Structured Evaluation of adRENal Tumors Discovered Incidentally - Prospectively Investigating the Testing Yield (SERENDIPITY)

Standard diagnostic work-up for adrenal incidentalomas (AI) consists of periodical biochemical analysis and CT-scanning in case the initial work-up does not demonstrate the presence of hormonal hypersecretion or adrenocortical carcinoma (ACC), respectively. The overall aim of this study is to improve the cost-effectiveness of the diagnostic strategy for AI. Cost-effectiveness of urine steroid profiling (USP) will be compared to the standard diagnostic strategy of repeated CT-imaging.

Study Overview

• Status: Recruiting
• Conditions: Adrenocortical Carcinoma; Adrenal Incidentaloma

Detailed Description

Rationale: Standard diagnostic work-up for adrenal incidentalomas (AI) consists of periodical biochemical analysis and CT-scanning in case the initial work-up does not demonstrate the presence of hormonal hypersecretion or adrenocortical carcinoma (ACC),respectively. With respect to the diagnosis of ACC, the health benefits of this strategy are controversial for the following reasons: a. critical appraisal of literature has revealed a much lower ACC frequency of 1.9% than previously presumed; b. CT sensitivity and specificity are suboptimal; c. risk of unnecessary adrenalectomies; d. exposure to ionising radiation; e. risk of CT contrast reactions (nephropathy, allergic reaction); f. health care related and economical costs. The hypothesis to be tested is that incorporation of a single baseline urinary steroid profiling (USP) into the management algorithm of AI is more cost-effective than a strategy solely based on repeat CT-scanning.

Objective: SERENDIPITY aims to improve the cost-effectiveness of the diagnostic strategy for AI by the application of a single baseline USP. In addition, we aim to examine the psychological impact for patients with AI being currently subjected to repeated laboratory tests and CT-scanning during several years.

Study design: This is a prospective observational multicenter study. Study population: Patients are eligible if they meet the following inclusion criteria: adrenal mass > 1 cm in diameter incidentally discovered during CT or MRI-scanning, performed for reasons other than an evaluation for adrenal disease and age 18 years or older. The exclusion criteria are: extra-adrenal malignancy (i.e. active or past medical history of malignancy, except for basal cell carcinoma), radiologic diagnosis of simple cyst or bilateral adrenal masses, allergy to radiocontrast, renal insufficiency (i.e. eGFR < 30 ml/min/1.73m2), pregnancy or inability to understand written Dutch.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

• Study Contact: Name: Michiel N Kerstens, MD, PhD; Phone Number: 0031-503613518; Email: m.n.kerstens@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9700 RB
    • Recruiting
    • University Medical Center Groningen
    • Contact: M N Kerstens, MD, PhD; Phone Number: 0031-503613518; Email: m.n.kerstens@umcg.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The research population consists of adult patients with a recently discovered adrenal incidentaloma who meet the selection criteria of SERENDIPITY. A total number of 1000 patients will be included. These subjects will be recruited from the group of patients in whom CT/MRI-scanning has been performed with visualization of the adrenal glands (i.e. CT/MRI scans of abdomen and/or chest, as the latter often include imaging of the upper abdominal region).

Description

Inclusion Criteria:

• discrete adrenal mass > 1 cm in diameter incidentally discovered during CT/MRI-scanning, performed for reasons other than an evaluation for adrenal disease
• detection CT/MRI-scan performed ≤ 4 months ago
• age 18 years or older.

Exclusion Criteria:

• extra-adrenal malignancy (i.e. active or past medical history of malignancy, except for basal cell carcinoma)
• radiologic diagnosis of simple cyst or bilateral adrenal masses
• allergy to radiocontrast
• renal insufficiency (i.e. eGFR < 30 ml/min/1.73m2)
• pregnancy
• adrenal incidentaloma visible on previous (i.e. > 4 months ago) CT/MRI-scan
• inability to understand written Dutch.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost-effectiveness	difference in cost-effectiveness of the current management strategy based on repeat CT-scanning to detect ACC among patients with an AI compared with a strategy using a single baseline USP	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
frequency of ACC among patients with AI at baseline or during follow-up	2 years
determination of the percentage of AI that meets the criteria of a malignant CT- phenotype at baseline or during follow-up	2 years
distribution of pathologic diagnosis in surgically removed adrenal glands	2 years
QoL in patients with an AI at baseline and during follow-up	2 years
frequency distribution between hormonal hypersecreting and non-functional AI	2 years
conversion rate from non-functioning AI towards a hypersecreting AI during follow-up	2 years
costs of diagnostic procedures and surgical interventions	2 years

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Collaborators: Radboud University Medical Center; Maastricht University Medical Center; UMC Utrecht; Erasmus Medical Center; Amsterdam UMC, location VUmc; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); St. Antonius Hospital; Leiden University Medical Center; Medical Centre Leeuwarden; Maxima Medical Center; Elisabeth-TweeSteden Ziekenhuis; Rijnstate Hospital; Diakonessenhuis, Utrecht; Onze Lieve Vrouwe Gasthuis; Medical Center Alkmaar; Haga Hospital; Isala; Vlietland Ziekenhuis; Canisius-Wilhelmina Hospital; Meander Medical Center; Kennemer Gasthuis; Martini Hospital Groningen; Medisch Spectrum Twente; Tergooi Hospital; Scheper Hospital; Flevo Hospital
• Investigators: Study Director: Michiel N Kerstens, MD, PhD, University Medical Center Groningen; Principal Investigator: E Buitenwerf, MD, University Medical Center Groningen; Principal Investigator: P.H.L.T. Bisschop, MD, PhD, Amsterdam UMC, location VUmc; Principal Investigator: E.M.W. Eekhoff, MD, PhD, Free University UMC Amsterdam; Principal Investigator: E.P.M. van der Kleij-Corssmit, MD, PhD, Leiden University Medical Center; Principal Investigator: R.A. Feelders, MD, PhD, Erasmus Medical Center; Principal Investigator: B. Havekes, MD, PhD, Maastricht University Medical Center; Principal Investigator: H.J.L.M Timmers, MD, PhD, UMC St Radboud Nijmegen; Principal Investigator: G.D. Valk, MD, PhD, UMC Utrecht; Principal Investigator: P.H.N. Oomen, MD, PhD, Medical Center Leeuwarden; Principal Investigator: K.M. van Tol, MD, PhD, Martini Hospital Groningen; Principal Investigator: R.S.M.E. Wouters, MD, Scheper Hospital; Principal Investigator: A.A.M. Franken, MD, PhD, Isala; Principal Investigator: J.R. Meinardi, MD, PhD, Canisius-Wilhelmina Hospital; Principal Investigator: R. GrooteVeldman, MD, PhD, Medisch Spectrum Twente; Principal Investigator: P.C. Oldenburg-Ligtenberg, MD, PhD, Meander Medical Center; Principal Investigator: A.F. Muller, MD, PhD, Diakonessenhuis, Utrecht; Principal Investigator: M.O. van Aken, MD, PhD, Haga Hospital; Principal Investigator: W. de Ronde, MD, PhD, Kennemer Gasthuis; Principal Investigator: H.R. Haak, MD, PhD, Maxima Medical Center; Principal Investigator: S. Simsek, MD, PhD, Medical Center Alkmaar; Principal Investigator: I.M.M.J. Wakelkamp, MD, PhD, St. Antonius Hospital; Principal Investigator: I.I.L. Berk-Planken, MD, PhD, Vlietland ziekenhuis; Principal Investigator: P.S. van Dam, MD, PhD, Onze Lieve Vrouwe Gasthuis; Principal Investigator: H. de Boer, MD, PhD, Rijnstate Hospital; Principal Investigator: J.J.J. de Sonnaville, MD, PhD, Tergooi Hospital; Principal Investigator: E. Donga, MD, St.Elisabeth Hospital; Principal Investigator: N. Smit, MD, Flevoland Hospital

Publications and helpful links

General Publications

• Brazier J, Roberts J, Deverill M. The estimation of a preference-based measure of health from the SF-36. J Health Econ. 2002 Mar;21(2):271-92. doi: 10.1016/s0167-6296(01)00130-8.
• Grumbach MM, Biller BM, Braunstein GD, Campbell KK, Carney JA, Godley PA, Harris EL, Lee JK, Oertel YC, Posner MC, Schlechte JA, Wieand HS. Management of the clinically inapparent adrenal mass ("incidentaloma"). Ann Intern Med. 2003 Mar 4;138(5):424-9. doi: 10.7326/0003-4819-138-5-200303040-00013.
• Young WF Jr. Clinical practice. The incidentally discovered adrenal mass. N Engl J Med. 2007 Feb 8;356(6):601-10. doi: 10.1056/NEJMcp065470. No abstract available.
• Nawar R, Aron D. Adrenal incidentalomas -- a continuing management dilemma. Endocr Relat Cancer. 2005 Sep;12(3):585-98. doi: 10.1677/erc.1.00951.
• Kievit J, Haak HR. Diagnosis and treatment of adrenal incidentaloma. A cost-effectiveness analysis. Endocrinol Metab Clin North Am. 2000 Mar;29(1):69-90, viii-ix. doi: 10.1016/s0889-8529(05)70117-1.
• Cawood TJ, Hunt PJ, O'Shea D, Cole D, Soule S. Recommended evaluation of adrenal incidentalomas is costly, has high false-positive rates and confers a risk of fatal cancer that is similar to the risk of the adrenal lesion becoming malignant; time for a rethink? Eur J Endocrinol. 2009 Oct;161(4):513-27. doi: 10.1530/EJE-09-0234. Epub 2009 May 13.
• Johnson PT, Horton KM, Fishman EK. Adrenal mass imaging with multidetector CT: pathologic conditions, pearls, and pitfalls. Radiographics. 2009 Sep-Oct;29(5):1333-51. doi: 10.1148/rg.295095027.
• Wolthers BG, Kraan GP. Clinical applications of gas chromatography and gas chromatography-mass spectrometry of steroids. J Chromatogr A. 1999 May 28;843(1-2):247-74. doi: 10.1016/s0021-9673(99)00153-3.
• Grondal S, Eriksson B, Hagenas L, Werner S, Curstedt T. Steroid profile in urine: a useful tool in the diagnosis and follow up of adrenocortical carcinoma. Acta Endocrinol (Copenh). 1990 May;122(5):656-63. doi: 10.1530/acta.0.1220656.
• Khorram-Manesh A, Ahlman H, Jansson S, Wangberg B, Nilsson O, Jakobsson CE, Eliasson B, Lindstedt S, Tisell LE. Adrenocortical carcinoma: surgery and mitotane for treatment and steroid profiles for follow-up. World J Surg. 1998 Jun;22(6):605-11; discussion 611-2. doi: 10.1007/s002689900442.
• Kikuchi E, Yanaihara H, Nakashima J, Homma K, Ohigashi T, Asakura H, Tachibana M, Shibata H, Saruta T, Murai M. Urinary steroid profile in adrenocortical tumors. Biomed Pharmacother. 2000 Jun;54 Suppl 1:194s-197s. doi: 10.1016/s0753-3322(00)80043-8.
• Minowada S, Kinoshita K, Hara M, Isurugi K, Uchikawa T, Niijima T. Measurement of urinary steroid profile in patients with adrenal tumor as a screening method for carcinoma. Endocrinol Jpn. 1985 Feb;32(1):29-37. doi: 10.1507/endocrj1954.32.29.
• Arnaldi G, Boscaro M. Adrenal incidentaloma. Best Pract Res Clin Endocrinol Metab. 2012 Aug;26(4):405-19. doi: 10.1016/j.beem.2011.12.006. Epub 2012 May 22.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: December 19, 2014
• First Submitted That Met QC Criteria: December 19, 2014
• First Posted (Estimate): December 24, 2014

Study Record Updates

• Last Update Posted (Actual): September 30, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: cost-effectiveness; Adrenocortical carcinoma; Urinary steroid profiling; Adrenal incidentaloma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Adrenal Gland Diseases; Adrenal Cortex Neoplasms; Adrenal Cortex Diseases; Adrenocortical Carcinoma; Adrenal Gland Neoplasms; Adrenocortical Adenoma
• Other Study ID Numbers: UGroningen; 4799 (Registry Identifier: Nederlands Trial Register)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: undecided