Morbidity and Mortality in Autonomous Cortisol Secretion

NCT03919734 | Completed

• 1 other identifier: 1
• Study Type: observational
• Target: 4,596
• Locations: 1 country
• Sites: 1

Brief Summary

Benign enlargements of the adrenal glands (adrenal adenomas) are frequent in adults. In the general population these adenomas are rare in subjects below 40 years of age but at the age of 60 and 80 years the prevalence is 6 and 8-10 % respectively. Since these adenomas do not causes obvious symptoms they are almost exclusively found incidentally in patients examined radiologically for other reasons than suspected adrenal disease. These enlargements are thus termed adrenal incidentalomas (AI). AI may secrete cortisol and more than 25 percent of patients with an AI have increased cortisol levels called autonomous cortisol secretion (ACS). Such increased secretion of cortisol may cause metabolic complications such as hypertension, high cholesterol, diabetes and cardiovascular disease. Studies have shown that ACS may cause increased mortality. These studies are however small and have not adequately taking other conditions into account which most likely influences the result. The investigators hypothesis is that ACS is linked to increased mortality as the previous studies have shown. The aim is to perform a larger study on patients with adrenal incidentalomas, both with and without ACS, and compare the mortality rates with a control group matched for age and sex. This study may more precisely describe the cardiovascular risk for ACS and define the risk at different levels of ACS.

Conditions

Adrenal Incidentaloma; Cortisol Overproduction

Outcome Measures

Primary Outcomes (1)

• Number of patients deceased, both totally and divided into three specified diagnose groups (cardiovascular disease, infections and cancer).

  The cause of death is defined by the ICD-10 code reported by The National Board of Health and Welfare.

  From date of enrollment until December 31, 2018.

Secondary Outcomes (1)

• A composite of cardiovascular death, nonfatal myocardial infarction (excluding silent myocardial infarction), nonfatal stroke, hospitalization for heart failure and revascularization (CABG and PCI). The endpoints will also be calculated separately.

  From date of enrollment until December 31, 2017.

Study Arms (5)

AI ACS/possible ACS

Patients with adrenal incidentalomas and cortisol following overnight 1-mg dexamethasone suppression equal to or above 50 nmol/l. The patients should not have clinical signs of Cushing Syndrome, such as catabolic skin and muscle changes.

AI non-ACS

Patients with adrenal incidentalomas and cortisol following overnight 1-mg dexamethasone suppression below 50 nmol/l.

Treatment with Inhalation Steroids

Patients treated with inhalation steroids with and without ACS/possible ACS but not operated with adrenalectomy.

Adrenalectomy

Patients with unilateral AI operated with adrenalectomy

Controls

A Group of Controls matched for sex and age, achieved by the government agency "Statistics Sweden" (SCB).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients examined at the Endocrine outpatient ambulatory first time for adrenal incidentalomas during the period from January 1, 2005 to September 15, 2015. A Group of Age and sex matched controls developed by SCB.

You may qualify if:

• Patients with adrenal incidentalomas examined at Skane University Hospital and Helsingborg Hospital during the period from January 1, 2005 to September 15, 2015.

You may not qualify if:

• Size of incidentaloma below 1 cm
• Malignant disease with metastases,
• Incidentaloma not an adenoma but for example malignancy, myelolipoma and bleedings
• Pheochromocytomas
• Primary aldosteronism
• Continuous treatment with systemic glucocorticoid under the last 3 months.
• Cushing Syndrome
• Medication affecting dexamethasone metabolism.
• Treatment with systemic estrogen

Sponsors & Collaborators

• Region Skane: lead

Study Sites (1)

Dept. of Endocrinology, Skåne University Hospital

Lund, Skåne County, 25656, Sweden

Location

Related Publications (7)

• Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, Tabarin A, Terzolo M, Tsagarakis S, Dekkers OM. 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 Aug;175(2):G1-G34. doi: 10.1530/EJE-16-0467.

  PMID: 27390021 BACKGROUND

• 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 Dec;99(12):4462-70. doi: 10.1210/jc.2014-3007.

  PMID: 25238207 BACKGROUND

• 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 May;2(5):396-405. doi: 10.1016/S2213-8587(13)70211-0. Epub 2014 Jan 29.

  PMID: 24795253 BACKGROUND

• 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 Nov;58(2):267-275. doi: 10.1007/s12020-017-1400-8. Epub 2017 Sep 8.

  PMID: 28887710 BACKGROUND

• Olsen H, Kjellbom A, Londahl M, Lindgren O. Suppressed ACTH Is Frequently Unrelated to Autonomous Cortisol Secretion in Patients With Adrenal Incidentalomas. J Clin Endocrinol Metab. 2019 Feb 1;104(2):506-512. doi: 10.1210/jc.2018-01029.

  PMID: 30265354 BACKGROUND

• Kjellbom A, Lindgren O, Danielsson M, Olsen H, Londahl M. Mortality Not Increased in Patients With Nonfunctional Adrenal Adenomas: A Matched Cohort Study. J Clin Endocrinol Metab. 2023 Jul 14;108(8):e536-e541. doi: 10.1210/clinem/dgad074.

  PMID: 36800277 DERIVED

• Kjellbom A, Lindgren O, Puvaneswaralingam S, Londahl M, Olsen H. Association Between Mortality and Levels of Autonomous Cortisol Secretion by Adrenal Incidentalomas : A Cohort Study. Ann Intern Med. 2021 Aug;174(8):1041-1049. doi: 10.7326/M20-7946. Epub 2021 May 25.

  PMID: 34029490 DERIVED

MeSH Terms

Conditions

Adrenal incidentaloma; ACTH Syndrome, Ectopic

Condition Hierarchy (Ancestors)

Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Neoplasms

Study Officials

• Henrik Olsen, MD, PhD

  Medical Faculty, University of Lund

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator Henrik Olsen, MD, PhD.

Study Record Dates

• First Submitted: April 7, 2019
• First Posted: April 18, 2019
• Study Start: September 15, 2015
• Primary Completion: January 3, 2020
• Study Completion: January 3, 2020
• Last Updated: March 26, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)