Jisook Yim

Jisook Yim, M.D., Ph.D., Kyung Sun Park, M.D., Ph.D., and Eul-Ju Seo, M.D., Ph.D.. Ann Lab Med -0001;0:. https://doi.org/10.3343/alm.2025.0134

Plasma-free metanephrines are the most sensitive and specific biochemical markers for diagnosing catecholamine-secreting tumors, such as pheochromocytoma and paraganglioma. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry method for quantifying metanephrine and normetanephrine in human plasma, using solid-phase extraction with a weak cation-exchange mechanism. Validation was performed according to the FDA Bioanalytical Method Validation Guidance and CLSI guideline C62-A. The method showed excellent linearity over concentration ranges of 0.11–13.92 nmol/L for metanephrine and 0.14–26.43 nmol/L for normetanephrine, with correlation coefficients exceeding 0.999. The accuracy, precision, and lower limit of quantification met the acceptance criteria of the study. Matrix effect evaluation revealed a process efficiency of 121% for metanephrine at the lowest concentration, slightly exceeding the acceptable range of 100 ± 15%. This was likely because of matrix-induced ion enhancement or variability in extraction efficiency. However, all other tested concentrations were within the acceptable limits. Overall, this method demonstrated high sensitivity, specificity, and reproducibility, making it suitable for routine clinical applications. Minor deviations at low concentrations do not compromise reliability; however, future optimizations, such as matrix-matched calibration, may further improve performance.

Plasma-free metanephrines are considered the most sensitive and specific biochemical markers for the diagnosis of catecholamine-secreting tumors, such as pheochromocytoma and paraganglioma. In this study, we developed and validated a liquid chromatography–tandem mass spectrometry method for quantifying metanephrine and normetanephrine in human plasma, using solid-phase extraction with a weak cation-exchange mechanism. The method was validated according to the FDA Bioanalytical Method Validation Guidance and CLSI guideline C50-A. The method showed excellent linearity over concentration ranges of 0.11–13.92 nmol/L for metanephrine and 0.14–26.43 nmol/L for normetanephrine, with correlation coefficients greater than 0.999. The accuracy, precision, and lower limit of quantification met the acceptance criteria. Matrix effect evaluation revealed a process efficiency of 121% for metanephrine at the lowest concentration, slightly exceeding the acceptable range of 100 ± 15%. This was likely because of matrix-induced ion enhancement or variability in extraction efficiency. However, all other concentrations were within acceptable limits. Overall, this method demonstrated high sensitivity, specificity, and reproducibility, making it suitable for routine clinical use. Minor deviations at low concentrations do not compromise the reliability of the method, however, suggest that future optimization, such as matrix-matched calibration, can further improve performance.

Jisook Yim, M.D.. Lab Med Online 2024;14:191-200. https://doi.org/10.47429/lmo.2024.14.3.191

Childhood adrenocortical carcinoma (ACC) is a rare disease that is mostly linked to familial cancer syndrome. Although the prevalence of ACC is extremely low in children, it is clinically important to diagnose ACC early because age and tumor stage are closely related to prognosis. From this perspective, understanding the underlying genetics and possible symptoms of ACC is crucial in managing ACC with familial cancer syndromes. In this report, we present the case of a 3-year-old girl who initially presented with symptoms of precocious puberty and was later found to have ACC by imaging analysis. On genetic analysis, the patient was found to have a MEN1 gene mutation. MEN1 mutations are found in patients with multiple endocrine neoplasia type 1 (MEN1), usually precipitating multiple endocrine tumors, including pituitary adenoma, parathyroid hyperplasia, and adrenal tumors. Although MEN1 mutation is usually inherited in an autosomal dominant manner, neither of the patient’s parents had the same mutation, making hers a case of sporadic MEN1 mutation with initial presentation of ACC. The clinical course and further investigations of this patient are discussed in detail in this report.

18p deletion (18p-) syndrome is a rare chromosome abnormality that has a wide range of phenotypes, with short stature, intellectual disability, and facial dysmorphism being the main clinical features. Here, we report the first case in Korea of a 16-year-old male adolescent with 18p- syndrome resulting from de novo unbalanced whole-arm translocation between chromosomes 13 and 18 (45, XY, der(13;18)(q10:q10)). Three rare clinical findings were discovered that had not been reported in the previous literature; morbid obesity without other hormonal disturbances, rib cage deformity leading to the direct compression of the liver, and lumbar spondylolisthesis at the L5-S1 level. This case expands the phenotypic spectrum of 18p- syndrome and highlights the importance of considering chromosomal analysis, since this syndrome can be easily overlooked in a clinical setting, especially without distinctive symptoms of other organs, due to its nonspecific but typical features of short stature and mild intellectual disability with a mildly dysmorphic face. Moreover, since not all cases of 18p- syndrome with unbalanced translocation (13;18) show the same phenotype, multidisciplinary examinations and follow-up seem to be important to monitor evolving and developing clinical manifestations and to predict prognosis in advance associated with the specific genes of 18p breakpoint regions.

Choi KE, et al. J Clin Neurol. 2022 Mar;18(2):244-246. https://doi.org/10.3988/jcn.2022.18.2.244