A CT-based Deep Learning Model for Predicting Subsequent Fracture Risk in Patients with Hip Fracture.

Background Patients have the highest risk of subsequent fractures in the first few years after an initial fracture, yet models to predict short-term subsequent risk have not been developed. Purpose To develop and validate a deep learning prediction model for subsequent fracture risk using digitally reconstructed radiographs from hip CT in patients with recent hip fractures. Materials and Methods This retrospective study included adult patients who underwent three-dimensional hip CT due to a fracture from January 2004 to December 2020. Two-dimensional frontal, lateral, and axial digitally reconstructed radiographs were generated and assembled to construct an ensemble model. DenseNet modules were used to calculate risk probability based on extracted image features and fracture-free probability plots were output. Model performance was assessed using the C index and area under the receiver operating characteristic curve (AUC) and compared with other models using the paired t test. Results The training and validation set included 1012 patients (mean age, 74.5 years ± 13.3 [SD]; 706 female, 113 subsequent fracture) and the test set included 468 patients (mean age, 75.9 years ± 14.0; 335 female, 22 subsequent fractures). In the test set, the ensemble model had a higher C index (0.73) for predicting subsequent fractures than that of other image-based models (C index range, 0.59-0.70 for five of six models; P value range, < .001 to < .05). The ensemble model achieved AUCs of 0.74, 0.74, and 0.73 at the 2-, 3-, and 5-year follow-ups, respectively; higher than that of most other image-based models at 2 years (AUC range, 0.57-0.71 for five of six models; P value range, < .001 to < .05) and 3 years (AUC range, 0.55-0.72 for four of six models; P value range, < .001 to < .05). Moreover, the AUCs achieved by the ensemble model were higher than that of a clinical model that included known risk factors (2-, 3-, and 5-year AUCs of 0.58, 0.64, and 0.70, respectively; P < .001 for all). Conclusion In patients with recent hip fractures, the ensemble deep learning model using digital reconstructed radiographs from hip CT showed good performance for predicting subsequent fractures in the short term. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Li and Jaremko in this issue.

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.

Development and validation of common data model-based fracture prediction model using machine learning algorithm.

The need for an accurate country-specific real-world-based fracture prediction model is increasing. Thus, we developed scoring systems for osteoporotic fractures from hospital-based cohorts and validated them in an independent cohort in Korea. The model includes history of fracture, age, lumbar spine and total hip T-score, and cardiovascular disease. PURPOSE: Osteoporotic fractures are substantial health and economic burden. Therefore, the need for an accurate real-world-based fracture prediction model is increasing. We aimed to develop and validate an accurate and user-friendly model to predict major osteoporotic and hip fractures using a common data model database. METHODS: The study included 20,107 and 13,353 participants aged ≥ 50 years with data on bone mineral density using dual-energy X-ray absorptiometry from the CDM database between 2008 and 2011 from the discovery and validation cohort, respectively. The main outcomes were major osteoporotic and hip fracture events. DeepHit and Cox proportional hazard models were used to identify predictors of fractures and to build scoring systems, respectively. RESULTS: The mean age was 64.5 years, and 84.3% were women. During a mean of 7.6 years of follow-up, 1990 major osteoporotic and 309 hip fracture events were observed. In the final scoring model, history of fracture, age, lumbar spine T-score, total hip T-score, and cardiovascular disease were selected as predictors for major osteoporotic fractures. For hip fractures, history of fracture, age, total hip T-score, cerebrovascular disease, and diabetes mellitus were selected. Harrell's C-index for osteoporotic and hip fractures were 0.789 and 0.860 in the discovery cohort and 0.762 and 0.773 in the validation cohort, respectively. The estimated 10-year risks of major osteoporotic and hip fractures were 2.0%, 0.2% at score 0 and 68.8%, 18.8% at their maximum scores, respectively. CONCLUSION: We developed scoring systems for osteoporotic fractures from hospital-based cohorts and validated them in an independent cohort. These simple scoring models may help predict fracture risks in real-world practice.

Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma.

BACKGROUND: Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing neuroendocrine tumours. PPGLs are a rare but important cause of secondary hypertension owing to their high morbidity and mortality. Patients with PPGL exhibit an increased prevalence of mutations in one of the PPGL susceptibility genes according to previous studies. We aimed to investigate the characteristics of germline mutations in the largest number of Korean patients with PPGL. METHODS: In this study, 161 patients with PPGL were evaluated. Phenotype data, including biochemical, pathological and anatomical imaging results, were collected. Germline mutations in 10 PPGL-related genes were tested by targeted next-generation sequencing (NGS), Sanger sequencing and multiplex ligation-dependent probe amplification. RESULTS: Approximately 21% of apparently sporadic PPGLs harboured germline mutations of the PPGL-related genes. The mutation carriers were younger at the first diagnosis and had more bilateral (28.6% vs 4.0%, p<0.001) and multifocal (11.4% vs 1.6%, p=0.027) PPGLs, but showed no metastatic risk (17.1% vs 11.1%, p=0.504), than non-mutation carriers. Missense mutation of SDHD p.V111I was found in this cohort of Asian patients, which was associated with unilateral pheochromocytoma with dominantly epinephrine production. CONCLUSION: This study covered the largest number of Korean patients with PPGL. To our knowledge, it is the first to compare results of targeted NGS panel with those of conventional sequencing methods in Asia. We demonstrated that the variant type, as well as the mutated gene, may determine the phenotype and prognosis of PPGLs.

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.

Skeletal effects of combined bisphosphonates treatment and parathyroidectomy in osteoporotic patients with primary hyperparathyroidism.

INTRODUCTION: Bone loss caused by primary hyperparathyroidism (PHPT) is an indication for parathyroidectomy (PTX). However, whether adding bisphosphonates would be superior to PTX alone to increase bone mass remains unclear. We thus aimed to compare the skeletal effects of the combination treatment of bisphosphonates and PTX with PTX alone. MATERIALS AND METHODS: In this retrospective analysis, bone mineral density (BMD) changes after 1 year of combination treatment and PTX alone were compared. We also analyzed the correlation between changes in serum biochemical parameters and BMD after 1 year of treatment in both groups. RESULTS: The baseline characteristics of patients treated with PTX alone (n = 24) and combination treatment (n = 26) were comparable. BMD significantly increased after 1 year of treatment in both groups (all p < 0.001), and the increase in BMD at the femur neck was higher in the PTX alone group than in the combination group (p = 0.011). There was a decreasing trend in serum alkaline phosphatase (ALP) levels in PTX alone compared to the combination treatment group (p = 0.053). In the study cohort, lower BMD and higher ALP levels at baseline were associated with higher 1-year BMD changes at all sites. Interestingly, a significant association was found between changes in ALP and BMD at the femur neck in the PTX alone group (p = 0.003), but abolished in the combination group (p = 0.946). CONCLUSIONS: There is no additional benefit of BMD in combination treatment with bisphosphonates and PTX over PTX alone in osteoporotic patients with PHPT. Combined bisphosphonate treatment might interfere with the increase in bone mass caused by PTX.

Long-term Outcome of Microscopic Transsphenoidal Surgery for Prolactinomas as an Alternative to Dopamine Agonists.

BACKGROUND: Although long-term dopamine agonist (DA) therapy is recommended as a first-line treatment for prolactinoma, some patients may prefer surgical treatment because of the potential adverse effects of long-term medication, or the desire to become pregnant. This study aimed to determine whether surgical treatment of prolactinomas could be an alternative to DA therapy. METHODS: In this retrospective study, 96 consecutive patients (74 female, 22 male) underwent primary pituitary surgery without long-term DA treatment for prolactinomas at a single institution from 1990 to 2010. All patients underwent primary surgical treatment in the microscopic transsphenoidal approach (TSA). RESULTS: The median age and median follow-up period were 31 (16-73) years and 139.1 (12.2-319.6) months, respectively. An initial overall remission was accomplished in 47.9% (46 of 96 patients, 33 macroadenomas, and 13 microadenomas) of patients. DA dose reduction was achieved in all patients after TSA. A better remission rate was independently predicted by lower diagnostic prolactin levels and by a greater extent of surgical resection. Overall remission at the last follow-up was 33.3%, and the overall recurrence rate was 30.4%. The permanent complication rate was 3.1%, and there was no mortality. CONCLUSION: TSA can be considered a safe and potentially curative treatment for selective microprolactinomas as an alternative to treatment with a long-term DA.

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.

Nonfunctioning Adrenal Incidentalomas are not Clinically Silent: A Longitudinal Cohort Study.

OBJECTIVE: The association between nonfunctioning adrenal incidentalomas (NFAIs) and cardiometabolic diseases remains controversial. This retrospective cohort study investigated whether NFAIs are related with prevalent and incident cardiometabolic diseases. METHODS: This study included 154 patients with biochemically confirmed NFAIs and 1:3 age and sex-matched controls without adrenal incidentalomas (n = 462) among subjects who underwent abdominal computed tomography at a single healthcare center in 2003-2012. Electronic medical records were reviewed for comorbidities at baseline and during a mean follow-up of 7.5 years. The logistic regression analysis for prevalent cardiometabolic diseases and the survival analysis for incident cardiometabolic diseases were performed. RESULTS: The subjects were 55.7±8.8 years of age and predominantly male (73.1%). The NFAI group had a higher body mass index compared to the age and sex-matched control group (25.1±2.8 vs. 24.0±2.8 kg/m2; P<.001). In a cross-sectional design, covariate-adjusted logistic regression showed significantly higher odds ratios (ORs) for diabetes mellitus and hypertension in the NFAI group (adjusted OR [95% confidence interval [CI]], 1.89 [1.17 to 3.06] and 2.26 [1.47 to 3.50], respectively). The NFAI group had a 2-fold higher risk of insulin resistance (adjusted ORs [95% CI], 2.03 [1.06 to 3.90]). Moreover, NFAI subjects with diabetes mellitus had a greater increase in size of adrenal lesions than those without diabetes mellitus (3.4±5.5 vs. 1.4±5.5 mm; P =.048). However, in the survival analysis, the incidence of any cardiometabolic diseases did not differ between the NFAI and control groups. CONCLUSION: NFAIs are related to prevalent diabetes mellitus or hypertension in our cross-sectional study. However, the presence of NFAIs did not affect the development of cardiometabolic diseases. ABBREVIATIONS: ACTH = adrenocorticotropic hormone; AI = adrenal incidentaloma; BMI = body mass index; CI = confidence interval; CT = computed tomography; HbA1c = hemoglobin A1c; HOMA-IR = homeostasis model assessment of insulin resistance; HU = Hounsfield units; MACE = mild autonomous cortisol excess; NFAI = nonfunctioning adrenal incidentaloma; OR = odds ratio.

Effect of Endogenous Parathyroid Hormone on Bone Geometry and Skeletal Microarchitecture.

Parathyroid hormone (PTH) has anabolic or catabolic effects on bones; however, the skeletal effect of endogenous PTH on cortical and trabecular bones is not yet clear. Therefore, we aimed to examine the effects of an excess and a deficiency of endogenous PTH on the lumbar spine trabecular bone score (TBS) and bone geometry using dual-energy X-ray absorptiometry. We retrospectively included 70 patients with primary hyperparathyroidism (PHPT), 26 patients with idiopathic or postoperative hypoparathyroidism (HypoPT), and 96 normal controls matched by age, sex, and body mass index. The bone mineral density (BMD) at the lumbar spine, femur neck, and total hip was higher in the HypoPT, followed by the controls and PHPT group (all P < 0.001). The TBS was significantly decreased in the PHPT group compared to the controls (P = 0.021); however, statistical significance disappeared after adjusting for the lumbar BMD (P = 0.653). There were no significant differences in the TBS between the HypoPT group and controls as well as the PHPT and HypoPT group. As for bone geometry parameters, the cross-sectional area, cross-sectional moment of inertia, and section modulus were higher in the HypoPT, followed by the controls and PHPT group (all P < 0.001); statistical significance remained after adjusting for the total hip BMD. We also observed a significantly increased cortical neck width in the HypoPT group compared to the PHPT group (P = 0.009). The buckling ratio was higher in the PHPT than the HypoPT group and controls (P = 0.018 and P = 0.013, respectively). The present study demonstrated that an excess of endogenous PTH had catabolic effects on both cortical and trabecular bones. Under conditions of endogenous PTH deficiency, the effect on cortical bone was pronounced, but that on trabecular bone was modest.

Dehydroepiandrosterone Sulfate and Free Testosterone but not Estradiol are Related to Muscle Strength and Bone Microarchitecture in Older Adults.

The study aimed to elucidate the relationship between sex steroids and muscle mass, muscle strength, and trabecular bone score (TBS) in a community-dwelling aged population. We analyzed 922 men > 60 years of age and 1244 postmenopausal women. Weak muscle strength was defined as hand grip strength < 26 kg for men and < 18 kg for women, whereas degraded bone microarchitecture was defined as a TBS ≤ 1.2. The mean age was 70.2 ± 6.8 years for men and 71.2 ± 6.7 years for women. Participants within higher dehydroepiandrosterone sulfate (DHEAS) and free testosterone (FT) tertiles were likely to be younger, have greater muscle mass, and have stronger hand grip strength. Based on logistic regression models, men within the lowest FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted odds ratio [OR] 2.28; 95% confidence interval [CI] 1.33-3.91). Women within the lowest DHEAS and FT tertile had weaker muscle strength compared to those in the highest tertile (adjusted OR for DHEAS 1.42; 95% CI 1.02-1.99; adjusted OR for FT 1.77, 95% CI 1.26-2.48). Moreover, men within the lowest FT tertile exhibited degraded bone microarchitecture compared to those in the highest tertile (adjusted OR 2.57, 95% CI 1.46-4.51). However, estradiol was not related to muscle strength or bone microarchitecture in both sexes. In conclusion, in aged men, serum FT was closely associated with muscle strength and bone microarchitecture and in postmenopausal women, serum DHEAS and FT were related to muscle strength.

Metabolic characteristics of subjects with spine-femur bone mineral density discordances: the Korean National Health and Nutrition Examination Survey (KNHANES 2008-2011).

The diagnosis of osteoporosis is determined based on the lowest bone mineral density (BMD) T-score at the lumbar spine (LS) and hip. However, there are occasional marked discordances between the T-score of LS and femur neck (FN). We aimed to examine the prevalence and characteristics of individuals with spine-femur BMD discordance using a nationwide survey. A total of 3233 men aged ≥ 50 years and 2915 postmenopausal women were included from the Korean National Health and Nutrition Examination Surveys (2008-2011). The spine-femur discordance was defined as a difference of ≥ 1.5 SD between LS and FN BMD. Subjects were divided into three groups: low LS (LS < FN), low FN (LS > FN), and no discordance. Four-hundred and seventeen men (12.9%) and two hundred and ninety women (10%) exhibited spine-femur BMD discordance. The prevalence of hypertension and diabetes was higher in men and women with low FN BMD than in any other group. Fasting plasma glucose and homeostasis model assessment of insulin resistance was the highest in subjects with low FN BMD among the three groups. Low FN BMD revealed higher serum parathyroid hormone and lower 25-hydroxyvitamin D3 levels compared to any other group in women, but this was not observed in men. Osteoporosis was prevalent in subjects with discordance in both genders, particularly, in those with low LS BMD (31.6% in men and 63.5% in women). Given the high prevalence of spine-femur BMD discordance, low FN BMD may be associated with vitamin D deficiency and insulin resistance, but low LS BMD may present severe osteoporosis.

Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

Amount of smoking, pulmonary function, and bone mineral density in middle-aged Korean men: KNHANES 2008-2011.

Smoking induces bone loss; however, data on the relationship between smoking history and bone mineral density (BMD) are lacking. Age and pulmonary function can affect BMD. We investigated the relationships among pack-years (PYs) of smoking, pulmonary function, and BMD in middle-aged Korean men (50-64 years old). This cross-sectional study used data from the Korean National Health and Nutrition Examination Survey, 2008-2011. All participants underwent BMD measurements using dual energy X-ray absorptiometry and pulmonary function tests using standardized spirometry. In total, 388 never-smokers and 1088 ever-smokers were analyzed. The number of PYs of smoking was negatively correlated with total hip BMD (r = -0.088; P = 0.004) after adjusting for age, height, and weight. Ever-smokers were classified into 3 groups according to PYs of smoking. The highest tertile (n = 482) exhibited significantly lower total hip bone mass than the lowest tertile (n = 214) after adjusting for confounding factors (age, height, weight, forced expiratory volume in 1 s (FEV1), alcohol consumption, physical activity, and vitamin D levels) that could affect bone metabolism (P = 0.003). In conclusion, smoking for >30 PYs was significantly associated with low hip BMD after adjusting for pulmonary function in middle-aged Korean men. Long-term smoking may be a risk factor for bone loss in middle-aged men independent of age, height, weight, and pulmonary function.

The efficacy of medical treatment in patients with acromegaly in clinical practice.

Although somatostatin analogues (SSAs) are recommended as the first-line medical therapy for acromegaly, dopamine agonists (DAs) are also a therapeutic option for treatment. We aimed to assess and compare the efficacies of DAs and SSAs in treating acromegaly in clinical practice. We included 89 patients with acromegaly who took DAs (bromocriptine [BCT], n = 63; cabergoline [CAB], n = 11) or SSAs (n = 15) as a primary medical therapy for more than 3 months in the Seoul National University Hospital. The CAB (45.5%) and SSA (33.3%) groups achieved random GH levels of <2.5 ng/mL and the normal IGF-1 levels were significantly higher than in the BCT group (11.1%) (p = 0.009). We further included all the patients with acromegaly (n = 132) who had taken CAB, BCT, and SSAs as first- or second-line medical therapy. The CAB group showed similar efficacy as the SSA group in terms of the GH and insulin-like growth factor-1 (IGF-1) levels (57.6% for random GH level <2.5 ng/mL, 42.4% for normal IGF-1 levels, 36.4% for both). Logistic regression analysis revealed that medications, age, GH level, or IGF-1 level before medication, hyperprolactinemia, and prior gamma-knife surgery or radiation therapy, did not affect the therapeutic response. High pretreatment GH levels predicted poor treatment outcomes (odds ratio [95% confidence interval] = 0.95 [0.90-0.99]). CAB was effective in treating acromegaly at a relatively lower cost in patients with low pretreatment GH levels.

The natural history and hip geometric changes of primary hyperparathyroidism without parathyroid surgery.

There have been few reports on changes in bone geometry in asymptomatic patients with primary hyperparathyroidism (PHPT) not treated surgically. We reviewed the records concerning biochemical parameters, bone mineral density (BMD), and hip geometry in 119 PHPT patients who did not undergo parathyroidectomy, followed up at one of three hospitals affiliated to Seoul National University from 1997 to 2013. We examined biochemical parameters over 7 years and BMD and hip geometry over 5 years of follow-up. We further compared hip geometry and BMD derived from dual-energy X-ray absorptiometry (DXA) between patients and age- and sex-matched controls. The median follow-up duration of 56 patients for whom surgery was not indicated was 33.9 months (range 11.2-131.2 months), and 19.6 % of these patients had disease progression during follow-up. Serum calcium levels remained stable for 7 years in all 119 patients. From a comparison of the PHPT patients for whom surgery was not indicated with controls, both male and postmenopausal female patients had significantly lower hip axis length (P < 0.001), cross-sectional moment of inertia (P < 0.001), cross-sectional area (P < 0.001), and section modulus (P < 0.001). In addition, cortical thickness was significantly decreased at 5 years compared with individual baseline values (P = 0.003). However, there was no significant change in BMD for the duration of the 5-year follow-up. DXA-derived geometry can detect skeletal change in asymptomatic PHPT patients for whom surgery is not indicated, supporting the concept that even mild PHPT can eventually compromise the cortical bones. Hip geometry is a potential tool for monitoring skeletal complication in asymptomatic PHPT patients.

Best candidates for dopamine agonist withdrawal in patients with prolactinomas.

PURPOSE: Dopamine agonist (DA) therapy is recommended as the first-line treatment for prolactinomas. However, it requires long treatment duration, and a high recurrence rate after DA withdrawal has been reported. We aimed to elucidate the predictors for long-term remission following DA withdrawal and propose the best candidates who can achieve complete remission after DA withdrawal. METHODS: In a retrospective cohort study, we included 89 patients with prolactinoma who have withdrawn DAs with normal prolactin (PRL) levels at Seoul National University Hospital, from 2000 to 2016. Patient's data were retrieved from the electronic medical records. RESULTS: The median age and median treatment duration of the study patients were 33 (15-73) years and 69.5 (8.3-277.4) months, respectively. The recurrence rate after drug withdrawal was 57.3% during the 23.9 (3.0-176.8) month follow-up period. Age, gender, baseline PRL level, and baseline maximum tumor diameter were similar between the remission and recurrence group. In the Cox-proportional hazard model analysis, the significant predictors for remission were nadir PRL level of <1 ng/dL (hazard ratio [95% confidence interval] = 0.37 [0.18-0.74]), invisible tumors on magnetic resonance imaging (MRI) (0.42 [0.24-0.74]), and treatment duration of >72 months (0.54 [0.30-0.96]). Of the subjects who met all the three criteria, 66.7% achieved long-term remission. CONCLUSIONS: Patients who have no tumor visible on MRI, have a nadir PRL level <1 ng/dL during drug treatment, and received drug treatment for >6 years may be the best candidates for DA withdrawal.

Outcomes analysis of surgical and medical treatments for patients with primary aldosteronism.

Patients with aldosterone-producing adenomas are treated using surgery, and patients with idiopathic hyperaldosteronism receive medical treatment using mineralocorticoid receptor antagonists (MRAs). However, the outcomes of surgical and medical treatment for primary aldosteronism (PA) remain unclear. Therefore, we compared the outcomes of surgical and medical treatment for PA and aimed to identify a specific subgroup that might benefit from medical treatment. We identified 269 patients who were treated for PA (unilateral excess: 221 cases; bilateral excess: 48 cases) during 2000-2015 at the Seoul National University Hospital and two other tertiary centers. The main outcomes were the amelioration of hypertension and hypokalemia. Treatment improved hypertension in the surgical treatment group (78.2%) and the medical treatment group (55.6%) (p = 0.001). At the last follow-up, hypokalemia was normalized in the surgical treatment group (97.1%) and the medical treatment group (93.7%, p = 0.046). Among patients with unilateral aldosterone excess, surgery provided advantages in resolving hypertension without worsening renal function. Among patients who were >60 years old or had impaired renal function, surgical and medical treatment provided similar amelioration of hypokalemia and hypertension. Three patients developed hyperkalemia after surgery, and no patients developed hyperkalemia after initiating medical treatment. The surgical treatment group exhibited a lower postoperative estimated glomerular filtration rate (eGFR) and higher serum potassium levels, compared to the medical treatment group. Surgical treatment provided better hypertension and hypokalemia outcomes among patients with PA, compared to medical treatment. However, MRAs may be appropriate for elderly patients with impaired renal function.

Intermittent PTH treatment can delay the transformation of mature osteoblasts into lining cells on the periosteal surfaces.

Mature osteoblasts have three fates: as osteocytes, quiescent lining cells, or osteoblasts that undergo apoptosis. However, whether intermittent parathyroid hormone (PTH) can modulate the fate of mature osteoblasts in vivo is uncertain. We performed a lineage-tracing study using an inducible gene system. Dmp1-CreERt2 mice were crossed with Rosa26R reporter mice to obtain targeted mature osteoblasts and their descendants, lining cells or osteocytes, which were detected using X-gal staining. Rosa26R:Dmp1-CreERt2(+) mice were injected with 0.25 mg 4-OH-tamoxifen (4-OHTam) on postnatal days 5, 7, 9, 16, and 23. In a previous study, at 22 days after the last 4-OHTam, most LacZ+ cells on the periosteal surface were inactive lining cells. On day 25 (D25), the mice were challenged with an injection of human PTH (1-34, 80 µg/kg) or vehicle daily for 10 (D36) or 20 days (D46). We evaluated the number and thickness of LacZ+ osteoblast descendants in the calvaria and tibia. In the vehicle group, the number and thickness of LacZ+ osteoblast descendants at both D36 and D46 significantly decreased compared to D25, which was attenuated in the PTH group. In line with these results, PTH inhibited the decrease in the number of LacZ+/osteocalcin-positive cells compared to vehicle at both D36 and D46. As well, the serum levels of sclerostin decreased, as did the protein expression of sclerostin in the cortical bone. These results suggest that intermittent PTH treatment can increase the number of periosteal osteoblasts by preventing mature osteoblasts from transforming into lining cells in vivo.

Sex differences in the prevalence of metabolic syndrome and its components in hypopituitary patients: comparison with an age- and sex-matched nationwide control group.

PURPOSE: Hypopituitary patients have a reduced life expectancy owing to cardiovascular events. We investigated the prevalence of metabolic syndrome in hypopituitary patients for a follow-up period of at least 1 year in comparison with an age- and sex-matched nationwide control group. METHODS: A total of 515 patients with hypopituitarism who visited Seoul National University Hospital between January 2000 and December 2010 were included. Data for an age- and sex-matched control group were obtained from the Korean National Health and Nutrition Examination Surveys (KNHANES) (n = 1545). Metabolic syndrome was defined according to the modified National Cholesterol Education Program (NCEP-ATPIII). RESULTS: The prevalence of metabolic syndrome did not differ significantly between the hypopituitary and control groups for men (34.9 versus 30.3 %), but the risk of metabolic syndrome was higher in hypopituitary women than in controls (39.8 versus 28.5 %). In both sexes, the risks of central obesity and dyslipidemia were higher in the hypopituitary group than in the control group. Men had lower risks of hypertension and hyperglycemia in the hypopituitary group, which attenuated the risk of metabolic syndrome. Age greater than 40 years and obesity (BMI ≥25 kg/m2) contributed to a higher risk of metabolic syndrome. CONCLUSIONS: The metabolic syndrome prevalence was higher in the hypopituitry group than in the control group in Korean women, and this was attributed to an increased risk of central obesity and dyslipidemia. Accordingly, early intervention to reduce metabolic syndrome needed in hypopituitary patients, i.e. women.