Clinical course of patients with adrenal incidentalomas and cortisol autonomy: a German retrospective single center cohort study.
adrenal imaging
adrenal tumours
autonomous cortisol secretion
cardiovascular events
cardiovascular risk factors
dexamethasone suppression test
morbidity
mortality
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2023
2023
Historique:
received:
13
12
2022
accepted:
01
03
2023
medline:
26
5
2023
pubmed:
24
5
2023
entrez:
24
5
2023
Statut:
epublish
Résumé
Adrenal incidentalomas with cortisol autonomy are associated with increased cardiovascular morbidity and mortality. Specific data on the clinical and biochemical course of affected patients are lacking. Retrospective study from a tertiary referral centre in Germany. After exclusion of overt hormone excess, malignancy and glucocorticoid medication, patients with adrenal incidentalomas were stratified according to serum cortisol after 1 mg dexamethasone: autonomous cortisol secretion (ACS), >5.0; possible ACS (PACS), 1.9-5.0; non-functioning adenomas (NFA), ≤1.8 µg/dl. A total of 260 patients were enrolled (147 women (56.5%), median follow-up 8.8 (2.0-20.8) years). At initial diagnosis, median age was 59.5 (20-82) years, and median tumour size was 27 (10-116) mm. Bilateral tumours were more prevalent in ACS (30.0%) and PACS (21.9%) than in NFA (8.1%). Over time, 40/124 (32.3%) patients had a shift of their hormonal secretion pattern (NFA to PACS/ACS, n=15/53; PACS to ACS, n=6/47; ACS to PACS, n=11/24; PACS to NFA, n=8/47). However, none of the patients developed overt Cushing's syndrome. Sixty-one patients underwent adrenalectomy (NFA, 17.9%; PACS, 24.0%; ACS, 39.0%). When non-operated patients with NFA were compared to PACS and ACS at last follow-up, arterial hypertension (65.3% vs. 81.9% and 92.0%; p<0.05), diabetes (23.8% vs. 35.6% and 40.0%; p<0.01), and thromboembolic events (PACS: HR 3.43, 95%-CI 0.89-13.29; ACS: HR 5.96, 95%-CI 1.33-26.63; p<0.05) were significantly less frequent, along with a trend towards a higher rate of cardiovascular events in case of cortisol autonomy (PACS: HR 2.23, 95%-CI 0.94-5.32; ACS: HR 2.60, 95%-CI 0.87-7.79; p=0.1). Twenty-five (12.6%) of the non-operated patients died, with higher overall mortality in PACS (HR 2.6, 95%-CI 1.0-4.7; p=0.083) and ACS (HR 4.7, 95%-CI 1.6-13.3; p<0.005) compared to NFA. In operated patients, prevalence of arterial hypertension decreased significantly (77.0% at diagnosis to 61.7% at last follow-up; p<0.05). The prevalence of cardiovascular events and mortality did not differ significantly between operated and non-operated patients, whereas thromboembolic events were significantly less frequent in the surgical treatment group. Our study confirms relevant cardiovascular morbidity in patients with adrenal incidentalomas (especially those with cortisol autonomy). These patients should therefore be monitored carefully, including adequate treatment of typical cardiovascular risk factors. Adrenalectomy was associated with a significantly decreased prevalence of hypertension. However, more than 30% of patients required reclassification according to repeated dexamethasone suppression tests. Thus, cortisol autonomy should ideally be confirmed before making any relevant treatment decision (e.g. adrenalectomy).
Sections du résumé
Background
Adrenal incidentalomas with cortisol autonomy are associated with increased cardiovascular morbidity and mortality. Specific data on the clinical and biochemical course of affected patients are lacking.
Methods
Retrospective study from a tertiary referral centre in Germany. After exclusion of overt hormone excess, malignancy and glucocorticoid medication, patients with adrenal incidentalomas were stratified according to serum cortisol after 1 mg dexamethasone: autonomous cortisol secretion (ACS), >5.0; possible ACS (PACS), 1.9-5.0; non-functioning adenomas (NFA), ≤1.8 µg/dl.
Results
A total of 260 patients were enrolled (147 women (56.5%), median follow-up 8.8 (2.0-20.8) years). At initial diagnosis, median age was 59.5 (20-82) years, and median tumour size was 27 (10-116) mm. Bilateral tumours were more prevalent in ACS (30.0%) and PACS (21.9%) than in NFA (8.1%). Over time, 40/124 (32.3%) patients had a shift of their hormonal secretion pattern (NFA to PACS/ACS, n=15/53; PACS to ACS, n=6/47; ACS to PACS, n=11/24; PACS to NFA, n=8/47). However, none of the patients developed overt Cushing's syndrome. Sixty-one patients underwent adrenalectomy (NFA, 17.9%; PACS, 24.0%; ACS, 39.0%). When non-operated patients with NFA were compared to PACS and ACS at last follow-up, arterial hypertension (65.3% vs. 81.9% and 92.0%; p<0.05), diabetes (23.8% vs. 35.6% and 40.0%; p<0.01), and thromboembolic events (PACS: HR 3.43, 95%-CI 0.89-13.29; ACS: HR 5.96, 95%-CI 1.33-26.63; p<0.05) were significantly less frequent, along with a trend towards a higher rate of cardiovascular events in case of cortisol autonomy (PACS: HR 2.23, 95%-CI 0.94-5.32; ACS: HR 2.60, 95%-CI 0.87-7.79; p=0.1). Twenty-five (12.6%) of the non-operated patients died, with higher overall mortality in PACS (HR 2.6, 95%-CI 1.0-4.7; p=0.083) and ACS (HR 4.7, 95%-CI 1.6-13.3; p<0.005) compared to NFA. In operated patients, prevalence of arterial hypertension decreased significantly (77.0% at diagnosis to 61.7% at last follow-up; p<0.05). The prevalence of cardiovascular events and mortality did not differ significantly between operated and non-operated patients, whereas thromboembolic events were significantly less frequent in the surgical treatment group.
Conclusion
Our study confirms relevant cardiovascular morbidity in patients with adrenal incidentalomas (especially those with cortisol autonomy). These patients should therefore be monitored carefully, including adequate treatment of typical cardiovascular risk factors. Adrenalectomy was associated with a significantly decreased prevalence of hypertension. However, more than 30% of patients required reclassification according to repeated dexamethasone suppression tests. Thus, cortisol autonomy should ideally be confirmed before making any relevant treatment decision (e.g. adrenalectomy).
Identifiants
pubmed: 37223045
doi: 10.3389/fendo.2023.1123132
pmc: PMC10200872
doi:
Substances chimiques
Hydrocortisone
WI4X0X7BPJ
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1123132Informations de copyright
Copyright © 2023 Remde, Kranz, Morell, Altieri, Kroiss, Detomas, Fassnacht and Deutschbein.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Eur J Endocrinol. 2013 Jan 17;168(2):235-41
pubmed: 23169694
Ann Surg. 2009 Mar;249(3):388-91
pubmed: 19247023
Ann Intern Med. 2022 Mar;175(3):325-334
pubmed: 34978855
Endocrine. 2017 May;56(2):262-266
pubmed: 27406391
J Clin Endocrinol Metab. 2014 Dec;99(12):4462-70
pubmed: 25238207
Eur J Endocrinol. 2016 Aug;175(2):G1-G34
pubmed: 27390021
J Clin Endocrinol Metab. 2022 Jan 18;107(2):e594-e603
pubmed: 34534321
Ann Intern Med. 2021 Aug;174(8):1041-1049
pubmed: 34029490
Eur J Endocrinol. 2014 Jul;171(1):37-45
pubmed: 24743396
Endocrine. 2017 Nov;58(2):267-275
pubmed: 28887710
J Clin Endocrinol Metab. 2020 Dec 1;105(12):
pubmed: 32875319
Eur J Endocrinol. 2016 Dec;175(6):R283-R295
pubmed: 27450696
J Clin Endocrinol Metab. 2010 Jun;95(6):2736-45
pubmed: 20375210
World J Surg. 1999 Apr;23(4):389-96
pubmed: 10030863
Endocr J. 2008 Aug;55(4):737-45
pubmed: 18506093
Ann Intern Med. 2019 Jul 16;171(2):107-116
pubmed: 31234202
Front Endocrinol (Lausanne). 2022 Jun 02;13:898084
pubmed: 35721734
Lancet Diabetes Endocrinol. 2014 May;2(5):396-405
pubmed: 24795253
J Clin Endocrinol Metab. 2016 Sep;101(9):3526-38
pubmed: 27389594
Internist (Berl). 2022 Jan;63(1):18-24
pubmed: 34709420
J Endocrinol Invest. 2017 Mar;40(3):331-333
pubmed: 27744612
Eur J Endocrinol. 2009 Oct;161(4):513-27
pubmed: 19439510
N Engl J Med. 2014 Mar 13;370(11):1019-28
pubmed: 24571724
Endocr Rev. 2020 Dec 1;41(6):
pubmed: 32266384
Exp Clin Endocrinol Diabetes. 2021 May;129(5):349-356
pubmed: 31958848
Clin Endocrinol (Oxf). 2017 Apr;86(4):488-498
pubmed: 27992961
Lancet Diabetes Endocrinol. 2022 Jul;10(7):499-508
pubmed: 35533704
Clin Endocrinol (Oxf). 2012 Jan;76(1):12-8
pubmed: 21988204
Br J Surg. 2015 Mar;102(4):318-30
pubmed: 25640696
Lancet. 2015 Aug 29;386(9996):913-27
pubmed: 26004339