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01-12-2021 | Dexamethasone | Original Article

Accuracy of the dexamethasone suppression test for the prediction of autonomous cortisol secretion-related comorbidities in adrenal incidentalomas

Authors: Marta Araujo-Castro, Paola Parra Ramírez, Cristina Robles Lázaro, Rogelio García Centeno, Paola Gracia Gimeno, Mariana Tomé Fernández-Ladreda, Miguel Antonio Sampedro Núñez, Mónica Marazuela, Héctor F. Escobar-Morreale, Pablo Valderrabano

Published in: Hormones | Issue 4/2021

Abstract

Purpose

The aim of this study was to evaluate the diagnostic accuracy of the 1 mg dexamethasone suppression test (DST) for the prediction of autonomous cortisol secretion (ACS)-related comorbidities in patients with adrenal incidentalomas (AIs).

Methods

This was a retrospective multicenter study. We recruited patients with AI/s ≥ 1 cm, excluding those who, during the study, were found during the extension study of an extra-adrenal cancer, with a known diagnosis of hereditary syndromes characterized by adrenal tumors, those presenting with overt hormonal excess syndromes, and those in whom the DST results were missing.

Results

A total of 823 patients met the inclusion criteria. Based on the 1.8, 3.0, and 5.0 µg/dl post-DST cortisol thresholds, the prevalence of ACS was 33.5%, 13.7%, and 5.6%, respectively. The prevalence of hypertension (OR = 1.8, 95% CI = 1.3–2.4), diabetes (OR = 1.6, 95% CI = 1.2–2.2), and dyslipidemia (OR = 1.4, 95% CI = 1.0–1.9) was higher with cortisol post-DST ≥ 1.8 µg/dl; the prevalence of hypertension (OR = 2.1, 95% CI = 1.4–3.3) and diabetes (OR = 1.7, 95% CI = 1.1–2.6) was higher with values ≥ 3.0 µg/dl; and the prevalence of hypertension (OR = 2.0, 95% CI = 1.0–3.7) was higher with levels ≥ 5.0 µg/dl. However, the diagnostic accuracy of the DST for the prediction of cardiometabolic comorbidities in patients with AIs was poor, with areas under the ROC curve < 0.61.

Conclusions

The DST is a poor predictor of cardiometabolic comorbidities in patients with AIs regardless of the cortisol cut-off values applied. This finding suggests that the diagnosis of ACS should not be based solely on the results of the DST. Other clinical, metabolic, or imaging markers showing a better performance for the prediction of the development and progression of cardiometabolic comorbidities in AIs need to be identified.

Wagner J, Aron DC (2012) Incidentalomas - a “disease” of modern imaging technology. Best Pract Res Clin Endocrinol Metab 26(1):3–8. https://doi.org/10.1016/j.beem.2011.08.006CrossRefPubMed

Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A et al (2016) 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 175(2):G1–G34. https://doi.org/10.1530/EJE-16-0467CrossRefPubMed

Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B (1997) Incidentally discovered adrenal masses. Cancer Treat Res 89:263–292. https://doi.org/10.1007/978-1-4615-6355-6_13CrossRefPubMed

Araujo-Castro M, Iturregui Guevara M, Calatayud Gutiérrez M, Parra Ramírez P, Gracia Gimeno P, Hanzu FA et al (2020) Practical guide on the initial evaluation, follow-up, and treatment of adrenal incidentalomas Adrenal Diseases Group of the Spanish Society of Endocrinology and Nutrition. Endocrinol Diabetes Nutr 67(6):408–419. https://doi.org/10.1016/j.endinu.2020.03.002CrossRef

Terzolo M, Stigliano A, Chiodini I, Furlani L, Arnaldi G, Reimondo G et al (2011) AME position statement on adrenal incidentaloma. Eur J Endocrinol 164(6):851–870. https://doi.org/10.1530/EJE-10-1147CrossRefPubMed

Araujo-Castro M, Sampedro Núñez MA, Marazuela M (2019) Autonomous cortisol secretion in adrenal incidentalomas. Endocrine 64(1):1–13. https://doi.org/10.1007/s12020-019-01888-yCrossRefPubMed

Osella G, Terzolo M, Borretta G, Magro G, Ali A, Piovesan A, Paccotti P et al (1994) Endocrine evaluation of incidentally discovered adrenal masses (incidentalomas). J Clin Endocrinol Metab 79(6):1532–1539. https://doi.org/10.1210/jcem.79.6.7989452CrossRefPubMed

Glazer D, Mayo-Smith W (2020) Management of incidental adrenal masses: an update. Abdom Radiol (NY) 45(4):892–900. https://doi.org/10.1007/s00261-019-02149-2CrossRef

Tabarin A, Bardet S, Bertherat J, Dupas B, Chabre O, Hamoir E et al (2008) Exploration and management of adrenal incidentalomas. French Society of Endocrinology Consensus. Ann Endocrinol (Paris) 69(6):487–500. https://doi.org/10.1016/j.ando.2008.09.003CrossRef

10.

Zeiger MA, Thompson GB, Duh Q-YY, Hamrahian AH, Angelos P, Elaraj D et al (2009) American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons Medical Guidelines for the Management of Adrenal Incidentalomas: executive summary of recommendations. Endocr Pract 15(5):450–453. https://doi.org/10.4158/EP.15.5.450CrossRefPubMed

11.

Grumbach MM, Biller BMK, Braunstein GD, Campbell KK, Carney JA, Godley PA et al (2003) Management of the clinically inapparent adrenal mass (“incidentaloma”). Ann Intern Med 138(5):424–429. https://doi.org/10.7326/0003-4819-138-5-200303040-00013CrossRefPubMed

12.

Barzon L, Sonino N, Fallo F, Palù G, Boscaro M (2003) Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol 149(4):273–285. https://doi.org/10.1530/eje.0.1490273CrossRefPubMed

13.

Yilmaz N, Avsar E, Tazegul G, Sari R, Altunbas H, Balci MK (2020) Clinical characteristics and follow-up results of adrenal incidentaloma. Exp Clin Endocrinol Diabetes. https://doi.org/10.1055/a-1079-4915

14.

Di Dalmazi G, Vicennati V, Rinaldi E, Morselli-Labate AM, Giampalma E, Mosconi C et al (2012) Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: a large cross-sectional study. Eur J Endocrinol 166(4):669–677. https://doi.org/10.1530/EJE-11-1039CrossRefPubMed

15.

Chiodini I, Morelli V, Masserini B, Salcuni AS, Eller-Vainicher C, Francesca Coletti RF et al (2009) Bone mineral density, prevalence of vertebral fractures, and bone quality in patients with adrenal incidentalomas with and without subclinical hypercortisolism: an Italian multicenter study. J Clin Endocrinol Metab 94(9):3207–3214. https://doi.org/10.1210/jc.2009-0468CrossRefPubMed

16.

Araujo-Castro M, Robles Lázaro C, Parra-Ramírez P, Cuesta Hernández M, Sampedro Núñez MA et al (2019) Cardiometabolic profile of non-functioning and autonomous cortisol-secreting adrenal incidentalomas. Is the cardiometabolic risk similar or are there differences? Endocrine 66(3):650–659. https://doi.org/10.1007/s12020-019-02066-wCrossRefPubMed

17.

Morelli V, Masserini B, Salcuni AS, Eller-Vainicher C, Savoca C, Viti R et al (2010) Subclinical hypercortisolism: correlation between biochemical diagnostic criteria and clinical aspects. Clin Endocrinol (Oxf) 73(2):161–166. https://doi.org/10.1111/j.1365-2265.2010.03794.xCrossRef

18.

Eller-Vainicher C, Morelli V, Salcuni AS, Battista C, Torlontano M, Coletti F et al (2010) Accuracy of several parameters of hypothalamic-pituitary-adrenal axis activity in predicting before surgery the metabolic effects of the removal of an adrenal incidentaloma. Eur J Endocrinol 163(6):925–935. https://doi.org/10.1530/EJE-10-0602CrossRefPubMed

19.

Association American Diabetes (2018) Updates to the Standards of Medical Care in Diabetes-2018. Diabetes Care 41(9):2045–2047. https://doi.org/10.2337/dc18-su09CrossRef

20.

Third Report of the National Cholesterol Education Program (NCEP) (2002) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 106(25):3143–3421CrossRef

21.

Ekelund S (2012) ROC curves – what are they and how are they used? J Near-Patient Test Technol 11(1):16–21. https://doi.org/10.1097/POC.0b013e318246a642”CrossRef

22.

Morelli V, Reimondo G, Giordano R, Della Casa S, Policola C, Palmieri S et al (2014) Long-term follow-up in adrenal incidentalomas: an Italian multicenter study. J Clin Endocrinol Metab 99(3):827–834. https://doi.org/10.1210/jc.2013-3527CrossRefPubMed

23.

Morelli V, Palmieri S, Lania A, Tresoldi A, Corbetta S, Cairoli E et al (2017) Cardiovascular events in patients with mild autonomous cortisol secretion: analysis with artificial neural networks. Eur J Endocrinol 177(1):73–83. https://doi.org/10.1530/EJE-17-0047CrossRefPubMed

24.

Yener S, Ertilav S, Secil M, Akinci B, Demir T, Kebapcilar L et al (2012) Increased risk of unfavorable metabolic outcome during short-term follow-up in subjects with nonfunctioning adrenal adenomas. Med Princ Pract 21(5):429–434. https://doi.org/10.1159/000336589CrossRefPubMed

25.

Elhassan YS, Alahdab F, Prete A, Delivanis DA, Khanna A, Prokop L et al (2019) Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess. Ann Intern Med 171(2):107–116. https://doi.org/10.7326/M18-3630.30CrossRefPubMed

26.

Peppa M, Boutati E, Koliaki C, Papaefstathiou N, Garoflos E, Economopoulos T et al (2010) Insulin resistance and metabolic syndrome in patients with nonfunctioning adrenal incidentalomas: a cause-effect relationship? Metabolism 59(10):1435–1441. https://doi.org/10.1016/j.metabol.2010.01.007CrossRefPubMed

27.

Androulakis II, Kaltsas GA, Kollias GE, Markou AC, Gouli AK, Thomas DA et al (2014) Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion. J Clin Endocrinol Metab 99(8):2754–2762. https://doi.org/10.1210/jc.2013-4064CrossRefPubMed

28.

Bansal V, Asmar N, Selman W, Arafah B (2015) Pitfalls in the diagnosis and management of Cushing’s syndrome. Neurosurg Focus 38(2):E4. https://doi.org/10.3171/2014.11.FOCUS14704CrossRefPubMed

29.

Peppa M, Koliaki C, Raptis SA (2010) Adrenal incidentalomas and cardiometabolic morbidity: an emerging association with serious clinical implications. J Intern Med 268(6):555–566. https://doi.org/10.1111/j.1365-2796.2010.02291.xCrossRefPubMed

30.

Kotłowska A, Maliński E, Sworczak K, Kumirska J, Stepnowski P (2009) The urinary steroid profile in patients diagnosed with adrenal incidentaloma. Clin Biochem 42(6):448–454. https://doi.org/10.1016/j.clinbiochem.2008.12.027CrossRefPubMed

31.

Giordano R, Marinazzo E, Berardelli R, Picu A, Maccario M, Ghigo E et al (2010) Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas. Eur J Endocrinol 162(4):779–785. https://doi.org/10.1530/EJE-09-0957CrossRefPubMed

32.

Vassilatou E, Vryonidou A, Michalopoulou S, Manolis J, Caratzas J, Phenekos C et al (2009) Hormonal activity of adrenal incidentalomas: results from a long-term follow-up study. Clin Endocrinol (Oxf) 70(5):674–679. https://doi.org/10.1111/j.1365-2265.2008.03492.xCrossRef

33.

Di Dalmazi G, Vicennati V, Garelli S, Casadio E, Rinaldi E, Giampalma E et al (2014) 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 2(5):396–405. https://doi.org/10.1016/S2213-8587(13)70211-0CrossRefPubMed

34.

Chiodini I, Gaudio A, Eller-Vainicher C, Morelli V, Aresta C, Zhukouskaya VV et al (2019) Cortisol secretion, sensitivity, and activity are associated with hypertension in postmenopausal eucortisolemic women. J Clin Endocrinol Metab 104(10):4441–4448. https://doi.org/10.1210/jc.2019-00037CrossRefPubMed

35.

Ceccato F, Artusi C, Barbot M, Lizzul L, Pinelli S, Costantini G et al (2020) Dexamethasone measurement during low-dose suppression test for suspected hypercortisolism: threshold development with and validation. J Endocrinol Invest 43(8):1105–1113. https://doi.org/10.1007/s40618-020-01197-6CrossRefPubMed

36.

Hepsen S, Sencar E, Sakiz D, Akhanli P, Ucan B, Unsal I et al (2020) Serum cortisol level after low dose dexamethasone suppression test may be predictive for diabetes mellitus and hypertension presence in obese patients: a retrospective study. Diabetes Res Diabetes Res Clin Pract 161:108081. https://doi.org/10.1016/j.diabres.2020.108081CrossRefPubMed

Title: Accuracy of the dexamethasone suppression test for the prediction of autonomous cortisol secretion-related comorbidities in adrenal incidentalomas
Authors: Marta Araujo-Castro
Paola Parra Ramírez
Cristina Robles Lázaro
Rogelio García Centeno
Paola Gracia Gimeno
Mariana Tomé Fernández-Ladreda
Miguel Antonio Sampedro Núñez
Mónica Marazuela
Héctor F. Escobar-Morreale
Pablo Valderrabano
Publication date: 01-12-2021
Publisher: Springer International Publishing
Keywords: Dexamethasone
Dyslipidemia
Published in: Hormones / Issue 4/2021
Print ISSN: 1109-3099
Electronic ISSN: 2520-8721
DOI: https://doi.org/10.1007/s42000-021-00308-z

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