Endocrinology and Metabolism

Original Articles

Thyroid
Clinical Utility of Liquid Chromatography-Tandem Mass Spectrometry for Thyroglobulin Measurement in Comparison with Immunoradiometric Assay and Chemiluminescence Microparticle Immunoassay: Hyunju Park, Eungjun Yoon, Sang-Mi Kim, Tae Hyuk Kim, Jae Hoon Chung, Soo-Youn Lee, Sun Wook Kim; Endocrinol Metab. 2025;40(6):928-939. Published online August 26, 2025; DOI: https://doi.org/10.3803/EnM.2025.2413

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Background
The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to overcome interference from thyroglobulin autoantibodies (TgAb); however, it has not yet been implemented in Korea. This study aimed to confirm the accuracy of LC-MS/MS compared to conventional methods and to identify its advantages in patients with thyroid carcinoma (TC).
Methods
A total of 206 TC and 18 Hashimoto’s thyroiditis samples were collected. TgAb-positive (TgAb-P) was defined as TgAb >60 U/mL. Tg testing was performed using LC-MS/MS, immunoradiometric assay (Tg-IRMA), and chemiluminescence microparticle immunoassay (Tg-CMIA). The interference of TgAb in LC-MS/MS and CMIA methods was evaluated through an in vitro TgAb spiking experiment.
Results
The frequency of TgAb-P in TC samples was 76.2%. Correlations between assays were as follows: Tg measurements made by LC-MS/MS (Tg-MS) and Tg-IRMA (R=0.93), Tg-MS and Tg-CMIA (R=0.96), and Tg-CMIA and Tg-IRMA (R=0.99), and it was lower in TgAb-P than TgAb-negative group. Clinical factors (total thyroidectomy, thyroid lobectomy, and Hashimoto’s thyroiditis) did not affect these correlations. In TgAb spiking experiments, Tg-CMIA showed false negatives in TgAb-P, whereas Tg-MS did not. Among 21 TC cases with highly suspicious disease recurrence but Tg-IRMA <1 ng/mL, Tg-MS detected Tg ≥0.5 ng/mL in six samples. However, there was no consistent pattern of recurrence or TgAb trends.
Conclusion
Correlations between assays were lower in TgAb-P cases. The spike test results show Tg-MS is less prone to false negatives in TgAb-P cases. Tg-MS may improve Tg detection in TgAb-P cases. However, we could not identify a distinct patient group with shared clinical features that would benefit from Tg-MS.

Citations

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LC‑MS/MS for Thyroglobulin: A Complementary Approach to Immunoassay Limitations for Thyroid Cancer
Se Hee Park, Dong Yeob Shin
Endocrinology and Metabolism.2025; 40(6): 866. CrossRef

Adrenal gland
Liquid Chromatography-Tandem Mass Spectrometry Outperforms Radioimmunoassay in Guiding Surgical Decisions Based on Adrenal Venous Sampling in Primary Aldosteronism: Bo-Ching Lee, Chien-Wei Huang, Chin-Chen Chang, Guan-Yuan Chen, Jia-Zheng Huang, Pin-Chen Chen, Te-I Weng, Kao-Lang Liu, Vin-Cent Wu, Yen-Hung Lin, on Behalf of the TAIPAI Study Group; Endocrinol Metab. 2025;40(6):1002-1011. Published online July 1, 2025; DOI: https://doi.org/10.3803/EnM.2024.2237

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Abstract PDF Supplementary Material PubReader ePub: Background
Adrenal venous sampling (AVS) is essential for diagnosing unilateral aldosterone oversecretion in primary aldosteronism (PA). Traditionally, AVS relies on radioimmunoassay (RIA) to measure plasma aldosterone concentration (PAC), although RIA has limited specificity and considerable variability. This study evaluated the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in AVS and its impact on clinical outcomes.
Methods
Among 230 patients with PA (May 2020 to April 2023) who underwent AVS, successful sampling was achieved in 182 patients (79.1%) under unstimulated conditions and 206 patients (89.6%) under stimulated conditions. PAC levels from peripheral and adrenal veins measured by LC-MS/MS were compared with RIA results. Patient outcomes were categorized according to the Primary Aldosteronism Surgical Outcomes criteria.
Results
LC-MS/MS showed significant correlations with PAC levels measured by RIA in AVS (r=0.40 [unstimulated] and r=0.56 [stimulated]; both P<0.001). However, lateralization concordance between RIA and LC-MS/MS was moderate, at only 57.7% (unstimulated) and 64.6% (stimulated). LC-MS/MS identified more unilateral disease than RIA under both unstimulated (61.5% vs. 37.4%, P<0.001) and stimulated conditions (36.4% vs. 9.7%, P<0.001). Patients achieving complete clinical success after adrenalectomy were more accurately identified by LC-MS/MS than RIA under stimulated (55.6% vs. 22.2%, P=0.035), but not in unstimulated conditions.
Conclusion
LC-MS/MS outperformed RIA in identifying unilateral disease, resulting in higher rates of complete clinical success in adrenalectomy patients when surgical decisions were based on LC-MS/MS lateralization results.

Thyroid
Comprehensive Proteomics and Machine Learning Analysis to Distinguish Follicular Adenoma and Follicular Thyroid Carcinoma from Indeterminate Thyroid Nodules: Hee-Sung Ahn, Eyun Song, Chae A Kim, Min Ji Jeon, Yu-Mi Lee, Tea-Yon Sung, Dong Eun Song, Jiyoung Yu, Ji Min Shin, Yeon-Sook Choi, Kyunggon Kim, Won Gu Kim; Endocrinol Metab. 2025;40(4):623-636. Published online April 10, 2025; DOI: https://doi.org/10.3803/EnM.2024.2208

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The preoperative diagnosis of follicular thyroid carcinoma (FTC) is challenging because it cannot be readily distinguished from follicular adenoma (FA) or benign follicular nodular disease (FND) using the sonographic and cytological features typically employed in clinical practice.
Methods
We employed comprehensive proteomics and machine learning (ML) models to identify novel diagnostic biomarkers capable of classifying three subtypes: FTC, FA, and FND. Bottom-up proteomics techniques were applied to quantify proteins in formalin-fixed, paraffin-embedded (FFPE) thyroid tissues. In total, 202 FFPE tissue samples, comprising 62 FNDs, 72 FAs, and 68 FTCs, were analyzed.
Results
Close spectrum-spectrum matching quantified 6,332 proteins, with approximately 9% (780 proteins) differentially expressed among the groups. When applying an ML model to the proteomics data from samples with preoperative indeterminate cytopathology (n=183), we identified distinct protein panels: five proteins (CNDP2, DNAAF5, DYNC1H1, FARSB, and PDCD4) for the FND prediction model, six proteins (DNAAF5, FAM149B1, RPS9, TAGLN2, UPF1, and UQCRC1) for the FA model, and seven proteins (ACTN4, DSTN, MACROH2A1, NUCB1, SPTAN1, TAGLN, and XRCC5) for the FTC model. The classifiers’ performance, evaluated by the median area under the curve values of the random forest models, was 0.832 (95% confidence interval [CI], 0.824 to 0.839) for FND, 0.826 (95% CI, 0.817 to 0.835) for FA, and 0.870 (95% CI, 0.863 to 0.877) for FTC.
Conclusion
Quantitative proteome analysis combined with an ML model yielded an optimized multi‐protein panel that can distinguish FTC from benign subtypes. Our findings indicate that a proteomic approach holds promise for the differential diagnosis of FTC.

Brief Reports

Adrenal gland
Comparative Analysis of Liquid Chromatography-Tandem Mass Spectrometry and Radioimmunoassay in Determining Plasma Aldosterone Concentration and Plasma Renin Activity for Primary Aldosteronism Screening: So Yoon Kwon, Kyeong-Jin Kim, Soo-Youn Lee, Jae Hyeon Kim; Endocrinol Metab. 2024;39(6):965-969. Published online November 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.1985

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Liquid chromatography-tandem mass spectrometry (LC-MS/MS) accurately measures plasma aldosterone concentration (PAC), but its correlation with radioimmunoassay (RIA), equivalent RIA levels, and optimal cutoff for PAC and aldosterone-to-renin ratio (ARR) in primary aldosteronism (PA) screening have not been determined in a Korean population. Our study of 127 patients who underwent diagnostic testing for PA showed that the LC-MS/MS and RIA methods have good correlation, with a mean bias of 29.3% for PAC. An LC-MS/MS PAC level of 11.7 ng/dL was equivalent to an RIA PAC level of 15 ng/dL. Receiver operating characteristic curve analysis showed that an LC-MS/MS PAC level of 10.3 ng/dL and LC-MS/MS ARR level of 20.0 provided sensitivity of 73.1% with a specificity of 57.3% and sensitivity of 92.3% with a specificity of 14.7%, respectively. When the LC-MS/MS method is used for PA screening, an adjustment of cutoff values is necessary.

Citations

Citations to this article as recorded by

Magnetic bead-assisted extraction combined with LC–MS/MS for simultaneous quantification of aldosterone and related steroids in human plasma
Yudong Chu, Qin Su, Ziyuan Huang, Chenyi Yuan, Shazhou Ye, Xueyan Bian
Analytical and Bioanalytical Chemistry.2026; 418(1): 343. CrossRef

Adrenal Gland
Aldosterone Immunoassay-Specific Cutoff Value for Seated Saline Suppression Test for Diagnosing Primary Aldosteronism: So Yoon Kwon, Jiyun Park, So Hee Park, So Hyun Cho, You-Bin Lee, Soo-Youn Lee, Jae Hyeon Kim; Endocrinol Metab. 2022;37(6):938-942. Published online December 6, 2022; DOI: https://doi.org/10.3803/EnM.2022.1535

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A seated saline loading test (SLT) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is one of the most accepted confirmatory tests of primary aldosteronism. However, LC-MS/MS is time-consuming and is not widely available in diagnostic laboratories compared to immunoassay. With immunoassay, it is unknown whether SLT in the seated position is more accurate than that of the supine position, and a cutoff value of post-seated SLT plasma aldosterone concentration (PAC) must be established in the Korean population. Ninety-eight patients underwent SLT in both positions, and post-SLT PAC was measured by LC-MS/MS and radioimmunoassay. We confirmed primary aldosteronism if post-seated SLT PAC by LC-MS/MS exceeded 5.8 ng/dL. The area under the receiver operating characteristic curve was greater for seated than supine SLT (0.928 vs. 0.834, P=0.003). The optimal cutoff value of post-seated SLT by radioimmunoassay was 6.6 ng/dL (sensitivity 83.3%, specificity 92.2%).

Citations

Citations to this article as recorded by

Investigating the cut-off values of captopril challenge test for primary aldosteronism using the novel chemiluminescent enzyme immunoassay method: a retrospective cohort study
Yuta Tezuka, Kei Omata, Yoshikiyo Ono, Kengo Kambara, Hiroki Kamada, Sota Oguro, Yuto Yamazaki, Celso E. Gomez-Sanchez, Akihiro Ito, Hironobu Sasano, Kei Takase, Tetsuhiro Tanaka, Hideki Katagiri, Fumitoshi Satoh
Hypertension Research.2024; 47(5): 1362. CrossRef
Usefulness of the Upright Posture Test in the Diagnosis of Primary Aldosteronism
Nada Younes, Matthieu St-Jean, Marie-Josée Desrochers, Eric Therasse, Mathieu Latour, Isabelle Bourdeau, André Lacroix
Journal of the Endocrine Society.2024;[Epub] CrossRef
Screening and treatment of endocrine hypertension focusing on adrenal gland disorders: a narrative review
Seung Min Chung
Journal of Yeungnam Medical Science.2024; 41(4): 269. CrossRef
Comparative Analysis of Liquid Chromatography-Tandem Mass Spectrometry and Radioimmunoassay in Determining Plasma Aldosterone Concentration and Plasma Renin Activity for Primary Aldosteronism Screening
So Yoon Kwon, Kyeong-Jin Kim, Soo-Youn Lee, Jae Hyeon Kim
Endocrinology and Metabolism.2024; 39(6): 965. CrossRef

Review Articles

Adrenal Gland
Clinical and Technical Aspects in Free Cortisol Measurement: Man Ho Choi; Endocrinol Metab. 2022;37(4):599-607. Published online August 19, 2022; DOI: https://doi.org/10.3803/EnM.2022.1549

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Accurate measurement of cortisol is critical in adrenal insufficiency as it reduces the risk associated with misdiagnosis and supports the optimization of stress dose. Comprehensive assays have been developed to determine the levels of bioactive free cortisol and their clinical and analytical efficacies have been extensively discussed because the level of total cortisol is affected by changes in the structure or circulating levels of corticoid-binding globulin and albumin, which are the main reservoirs of cortisol in the human body. Antibody-based immunoassays are routinely used in clinical laboratories; however, the lack of molecular specificity in cortisol assessment limits their applicability to characterize adrenocortical function. Improved specificity and sensitivity can be achieved by mass spectrometry coupled with chromatographic separation methods, which is a cutting-edge technology to measure individual as well as a panel of steroids in a single analytical run. The purpose of this review is to introduce recent advances in free cortisol measurement from the perspectives of clinical specimens and issues associated with prospective analytical technologies.

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Diabetes, Obesity and Metabolism
Understanding Metabolomics in Biomedical Research: Su Jung Kim, Su Hee Kim, Ji Hyun Kim, Shin Hwang, Hyun Ju Yoo; Endocrinol Metab. 2016;31(1):7-16. Published online March 16, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.1.7

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The term "omics" refers to any type of specific study that provides collective information on a biological system. Representative omics includes genomics, proteomics, and metabolomics, and new omics is constantly being added, such as lipidomics or glycomics. Each omics technique is crucial to the understanding of various biological systems and complements the information provided by the other approaches. The main strengths of metabolomics are that metabolites are closely related to the phenotypes of living organisms and provide information on biochemical activities by reflecting the substrates and products of cellular metabolism. The transcriptome does not always correlate with the proteome, and the translated proteome might not be functionally active. Therefore, their changes do not always result in phenotypic alterations. Unlike the genome or proteome, the metabolome is often called the molecular phenotype of living organisms and is easily translated into biological conditions and disease states. Here, we review the general strategies of mass spectrometry-based metabolomics. Targeted metabolome or lipidome analysis is discussed, as well as nontargeted approaches, with a brief explanation of the advantages and disadvantages of each platform. Biomedical applications that use mass spectrometry-based metabolomics are briefly introduced.

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