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Precision medicine, which optimizes diagnosis and treatment of diseases according to individualized characteristics, is becoming a reality in the field of diabetes, especially for monogenic diabetes. Maturityonset diabetes of the young (MODY) is a type of monogenic diabetes characterized by early onset, relative non-obesity, non-insulin dependence, and autosomal dominant inheritance. With the trend toward precision medicine and improvement in genetic testing, there have been advances in the classification, diagnosis, and treatment of MODY. MODY accounts for about 1% of diabetes in Korea, with GCK (glucokinase)-MODY, HNF1α (hepatocyte nuclear factor-1 alpha)-MODY, and HNF4α (hepatocyte nuclear factor-4 alpha)-MODY being most common. In the diagnosis of MODY, applying guidelines for interpretation of variant pathogenicity is important. For the treatment of MODY, individualized treatment strategies according to the causative gene of MODY should be applied when available. Still, the majority of MODY is misdiagnosed and more genetic testing is required in Korea. We review updates regarding the classification, diagnosis, and treatment of MODY.

Backgrounds Adrenal cortical carcinoma (ACC) is a rare malignant tumor derived from the adrenal gland with a poor prognosis. Since there is no effective medical treatment, early diagnosis and surgical resection are the only way to cure ACC completely. However, early diagnosis of ACC is sometimes tricky because there are no useful diagnostic biomarkers to differentiate ACC from benign adrenal tumors. Therefore, we aimed to identify circulating protein biomarkers to distinguish malignant from benign adrenal tumors using mass spectrometry-based proteomic analysis. Methods Plasma samples were obtained from 27 patients with ACC and 69 age- and sex-matched patients with adrenal adenoma. We performed the liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a data-independent acquisition (DIA) method in plasma samples. Among the quantified 381 proteins, differentially expressed proteins (DEPs) were selected using Student's t-tests for pairwise comparison with a false discovery rate < 0. 05 and |fold-change|> 1.5. In addition, we performed machine learning algorithms such as random forest and XGBoost to select featured DEPs to discriminate ACC. Results The mean age of patients was 52 years, and 38 (39.6%) patients were male. Among 19 DEPs, 8 proteins were overexpressed and 11 were underexpressed in ACC patients. In a further analysis using machine learning algorithms, random forest identified 4 proteins as important features for establishing the classifier. The panels with these four proteins showed a good discrimination performance with an area under the curve (AUC) of 0.94 and an accuracy of 0.96. Eight proteins were identified in the XGBoost algorithm. Four proteins in plasma samples were common DEPs from the traditional methods and machine learning algorithms. Conclusions High plasma levels of two proteins (One is involved in the migration, attachment and organization of cells into tissues. The other is V region of the variable domain of immunoglobulin light chains), and low plasma levels of two proteins (One is involved in cell-cell adhesion and recognition. The other is V region of the variable domain of immunoglobulin heavy chain) might be circulating protein biomarkers of ACCs compared with benign adrenal adenomas. Presentation: No date and time listed

Objective : Craniopharyngiomas (CPs) are associated with hypothalamic damage that causes hypothalamic obesity, however, the mechanisms underlying CP-related postoperative weight gain remain debatable. This study aimed to elucidate whether the major determinant of postoperative weight gain in patients with CP is hypothalamic injury or steroid replacement therapy.Methods : We included 48 adult patients with CP (age ≥18 years) who underwent transsphenoidal surgery between 2010 and 2018 in a single tertiary center, and whose body weight was measured pre- and postoperatively (

Objective Hyperprolactinemia in patients with nonfunctioning pituitary adenomas (NFPAs) has been explained by the stalk compression of large pituitary adenomas. However, not all large NFPAs are associated with high serum prolactin levels. We aimed to elucidate and compare clinical, hormonal, and radiographic characteristics of NFPAs with and without hyperprolactinemia. Methods We included 201 patients with clinically NFPAs who underwent transsphenoidal surgery performed by a single surgeon during 2010–2017 at a single center in Korea. We measured the three-dimensional diameters (anteroposterior [AP], width, height) and volumes of NFPA on magnetic resonance imaging. We conducted morning basal hormone measurements and dynamic tests preoperatively and 3 months postoperatively. Results All NFPAs were macroadenomas, and mean tumor volume was 10.4 ± 7.7 cm3. Of 201 patients, 59 (29.4%) had preoperative hyperprolactinemia. Hormone recovery rate was higher in patients with hyperprolactinemia compared with patients without hyperprolactinemia after age, sex, body mass index, tumor volume, and gross total resection adjustments (odds ratio [95% confidence interval]: 2.55 [1.10–5.92]). Tumor width/AP diameter ratio positively correlated with serum prolactin levels (r = 0.186, P = 0.008). Tumor volume was not significantly different between the 2 groups. Conclusions Preoperative prolactin level is a useful marker to predict hormone recovery after surgery. Patients with NFPA and hyperprolactinemia tended to have a higher width/AP diameter ratio. Hyperprolactinemia of NFPA is more likely affected by tumor growth pattern, such as width/AP diameter ratio, than tumor volume.

Background: Craniopharyngiomas (CPs) are associated with hypothalamic damage that causes hypothalamic obesity in 30-70% of cases. However, there is an issue of debate for the mechanisms by which CPs cause body weight gain after surgery. In this study, we aimed to reveal the determinants of postoperative weight gain in CP patients compared with non-functioning pituitary adenoma (NFPA) patients. Materials and Methods: We included 48 CP patients aged ≥18 years, who underwent transsphenoidal surgery and measured pre- and postoperative body weight (

Purpose Monogenic diabetes is a specific type of diabetes in which precision medicine could be applied. In this study, we used targeted panel sequencing to investigate pathogenic variants in Korean patients with clinically suspected monogenic diabetes. Methods The eligibility criteria for inclusion were patients with nontype 1 diabetes with age at onset ≤30 years and body mass index (BMI) ≤30 kg/m2. Among the 2090 patients with nontype 1 diabetes, 109 had suspected monogenic diabetes and underwent genetic testing. We analyzed 30 monogenic diabetes genes using targeted panel sequencing. The pathogenicity of the genetic variants was evaluated according to the American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Results Among the 109 patients with suspected monogenic diabetes, 23 patients (21.1%) harbored pathogenic/likely pathogenic variants. A total of 14 pathogenic/likely pathogenic variants of common maturity-onset diabetes of the young (MODY) genes were identified in GCK, HNF1A, HNF4A, and HNF1B. Other pathogenic/likely pathogenic variants were identified in WFS1, INS, ABCC8, and FOXP3. The mitochondrial DNA 3243A>G variant was identified in five participants. Patients with pathogenic/likely pathogenic variants had a significantly higher MODY probability, a lower BMI, and a lower C-peptide level than those without pathogenic/likely pathogenic variants (P = 0.007, P = 0.001, and P = 0.012, respectively). Conclusions Using targeted panel sequencing followed by pathogenicity evaluation, we were able to make molecular genetic diagnoses for 23 patients (21.1%) with suspected monogenic diabetes. Lower BMI, higher MODY probability, and lower C-peptide level were characteristics of these participants.

Background: Targeted exome sequencing is widely used for genetic diagnosis of rare disease and it is replacing Sanger sequencing. In this study we investigated pathogenic variants of monogenic diabetes genes in Korean early onset diabetes patients using targeted exome sequencing. Method: The main eligible criteria for this study was: non-type 1 diabetes patients with age of onset < 30 years old and body mass index (BMI) < 30 kg/m2. Among the 2353 patients screened from the diabetes registry of Seoul National University Hospital Diabetes Clinic, a total of 93 participants were eligible. We analyzed 30 monogenic diabetes genes using targeted exome sequencing. Identified genetic variants were evaluated by ACMG-AMP guideline for their pathogenicity. Result: Among the 93 index patients, a total of 83 rare (minor allele frequency < 0.5%), non-silent variants were found and evaluated for its pathogenicity according to the ACMG-AMP guideline. These variants were classified as likely benign (N=8), uncertain significance (N=59), likely pathogenic (N=13), and pathogenic (N=5). Three causative mutations were identified in HNF4A (p.R136W, p.M1I, p.R89Q), four mutations in five patients were identified in HNF1A (c.G-124C, p.Y166N, p.L26Q, p.R278Q), four mutations were found in GCK (p.G410S, p.N231S, p.L164F, p.H156fs) and one mutation was identified in HNF1B (p.L168P). Other causative mutations were identified in WFS1 (p.R629W), INS (c.C-60G), ABCC8 (p.R933Q) and FOXP3 (p.Q200R). Mitochondria 3243 A>G variant was identified in two patients. Patients with pathogenic variants had higher MODY probability score and lower BMI than those without causative gene variants (p=0.015, p=0.039, respectively). Conclusions: In this study, a total of 19 (20.4%) participants were identified to have monogenic cause of diabetes among 93 early onset diabetes patients. Further research is required to validate the clinical utility of targeted exome sequencing in early onset diabetes patients. Disclosure S. Park: None. S. Jang: None. Y. Lee: None. Y. Cho: None. H. Jang: None. K. Park: None. S. Kwak: None.