Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) cause thyroid immune-related adverse effects (irAEs). However, associations between each type of thyroid immune-related adverse effect (irAE) and the anti-tumor effect of ICI remains unknown. This study aimed to determine the effects of each type of thyroid dysfunction on patient survival. METHODS: Patients who initiated ICI treatment from January 2015 to December 2019 in Seoul St. Mary's Hospital were retrospectively analyzed. Thyroid dysfunction was classified into four types: newly developed overt or subclinical hypothyroidism, thyrotoxicosis, worsened hypothyroidism, and subclinical hyperthyroidism. Patients were divided into two groups according to the presence or absence of thyroid dysfunction. RESULTS: Among the 191 patients, 64 (33.5%) developed thyroid irAEs. There was no significant difference in age, sex, or cancer type between the two groups. The overall survival in patients with thyroid irAEs was significantly higher than that in patients without thyroid irAEs (25 months vs. 18 months, respectively, p = 0.005). After adjusting for confounding factors, the hazard ratio for mortality in the thyroid irAE group compared to the no thyroid irAE group was 0.480 (p = 0.006). Newly developed overt or subclinical hypothyroidism patients showed a significantly lower hazard ratio for mortality of 0.324 (p = 0.002). Patients with thyrotoxicosis showed a worse hazard ratio for mortality than those without thyroid irAE, although the difference was not statistically significant. CONCLUSIONS: It was verified that ICI treatment-induced thyroid dysfunction was associated with better survival, even in the real-world practice. Thus, endocrinologists should cooperate with oncologists to monitor patients treated with ICIs.

Associations of variability in body weight and glucose levels with the risk of hip fracture in people with diabetes.

BACKGROUND: Diabetes is associated with a high risk of fragility fracture. However, there are controversies regarding the effect of fluctuations in metabolic parameters on the risk of fracture. We aimed to investigate the associations of body weight or glucose variability or their combination with the risk of hip fracture in people with diabetes. METHODS: A population-based cohort study with 480,539 subjects over 40 years who had undergone three or more health examinations was performed. The degree of variability was evaluated using variability independent of the mean (VIM, 100 × standard deviation / meanbeta), coefficient of variation (CV), and average real variability (ARV, average of the absolute differences between consecutive values). High variability was defined as having values in the highest quartile. Cox proportional hazards models were used to estimate the risk of hip fracture. RESULTS: There were 2834 hip fracture events (0.59%) during the mean follow-up of 8.1 years. After multivariable adjustment for age, sex, alcohol consumption, smoking, regular exercise, income, glucose, body mass index, hemoglobin, estimated glomerular filtration rate, diabetes duration, diabetes treatment with multiple agents, and osteoporosis, the HRs (95% CI) of hip fracture were 1.36 (1.24-1.50) and 1.29 (1.16-1.43) for high body weight VIM and high glucose VIM, respectively. The HR (95% CI) of both high VIM group was 1.63 (1.44-1.83), suggesting an additive effect of variabilities in body weight and glucose. The results were consistent when using CV and ARV and in various sensitivity analyses. CONCLUSIONS: High variability in body weight and glucose levels is associated with an increased incidence rate and risk of hip fracture in people with diabetes.

Changes in Serum Dickkopf-1, RANK Ligand, Osteoprotegerin, and Bone Mineral Density after Allogeneic Hematopoietic Stem Cell Transplantation Treatment.

BACKGROUND: Dickkopf-1 (DKK1) regulates bone formation by inhibiting canonical Wnt/ß-catenin pathway signaling, and indirectly enhances osteoclastic activity by altering the expression ratio of receptor activator of nuclear factor-κB ligand (RANKL) relative to osteoprotegerin (OPG). However, it is difficult to explain continued bone loss after allogeneic stem cell transplantation (allo-SCT) in terms of changes in only RANKL and OPG. Few studies have evaluated changes in DKK1 after allo-SCT. METHODS: We prospectively enrolled 36 patients with hematologic malignancies who were scheduled for allo-SCT treatment. Serum DKK1, OPG, and RANKL levels were measured before (baseline), and at 1, 4, 12, 24, and 48 weeks after allo-SCT treatment. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry before (baseline) and 24 and 48 weeks after allo-SCT treatment. RESULTS: After allo-SCT treatment, the DKK1 level decreased rapidly, returned to baseline during the first 4 weeks, and remained elevated for 48 weeks (P<0.0001 for changes observed over time). The serum RANKL/OPG ratio peaked at 4 weeks and then declined (P<0.001 for changes observed over time). BMD decreased relative to the baseline at all timepoints during the study period, and the lumbar spine in female patients had the largest decline (-11.3%±1.6% relative to the baseline at 48 weeks, P<0.05). CONCLUSION: Serum DKK1 levels rapidly decreased at 1 week and then continued to increase for 48 weeks; bone mass decreased for 48 weeks following engraftment in patients treated with allo-SCT, suggesting that DKK1-mediated inhibition of osteoblast differentiation plays a role in bone loss in patients undergoing allo-SCT.

Heart Rate Variability in Postoperative Patients with Nonfunctioning Pituitary Adenoma.

BACKGROUND: Decreased heart rate variability (HRV) has been reported to be associated with cardiac autonomic dysfunction. Hypopituitarism in nonfunctioning pituitary adenoma (NFPA) is often linked to increased cardiovascular mortality. We therefore hypothesized that postoperative NFPA patients with hormone deficiency have an elevated risk of HRV alterations indicating cardiac autonomic dysfunction. METHODS: A total of 22 patients with NFPA were enrolled in the study. Between 3 and 6 months after surgery, a combined pituitary function test (CPFT) was performed, and HRV was measured. The period of sleep before the CPFT was deemed the most stable period, and the hypoglycemic period that occurred during the CPFT was defined as the most unstable period. Changes in HRV parameters in stable and unstable periods were observed and compared depending on the status of hormone deficiencies. RESULTS: In patients with adrenocorticotropic hormone (ACTH) deficiency with other pituitary hormone deficiencies, the low frequency to high frequency ratio, which represents overall autonomic function and is increased in the disease state, was higher (P=0.005). Additionally, the standard deviation of the normal-to-normal interval, which decreases in the autonomic dysfunction state, was lower (P=0.030) during the hypoglycemic period. In panhypopituitarism, the low frequency to high frequency ratio during the hypoglycemic period was increased (P=0.007). CONCLUSION: HRV analysis during CPFT enables estimation of cardiac autonomic dysfunction in patients with NFPA who develop ACTH deficiency with other pituitary hormone deficiencies or panhypopituitarism after surgery. These patients may require a preemptive assessment of cardiovascular risk.

Serum CYFRA 21.1 Level Predicts Disease Course in Thyroid Cancer with Distant Metastasis.

BACKGROUND: Serum Cyfra 21.1, the soluble fragment of CK19, has been used as a prognostic tumor marker in various cancers, indicating poor tumor differentiation and increased metastasis. METHODS: We analyzed the serum Cyfra 21.1 level in 51 consecutive patients with thyroid cancer manifesting distant metastasis treated with prior total thyroidectomy. Serum Cyfra 21.1 levels of 26 thyroid cancer patients without metastasis and 50 healthy individuals were used for comparison. RESULTS: Higher serum Cyfra 21.1 levels were detected in thyroid cancer patients with distant metastasis compared with healthy subjects and thyroid cancer patients without metastasis (p = 0.012). Serum Cyfra 21.1 levels were significantly increased in patients with positive BRAF V600E mutation (p = 0.019), undergoing Tyrosine Kinase Inhibitor (TKI) therapy (p = 0.008), with radioiodine-refractory status (p = 0.047), and in disease progression compared with those manifesting stable disease (p = 0.007). In progressive disease with undetectable or unmonitored thyroglobulin because of thyroglobulin antibody, serum Cyfra 21.1 was useful as a biomarker for follow-up of disease course. CONCLUSION: Serum Cyfra 21.1 in thyroid cancer patients might represent an alternative biomarker predicting tumor progression, especially in cases not associated with serum Tg levels.

Feasibility of Iodine-131 6ß-Methyl-Iodo-19 Norcholesterol (NP-59) Scintigraphy to Complement Adrenal Venous Sampling in Management of Primary Aldosteronism: A Case Series.

PURPOSE: Primary aldosteronism (PA) is mainly comprised of aldosterone-producing adenoma and bilateral idiopathic adrenal hyperplasia. Current guidelines recommend adrenal venous sampling (AVS) as a gold standard method to classify the subtypes. However, because of technical challenges in AVS including invasiveness of AVS and a wide range of success rate for cannulation, it is not uncommon that appropriate decisions could not be made depending on AVS. The aim of this study is to elucidate the proper role of I­131­6ß­iodomethyl­norcholesterol (NP-59) scintigraphy in management of PA. PATIENTS AND METHODS: Between January 2009 and October 2018, patients with PA were retrospectively reviewed for the study. Five patients were included in the study who had NP-59 scintigraphy with non-conclusive AVS results or without AVS. We described the clinical outcome of patients in whom clinical decisions were made according to NP-59 scintigraphy results. RESULTS: Patients in the presenting cases were diagnosed for PA. AVS, the most reliable test to identify unilateral APA, were not applicable because of hypersensitivity to contrast dye (patient 1), and use of antiplatelet agents after acute cerebral infarction (patient 2). NP-59 scintigraphy was performed in patients 3 and 4 whose result of AVS and CT scan were inconsistent. In patient 5, who had bilateral adrenal adenomas (two in the left and one in the right adrenal gland), both unsuccessful catheterization and coexistence of cortisol overproduction made AVS results unreliable. CONCLUSION: Based on clinical outcomes of these case series, it is noticeable that NP-59 scintigraphy could play a substantial role in management of PA in selected cases.

Association of Hyperparathyroidism and Papillary Thyroid Cancer: A Multicenter Retrospective Study.

BACKGROUND: Concomitant papillary thyroid cancer (PTC) and hyperparathyroidism (HPT) have been reported in several studies. Our study aimed to investigate the incidence of concomitant PTC in HPT patients upon preoperative diagnosis and present a clinical opinion on detecting thyroid malignancy in case of parathyroidectomy. METHODS: Patients who underwent parathyroidectomy between January 2009 and December 2019 in two medical centers were included. Of the 279 participants 154 were diagnosed as primary hyperparathyroidism (pHPT) and 125 as secondary hyperparathyroidism (sHPT). The incidence of concomitant PTC and its clinical characteristics were compared with 98 patients who underwent thyroidectomy and were diagnosed with classical PTC during the same period. RESULTS: Concurrent PTC was detected in 14 patients (9.1%) with pHPT and in nine patients (7.2%) with sHPT. Ten (71.4%) and seven (77.8%) PTCs were microcarcinomas in the pHPT and sHPT cases respectively. In the pHPT patients, vitamin D was lower in the pHPT+PTC group (13.0±3.7 ng/mL) than in the pHPT-only group (18.5±10.4 ng/mL; P=0.01). Vitamin D levels were also lower in the sHPT+PTC group (12.3±5.6 ng/mL) than in the sHPT-only group (18.0±10.2 ng/mL; P=0.12). In the concomitant PTC group, lymph node ratio was higher than in the classical PTC group (P=0.00). CONCLUSION: A high prevalence of concomitant PTC was seen in patients with pHPT and sHPT. Those concomitant PTCs were mostly microcarcinomas and had more aggressive features, suggesting that efforts should be made to detect concomitant malignancies in the preoperative parathyroidectomy evaluation.

Fine-Needle Aspiration of Subcentimeter Thyroid Nodules in the Real-World Management.

BACKGROUND: The Korea Thyroid Association published the revised guidelines for thyroid nodules in 2016. However, whether fine-needle aspiration is accurately performed based on indications and whether the results of this procedure are appropriately addressed according to clinical guidelines, particularly in subcentimeter nodules, are unclear. METHODS: We retrospectively analyzed the fine-needle aspiration data of 331 thyroid nodules of patients who were referred to a tertiary hospital clinic for fine-needle aspiration. Each nodule was categorized according to ultrasonography findings based on the recommendations of the Korea Thyroid Association for fine-needle aspiration. Only nodules with a final pathological diagnosis of benign or malignant made using the Bethesda system were included. RESULTS: Up to 32% of thyroid nodules that were not indicated for fine-needle aspiration were aspirated. Regarding subcentimeter nodules, only 28 of 123 (22.8%) aspirated nodules were indicated for fine-needle aspiration. Of the 49 malignant subcentimeter nodules, 33 (67.3%) underwent immediate surgery. Meanwhile, 14 (28.6%) nodules were lost to follow-up, and two (4.1%) were under active surveillance. Eighteen (36.7%) malignant subcentimeter nodules were not indicated for fine-needle aspiration but underwent surgical resection instead of active surveillance. CONCLUSION: Despite the recommendations in the revised guidelines, several thyroid nodules that do not meet the indications for FNA are aspirated in real-world practice. To reduce overtreatment, a widespread knowledge of the correct indications for fine-needle aspiration is important in clinical practice, particularly for subcentimeter nodules.

Clinical outcomes of primary aldosteronism based on lateralization index and contralateral suppression index after adrenal venous sampling in real-world practice: a retrospective cohort study.

BACKGROUND: We investigated whether the contralateral suppression index in aldosterone-producing adrenal adenoma could be used as a diagnostic criterion when catheterization in either right or left adrenal vein fails or when a discrepancy in the adrenal vein sampling (AVS) results and imaging findings occurs in the real-world practice. METHODS: We retrospectively reviewed 48 patients who had resistant hypertension (HTN) or hypokalemia with a biochemical diagnosis of primary aldosteronism and who underwent AVS from January 2009 to June 2017 at a tertiary referral hospital. Selection index (SI), lateralization index (LI), and contralateral suppression index (CSI) were calculated based on AVS results and the final clinical outcomes were evaluated. RESULTS: The catheterization of both adrenal veins was successful in 43 of 48 (89.6%) patients. The lateralization based only on LI was performed in 23 out of 43 (53.5%) patients. When CSI and LI were combined in decision making, the concordance between adrenal computed tomography scan and AVS for unilateral lesion improved from 59.3% (19/32) to 75.0% (24/32). CSI also correlated well with unilateral adrenal disease in the catheterization failure group. The final outcomes of HTN were better in the contralateral suppression group. CONCLUSION: CSI combined with LI could be a supplementary diagnostic tool in patients with non-lateralization or catheterization failure and predict the clinical outcomes of HTN in patients with primary aldosteronism.

Effects of Hormone Replacement Therapy on Bone Mass After Allogeneic Hematopoietic Stem Cell Transplantation.

CONTEXT AND OBJECTIVES: This study aimed to assess the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) in young women who underwent allogeneic hematopoietic stem cell transplantation (HSCT). PARTICIPANTS AND METHODS: This retrospective cohort included 234 female patients with premature ovarian insufficiency (POI) who underwent allogeneic HSCT between April 2009 and April 2016 at Seoul St. Mary's Hospital in Seoul, Korea. Inclusion criteria included adult patients who were age 40 years or younger at the time of transplantation and were followed for at least 3 years after HSCT. RESULTS: At the first and second years after HRT, there was a significant increase in the BMD of the lumbar spine of the HRT group (n = 170) compared to that of the non-HRT group (n = 64) (P = .033 and P = .047, respectively). The BMD of the lumbar spine significantly increased from baseline by 4.16 ±â€…4.39% and 5.42 ±â€…5.86% after 1 and 2 years of HRT, respectively (P = .037 and P = .021). The BMD of the femoral neck and total hip also showed a significant percentage increase from baseline after 2 years of HRT. These changes were significant even in the presence of graft-versus-host disease or steroid exposure. For HRT that was initiated within 12 months after HSCT, the increase in BMD in the lumbar spine was greatest after 2 years of HRT. CONCLUSIONS: These results support that early and active hormonal therapy might be beneficial for BMD in female HSCT recipients with POI.

Effect of Denosumab on Bone Mineral Density of Hematopoietic Stem Cell Transplantation Recipients.

PURPOSE: Denosumab is a monoclonal antibody that prevents the development of osteoclasts. The effect of denosumab in solid organ transplant recipients has been elucidated, but its effect in haematopoietic stem cell transplantation recipients has not been studied yet. The aim of this study was to determine the effectiveness and safety of denosumab in haematopoietic stem cell transplantation recipients. METHODS: We retrospectively evaluated 33 female patients with osteoporosis (mean age 52.6 ± 9.8 years) following allogeneic haematopoietic stem cell transplantation. Patients were treated with denosumab every 6 months for 12 months. Changes in bone mineral density were evaluated for denosumab-treated patients in a 12-month interval after the first administration of denosumab. RESULTS: Significant increases in bone mineral density were observed in all measured skeletal sites including 4.39 ± 6.63% in the lumbar spine (p=0.014), 3.11 ± 7.69% in the femoral neck (p=0.048), and 1.97 ± 6.01% in the total hip (p=0.138). The bone turnover marker serum cross-linked C-terminal telopeptide of type 1 collagen was decreased at 18 months (-51.6 ± 17.6%, p < 0.001). No serious symptomatic hypocalcaemia was observed. Serious adverse drug reactions requiring drug discontinuation were not observed. CONCLUSION: Denosumab improved bone mineral density in haematopoietic stem cell transplantation recipients. The use of denosumab could be a good therapeutic option without causing severe adverse effects in recipients of haematopoietic transplantation.

Effect of bisphosphonate on the prevention of bone loss in patients with gastric cancer after gastrectomy: A randomized controlled trial.

BACKGROUND: Bone loss is highly prevalent after gastrectomy in gastric cancer patients. Therefore, the efficacy of medical treatment should be evaluated in patients undergoing gastrectomy. METHODS: We conducted an unblinded, randomized controlled trial of patients who underwent gastrectomy to treat gastric cancer. The intention-to-treat participants (n = 107) were randomly assigned to receive either alendronate at a weekly dose of 70 mg and daily elemental calcium (500 mg) with cholecalciferol (1000 IU) or daily elemental calcium (500 mg) with cholecalciferol (1000 IU) only. The primary endpoint was defined by the changes in bone mineral density of four measurement sites: the lumbar spine, femur neck, total hip, and trochanter. Changes in bone turnover markers, osteocalcin and collagen I carboxyterminal telopeptide were also observed. RESULTS: At baseline, there were no differences between the two groups in bone mineral density. In the lumbar spine and trochanter, there were no significant percentage changes compared with the baseline in the alendronate group, but a significant decrease was noted in the control group (p < 0.001 for both lumbar spine and trochanter). In the femur neck and total hip, a larger decrease was observed compared with the baseline in the control group (p < 0.001 for both femur neck and total hip). Significant percentage increases in serum osteocalcin compared with baseline were noted in the control group (p for trend <0.001), but there was no change in the alendronate group (p for trend = 0.713). Collagen I carboxyterminal telopeptide significantly declined in the alendronate group over 12 months (p for trend <0.001). CONCLUSIONS: Prevention and treatment with bisphosphonate effectively reduces bone loss by suppressing bone resorption in gastric cancer patients undergoing gastrectomy.

Comparison of Natural Course between Thyroid Cancer Nodules and Thyroid Benign Nodules.

BACKGROUND: The natural course of thyroid cancer nodules and benign nodules is different. This study was to compare the changes in size between thyroid cancer nodules and thyroid benign nodules. The risk factors associated with the changes of thyroid cancer nodules were assessed. METHODS: This study contains retrospective observational and prospective analysis. A total of 113 patients with 120 nodules were recruited in the cancer group, and 116 patients with 119 nodules were enrolled in the benign group. Thyroid ultrasonography was performed at least two times at more than 1-year interval. RESULTS: The mean follow-up durations were 29.5±18.8 months (cancer group) and 31.9±15.8 months (benign group) (P=0.32). The maximum diameter change in length was 0.36±0.97 mm/year in the cancer group and -0.04±0.77 mm/year in the benign group (P<0.01). The volume was significantly increased in the cancer group compared with the benign group (0.06±0.18 mL/year vs. 0.004±0.05 mL/year, respectively, P<0.01; 26.9%±57.9%/year vs. 1.7%±26.0%/year, P<0.01). Initial maximum diameter (ß=0.02, P<0.01) and initial volume (ß=0.13, P<0.01) were significantly associated with volume change (mL)/year. Initial maximum standardized uptake value did not predict the nodule growth. CONCLUSION: It is suggested that thyroid cancer nodules progress rapidly compared with benign nodules. Initial size and volume of nodule were independent risk factors for cancer nodule growth.

CYFRA 21-1 in Lymph Node Fine Needle Aspiration Washout Improves Diagnostic Accuracy for Metastatic Lymph Nodes of Differentiated Thyroid Cancer.

Fine needle aspiration cytology (FNAC) and washout thyroglobulin (Tg) measurements are the standard for evaluating a metastatic lymph node (LN) in thyroid cancer. However, patients rarely benefit from these procedures due to false results. This study aims to identify a reliable biomarker that significantly improves the diagnosis of metastatic LNs, in addition to FNAC and washout Tg. This study analyzed 130 LNs that were suspected to have metastases on thyroid ultrasonography, from June 2016 to December 2017. All subjects underwent FNAC, washout Tg measurements and a new biomarker, washout Cytokeratin fragment 21-1 (CYFRA 21-1) measurement. The final LN outcomes were confirmed by surgical histology, repeat FNAC, or follow-up image. The diagnostic values of the presence of washout CYFRA 21-1 for diagnosing metastatic LNs were evaluated according to final LN outcomes. Among the 130 LNs, 42 were metastatic lesions and 88 were benign. The washout CYFRA 21-1 levels were significantly higher in metastatic LNs than in benign LNs. In contrast to the findings of washout Tg, washout CYFRA 21-1 showed little overlap between benign and malignant LNs, and its diagnostic cutoff values were not affected by surgery. The combinations of FNAC and washout CYFRA 21-1 showed higher sensitivity (91.9%), specificity (96.5%), negative predictive value (98.8%), and diagnostic accuracy (94.2%) than FNAC with washout Tg. The combination of FNAC, washout Tg, and washout CYFRA 21-1 showed the best sensitivity (98.8%). When washout CYFRA 21-1 was applied to the discordant results that were observed between FNAC and washout Tg, 20 of 22 LNs were correctly diagnosed. Washout CYFRA 21-1 measurements in thyroid LNs provide a diagnostic modality.

Changes in trabecular bone score and bone mineral density following allogeneic hematopoietic stem cell transplantation.

PURPOSE: It has been demonstrated that bone mineral density (BMD) loss is substantial within the first 12 months after allogeneic hematopoietic stem cell transplantation (alloHSCT). Declines in BMD showed a disproportionate cortical bone loss even though trabecular bone is metabolically more active than cortical bone. This finding suggests a unique mechanism. However, the structural bone deficits after alloHSCT have not been well characterized. The trabecular bone score (TBS) has emerged as a method to assess bone microarchitecture. The aim of this study was to evaluate the changes in BMD and TBS in patients who received alloHSCT with follow-up of two years. METHODS: All patients 18 years and older who received alloHSCT between 2009 and 2015 at Seoul St. Mary's Hospital, Korea were included. They were segregated into a first group (A, n = 24) that was evaluated for BMD at the time of alloHSCT and 12 months posttransplant and a second group (B, n = 44) that was evaluated for BMD at 12 and 24 months following alloHSCT. RESULTS: Subjects in group A experienced a decrease in BMD at the femoral neck and total hip between the time of transplantation and 12 months posttransplantation: 0.056 ±â€¯0.057 (5.48%) and 0.072 ±â€¯0.063 (6.84%), respectively. Subjects in group B experienced an increase in BMD at the lumbar spine and total hip between 12 and 24 months post-alloHSCT: 0.047 ±â€¯0.064 (4.90%) and 0.017 ±â€¯0.045 (2.16%), respectively. In group A, TBS at 12 months post-alloHSCT decreased 0.028 ±â€¯0.067 (1.92%) from the baseline (p = 0.086). In group B, TBS at 24 months post-alloHSCT increased 0.010 ±â€¯0.049 (0.78%) from the 12 months post-alloHSCT evaluation (p = 0.149). TBS change was positively associated with BMD changes at all measured sites. The cumulative dose of glucocorticoid therapy was associated with loss of BMD at all measured sites and TBS. In addition, the dose of total body irradiation (TBI) was negatively associated with TBS. CONCLUSIONS: In summary, this study delineated longitudinal microarchitectural changes in bone structure occurring in the context of alloHSCT. TBS change per 12 months was insignificant during the two years following alloHSCT. Therefore, our data represented disproportionate cortical bone loss in the context of the microarchitecture.

Risk factors for hypothyroidism in euthyroid thyroid nodule patients with lymphocytic thyroiditis on fine needle aspiration cytology.

BACKGROUND/AIMS: Lymphocytic thyroiditis as cytology diagnosis from fine needle aspiration (FNA) is frequently detected in patients with thyroid nodules. However, the clinical outcome for upcoming hypothyroid events has been rarely clarified in euthyroid patients. METHODS: We retrospectively reviewed the data of patient who had lymphocytic thyroitidis on FNA cytology of thyroid nodule from January 2005 to December 2010 at a tertiary referral hospital. In total, 109 patients with follow-up thyroid function tests (TFT) were enrolled. Final outcomes included overt and subclinical hypothyroidism with thyroid stimulating hormone (TSH) levels ≥ 10 mIU/L. Potential parameters predicting clinical hypothyroidism were analyzed by multivariate analysis. RESULTS: Over the mean follow-up duration of 51.6 months, 14 out of 109 patients (12.8%) developed clinical hypothyroidism that required thyroid hormone replacement. The median onset time to hypothyroidism was 16 months (range, 3 to 88) and ≥ 60% of patients experienced clinical hypothyroidism within 1 year. By multivariate analysis, background thyroiditis (relative risk [RR], 9.78; p = 0.004), thyroid peroxidase antibody positivity (RR, 9.90; p = 0.003), nodule size (RR, 1.24; p < 0.001), and initial TSH (RR, 1.47; p = 0.009) were the independent risk factors for predicting hypothyroidism in euthyroid patients. CONCLUSION: Hypothyroidism frequently occurs during the follow-up in euthyroid patients with thyroid nodules which show lymphocytic thyroiditis on FNA cytology. Close surveillance and regular TFT are needed in high-risk patients for upcoming clinical hypothyroidism.

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.

Calcification Patterns in Papillary Thyroid Carcinoma are Associated with Changes in Thyroid Hormones and Coronary Artery Calcification.

Recent studies suggested that a lower serum thyroid hormone level is associated with more vascular calcification. However, it has been rarely evaluated whether lower thyroid hormone levels affect the calcification of thyroid cancer and there is a relationship between calcification patterns of papillary thyroid carcinoma (PTC) and coronary artery calcification (CAC). The study was divided into two groups: First, we retrospectively reviewed 182 PTC patients and examined the correlation between PTC calcification patterns and CAC by coronary computed tomography (CT). Second, the correlation between the calcification pattern of PTC and thyroid hormone concentration was investigated (n = 354). The calcification pattern of PTC was evaluated by thyroid ultrasonography and classified into four groups: no-calcification, microcalcification, macrocalcification, and mixed-calcification. In PTC patients with microcalcification and mixed calcification, more CAC was observed and coronary calcium score (CCS) was higher. Lower free T4 and higher thyroid-stimulating hormone (TSH) levels were associated with microcalcification and mixed calcification, not with macrocalcification and no calcification. PTC with microcalcification and mixed calcification showed more aggressive phenotypes like lymph node metastasis and more advanced TNM (tumor, node, and metastasis) stage than those with no calcification and macrocalcification. Calcification patterns of PTC showed close association with thyroid hormone levels and CAC. Further research is needed to determine how these findings are related to cardiovascular risk and disease-specific mortality.

Sex differences in risk factors for subclinical hypothyroidism.

OBJECTIVE: To investigate the prevalence of subclinical hypothyroidism (SCH) in Korean adults and identify the risk factors for the occurrence of SCH by sex. DESIGN AND METHODS: This study used data from the Sixth Korea National Health and Nutrition Examination Survey (KNHANES VI), a cross-sectional, nationally representative survey, which comprises a health interview survey, a health examination survey and a nutrition survey. To examine SCH, the reference range of thyroid-stimulating hormone (TSH) was defined using both the range provided by the test kit manufacturer (SCH-M) and a population-based range (SCH-P). We investigated the prevalence of SCH and its risk factors by sex using both reference ranges. RESULTS: The prevalence of SCH in Koreans according to SCH-M (0.35-5.5 µIU/mL) was 5.6%, and 3.3% with SCH-P (0.62-6.68 µIU/mL). For men, smoking significantly reduced the incidence of SCH, positive anti-thyroid peroxidase antibody (TPOAb) significantly increased the risk of SCH, and in an adjusted model, the risk of SCH in all quartiles increased as the urine iodine creatinine ratio (UICR) quartile increased. For women, positive TPOAb was confirmed as a risk factor for SCH, as was the highest UICR quartile. Furthermore, the odds ratio for SCH in urban vs rural residence was 1.78. CONCLUSIONS: The prevalence rates of SCH were similar to those reported in the literature and previously known risk factors were confirmed using both TSH reference ranges. The notable findings from this study are that the increased risk of SCH with increased iodine intake was more marked in men than in women and that residential area may be a risk factor for SCH in women.