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

홍아람,강호철 대한내분비학회 2023 Endocrinology and metabolism Vol.38 No.2

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.

갑상선암에서 BRAF 돌연변이의 임상적 의미

홍아람,박영주,A Ram Hong,Young Joo Park 대한갑상선-내분비외과학회 2014 The Koreran journal of Endocrine Surgery Vol.14 No.3

The BRAF^V600E mutation is the most common genetic alteration and presents in 40∼80% of all papillary thyroid cancer (PTC), showing the highest prevalence in the Korean population, close to 80%. Previous studies published in the past 10 years showed a significant correlation between BRAF^V600E mutation and poor prognostic outcomes of PTC, including recurrence and mortality. Therefore, its clinical application for the diagnosis of thyroid nodule or for decisions regarding the management policy by prediction of the prognosis of thyroid cancer has been proposed. However, some recent studies have reported conflict results, and there appear to be growing concerns regard to the cost-benefit of tests for detection of the BRAF^V600E mutation. In this paper, we reviewed previous studies regarding the BRAF^V600E mutation and attempted to evaluate the clinical implication of the BRAFV600E mutation in clinical practice.

The Frequency and Clinical Implications of the BRAFV600E Mutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades

홍아람,임정아,김태현,최훈성,유원상,민혜숙,원재경,이규은,정경천,박도준,박영주 대한내분비학회 2014 Endocrinology and metabolism Vol.29 No.4

Background: Over the past several decades, there has been a rapid worldwide increase in the prevalence of papillary thyroid cancer (PTC) as well as a number of changes in the clinicopathological characteristics of this disease. BRAFV600E, which is a mutation of the proto-oncogene BRAF, has become the most frequent genetic mutation associated with PTC, particularly in Korea. Thus, the present study investigated whether the prevalence of the BRAFV600E mutation has increased over the past two decades in the Korean population and whether various PTC-related clinicopathological characteristics have changed. Methods: The present study included 2,624 patients who underwent a thyroidectomy for PTC during two preselected periods; 1995 to 2003 and 2009 to 2012. The BRAFV600E mutation status of each patient was confirmed using the polymerase chain reaction-restriction fragment length polymorphism method or by the direct sequencing of DNA. Results: The prevalence of the BRAFV600E mutation in Korean PTC patients increased from 62.2% to 73.7% (P=0.001) over the last two decades. Additionally, there was a greater degree of extrathyroidal extension (ETE) and lymph node metastasis in 2009 to 2012 patients with the BRAFV600E mutation and a higher frequency of thyroiditis and follicular variant-PTC in 2009 to 2012 patients with wild-type BRAF. However, only the frequency of ETE was significantly higher in 1995 to 2003 patients with the BRAFV600E mutation (P=0.047). Long-term recurrence rates during a 10-year median follow-up did not differ based on BRAFV600E mutation status. Conclusion: The BRAFV600E mutation rate in Korean PTC patients has been persistently high (approximately 70%) over the past two decades and continues to increase. The present findings demonstrate that BRAFV600E-positive PTC was associated with more aggressive clinicopathological features, especially in patients who were recently diagnosed, suggesting that BRAFV600E mutation status may be a useful prognostic factor for PTC in patients recently diagnosed with this disease.

Transformation of Mature Osteoblasts into Bone Lining Cells and RNA Sequencing-Based Transcriptome Profiling of Mouse Bone during Mechanical Unloading

홍아람,김광수,이지연,양재연,김정희,신찬수,김상완 대한내분비학회 2020 Endocrinology and metabolism Vol.35 No.2

Background: We investigated RNA sequencing-based transcriptome profiling and the transformation of mature osteoblasts intobone lining cells (BLCs) through a lineage tracing study to better understand the effect of mechanical unloading on bone loss. Methods: Dmp1-CreERt2(+):Rosa26R mice were injected with 1 mg of 4-hydroxy-tamoxifen three times a week starting at postnatal week 7, and subjected to a combination of botulinum toxin injection with left hindlimb tenotomy starting at postnatal week 8 to10. The animals were euthanized at postnatal weeks 8, 9, 10, and 12. We quantified the number and thickness of X-gal(+) cells onthe periosteum of the right and left femoral bones at each time point. Results: Two weeks after unloading, a significant decrease in the number and a subtle change in the thickness of X-gal(+) cells wereobserved in the left hindlimbs compared with the right hindlimbs. At 4 weeks after unloading, the decrease in the thickness was accelerated in the left hindlimbs, although the number of labeled cells was comparable. RNA sequencing analysis showed downregulation of 315 genes in the left hindlimbs at 2 and 4 weeks after unloading. Of these, Xirp2, AMPD1, Mettl11b, NEXN, CYP2E1, Bche,Ppp1r3c, Tceal7, and Gadl1 were upregulated during osteoblastogenic/osteocytic and myogenic differentiation in vitro. Conclusion: These findings demonstrate that mechanical unloading can accelerate the transformation of mature osteoblasts intoBLCs in the early stages of bone loss in vivo. Furthermore, some of the genes involved in this process may have a pleiotropic effecton both bone and muscle.

Limited Diagnostic Utility of Plasma Adrenocorticotropic Hormone for Differentiation between Adrenal Cushing Syndrome and Cushing Disease

홍아람,김정희,홍은실,김이경,박경선,안창호,김상완,신찬수,김성연 대한내분비학회 2015 Endocrinology and metabolism Vol.30 No.3

Background: Measurement of the plasma adrenocorticotropic hormone (ACTH) level has been recommended as the first diagnostic test for differentiating between ACTH-independent Cushing syndrome (CS) and ACTH-dependent CS. When plasma ACTH values are inconclusive, a differential diagnosis of CS can be made based upon measurement of the serum dehydroepiandrosterone sulfate (DHEA-S) level and results of the high-dose dexamethasone suppression test (HDST). The aim of this study was to assess the utility of plasma ACTH to differentiate adrenal CS from Cushing’ disease (CD) and compare it with that of the HDST results and serum DHEA-S level. Methods: We performed a retrospective, multicenter study from January 2000 to May 2012 involving 92 patients with endogenous CS. The levels of plasma ACTH, serum cortisol, 24-hour urine free cortisol (UFC) after the HDST, and serum DHEA-S were measured. Results: Fifty-seven patients had adrenal CS and 35 patients had CD. The area under the curve of plasma ACTH, serum DHEA-S, percentage suppression of serum cortisol, and UFC after HDST were 0.954, 0.841, 0.950, and 0.997, respectively (all P<0.001). The cut-off values for plasma ACTH, percentage suppression of serum cortisol, and UFC after HDST were 5.3 pmol/L, 33.3%, and 61.6%, respectively. The sensitivity and specificity of plasma ACTH measurement were 84.2% and 94.3%, those of serum cortisol were 95.8% and 90.6%, and those of UFC after the HDST were 97.9% and 96.7%, respectively. Conclusion: Significant overlap in plasma ACTH levels was seen between patients with adrenal CS and those with CD. The HDST may be useful in differentiating between these forms of the disease, especially when the plasma ACTH level alone is not conclusive.

Characteristics of Korean Patients with Primary Adrenal Insufficiency: A Registry-Based Nationwide Survey in Korea

홍아람,류옥현,김성연,김상완,The Korean Adrenal Gland and Endocrine Hypertension Study Group, Korea 대한내분비학회 2017 Endocrinology and metabolism Vol.32 No.4

Background: Primary adrenal insufficiency (PAI) is a rare, potentially life-threatening condition. There are few Korean studies on PAI, and most have had small sample sizes. We aimed to examine the etiology, clinical characteristics, treatment, and mortality of PAI in Korean patients. Methods: A nationwide, multicenter, registry-based survey was conducted to identify adults diagnosed with or treated for PAI at 30 secondary or tertiary care institutions in Korea between 2000 and 2014. Results: A total of 269 patients with PAI were identified. The prevalence of PAI was 4.17 per million. The estimated incidence was 0.45 per million per year. The mean age at diagnosis was 49.0 years, and PAI was more prevalent in men. Adrenal tuberculosis was the most common cause of PAI in patients diagnosed before 2000; for those diagnosed thereafter, adrenal metastasis and tuberculosis were comparable leading causes. The etiology of PAI was not identified in 34.9% of cases. Of the patients receiving glucocorticoid replacement therapy, prednisolone was more frequently administered than hydrocortisone (69.4% vs. 26.5%, respectively), and only 27.1% of all patients received fludrocortisone. We observed an increased prevalence of metabolic disease and osteoporosis during the follow-up period (median, 60.2 months). The observed overall mortality and disease-specific mortality rates were 11.9% and 3.1%, respectively. Conclusion: The prevalence of PAI is significantly lower in Koreans than in reports from Western countries. The high frequency undetermined etiology in patients with PAI suggests the need to reveal accurate etiology of PAI in Korea.

Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Korean Patients with Type 2 Diabetes Mellitus in Real-World Clinical Practice

홍아람,구보경,김상완,이가희,문민경 대한당뇨병학회 2019 Diabetes and Metabolism Journal Vol.43 No.5

Background: This study aimed to evaluate the efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in Koreanpatients who had inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice. Methods: We included 410 patients who started SGLT2 inhibitors (empagliflozin or dapagliflozin) as add-on therapy or switchtherapy between February 2015 and June 2017. The primary efficacy endpoint was a change in glycosylated hemoglobin (HbA1c)from baseline to week 12. The secondary endpoints were patients achieving HbA1c <7.0% and changes in the fasting plasma glucose(FPG), lipid profiles, body weight, and blood pressure (BP). Results: The mean HbA1c at baseline was 8.5% (8.6% in the add-on group and 8.4% in the switch group). At week 12, the mean adjustedHbA1c decreased by –0.68% in the overall patients (P<0.001), by –0.94% in the add-on group, and by –0.42% in the switchgroup. Significant reductions in FPG were also observed both in the add-on group and switch group (–30.3 and –19.8 mg/dL, respectively). Serum triglyceride (–16.5 mg/dL), body weight (–2.1 kg), systolic BP (–4.7 mm Hg), and diastolic BP (–1.3 mm Hg)were significantly improved in the overall patients. Approximately 18.3% of the patients achieved HbA1c <7.0% at week 12. A lowincidence of hypoglycemia and genital tract infection was observed (6.3% and 2.2%, respectively). Conclusion: SGLT2 inhibitors can be a suitable option as either add-on or switch therapy for Korean patients with inadequatelycontrolled T2DM.

웨어러블 기기를 통한 신체정보기반 정신병리 진단 기준에 대한 연구

홍아람,신지영,박민재 한국경영정보학회 2023 한국경영정보학회 학술대회논문집 Vol.2023 No.06

갑상선질환에서 골건강 평가 및 관리 권고안

홍아람,안화영,김부경,안성희,박소영,김민희,이정민,조선욱,강호철 대한갑상선학회 2022 International Journal of Thyroidology Vol.15 No.1

Thyroid hormones have an important physiological role in maintaining adult bone structure and strength. Therefore, thyroid dysfunction is inevitably associated with various degrees of skeletal consequences. Endogenousovert hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, resulting inosteoporosis and an increased risk of fractures. Hyperthyroidism induced by thyroid stimulating hormonesuppression therapy in patients with differentiated thyroid cancer also has emerged as a contributing factor toosteoporosis and fragility fractures. While, there is lack of evidence that hypothyroidism negatively affects bonehealth. Although there is growing clinical evidence of the importance of bone health in hyperthyroidism, clinicalguidelines on how to evaluate and manage bone health in these diseases have not yet been published worldwide. The Task Force from the Korean Thyroid Association Committee of Clinical Practice Guideline has developed thisposition statement for the evaluation and management of bone health in patients with thyroid diseases,particularly focused on endogenous hyperthyroidism and thyroid stimulating hormone suppression therapyassociatedhyperthyroidism in patients with differentiated thyroid cancer.

Effects of Resistance Exercise on Bone Health

홍아람,김상완 대한내분비학회 2018 Endocrinology and metabolism Vol.33 No.4

The prevalence of chronic diseases including osteoporosis and sarcopenia increases as the population ages. Osteoporosis and sarcopenia are commonly associated with genetics, mechanical factors, and hormonal factors and primarily associated with aging. Manyolder populations, particularly those with frailty, are likely to have concurrent osteoporosis and sarcopenia, further increasing theirrisk of disease-related complications. Because bones and muscles are closely interconnected by anatomy, metabolic profile, andchemical components, a diagnosis should be considered for both sarcopenia and osteoporosis, which may be treated with optimaltherapeutic interventions eliciting pleiotropic effects on both bones and muscles. Exercise training has been recommended as apromising therapeutic strategy to encounter the loss of bone and muscle mass due to osteosarcopenia. To stimulate the osteogenic effects for bone mass accretion, bone tissues must be exposed to mechanical load exceeding those experienced during daily living activities. Of the several exercise training programs, resistance exercise (RE) is known to be highly beneficial for the preservation ofbone and muscle mass. This review summarizes the mechanisms of RE for the preservation of bone and muscle mass and supportsthe clinical evidences for the use of RE as a therapeutic option in osteosarcopenia.