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Published in: Cardiovascular Diabetology 1/2023

Open Access 01-12-2023 | Obesity | Research

The degree of cortisol secretion is associated with diabetes mellitus and hypertension in patients with nonfunctioning adrenal tumors

Authors: Vittoria Favero, Carmen Aresta, Chiara Parazzoli, Elisa Cairoli, Cristina Eller-Vainicher, Serena Palmieri, Antonio Stefano Salcuni, Maura Arosio, Luca Persani, Alfredo Scillitani, Valentina Morelli, Iacopo Chiodini

Published in: Cardiovascular Diabetology | Issue 1/2023

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Abstract

Background

Similarly to cortisol-secreting adrenal tumors, also non-functioning adrenal tumors (NFAT) may be associated with an increased cardiovascular risk. We assessed in NFAT patients: (i) the association between hypertension (HT), diabetes mellitus (DM), obesity (OB), dyslipidemia (DL) and cardiovascular events (CVE) and cortisol secretion; (ii) the cut-off of the cortisol secretion parameters for identifying NFAT patients with a worse cardiometabolic profile.

Patients and methods

In 615 NFAT patients (with cortisol levels after 1 mg overnight dexamethasone suppression test, F-1mgDST < 1.8 µg/dL [50 nmol/L]) F-1mgDST and adrenocorticotroph hormone (ACTH) levels and data on HT, DM, OB, DL and CVEs prevalence were retrospectively collected.

Results

HT, DM and HT plus DM were associated with F-1mgDST levels (area under the ROC curve: 0.588 ± 0.023, 0.610 ± 0.028, 0.611 ± 0.033, respectively, p < 0.001 for all comparisons) but not with ACTH. The cut-off for identifying patients with either HT or DM or HT plus DM was set at ≥ 1.2 µg/dL (33 nmol/L). As compared with patients with F-1mgDST < 1.2 µg/dL (n = 289), patients with F-1mgDST 1.2–1.79 µg/dL (33–49.4 nmol/L) (n = 326) had lower ACTH levels (17.7 ± 11.9 vs 15.3 ± 10.1 pg/mL, respectively, p = 0.008), older age (57.5 ± 12.3 vs 62.5 ± 10.9 years, respectively, p < 0.001), and higher prevalence of HT (38.1% vs 52.5% respectively p < 0.001), DM (13.1% vs 23.3%, respectively, p = 0.001), HT plus DM (8.3% vs 16.9%, respectively, p < 0.002) and CVE (3.2% vs 7.3%, respectively, p = 0.028). F-1mgDST 1.2–1.79 µg/dL was associated with either HT (odd ratio, OR, 1.55, 95% confidence interval, 95% CI 1.08–2.23, p = 0.018) or DM (OR 1.60, 95% CI 1.01–2.57, p = 0.045) after adjusting for age, gender, OB, DL, and DM (for HT) or HT (for DM), and with the presence of HT plus DM (OR 1.96, 95% CI 1.12–3.41, p = 0.018) after adjusting for age, gender, OB and DL.

Conclusions

In NFAT patients, F-1mgDST 1.2–1.79 µg/dL seems to be associated with a higher prevalence of HT and DM and a worse cardiometabolic profile, even if the poor accuracy of these associations suggests caution in interpreting these results.
Literature
1.
go back to reference Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016;175:G1-34.CrossRefPubMed Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, et al. Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2016;175:G1-34.CrossRefPubMed
3.
go back to reference Chiodini I. Clinical review: diagnosis and treatment of subclinical hypercortisolism. J Clin Endocrinol Metab. 2011;96(5):1223–36.CrossRefPubMed Chiodini I. Clinical review: diagnosis and treatment of subclinical hypercortisolism. J Clin Endocrinol Metab. 2011;96(5):1223–36.CrossRefPubMed
4.
go back to reference Park J, de Luca A, Dutton H, Malcolm JC, Doyle MA. Cardiovascular outcomes in autonomous cortisol secretion and nonfunctioning adrenal adenoma: a systematic review. J Endocrine Soc. 2019;3:996–1008.CrossRef Park J, de Luca A, Dutton H, Malcolm JC, Doyle MA. Cardiovascular outcomes in autonomous cortisol secretion and nonfunctioning adrenal adenoma: a systematic review. J Endocrine Soc. 2019;3:996–1008.CrossRef
5.
go back to reference Deutschbein T, Reimondo G, di Dalmazi G, Bancos I, Patrova J, Vassiliadi DA, et al. Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study. Lancet Diabetes Endocrinol. 2022;10(7):499–508.CrossRefPubMed Deutschbein T, Reimondo G, di Dalmazi G, Bancos I, Patrova J, Vassiliadi DA, et al. Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: an international, retrospective, cohort study. Lancet Diabetes Endocrinol. 2022;10(7):499–508.CrossRefPubMed
6.
go back to reference Kjellbom A, Lindgren O, Puvaneswaralingam S, Löndahl M, Olsen H. Association between mortality and levels of autonomous cortisol secretion by adrenal incidentalomas. Ann Intern Med. 2021;174(8):1041–9.CrossRefPubMed Kjellbom A, Lindgren O, Puvaneswaralingam S, Löndahl M, Olsen H. Association between mortality and levels of autonomous cortisol secretion by adrenal incidentalomas. Ann Intern Med. 2021;174(8):1041–9.CrossRefPubMed
7.
go back to reference Debono M, Bradburn M, Bull M, Harrison B, Ross RJ, Newell-Price J. Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas. J Clin Endocrinol Metab. 2014;99(12):4462–70.CrossRefPubMedPubMedCentral Debono M, Bradburn M, Bull M, Harrison B, Ross RJ, Newell-Price J. Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas. J Clin Endocrinol Metab. 2014;99(12):4462–70.CrossRefPubMedPubMedCentral
8.
go back to reference Patrova J, Kjellman M, Wahrenberg H, Falhammar H. Increased mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: a 13-year retrospective study from one center. Endocrine. 2017;58:267–75.CrossRefPubMed Patrova J, Kjellman M, Wahrenberg H, Falhammar H. Increased mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: a 13-year retrospective study from one center. Endocrine. 2017;58:267–75.CrossRefPubMed
9.
go back to reference di Dalmazi G, Vicennati V, Garelli S, Casadio E, Rinaldi E, Giampalma E, et al. 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(5):396–405.CrossRefPubMed di Dalmazi G, Vicennati V, Garelli S, Casadio E, Rinaldi E, Giampalma E, et al. 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(5):396–405.CrossRefPubMed
10.
go back to reference Morelli V, Arosio M, Chiodini I. Cardiovascular mortality in patients with subclinical Cushing. Ann Endocrinol. 2018;79(3):149–52.CrossRef Morelli V, Arosio M, Chiodini I. Cardiovascular mortality in patients with subclinical Cushing. Ann Endocrinol. 2018;79(3):149–52.CrossRef
12.
go back to reference Chiodini I, Morelli V, Salcuni AS, Eller-Vainicher C, Torlontano M, Coletti F, et al. Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism. J Clin Endocrinol Metab. 2010;95(6):2736–45.CrossRefPubMed Chiodini I, Morelli V, Salcuni AS, Eller-Vainicher C, Torlontano M, Coletti F, et al. Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism. J Clin Endocrinol Metab. 2010;95(6):2736–45.CrossRefPubMed
13.
go back to reference Delivanis DA, Athimulam S, Bancos I. Modern management of mild autonomous cortisol secretion. Clin Pharmacol Ther. 2019;106(6):1209–21.CrossRefPubMed Delivanis DA, Athimulam S, Bancos I. Modern management of mild autonomous cortisol secretion. Clin Pharmacol Ther. 2019;106(6):1209–21.CrossRefPubMed
14.
go back to reference Bancos I, Alahdab F, Crowley RK, Chortis V, Delivanis DA, Erickson D, et al. Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: a systematic review and meta-analysis. Eur J Endocrinol. 2016;175(6):R283–95.CrossRefPubMed Bancos I, Alahdab F, Crowley RK, Chortis V, Delivanis DA, Erickson D, et al. Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: a systematic review and meta-analysis. Eur J Endocrinol. 2016;175(6):R283–95.CrossRefPubMed
15.
go back to reference Morelli V, Frigerio S, Aresta C, Passeri E, Pugliese F, Copetti M, et al. Adrenalectomy improves blood pressure and metabolic control in patients with possible autonomous cortisol secretion: results of a RCT. Front Endocrinol. 2022;2(13): 898084.CrossRef Morelli V, Frigerio S, Aresta C, Passeri E, Pugliese F, Copetti M, et al. Adrenalectomy improves blood pressure and metabolic control in patients with possible autonomous cortisol secretion: results of a RCT. Front Endocrinol. 2022;2(13): 898084.CrossRef
16.
go back to reference Androulakis II, Kaltsas GA, Kollias GE, Markou AC, Gouli AK, Thomas DA, et al. Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion. J Clin Endocrinol Metab. 2014;99(8):2754–62.CrossRefPubMed Androulakis II, Kaltsas GA, Kollias GE, Markou AC, Gouli AK, Thomas DA, et al. Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion. J Clin Endocrinol Metab. 2014;99(8):2754–62.CrossRefPubMed
17.
go back to reference Lopez D, Luque-Fernandez MA, Steele A, Adler GK, Turchin A, Vaidya A. “Nonfunctional” adrenal tumors and the risk for incident diabetes and cardiovascular outcomes: a cohort study. Ann Intern Med. 2016;165(8):533–42.CrossRefPubMedPubMedCentral Lopez D, Luque-Fernandez MA, Steele A, Adler GK, Turchin A, Vaidya A. “Nonfunctional” adrenal tumors and the risk for incident diabetes and cardiovascular outcomes: a cohort study. Ann Intern Med. 2016;165(8):533–42.CrossRefPubMedPubMedCentral
18.
go back to reference Tuna MM, Imga NN, Doǧan BA, Yilmaz FM, Topçuoǧlu C, Akbaba G, et al. Non-functioning adrenal incidentalomas are associated with higher hypertension prevalence and higher risk of atherosclerosis. J Endocrinol Invest. 2014;37(8):765–8.CrossRefPubMed Tuna MM, Imga NN, Doǧan BA, Yilmaz FM, Topçuoǧlu C, Akbaba G, et al. Non-functioning adrenal incidentalomas are associated with higher hypertension prevalence and higher risk of atherosclerosis. J Endocrinol Invest. 2014;37(8):765–8.CrossRefPubMed
19.
go back to reference Yener S, Genc S, Akinci B, Secil M, Demir T, Comlekci A, et al. Carotid intima media thickness is increased and associated with morning cortisol in subjects with non-functioning adrenal incidentaloma. Endocrine. 2009;35(3):365–70.CrossRefPubMed Yener S, Genc S, Akinci B, Secil M, Demir T, Comlekci A, et al. Carotid intima media thickness is increased and associated with morning cortisol in subjects with non-functioning adrenal incidentaloma. Endocrine. 2009;35(3):365–70.CrossRefPubMed
20.
go back to reference Elhassan YS, Alahdab F, Prete A, Delivanis DA, Khanna A, Prokop L, et al. Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess a systematic review and meta-analysis. Anna Intern Med. 2019;171:107–16.CrossRef Elhassan YS, Alahdab F, Prete A, Delivanis DA, Khanna A, Prokop L, et al. Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess a systematic review and meta-analysis. Anna Intern Med. 2019;171:107–16.CrossRef
21.
go back to reference Eller-Vainicher C, Morelli V, Aresta C, Salcuni AS, Falchetti A, Carnevale V, et al. Defining nonfunctioning adrenal adenomas on the basis of the occurrence of hypocortisolism after adrenalectomy. J Endocr Soc. 2020;4(8):bvaa079.CrossRefPubMedPubMedCentral Eller-Vainicher C, Morelli V, Aresta C, Salcuni AS, Falchetti A, Carnevale V, et al. Defining nonfunctioning adrenal adenomas on the basis of the occurrence of hypocortisolism after adrenalectomy. J Endocr Soc. 2020;4(8):bvaa079.CrossRefPubMedPubMedCentral
22.
go back to reference Morelli V, Reimondo G, Giordano R, della Casa S, Policola C, Palmieri S, et al. Long-term follow-up in adrenal incidentalomas: an Italian multicenter study. J Clin Endocrinol Metab. 2014;99(3):827–34.CrossRefPubMed Morelli V, Reimondo G, Giordano R, della Casa S, Policola C, Palmieri S, et al. Long-term follow-up in adrenal incidentalomas: an Italian multicenter study. J Clin Endocrinol Metab. 2014;99(3):827–34.CrossRefPubMed
23.
go back to reference Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC practice guidelines for the management of arterial hypertension. Blood Press. 2014;23(1):3–16.CrossRefPubMed Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, et al. 2013 ESH/ESC practice guidelines for the management of arterial hypertension. Blood Press. 2014;23(1):3–16.CrossRefPubMed
24.
go back to reference Classification and diagnosis of diabetes. Standards of medical care in diabetesd2019. Diabetes Care. 2019;1(42):S13-28. Classification and diagnosis of diabetes. Standards of medical care in diabetesd2019. Diabetes Care. 2019;1(42):S13-28.
25.
go back to reference Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults the third report of the expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) constitutes the National [Internet]. Available from: https://jamanetwork.com/ Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults the third report of the expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) constitutes the National [Internet]. Available from: https://​jamanetwork.​com/​
26.
go back to reference Husten CG. How should we define light or intermittent smoking? Does it matter? Nicotine Tobacco Res. 2009;11:111–21.CrossRef Husten CG. How should we define light or intermittent smoking? Does it matter? Nicotine Tobacco Res. 2009;11:111–21.CrossRef
27.
go back to reference Araujo-Castro M. Cardiometabolic profile and urinary metabolomic alterations in non-functioning adrenal incidentalomas: a review. Clin Endocrinol (Oxf). 2022;97(6):693–701.CrossRefPubMed Araujo-Castro M. Cardiometabolic profile and urinary metabolomic alterations in non-functioning adrenal incidentalomas: a review. Clin Endocrinol (Oxf). 2022;97(6):693–701.CrossRefPubMed
28.
go back to reference Morelli V, Minelli L, Eller-Vainicher C, Palmieri S, Cairoli E, Spada A, et al. Predictability of hypoadrenalism occurrence and duration after adrenalectomy for ACTH-independent hypercortisolism. J Endocrinol Invest. 2018;41(4):485–93.CrossRefPubMed Morelli V, Minelli L, Eller-Vainicher C, Palmieri S, Cairoli E, Spada A, et al. Predictability of hypoadrenalism occurrence and duration after adrenalectomy for ACTH-independent hypercortisolism. J Endocrinol Invest. 2018;41(4):485–93.CrossRefPubMed
29.
go back to reference Chiodini I, Morelli V. Subclinical hypercortisolism: how to deal with it? Front Hormone Res. 2016;46:28–38.CrossRef Chiodini I, Morelli V. Subclinical hypercortisolism: how to deal with it? Front Hormone Res. 2016;46:28–38.CrossRef
30.
go back to reference Araujo-Castro M, Sampedro Núñez MA, Marazuela M. Autonomous cortisol secretion in adrenal incidentalomas. Endocrine. 2019;64:1–13.CrossRefPubMed Araujo-Castro M, Sampedro Núñez MA, Marazuela M. Autonomous cortisol secretion in adrenal incidentalomas. Endocrine. 2019;64:1–13.CrossRefPubMed
31.
go back to reference Zhukouskaya VV, Eller-Vainicher C, Gaudio A, Cairoli E, Ulivieri FM, Palmieri S, et al. In postmenopausal female subjects with type 2 diabetes mellitus, vertebral fractures are independently associated with cortisol secretion and sensitivity. J Clin Endocrinol Metab. 2015;100(4):1417–25.CrossRefPubMed Zhukouskaya VV, Eller-Vainicher C, Gaudio A, Cairoli E, Ulivieri FM, Palmieri S, et al. In postmenopausal female subjects with type 2 diabetes mellitus, vertebral fractures are independently associated with cortisol secretion and sensitivity. J Clin Endocrinol Metab. 2015;100(4):1417–25.CrossRefPubMed
32.
go back to reference Chiodini I, Gaudio A, Eller-Vainicher C, Morelli V, Aresta C, Zhukouskaya VV, et al. Cortisol secretion, sensitivity, and activity are associated with hypertension in postmenopausal eucortisolemic women. J Clin Endocrinol Metab. 2019;104(10):4441–8.CrossRefPubMed Chiodini I, Gaudio A, Eller-Vainicher C, Morelli V, Aresta C, Zhukouskaya VV, et al. Cortisol secretion, sensitivity, and activity are associated with hypertension in postmenopausal eucortisolemic women. J Clin Endocrinol Metab. 2019;104(10):4441–8.CrossRefPubMed
Metadata
Title
The degree of cortisol secretion is associated with diabetes mellitus and hypertension in patients with nonfunctioning adrenal tumors
Authors
Vittoria Favero
Carmen Aresta
Chiara Parazzoli
Elisa Cairoli
Cristina Eller-Vainicher
Serena Palmieri
Antonio Stefano Salcuni
Maura Arosio
Luca Persani
Alfredo Scillitani
Valentina Morelli
Iacopo Chiodini
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2023
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-023-01836-1

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