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Letter to the Editor From Li and Lu: “Serum Steroid Profiling in the Diagnosis of Adrenocortical Carcinoma: A Prospective Cohort Study”
Lin Li1 .* and Youyi Lu20D
1Department of Cardiovascular, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong 264200, China
2Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China
Correspondence: Youyi Lu, MD, Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, NO.20 East Yuhuangding Rd, Yantai, Shandong 264000, China. Email: luyouyi@qdu.edu.cn.
*Lin Li contributed to this work as first author.
Dear Editor,
We read with great interest the recent article by Yu and col- leagues (1). Although this prospective cohort study provided valuable insights into serum steroid profiling for the diagnosis of adrenocortical carcinoma, several critical concerns warrant further clarification and discussion, which are essential for fu- ture research in this field.
First, we noticed that there seems to be an oversight in the method of enrolling the study population. The authors pro- spectively included patients with clinically available serum steroid measurements (2019-2023), which may introduce se- lection bias. The authors did not clearly describe the reasons for the undetected serum steroid profiling. Patients who refuse testing may be more likely to have small tumors and milder conditions, which could affect the representativeness and ac- curacy of the conclusions (2). The authors could collect base- line clinical data from patients without measured serum steroid profiling and compare these with the data from the in- cluded patients to evaluate the potential impact of bias. If ne- cessary, further subgroup analyses based on potential confounding factors could enhance the overall understanding of the conclusions. Additionally, the exclusion criteria were not sufficiently rigorous. The study did not account for the po- tential variability in serum steroid profiling related to co- morbid conditions (eg, hepatic or renal impairment), other medications (such as mineralocorticoid receptor antagonists, menopausal hormone therapy), or pregnancy and lactation, which could compromise the real-world reproducibility of this serum-based approach. We emphasize the importance of considering these factors in future research.
Second, it is worth mentioning that previous studies have prospectively obtained 6 to 11 types of steroid hormones (3, 4). This study only measured 3 serum steroids, which may have overlooked other steroid combinations with diag- nostic value. It would be more reasonable to expand the types of serum steroids tested and perform both univariate and
multivariate analyses to determine the most valuable steroid combination for diagnosis. Moreover, serum steroid levels are highly heterogeneous and influenced by factors such as morning fluctuations, age, and sex (5). Currently, there is lim- ited discussion on the sampling time, testing methods, and corresponding reference value ranges for serum steroids. These issues should be comprehensively defined in future re- search. Given that the authors acknowledge the limitations of serum steroid analysis compared to the 24-hour urine ster- oid test, the study could have been more impactful if it pro- vided a direct comparison between both methods, rather than relying solely on serum steroids.
Lastly, the authors suggested that the combined use of im- aging and serum steroids showed no significant advantage, which raises questions about the added value of imaging in this diagnostic algorithm. While imaging characteristics may improve diagnostic accuracy in some contexts, the authors failed to explain why the addition of imaging did not offer a substantial benefit in this particular study.
In conclusion, the authors provided valuable insights into this field. However, further validation in multicenter, pro- spective trials with larger, more diverse patient populations is essential before these findings can be translated into routine clinical practice.
Acknowledgments
None.
Funding
None.
Author Contributions
L.L. and Y.L. were involved in study design and drafting and revising the manuscript.
Disclosures
None to declare for all authors.
Provenance and Peer Review
Not commissioned, externally peer-reviewed.
References
1. 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.
2. Kimpel O, Altieri B, Dischinger U, et al. Early detection of recurrence and progress using serum steroid profiling by LC-MS/MS in patients with adrenocortical carcinoma. Metabolites. 2023;14(1):20.
3. Berke K, Constantinescu G, Masjkur J, et al. PlaFsma steroid profil- ing in patients with adrenal incidentaloma. J Clin Endocrinol Metab. 2022;107(3):e1181-e1192.
4. Schweitzer S, Kunz M, Kurlbaum M, et al. Plasma steroid metabo- lome profiling for the diagnosis of adrenocortical carcinoma. Eur J Endocrinol. 2019;180(2):117-125.
5. Weng Y, Tang JY, Zhang XY, et al. Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma. Front Endocrinol (Lausanne). 2024;15:1435102.
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