Reincke M. Genotype-specific steroid profiles associated with aldosterone-producing adenomas. Hypertension 2016; 67: 139-145