ENDOCRINE SOCIETY
OXFORD
Response to Letter to the Editor From Li and Lu: “Serum Steroid Profiling in the Diagnosis of Adrenocortical Carcinoma: A Prospective Cohort Study”
Kai Yu1,20D and Irina Bancos 1,3 iD
1Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN 55905, USA
2Division of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
3Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 555905, USA
Correspondence: Irina Bancos, MD, MSc, Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic, 200 1st St SW, Rochester, MN 55905, USA. Email: bancos.irina@mayo.edu.
TO THE EDITOR,
We thank Drs. Lu and Li (1) for their interest in our work “Serum steroid profiling in the diagnosis of adrenocortical car- cinoma: a prospective cohort study” (2), and we appreciate the opportunity to highlight the key messages of our study. In this study, we measured 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone in 263 patients with adrenal masses. We found that these 3 steroids distinguished adrenocortical carcinoma (ACC) than non-ACCs overall, as well as in a sub- set of patients with functioning adrenal masses or patients with indeterminate adrenal masses.
We acknowledge a referral and selection bias in our study, lack of biomaterial available for analysis in some patients, and the need for a multicenter prospective validation. Drs. Lu and Li suggest considering additional exclusion criteria, such as hepatic and renal impairment, medications, and other condi- tions. We are interested to see future studies investigating the impact of proposed variables on 11-deoxycortisol, 17OH- progesterone, and 17OH-pregnenolone. However, we dis- agree that adding these exclusion criteria would increase real-world reproducibility and would very likely limit general- izability of our findings. Many patients with ACC or other ad- renal malignancy have renal or hepatic impairment and may be treated with medications such as spironolactone (for ACC-associated severe glucocorticoid and/or mineralocortic- oid excess). Identifying biomarkers that can distinguish be- tween ACC and non-ACC despite multiple comorbidities are more reflective of a real-life diagnostic setting.
We discussed at length in our manuscript that others inves- tigated multisteroid panels in diagnosis of ACC. However, such panels are not widely available, and we intentionally con- centrated on the 3 steroids easily available in United States. We view this as a significant strength of our study, as our find- ings are directly transferrable to clinical practice. Cost is also a consideration. Future studies will have to weigh on the poten- tial incremental diagnostic value of adding a number of add- itional steroids to the panel against the increasing cost and delay in obtaining results due to added complexity of testing.
We would like to emphasize that we recommend serum ster- oid profiling with 11-deoxycortisol, 17OH-pregnenolone, and 17OH-progesterone only in patients with indeterminate adrenal masses. In our study, we did find that combining im- aging data (Hounsfield units and tumor size) with the serum steroid data led to a minor improvement in the diagnostic ac- curacy of ACCs. In a previous study examining urine steroid profiling (3), combining imaging and steroid data increased the diagnostic accuracy in a much more substantial way than in our study, mainly because the study had a higher pro- portion of smaller, lipid-rich adenomas (that could be diag- nosed based on imaging alone, as recommended by the guidelines (4)).
We thank Drs. Lu and Li for sharing their thoughts on our study, and we wholeheartedly agree that a multicenter diag- nostic accuracy prospective study is the next much needed step.
Disclosures
I.B. reports advisory board participation, data safety monitor- ing board participating in or consulting (fees to institution) with Corcept Therapeutics, Sparrow Pharmaceutics, Xeris, Recordati, Camurus, Crinetics, Diurnal, Spruce, NovoNordisk, AstraZeneca, Adrenas Pharmaceutics, and HRA Pharma with no relation to the submitted work. I.B. re- ports research support from Recordati and HRA Pharma, not related to this work. The remaining authors have no conflicts of interest to declare.
References
1. Li L, Lu Y. Letter to the editor from Li and Lu: “Serum steroid pro- filing in the diagnosis of adrenocortical carcinoma: a prospective co- hort study”. J Clin Endocrinol Metab.
2. Yu K, Athimulam S, Saini J, et al. Serum steroid profiling in the diag- nosis of adrenocortical carcinoma: a prospective cohort study. J Clin Endocrinol Metab. 2025;110(4):1177-1186.
3. Bancos I, Taylor AE, Chortis V, et al. Urine steroid metabolomics for the differential diagnosis of adrenal incidentalomas in the EURINE-ACT study: a prospective test validation study. Lancet Diabetes Endocrinol. 2020;8(9):773-781.
4. Fassnacht M, Tsagarakis S, Terzolo M, et al. European Society of Endocrinology clinical practice guidelines on the management of ad- renal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2023;189(1):G1-G42.
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