Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review.

BACKGRUOUND: Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS). METHODS: Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized. RESULTS: In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%-10.8% and 16.0%-25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%-1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered. CONCLUSION: AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

Elevated triglyceride levels are associated with increased risk for major adverse cardiovascular events in statin-naïve rheumatoid arthritis patients: A nationwide cohort study.

OBJECTIVES: To investigate the association between the four components of the lipid profile (total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)) at baseline and composite major adverse cardiovascular events (MACEs) in statin-naïve rheumatoid arthritis (RA) patients with no previous history of cardiovascular events. METHODS: This nationwide population-based cohort study was performed on a total of 15,216 statin-naïve RA patients. The end point was a composite of clinical events, including myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death. We compared the incidence of and risk for clinical events according to each lipid variable. RESULTS: During follow-up (median 4.70 years), the incidence of MACE per 1000 person-years was 7.27. Among the four lipid components, only higher baseline TG levels were significantly associated with increased risk for composite MACE in RA subjects. The risk for composite MACE was significantly higher in the third (adjusted hazard ratio (HR), 1.35 [95% confidence interval (CI), 1.03-1.78]) and highest quartiles (adjusted HR, 1.74 [95%CI, 1.33-2.28]) of baseline TG level versus the lowest quartile. CONCLUSIONS: In statin-naïve RA patients, increased TG level is associated with increased risk for MACE. Therefore, screening and intervention for increased TG level may be clinically beneficial in this population.

Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association.

Thyroid hormones play an important physiological role in maintaining adult bone structure and strength. Consequently, thyroid dysfunction is related to skeletal outcomes. Overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, leading to osteoporosis and increased fracture risk. Hyperthyroidism induced by thyroid-stimulating hormone-suppressive therapy in patients with differentiated thyroid cancer is a cause of secondary osteoporosis. In contrast, there is a lack of evidence on the negative impact of hypothyroidism on bone health. Considering the clinical updates on the importance of bone health in thyroid dysfunction, the Task Force from the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association recently developed a position statement on the evaluation and management of bone health of patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid-stimulating hormone-suppressive therapy-associated hyperthyroidism in patients with differentiated thyroid cancer. Herein, we review the Korean Thyroid Association's position statement on the evaluation and management of bone health associated with thyroid diseases.

Fracture Liaison Service in Korea: 2022 Position Statement of the Korean Society for Bone and Mineral Research.

Osteoporosis and osteoporotic fractures cause socioeconomic concerns, and medical system and policies appear insufficient to prepare for these issues in Korea, where the older adult population is rapidly increasing. Many countries around the world are already responding to osteoporosis and osteoporotic fractures by adopting fracture liaison service (FLS), and such an attempt has only begun in Korea. In this article, we introduce the operation methods for institutions implementing FLS and characteristics of services, and activities of the FLS Committee for FLS implementation in the Korean Society for Bone and Mineral Research. In addition, we hope that the current position statement will contribute to the implementation of FLS in Korea and impel policy changes to enable a multidisciplinary and integrated FLS operated under the medical system.

A Comprehensive Assessment of the Harms of Fine-Needle Aspiration Biopsy for Thyroid Nodules: A Systematic Review.

BACKGRUOUND: There have concerns related with the potential harms of fine-needle aspiration biopsy (FNAB). We aimed to summarize the clinical complications and evaluate the safety of FNAB. METHODS: Studies related with the harms of FNAB were searched on MEDLINE, Embase, Cochrane library, and KoreaMed from 2012 to 2022. Also, studies reviewed in the previous systematic reviews were evaluated. Included clinical complications were postprocedural pain, bleeding events, neurological symptoms, tracheal puncture, infections, post-FNAB thyrotoxicosis, and needle tract implantation of thyroid cancers. RESULTS: Twenty-three cohort studies were included in this review. Nine studies which were related with FNAB-related pain showed that most of the subjects had no or mild discomfort. The 0% to 6.4% of the patients had hematoma or hemorrhage after FNAB, according to 15 studies. Vasovagal reaction, vocal cord palsy, and tracheal puncture have rarely described in the included studies. Needle tract implantation of thyroid malignancies was described in three studies reporting 0.02% to 0.19% of the incidence rate. CONCLUSION: FNAB is considered to be a safe diagnostic procedure with rare complications, which are mainly minor events. Thorough assessement of the patients' medical condition when deciding to perform FNABs would be advisable to lower potential complications.

Reactivation of Bone Lining Cells are Attenuated Over Repeated Anti-sclerostin Antibody Administration.

Reactivation of bone lining cells (BLCs) is a crucial mechanism governing the anabolic action of anti-sclerostin antibody (Scl-Ab) via modeling-based bone formation; however, it remains unclear whether this reactivation can be attenuated after persistent administration of Scl-Ab. Here, we aimed to investigate the reproducibility of persistent Scl-Ab administration for the reactivation of BLCs, and to elucidate the relationship between the activity of BLCs and serum levels of N-terminal procollagen type I (P1NP) during chronic Scl-Ab administration. We conducted an osteoblast lineage tracing study. Briefly, Dmp1-CreERt2(+):Rosa26R mice were injected with 1 mg of 4-hydroxy-tamoxifen weekly from postnatal weeks four to eight. Mice were treated twice with either vehicle or Scl-Ab (25 mg/kg) at weeks 12, 16, and 20, and were euthanized at weeks 8, 12, 13, 16, 17, 20, and 21 (4-6 mice in each group). After euthanization, the number and thickness of X-gal (+) cells on the periosteum of the femoral bones and the serum levels of P1NP were quantified at each time point. Scl-Ab induced a significant increase in the thickness of X-gal (+) cells on periosteal bone surfaces at postnatal weeks 13 (after 1st dose), 17 (after 2nd dose), and 21 (after 3rd dose) compared to that in vehicle-treated mice (all P < 0.001). In the Scl-Ab group, significant increases in the thickness of labeled cells were observed between weeks 16 and 17 and weeks 20 and 21 (both P < 0.001). The percentage increase in X-gal (+) cell thickness was 108.9% from week 12 to week 13, 54.6% from week 16 to week 17, and 49.2% from week 20 to week 21 in the Scl-Ab group. Although Scl-Ab treatment increased the serum levels of P1NP at postnatal weeks 13 and 17 compared with those at week 12 (P = 0.017 and P = 0.038, respectively), the same was not observed at week 21 (P = 0.296). A significant increase in P1NP levels was observed between weeks 16 and 17 and weeks 20 and 21 in the Scl-Ab group (P = 0.005 and P = 0.007, respectively). The percentage increase in P1NP levels was 141.7% from weeks 12 to 13, 114.8% from weeks 16 to 17, and 99.4% from weeks 20 to 21. Serum P1NP levels were positively correlated with X-gal (+) cell thickness (R2 = 0.732, P < 0.001). Reactivation of BLCs is modestly attenuated, but reproducible, during persistent Scl-Ab administration. Serum P1NP levels appear to be an indicator of the impact of Scl-Ab on the conversion of BLCs into mature osteoblasts on periosteal bone surfaces, thus contributing to modeling-based bone formation.

Early Thyroid Volume Reduction in Subacute Thyroiditis Can be a Potential Indicator for Hypothyroidism.

Background: Thyroid volume has been reported to decrease significantly after episodes of subacute thyroiditis (SAT); however, the relationship between thyroid volume and hypothyroidism remains unclear. This study assessed the association between thyroid volume changes and the hypothyroid phase in patients with SAT, a condition that can progress to persistent hypothyroidism. Methods: This retrospective study evaluated 37 patients diagnosed with SAT at the Department of Endocrinology and Metabolism of Chonnam National University Hwasun Hospital (CNUHH) between 2016 and 2021. Since we could not determine the clinical characteristics of patients with SAT before their episodes, 120 healthy individuals who underwent thyroid ultrasonography during regular check-ups from 2019 to 2021 at CNUHH were selected for comparison. Subgroup analyses were performed on patients with SAT with and without the hypothyroid phase during their clinical course. Results: Thyroid volume was significantly greater in SAT patients at the first visit than in controls (p<0.05), and it decreased constantly throughout the follow-up period. Subgroup analysis showed that the initial thyroid volumes were similar in patients with SAT with and without the hypothyroid phase. However, SAT patients with the hypothyroid phase had significantly smaller thyroid volumes at the 1 month (p=0.025) and 3 month (p=0.006) follow-up visits. The reduction rate of the thyroid volume was significantly different within the first month (p=0.009). Conclusion: A greater reduction in thyroid volume in SAT patients within 1 month of episode had a higher chance of developing a subsequent hypothyroid phase, which can lead to persistent hypothyroidism. Serial thyroid ultrasonography in patients with SAT, especially within the first month, may help in predicting the disease course of SAT.

Determinants of Short-Term Weight Gain Following Surgical Treatment for Craniopharyngioma in Adults.

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 (<120 days after the surgery). We recruited 144 age- and body mass index-matched patients with non-functioning pituitary adenoma (NFPA) as controls. RESULTS: Patients with CP experienced greater postoperative weight gain than patients with NFPA (3.0±5.1 vs. 0.1±3.6 kg, p<0.001). The prevalence of postoperative steroid use was significantly higher in patients with CP than in those with NFPA (89.6% vs. 34.0%, p<0.001). Steroid replacement therapy and CP were associated with postoperative weight gain after adjusting for covariates in overall patients (p=0.032 and 0.007, respectively). In subgroup analysis with postoperative steroid users, weight gain was significantly greater in patients with CP (n=43, 0.96±0.25 kg/month) than in patients with NFPA (n=49, 0.26±0.23 kg/month) even after adjusting for the daily steroid dose (p=0.048). CONCLUSION: Patients with CP experience greater postoperative weight gain than those with NFPA. Hypothalamic damage itself as well as steroid replacement may contribute to the postoperative weight gain in patients with CP.

Improved Erythrocyte Deformability Induced by Sodium-Glucose Cotransporter 2 Inhibitors in Type 2 Diabetic Patients.

PURPOSE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are antidiabetic drugs that improve cardiovascular outcomes. Hemoglobin and hematocrit values increase after SGLT-2 inhibitor administration. Although these factors increase blood viscosity and the risk of cardiovascular disease, SGLT-2 inhibitors have protective effects on the cardiovascular system. The mechanisms for this paradoxical phenomenon remain unclear, and the effect of SGLT-2 inhibitors on hemorheology has not been studied. METHODS: We evaluated the hemorheological parameters of 63 patients of whom 38 received metformin with a dipeptidyl peptidase 4 (DPP-4) inhibitor, while 25 received metformin with SGLT-2 inhibitor. Blood viscosity was measured using a cone-and-plate viscometer, erythrocyte aggregation was measured using a modified erythrocyte sedimentation rate method, and erythrocyte membrane fluctuation was measured as deformability, using a diffraction optical tomography. RESULTS: Both blood viscosity and erythrocyte aggregation increased in the SGLT-2 inhibitor group, although erythrocyte deformability was significantly improved compared with that of the DPP-4 inhibitor group (DPP-4 inhibitor 43.71 ± 5.13 nm; SGLT-2 inhibitor 53.88 ± 4.88 nm; p < 0.001). When the two groups were compared after propensity score matching, no differences in blood viscosity at high shear rates and erythrocyte aggregation were observed, although erythrocyte deformability was significantly improved in the SGLT-2 inhibitor group (DPP-4 inhibitor 45.01 ± 5.28 nm; SGLT-2 inhibitor 53.14 ± 4.72 nm; p = 0.001). CONCLUSION: This study demonstrates that erythrocyte deformability was improved in the SGLT-2 inhibitor group compared with that in the DPP-4 inhibitor group. This improvement in erythrocyte deformability is expected to have a protective effect on the cardiovascular system.

Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study.

Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 µg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.98-0.99; P = 0.020) and megestrol acetate use (OR = 2.63, 95% CI 1.48-4.67; P = 0.001) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI (OR = 2.54, 95% CI 1.41-4.60; P = 0.002). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.

Clinical Characteristics and Prognosis of Coexisting Thyroid Cancer in Patients with Graves' Disease: A Retrospective Multicenter Study.

BACKGROUND: The association between Graves' disease (GD) and co-existing thyroid cancer is still controversial and most of the previously reported data have been based on surgically treated GD patients. This study investigated the clinicopathological findings and prognosis of concomitant thyroid cancer in GD patients in the era of widespread application of ultrasonography. METHODS: Data of GD patients who underwent thyroidectomy for thyroid cancer between 2010 and 2019 in three tertiary hospitals in South Korea (Asan Medical Center, Chonnam National University Hwasun Hospital, and Pusan National University Hospital) were collected and analyzed retrospectively. In the subgroup analysis, aggressiveness and clinical outcomes of thyroid cancer were compared nodular GD and non-nodular GD groups according to the presence or absence of the thyroid nodules other than thyroid cancer (index nodules). RESULTS: Of the 15,159 GD patients treated at the hospitals during the study period, 262 (1.7%) underwent thyroidectomy for coexisting thyroid cancer. Eleven patients (4.2%) were diagnosed with occult thyroid cancer and 182 patients (69.5%) had microcarcinomas. No differences in thyroid cancer aggressiveness, ultrasonographic findings, or prognosis were observed between the nodular GD and non-nodular GD groups except the cancer subtype. In the multivariate analysis, only lymph node (LN) metastasis was an independent prognostic factor for recurrent/persistent disease of thyroid cancer arising in GD (P=0.020). CONCLUSION: The prevalence of concomitant thyroid cancer in GD patients was considerably lower than in previous reports. The clinical outcomes of thyroid cancer in GD patients were also excellent but, more cautious follow-up is necessary for patients with LN metastasis in the same way as for thyroid cancer in non-GD patients.

Real-World Efficacy and Safety of Dulaglutide in Korean Patients with Type 2 Diabetes Mellitus: A Retrospective Study in a Tertiary Referral Center.

This study was conducted to evaluate the efficacy and safety of once-weekly dulaglutide therapy as add-on to oral antidiabetic drugs (OADs) and basal insulin in Korean patients with type 2 diabetes mellitus (T2DM) in real-world clinical practice. We retrospectively reviewed the medical records of 112 patients who received dulaglutide in a tertiary referral center. The primary efficacy endpoint was a change in glycated hemoglobin (HbA1c) between baseline and 6 months. The secondary endpoints were the percentage of patients achieving HbA1c <7.0% or ≤6.5% and the change of body weight at 6 months. At baseline, the mean HbA1c was 8.7 % (8.8% in the OAD combination and 8.5% in the basal insulin combination group). The mean adjusted HbA1c at 6 months decreased by -1.13% in all patients (p<0.001), and by -1.36 and -0.74% in the OAD combination and basal insulin combination group, respectively. A significant reduction of -2.9 kg in body weight was observed in all patients at 6 months (p<0.001). Approximately 34.8% and 23.2% of patients achieved HbA1c <7.0% and ≤6.5%, respectively. Higher baseline HbA1c and no previous insulin therapy were associated with positive responses to dulaglutide on multivariate analysis. Mild gastrointestinal issues (23.2%) were the most frequently observed adverse events. Dulaglutide is an effective and durable treatment option as OAD and basal insulin combination therapy in Korean patients with T2DM.

A beneficial role of computer-aided diagnosis system for less experienced physicians in the diagnosis of thyroid nodule on ultrasound.

Ultrasonography (US) is the primary diagnostic tool for thyroid nodules, while the accuracy is operator-dependent. It is widely used not only by radiologists but also by physicians with different levels of experience. The aim of this study was to investigate whether US with computer-aided diagnosis (CAD) has assisting roles to physicians in the diagnosis of thyroid nodules. 451 thyroid nodules evaluated by fine-needle aspiration cytology following surgery were included. 300 (66.5%) of them were diagnosed as malignancy. Physicians with US experience less than 1 year (inexperienced, n = 10), or more than 5 years (experienced, n = 3) reviewed the US images of thyroid nodules with or without CAD assistance. The diagnostic performance of CAD was comparable to that of the experienced group, and better than those of the inexperienced group. The AUC of the CAD for conventional PTC was higher than that for FTC and follicular variant PTC (0.925 vs. 0.499), independent of tumor size. CAD assistance significantly improved diagnostic performance in the inexperienced group, but not in the experienced groups. In conclusion, the CAD system showed good performance in the diagnosis of conventional PTC. CAD assistance improved the diagnostic performance of less experienced physicians in US, especially in diagnosis of conventional PTC.

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.

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.

Is acute kidney injury after laparoscopic adrenalectomy related to the progression of chronic kidney disease in patients with primary aldosteronism?

PURPOSE: This study was conducted to investigate the predictors of kidney outcome after laparoscopic adrenalectomy in patients with primary aldosteronism (PA). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 74 patients who underwent unilateral adrenalectomy for the treatment of PA from January 2011 to December 2019. Patient characteristics and serial data on postoperative changes in kidney function were analyzed and compared between the two groups according to the presence of acute kidney injury (AKI). Postoperative AKI was defined as a decline in the estimated glomerular filtration rate (eGFR) of >50% or an increase in the serum creatinine level of ≥0.3 mg/dL at 1 week after surgery compared with perioperative levels. Chronic kidney disease (CKD) was defined as an eGFR < 60 mL/min/1.73 m² present for 3 months. RESULTS: Nineteen patients (25.7%) had postoperative AKI. Patients who experienced postoperative AKI had higher aldosterone-to-renin ratios, higher rates of dyslipidemia, and more left ventricular hypertrophy than did patients without postoperative AKI (p=0.015, 0.036, and 0.033, respectively). Twenty-eight patients (37.8%) had CKD at 6 months after surgery, including 15 patients who had newly progressed to CKD postoperatively. In the multivariate regression analysis of patients without preoperative CKD, the only independent predictor of the progression to CKD was preoperative albuminuria (p=0.007). CONCLUSIONS: In this study, one-quarter of the patients had postoperative AKI after unilateral adrenalectomy for the treatment of PA. However, postoperative AKI was not directly correlated with CKD progression. Preoperative albuminuria was an independent predictor of the progression of CKD.

A challenging TSH/GH co-secreting pituitary adenoma with concomitant thyroid cancer; a case report and literature review.

BACKGROUND: Thyroid stimulating hormone (TSH) secreting pituitary adenoma (TSHoma) with coexisting thyroid cancer is extremely rare, and proper treatment of both diseases may pose a unique clinical challenge. When TSHoma has plurihormonality, particularly involving the co-secretion of growth hormone (GH), management can be more complicated. Herein, we present a difficult-to-manage case of papillary thyroid cancer with an incurable TSH/GH-secreting pituitary adenoma. CASE PRESENTATION: A 59-year-old man was referred to our hospital due to memory impairment and inappropriate TSH level. Sella magnetic resonance imaging revealed a huge pituitary mass extending to the suprasellar area. Clinical diagnosis of TSH/GH co-secreting pituitary adenoma was made based on elevated free T4, total T3, serum α-subunit, insulin-like growth factor-1 levels and non-suppressible GH levels after oral glucose loading. Rectal cancer and multifocal papillary thyroid microcarcinoma (PTMC) were diagnosed during initial screening for internal malignancy; lower anterior resection was performed and close observation was planned for PTMC. Long-acting octreotide therapy was commenced, which resulted in a dramatic reduction in TSHoma size and facilitated control of hormonal excess. Total thyroidectomy and radioactive iodine (RAI) therapy were needed during follow up due to the growth of PTMC. After the surgery, the pituitary adenoma represented resistance to somatostatin analogue therapy and the tumor size gradually increased despite the addition of dopamine agonist therapy. Furthermore, TSH suppressive therapy with levothyroxine was impossible and an adequate TSH level for RAI therapy was unmountable. Late debulking pituitary surgery was ineffective, and the patient gradually deteriorated and lost to follow up. CONCLUSION: We report the first aggravated case of TSH/GH co-secreting pituitary tumor after total thyroidectomy for concomitant multifocal PTMC. Deferring of thyroid surgery until the TSHoma is well controlled may be the optimal therapeutic strategy in patients with TSHoma and coexistent thyroid cancer; ablative thyroid surgery may result in catastrophic pituitary tumor growth.

Application of Machine Learning to Identify Clinically Meaningful Risk Group for Osteoporosis in Individuals Under the Recommended Age for Dual-Energy X-Ray Absorptiometry.

Dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing osteoporosis; it is generally recommended in men ≥ 70 and women ≥ 65 years old. Therefore, assessment of clinical risk factors for osteoporosis is very important in individuals under the recommended age for DXA. Here, we examine the diagnostic performance of machine learning-based prediction models for osteoporosis in individuals under the recommended age for DXA examination. Data of 2210 men aged 50-69 and 1099 women aged 50-64 obtained from the Korea National Health and Nutrition Examination Survey IV-V were analyzed. Extreme gradient boosting (XGBoost) was used to find relevant clinical features and applied to three machine learning models: XGBoost, logistic regression, and a multilayer perceptron. For the prediction of osteoporosis, the XGBoost model using the top 20 features extracted from XGBoost showed the most reliable performance with area under the receiver operating characteristic curve (AUROC) of 0.73 and 0.79 in men and women, respectively. We compared the diagnostic accuracy of the Shapley additive explanation values based on a risk-score model obtained from XGBoost and conventional osteoporosis risk assessment tools for prediction of osteoporosis using optimal cut-off values for each model. We observed that a cut-off risk score of ≥ 28 in men and ≥ 47 in women was optimal to classify a positive screening for osteoporosis (an AUROC of 0.86 in men and 0.91 in women). The XGBoost-based osteoporosis-prediction model outperformed conventional risk assessment tools. Therefore, machine learning-based prediction models are a more suitable option than conventional risk assessment methods for screening osteoporosis in individuals under the recommended age for DXA examination.