A Computed Tomography-Based Fracture Prediction Model With Images of Vertebral Bones and Muscles by Employing Deep Learning: Development and Validation Study.

BACKGROUND: With the progressive increase in aging populations, the use of opportunistic computed tomography (CT) scanning is increasing, which could be a valuable method for acquiring information on both muscles and bones of aging populations. OBJECTIVE: The aim of this study was to develop and externally validate opportunistic CT-based fracture prediction models by using images of vertebral bones and paravertebral muscles. METHODS: The models were developed based on a retrospective longitudinal cohort study of 1214 patients with abdominal CT images between 2010 and 2019. The models were externally validated in 495 patients. The primary outcome of this study was defined as the predictive accuracy for identifying vertebral fracture events within a 5-year follow-up. The image models were developed using an attention convolutional neural network-recurrent neural network model from images of the vertebral bone and paravertebral muscles. RESULTS: The mean ages of the patients in the development and validation sets were 73 years and 68 years, and 69.1% (839/1214) and 78.8% (390/495) of them were females, respectively. The areas under the receiver operator curve (AUROCs) for predicting vertebral fractures were superior in images of the vertebral bone and paravertebral muscles than those in the bone-only images in the external validation cohort (0.827, 95% CI 0.821-0.833 vs 0.815, 95% CI 0.806-0.824, respectively; P<.001). The AUROCs of these image models were higher than those of the fracture risk assessment models (0.810 for major osteoporotic risk, 0.780 for hip fracture risk). For the clinical model using age, sex, BMI, use of steroids, smoking, possible secondary osteoporosis, type 2 diabetes mellitus, HIV, hepatitis C, and renal failure, the AUROC value in the external validation cohort was 0.749 (95% CI 0.736-0.762), which was lower than that of the image model using vertebral bones and muscles (P<.001). CONCLUSIONS: The model using the images of the vertebral bone and paravertebral muscle showed better performance than that using the images of the bone-only or clinical variables. Opportunistic CT screening may contribute to identifying patients with a high fracture risk in the future.

Temporal trends in clinical features of patients with primary aldosteronism over 20 years.

Primary aldosteronism (PA) accounts for approximately 5-10% of hypertension cases. Over the past 20 years, the reported incidence of PA has increased due to widespread screening for secondary hypertension and imaging studies. We aimed to evaluate the temporal trends in the clinical characteristics and subtypes of PA. A total of 1064 patients with PA in two tertiary hospitals between 2000 and 2021 were categorized into three groups according to the year of diagnosis: 2000-2009, 2010-2015, and 2016-2021. The clinical characteristics of the patients over the three time periods were compared using a trend analysis. The age at diagnosis and sex of patients with PA did not change over 20 years. The proportion of patients with bilateral hyperaldosteronism (BHA) increased (11%, 25%, and 40%, P for trend <0.001). The proportion of hypokalemia (87%, 61%, and 40%) and plasma aldosterone concentration (36.0, 30.8, and 26.6 ng/dL) decreased (all P for trend <0.001). There was a trend toward an increased proportion of incidentally detected patients compared to clinically symptomatic patients (36%, 55%, and 61%, P for trend <0.001). The concordance rate of imaging and adrenal venous sampling results decreased (91%, 70%, and 57% P for trend <0.001). However, the proportion of patients with resistant hypertension and comorbidities did not differ. In conclusion, among patients with PA, patients with BHA and incidental detection have increased over 20 years, and more patients are likely to present with milder clinical symptoms and biochemical profiles.

Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality.

BACKGRUOUND: Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses. METHODS: We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis. RESULTS: The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations. CONCLUSION: Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.

In-depth proteomic signature of parathyroid carcinoma.

OBJECTIVE: Diagnosing parathyroid carcinoma (PC) is complicated and controversial that early diagnosis and intervention are often difficult. Therefore, we aimed to elucidate the protein signatures of PC through quantitative proteomic analyses to aid in the early and accurate diagnosis of PC. DESIGN: We conducted a retrospective cohort study. METHODS: We performed liquid chromatography with tandem mass spectrometry using formalin-fixed paraffin-embedded samples. For the analyses, 23 PC and 15 parathyroid adenoma (PA) tissues were collected from 6 tertiary hospitals in South Korea. RESULTS: The mean age of the patients was 52 years, and 63% were women. Proteomic expression profiling revealed 304 differentially expressed proteins (DEPs) with a cut-off of P < .05 and fold change >1.5. Among DEPs, we identified a set of 5 proteins that can discriminate PC from PA: carbonic anhydrase 4 (CA4), alpha/beta hydrolase domain-containing protein 14B (ABHD14B), laminin subunit beta-2 (LAMB2), CD44 antigen (CD44), and alpha-1-acid glycoprotein 1 (ORM1) that exhibited the highest area under the curve of 0.991 in neural network model. The nuclear percentage of CA4 and LAMB2 in immunohistochemistry was significantly lower in PC tissue than in the PA (CA4: 2.77 ± 1.96%, 26.2 ± 3.45%, P < .001; LAMB2: 6.86 ± 3.46%, 38.54 ± 4.13%, P < .001). The most enriched canonical pathways in PC included glycoprotein-6 signaling and mammalian target of rapamycin (mTOR). CONCLUSIONS: We identified key proteins differentially expressed between PC and PA using proteomic analyses of parathyroid neoplasms. These findings may help to diagnose PC accurately and elucidate potential therapeutic targets.

Gene expression profiles in parathyroid adenoma and normal parathyroid tissue.

A parathyroid adenoma comprises 80-85% as a cause of primary hyperparathyroidism. The clonal origin of most parathyroid adenomas suggests a defect at the level of the gene controlling growth of the parathyroid cell or the expression of parathyroid hormone (PTH). Two genes, MEN1 and CCND1, a tumor suppressor and a proto-oncogene respectively, have been solidly established as primary tumorigenic drivers in parathyroid adenomas. As well, germline and somatic mutation of other genes involved in cell cycle regulation or PTH regulation have been discovered in parathyroid adenomas. Moreover, comparative genomic studies between parathyroid adenomas and normal parathyroid tissues have suggested more complex genetic landscape. Microarray analysis have revealed differential expression profiles of genes involved in cell cycle regulation, growth factors, apoptotic pathway, or PTH synthesis or regulation pathway such as CASR, GCM2 and KL (Klotho). Furthermore, recent next-generation sequencing analysis reconfirmed previous finding or revealed novel finding, suggesting signal peptidase complex subunit (SPCS2), ribosomal proteins (RPL23, RPL26, RPN1, RPS25), the endoplasmic reticulum membrane (SEC11C, SEC11A, SEC61G), Klotho, cyclin D1, ß-catenin, VDR, CaSR and GCM2 may be important factors contributing to the parathyroid adenoma.

Outcome-Based Decision-Making Algorithm for Treating Patients with Primary Aldosteronism.

BACKGROUND: Optimal management of primary aldosteronism (PA) is crucial due to the increased risk of cardiovascular and cerebrovascular diseases. Adrenal venous sampling (AVS) is the gold standard method for determining subtype but is technically challenging and invasive. Some PA patients do not benefit clinically from surgery. We sought to develop an algorithm to improve decision- making before engaging in AVS and surgery in clinical practice. METHODS: We conducted the ongoing Korean Primary Aldosteronism Study at two tertiary centers. Study A involved PA patients with successful catheterization and a unilateral nodule on computed tomography and aimed to predict unilateral aldosterone-producing adenoma (n=367). Study B involved similar patients who underwent adrenalectomy and aimed to predict postoperative outcome (n=330). In study A, we implemented important feature selection using the least absolute shrinkage and selection operator regression. RESULTS: We developed a unilateral PA prediction model using logistic regression analysis: lowest serum potassium level ≤3.4 mEq/L, aldosterone-to-renin ratio ≥150, plasma aldosterone concentration ≥30 ng/mL, and body mass index <25 kg/m2 (area under the curve, 0.819; 95% confidence interval, 0.774 to 0.865; sensitivity, 97.6%; specificity, 25.5%). In study B, we identified female, hypertension duration <5 years, anti-hypertension medication <2.5 daily defined dose, and the absence of coronary artery disease as predictors of clinical success, using stepwise logistic regression models (sensitivity, 94.2%; specificity, 49.3%). We validated our algorithm in the independent validation dataset (n=53). CONCLUSION: We propose this new outcome-driven diagnostic algorithm, simultaneously considering unilateral aldosterone excess and clinical surgical benefits in PA patients.

Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) shows histological heterogeneity and clinical variability, including the coexistence of hypercortisolemia. Immunohistochemical analyses of steroidogenic enzymes in adrenal tissues have provided new insights into the pathogenesis of PA. However, a comprehensive analysis of the association between enzyme expression and clinical characteristics of PA has rarely been conducted. We aimed to investigate the correlation between clinical characteristics and steroidogenic enzyme expression in PA. DESIGN: A retrospective case-control study. PATIENTS: Consecutive patients who underwent unilateral adrenalectomy for PA (n = 180). Patients with adrenal Cushing's syndrome (CS) (n = 29) and nonfunctioning adenoma (n = 6) as comparator groups. MEASUREMENTS: A tissue microarray of adrenal adenomas was constructed and immunostained for CYP11B1, CYP11B2 and CYP17A1. The expression of the three enzymes was compared between PA and other adrenal diseases and between PA with and without mild autonomous cortisol excess (MACE). RESULTS: Adrenal adenomas in PA showed lower CYP11B1, higher CYP11B2 and lower CYP17A1 expression than those in adrenal CS (p < .001). Nonfunctioning adenomas showed low expression of the three enzymes. PA with MACE showed higher CYP11B1 expression than PA without MACE. CYP11B1 expression was positively correlated with the severity of hypercortisolemia, and CYP11B2 was positively correlated with that of hyperaldosteronism. The expression of CYP11B1 and CYP11B2 had a negative correlation. Patients with absent clinical improvement after adrenalectomy had lower CYP11B2 expression than those with complete success. CONCLUSIONS: Variable expression of steroidogenic enzymes in adrenal adenoma underlies the clinical heterogeneity of PA and is associated with treatment outcomes.

Indices of ACTH-stimulated adrenal venous sampling as predictors of postsurgical outcomes in primary aldosteronism.

OBJECTIVE: This study aimed to investigate the impact of indices of adrenal venous sampling (AVS) on postsurgical outcomes in patients with primary aldosteronism (PA). DESIGN AND PATIENTS: This retrospective study determined biochemical and clinical outcomes based on ACTH-stimulated AVS parameters (lateralisation index [LI], contralateral ratio [CLR], and ipsilateral ratio [ILR]) in 251 patients with PA at 3 months after surgery. RESULTS: Modified complete biochemical success was achieved in 8 of 12 (66.7%) patients with LI = 3-4, 39 of 47 (83.0%) with LI = 4-10, and 155 of 169 (91.7%) with LI ≥ 10 (p = .004 for trend). Modified complete biochemical success was achieved in 29 of 38 (76.3%) patients with CLR ≥ 1 and ILR ≤ 2, 73 of 86 (84.9%) with CLR = 0.25-1 and ILR > 2, and 100 of 104 (96.2%) with CLR < 0.25 and ILR > 2 (p = .001 for trend). After adjusting for confounders, modified complete biochemical success was associated with an LI ≥ 10 (odds ratio [OR] = 6.32; 95% confidence interval [CI] = 1.33-29.93) using LI = 3-4 as a reference and combined CLR < 0.25 and ILR > 2 (OR = 11.49; 95% confidence interval [CI] = 2.49-53.01) using combined CLR ≥ 1 and ILR ≤ 2 as a reference. Using combined CLR ≥ 1 and ILR ≤ 2 as a reference, complete clinical success was associated with combined CLR < 0.25 and ILR > 2 (OR = 3.10; 95% CI = 1.03-9.28) and combined CLR = 0.25-1 and ILR > 2 (OR = 4.92; 95% CI = 1.64-14.76). CONCLUSION: LI ≥ 10 may be appropriate for achieving biochemical success. With ILR > 2, CLR < 0.25, and CLR < 1 may be appropriate for achieving biochemical and clinical success, respectively.

Bone Lining Cells Could Be Sources of Bone Marrow Adipocytes.

Background: Recently, lineage-tracing studies demonstrated that parathyroid hormone and anti-sclerostin antibody (Scl-Ab) can convert bone lining cells (BLCs) into active osteoblasts. However, BLCs might also be differentiated into other lineages. Here we investigated whether BLCs could differentiate into bone marrow adipocytes (BMAds) and whether Scl-Ab could suppress this process. Methods: Dmp1-CreERt2:mTmG mice were injected with 0.5 mg of 4-hydroxytamoxifen once weekly from postnatal week 4 to week 8. The mice were treated with either vehicle or rosiglitazone for 8 weeks (weeks 12-20). Moreover, they were administered either vehicle or Scl-Ab (50 mg/kg) twice weekly for 4 weeks (weeks 16-20, N = 4-6/group). We chased the GFP+ cells from the endosteal surface to the bone marrow (BM) of the femur. Using immunohistochemical staining, the numbers of perilipin+ or GFP+/perilipin double+ cells in the BM were quantified. In addition, serum N-terminal propeptide of type I procollagen (P1NP) levels were measured at each time point, and bone mass was analyzed at 20 weeks using micro-computed tomography. Results: Scl-Ab administration significantly reversed the decreases in bone parameters induced by rosiglitazone. Plump GFP+ cells, presumably active osteoblasts, and extremely flat GFP+ cells, presumably BLCs, were present on the endosteal surface of the femur at 8 and 12 weeks, respectively, in line with prior findings. When we chased the GFP+ cells, rosiglitazone significantly increased the number of GFP/perilipin double+ BMAds compared to the effects of the vehicle (P < 0.001), and overlapping Scl-Ab administration decreased the number of GFP/perilipin double + BMAd compared to rosiglitazone alone (P < 0.001). In addition, we found that osteoblast lineage cells such as BLCs might express PPARγ on immunohistochemical staining. When rosiglitazone was administered to Rip-Cre:mTmG mice, GFP+ cells were not present on the endosteal surface or in the BM of the femur; however, they were present in the pancreas. Conclusion: BLCs could be sources of BMAds, and rosiglitazone could stimulate the differentiation of osteoblast lineage cells into BMAds. Suppression of the differentiation of osteoblast lineage cells into BMAds might contribute to anabolic effects resulting from the pharmacologic inhibition of sclerostin.

Long-Term Health Outcomes of Korean Adults With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.

There is a lack of studies regarding the long-term outcomes of Asian adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. We hypothesized that adults with CAH are at higher metabolic risk than their age-, and sex-matched controls. We further investigated the long-term health outcome-related factors in adults with CAH. We compared metabolic risk between adults with CAH (71 men, 93 women) and age-, and sex-matched controls (190 men, 261 women) from the Korean National Health and Nutrition Examination Survey data. The presence of obesity, testicular adrenal rest tumors (TARTs), and menstrual irregularity was assessed. Hormone status and treatment regimens were compared according to the presence of adverse outcomes. The median age was 27.0 y and 28.0 y for men and women, respectively. Adults with CAH had a higher waist circumference (88.0 vs. 82.3 cm in men, and 83.5 vs. 72.3 cm in women), and blood pressure (125.0 vs. 113.0 mmHg in men, and 120.0 vs. 104.0 mmHg in women) than age- and sex-matched controls (P<0.05 for all). The 2.7-fold increased risk for hypertension (men) and 2.0-fold increased risk for obesity (women) was significant in patients with CAH (P<0.05 for both). Obese adults with CAH showed significantly higher adrenal limb thicknesses (men) and 17-hydroxyprogesterone and dehydroepiandrosterone sulfate levels (women) (P<0.05 for both). TARTs occurred in 58.1% of men and did not differ by hormone or treatment regimen. Irregular menstruation was observed in 57.1% of women, with higher dehydroepiandrosterone sulfate levels in those with irregular periods. Adults with CAH had a higher metabolic risk than the general population. Poor disease control may increase their risk of metabolic morbidity and menstrual irregularity.

Metabolic Subtyping of Adrenal Tumors: Prospective Multi-Center Cohort Study in Korea.

BACKGROUND: Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids. METHODS: The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing's syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors. RESULTS: The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6ß-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT. CONCLUSION: The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.

Mass Spectrometry-Based Proteomic Discovery of Prognostic Biomarkers in Adrenal Cortical Carcinoma.

Adrenal cortical carcinoma (ACC) is an extremely rare disease with a variable prognosis. Current prognostic markers have limitations in identifying patients with a poor prognosis. Herein, we aimed to investigate the prognostic protein biomarkers of ACC using mass-spectrometry-based proteomics. We performed the liquid chromatography-tandem mass spectrometry (LC-MS/MS) using formalin-fixed paraffin-embedded (FFPE) tissues of 45 adrenal tumors. Then, we selected 117 differentially expressed proteins (DEPs) among tumors with different stages using the machine learning algorithm. Next, we conducted a survival analysis to assess whether the levels of DEPs were related to survival. Among 117 DEPs, HNRNPA1, C8A, CHMP6, LTBP4, SPR, NCEH1, MRPS23, POLDIP2, and WBSCR16 were significantly correlated with the survival of ACC. In age- and stage-adjusted Cox proportional hazard regression models, only HNRNPA1, LTBP4, MRPS23, POLDIP2, and WBSCR16 expression remained significant. These five proteins were also validated in TCGA data as the prognostic biomarkers. In this study, we found that HNRNPA1, LTBP4, MRPS23, POLDIP2, and WBSCR16 were protein biomarkers for predicting the prognosis of ACC.

Contralateral Suppression at Adrenal Venous Sampling Is Associated with Renal Impairment Following Adrenalectomy for Unilateral Primary Aldosteronism.

BACKGROUND: Adrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant0.26 after adjusting for other factors. CONCLUSION: CS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.

Radioactive Parathyroid Adenomas on Sestamibi Scans: Low Parathyroid Hormone Secretory Potential and Large Volume.

BACKGROUND: We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients. METHODS: The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent 99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid. RESULTS: Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [-] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m2. Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (-) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (-) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm3 [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm3 [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume. CONCLUSION: Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.

Epidemiology and prognosis of parathyroid carcinoma: real-world data using nationwide cohort.

PURPOSE: Parathyroid carcinoma (PC) is an exceedingly rare endocrine malignancy with a poor prognosis. Due to the rarity, the natural course and prognostic factors of the disease are yet unclear. Therefore, we aimed to identify the incidence, prognosis, and prognostic factors of PC in the nationwide cohort study. METHODS: The study is a nationwide study using the National Health Insurance Services database in Korea from 2002 to 2017. PC was defined as patients with ICD-10 code of PC and a procedural code for parathyroidectomy. RESULTS: From 2002 to 2017, 255 patients were diagnosed with PC whose mean age was 53.2 years, and 155 (60.2%) were women. The crude and age-standardized incidence were 10.2 and 6.6/10,000,000 person-year in 2016, rising from 4.1 and 3.8/10,000,000 person-year in 2003 (p < 0.001), respectively. The 5- and 10-year survival rates were 86.5 and 72.9%, respectively. In survival analysis, age over 50 years, thyroidectomy at the initial surgery, and reoperation had increased risk of mortality with HRs of 4.83 (95% CI 1.47-15.90), and 4.21 (95% CI 1.60-11.08), and 1.05 (95% CI 1.02-1.08) in multivariate analysis, respectively. CONCLUSION: Incidence of PC has been rising over time, similar to the trends in Western countries. The prognostic factors for mortality were old age, parathyroidectomy alone, and recurrence, emphasizing the importance of preoperative suspicion of the disease. The study is clinically meaningful in the first Asian nationwide study to reveal the natural course of PC.

Epidemiology and Comorbidity of Adrenal Cushing Syndrome: A Nationwide Cohort Study.

CONTEXT: Adrenal Cushing syndrome (CS) is a major subtype of CS and has a high surgical cure rate. However, only a few studies have investigated the epidemiology and long-term outcomes of adrenal CS. OBJECTIVE: We aimed to investigate the nationwide epidemiology, long-term prognosis, and postoperative glucocorticoid replacement therapies of adrenal CS in Korea. DESIGN: Retrospective cohort study. SETTING: A nationwide claim database. PATIENTS: Adrenal CS patients who were defined as having undergone adrenalectomy, a diagnosis code of CS, and not having pituitary gland surgery. MAIN OUTCOME MEASURES: Crude incidence and age-standardized incidence rates, long-term mortality, comorbidities diagnosed preoperatively or developed postoperatively, and the pattern of postoperative glucocorticoid replacement therapy. RESULTS: From 2002 to 2017, there were a total of 1199 new adrenal CS patients, including 72 patients with adrenocortical carcinoma (malignant adrenal CS), in Korea. The crude and age-standardized incidence rates were 1.51 and 1.27 per million person-years, respectively. The overall standardized mortality ratio was 3.0 (95% confidence interval [CI], 2.4-3.7) for benign adrenal CS and 13.1 (95% CI, 7.6-18.6) for malignant adrenal CS. Adrenal CS patients had a high risk of having coronary artery disease, stroke, metabolic diseases, and depression. A similar proportion of patients were diagnosed with these comorbidities both preoperatively and postoperatively, suggesting a significant residual risk even after adrenalectomy. The median time of postoperative glucocorticoid replacement therapy was 10.1 months, and the major types of glucocorticoids used were prednisolone (66.6%) and hydrocortisone (22.4%). CONCLUSIONS: Adrenal CS is associated with multiple comorbidities even after treatment, which necessitates meticulous postoperative care.

Feasibility of Attachable Ring Stimulator for Intraoperative Neuromonitoring during Thyroid Surgery.

OBJECTIVE: Stimulator-attached dissecting instruments are useful for intraoperative nerve monitoring during thyroidectomy. The aim of this study was to evaluate the feasibility of an attachable ring stimulator (ARS) by comparing the electromyography (EMG) amplitudes evoked by an ARS and a conventional stimulator. METHODS: Medical records of fourteen patients who underwent thyroidectomy using intraoperative neuromonitoring between June and August 2019 were retrospectively reviewed. The amplitudes of V1, R1, R2, and V2 signals were checked using both the ARS and a conventional stimulator, at the same point. RESULTS: Both stimulators were tested on 20 recurrent laryngeal nerves (RLNs) and 20 vagus nerves (VNs). In all the nerves, the amplitudes of V1, R1, R2, and V2 were greater than 500 µV. The mean amplitudes of V1, R1, R2, and V2 checked with the ARS were 1175, 1432, 1598, and 1279 µV, respectively. The mean amplitudes of V1, R1, R2, and V2 checked with the conventional stimulator were 1140, 1425, 1557, and 1217 µV, respectively. Difference between amplitudes evoked by the two stimulators for V1, R1, R2, and V2 was 77, 110, 102, and 99 µV, respectively. There was no statistical difference in the amplitudes between the two groups for V1, R1, R2, and V2. CONCLUSION: The ARS transferred electric stimulation as effectively as the conventional stimulator. It is an effective tool for repeated stimulation and facilitates continuous feedback regarding the functional integrity of nerves during thyroid surgery.

Aromatase inhibitors attenuate the effect of alendronate in women with breast cancer.

INTRODUCTION: Aromatase inhibitors are known to accelerate bone loss in patients with breast cancer. However, how much AIs affect the efficacy of antiresorptive agents has not been studied. The study aimed to compare the effect of alendronate on bone mineral density (BMD) between patients with and without AI treatment. MATERIALS AND METHODS: In this retrospective study, 90 postmenopausal women with early breast cancer who were being treated with both AI and alendronate 70 mg weekly (ALN + AI), and 90 age- and body mass index (BMI)-matched patients who were only taking alendronate (ALN-only) were analyzed. BMD and bone turnover markers (BTMs) were assessed at the baseline and 12 months. RESULTS: The mean age was 63 years. At baseline, the ALN-only group had lower lumbar spine (LS), femur neck (FN), and total hip (TH) BMD than ALN + AI group. After 1-year of alendronate treatment, the LS and FN BMD were improved more in the ALN-only group than those in the ALN + AI group after adjustments for age, BMI, baseline BMD, diabetes, hypertension, renal function, and previous fracture history [LS BMD: 6.2% (3.1%; 9.2%) in ALN-only, 3.5% (-0.5%; 6.5%) in ALN + AI, p = 0.001; FN BMD: 2.5% (0.3%; 5.7%) in ALN-only, 0.9% (- 1.8%; 3.6%) in ALD + AI, p = 0.032]. BTMs were significantly decreased in both groups, but the changes between groups were similar. CONCLUSION: The effect of alendronate on the LS and FN BMD was attenuated in postmenopausal women who were taking AI compared to those who were not on AI.

Comparative Gene Expression Profiles in Parathyroid Adenoma and Normal Parathyroid Tissue.

Parathyroid adenoma is the main cause of primary hyperparathyroidism, which is characterized by enlarged parathyroid glands and excessive parathyroid hormone secretion. Here, we performed transcriptome analysis, comparing parathyroid adenomas with normal parathyroid gland tissue. RNA extracted from ten parathyroid adenoma and five normal parathyroid samples was sequenced, and differentially expressed genes (DEGs) were identified using strict cut-off criteria. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DEGs as the input, and protein-protein interaction (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and visualized in Cytoscape. Among DEGs identified in parathyroid adenomas (n = 247; 45 up-regulated, 202 down-regulated), the top five GO terms for up-regulated genes were nucleoplasm, nucleus, transcription DNA-template, regulation of mRNA processing, and nucleic acid binding, while those for down-regulated genes were extracellular exosome, membrane endoplasmic reticulum (ER), membrane, ER, and melanosome. KEGG enrichment analysis revealed significant enrichment of five pathways: protein processing in ER, protein export, RNA transport, glycosylphosphatidylinositol-anchor biosynthesis, and pyrimidine metabolism. Further, PPI network analysis identified a densely connected sub-module, comprising eight hub molecules: SPCS2, RPL23, RPL26, RPN1, SEC11C, SEC11A, RPS25, and SEC61G. These findings may be helpful in further analysis of the mechanisms underlying parathyroid adenoma development.