Eon Ju Jeon

Diagnostic Whole-Body Scan May Not Be Necessary for Intermediate-Risk Patients with Differentiated Thyroid Cancer after Low-Dose (30 mCi) Radioactive Iodide Ablation

Background A diagnostic whole-body scan (WBS) is recommended 6 to 12 months after total thyroidectomy and radioactive iodide ablation in intermediate- or high-risk patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the necessity of a diagnostic WBS after radioactive iodide ablation in intermediate-risk patients with DTC. Methods A total of 438 subjects were included in the study: 183 low-risk subjects and 255 intermediate-risk subjects according to the American Thyroid Association guideline. All subjects diagnosed with DTC received 1,100 MBq (30 mCi) activity of radioiodine (I-131) following total thyroidectomy. On follow-up, all subjects underwent a diagnostic I-131 WBS after thyroid hormone withdrawal. Results After initial radioactive iodide ablation, 95.1% of low-risk patients and 91.4% of intermediate-risk patients showed no uptake on diagnostic WBS (P=0.135). Intermediate-risk patients with stimulated thyroglobulin (Tg) levels higher than 2.0 ng/mL showed a greater rate of radioactive iodine uptake on diagnostic WBS. Four intermediate-risk patients showed recurrence during the 16 to 80 months follow-up period. Three of the four patients with recurrence showed no uptake on diagnostic WBS and had a stimulated Tg level less than 2.0 ng/mL. Conclusion A diagnostic I-131 WBS after radioactive iodide ablation in intermediate-risk patients with DTC may not be necessary. A large prospective study is necessary to determine the necessity of diagnostic WBS in intermediate-risk patients with DTC.

Ultrasonographic Characteristics of the Follicular Variant Papillary Thyroid Cancer According to the Tumor Size

Follicular variant papillary thyroid cancer (FVPTC) is the second most common subtype after conventional PTC. We compared ultrasonographic (US) features of FVPTC to those of conventional PTC according to tumor size. We reviewed US findings, pathologic reports, and medical charts of 249 PTC patients with surgically proven disease (83 FVPTCs, 166 conventional PTCs) at our institution from January 2007 to December 2012. FVPTCs were divided into PTC-like and follicular neoplasm (FN)-like based on sonographic characteristics. PTC-like features were defined as having at least one malignant feature (taller-than-wide shape, infiltrative margin, marked hypoechogenicity, and micro-calcifications), whereas FN-like cancers showed oval solid features without malignant features. FVPTCs showed a higher rate of FN-like features than conventional PTCs. Of 166 conventional PTCs, 13 (7.8%) had FN-like features and 153 (92.2%) had PTC-like features, whereas of the 83 FVPTCs, 31 (37.3%) had FN-like features and 52 (62.7%) had PTC-like features. Macro-FVPTCs showed a higher rate of FN-like features than micro-FVPTCs (P < 0.001). Of 21 macro-FVPTCs, 18 (85.7%) had FN-like features and 3 (14.3%) had PTC-like features, whereas of the 62 micro-FVPTCs, 13 (21%) had FN-like features and 49 (79%) had PTC-like features. There were no differences in multifocality, extrathyroidal invasion, and lymph node metastasis between PTC-like FVPTCs and FN-like FVPTCs. FVPTCs showed fewer sonographic malignant features than conventional PTCs. In particular, FVPTCs larger than 1 cm had a more frequent benign sonographic appearance. Therefore, if fine-needle aspiration result is suspicious for PTC in a nodule larger than 1 cm with no suspicious US features, the possibility of FVPTC might be considered.

Radiofrequency Ablation for the Papillary Thyroid Micro-carcinoma in the HighriskSurgical Patient

Percutaneous ultrasound-guided Radiofrequencyablation (RFA) is a minimally invasive treatment that has been widely used as an alternative to surgery in the care of patients with malignant tumors of the liver, renal cell carcinoma, and other tumors. Recently, RFA is an alternative treatment modality for benign thyroid nodules instead of surgery, mainly for the cosmetic reasons, and limited cases of local recurrences or focal distant metastases of differentiated thyroid cancer in the high-risk reoperative condition or for the palliative purpose. However, RFA for the initial treatment of the DTC is rare. We report a case of RFA for the papillary thyroid microcarcinomain the high-risk surgical patient. A 49-years-old woman with congestive heart failure due to severe mitral valve regurgitation, chronic kidney disease, and type 2 diabetes was incidentally diagnosed with papillary microcarcinoma without metastasis. She underwent RFA. During 5-year follow-up, there is no recurrence of the findings.

Patient Understanding of Hypoglycemia in Tertiary Referral Centers

Background Hypoglycemia is an important complication in the treatment of patients with diabetes. We surveyed the insight by patients with diabetes into hypoglycemia, their hypoglycemia avoidance behavior, and their level of worry regarding hypoglycemia. Methods A survey of patients with diabetes, who had visited seven tertiary referral centers in Daegu or Gyeongsangbuk-do, Korea, between June 2014 and June 2015, was conducted. The survey contained questions about personal history, symptoms, educational experience, self-management, and attitudes about hypoglycemia. Results Of 758 participants, 471 (62.1%) had experienced hypoglycemia, and 250 (32.9%) had experienced hypoglycemia at least once in the month immediately preceding the study. Two hundred and forty-two (31.8%) of the participants had received hypoglycemia education at least once, but only 148 (19.4%) knew the exact definition of hypoglycemia. Hypoglycemic symptoms identified by the participants were dizziness (55.0%), sweating (53.8%), and tremor (40.8%). They mostly chose candy (62.1%), chocolate (37.7%), or juice (36.8%) as food for recovering hypoglycemia. Participants who had experienced hypoglycemia had longer duration of diabetes and a higher proportion of insulin usage. The mean scores for hypoglycemia avoidance behavior and worry about hypoglycemia were 21.2±10.71 and 23.38±13.19, respectively. These scores tended to be higher for participants with higher than 8% of glycosylated hemoglobin, insulin use, and experience of emergency room visits. Conclusion Many patients had experienced hypoglycemia and worried about it. We recommend identifying patients that are anxious about hypoglycemia and educating them about what to do when they develop hypoglycemic symptoms, especially those who have a high risk of hypoglycemia.

Adipokines and Insulin Resistance According to Characteristics of Pregnant Women with Gestational Diabetes Mellitus

Background The aim of this study was to evaluate adipokines concentration and insulin resistance according to maternal age or obesity at pregnancy and weight change at diagnosed gestational diabetes mellitus (GDM) in pregnant women with GDM. Methods This study included 57 pregnant women who were diagnosed with GDM at 24 to 28 weeks of gestation. The subjects were classified into two or three groups according to pre-pregnancy body mass index (BMI, <25 kg/m2 vs. ≥25 kg/m2), maternal age at pregnancy (<35 years old vs. ≥35 years old), and weight change during pregnancy at screening for GDM (weight change below, within, and in excess of the recommended range). They were respectively compared in each group. Results Leptin, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA2-%B were increased in the group with pre-pregnancy BMI ≥25 kg/m2. Leptin and HOMA-IR were positively correlated with BMI both before pregnancy and at screening for GDM. There were no significant correlations between HOMA-IR and adipokines. HOMA-IR showed positive correlation with HOMA2-%B and negative correlation with HOMA2-%S. Conclusion Leptin and HOMA-IR at diagnosed GDM were increased in the GDM patients with obesity before pregnancy. They were positively correlated with BMI both before pregnancy and at screening for GDM. The effect of maternal age at pregnancy and weight change during pregnancy at GDM screening on adipokines and insulin resistance might be less pronounced than the effect of maternal obesity.

Primary Mucosa-Associated Lymphoid Tissue Lymphoma of Thyroid with the Serial Ultrasound Findings.

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) of the thyroid gland is uncommon. Even though its natural history is not well defined, it is known to be indolent course. We present a case of primary MALT thyroid lymphoma with the serial sonographic findings in the patient presenting as the focal nodule. A 45-year-old woman visited our hospital for neck examination. Initially, fine-needle aspiration cytology in the focal hypoechoic lesion in the left thyroid lobe on ultrasound sonography was performed and consistent with Hashimotos thyroiditis. However, the results of serial ultrasounds and core-needle biopsy revealed an extranodal marginal zone lymphoma of MALT on 4-year follow-up. Patients with a focal hypoechoic nodule with linear echogenic strands and segmental pattern in the background of Hashimotos thyroiditis on ultrasonography should undergo careful surveillance for malignancy. Serial sonographic features in this case are meaningful in the understanding of the natural history of the extranodal marginal zone lymphoma of MALT of the thyroid.

A Calcitonin-Negative Neuroendocrine Tumor Derived from Follicular Lesions of the Thyroid

Neuroendocrine lesions of the thyroid are rare. The most common types are medullary thyroid carcinomas (MTCs) and C-cell hyperplasia. MTCs originate from thyroid parafollicular cells that secrete calcitonin which serves as a serum marker of MTCs. Here, the rare case of a calcitonin-negative neuroendocrine tumor (NET) derived from follicular lesions of the thyroid is described. A 34-year-old man presented at our hospital for the surgical management of an incidental thyroid nodule that was observed on an ultrasound sonography (USG) of the neck. Initially, USG-guided aspiration cytology was performed, and a MTC was suspected. The expressions of thyroglobulin and thyroid transcription factor-1, which are thyroid follicular cell markers, and synaptophysin and chromogranin A, which are neuroendocrine markers, was confirmed following surgical pathology. However, the staining of calcitonin, a marker of MTCs, was not observed. A nonmedullary NET of the thyroid is uncommon, and the distinction between calcitonin-negative NETs and MTCs of the thyroid may be important due to differences in their clinical courses and management.

Response: Adipokines and Insulin Resistance According to Characteristics of Pregnant Women with Gestational Diabetes Mellitus (Diabetes Metab J 2017;41:457-65)

Corresponding author: Ji Hyun Lee https://orcid.org/0000-0002-5671-0875 Department of Internal Medicine, Catholic University of Daegu School of Medicine, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea E-mail: jhlee9@cu.ac.kr We would like to thank Dr. Ryu’s interests and comments on our study titled “Adipokines and insulin resistance according to characteristics of pregnant women with gestational diabetes mellitus” published in Diabetes and Metabolism Journal [1]. As mentioned in the letter, the clinical implications of gestational diabetes mellitus (GDM) are associated with adverse outcomes in pregnancy, and GDM has long-term consequences both for the mother and her offspring, including the development of type 2 diabetes mellitus and cardiovascular diseases. Adipokines have an important role in the regulation of insulin resistance. During pregnancy, there is a significant increase in leptin and decreased in adiponectin compared with non-pregnant state. Most studies have shown that leptin is higher and adiponectin is lower in pregnant women with GDM than those without GDM, although there are differences between studies. It is well-known that GDM is associated with becoming pregnant at an older age, higher pre-pregnancy weight and body mass index (BMI), a history of GDM, higher parity, and Asian ethnicity. Therefore, identification and modification of modifiable risk factors is already emphasized for women of child-bearing age to prevent the onset of GDM. Lately, Cho et al. [2] first reported the relationship between gestational stagespecific weight gain and adverse outcomes in Korean women in a large cohort. The study suggested that the rate of gestational weight gain (RGWG) was significantly associated with a high risk of developing GDM at early pregnancy, and early RGWG in normal pre-pregnancy BMI group was significantly associated with GDM. We attempted to investigate the characteristic of the adipokines and insulin resistance according to maternal risk factors among pregnant women with GDM based on single, tertiary hospital patients. With the increase in GDM, pregnant women with GDM need to be classified and stratified according to clinical characteristics in the clinical setting because the management and the outcome may differ. Recently, Cho et al. [3] investigated the trends of incidence of GDM, insulin treatment for GDM, and the changes in its risk factors in Koreans based on a nation-wide population. The incidence of GDM increased from 3.86% in 2007 to 11.83% in 2010, and this increase was continuously observed even after adjustment for age. However, the number of GDM cases that required insulin treatment decreased significantly from 13.87% in 2007 to 5.94% in 2010. The proportion of pregnancy at an older maternal age and multiparity were increased, but the proportion of multiple pregnancies significantly decreased during the study period. The incidence of GDM increased in all age groups, with the highest incidence in the 30 to 34 age group. There were no changes in BMI (22.16±0.12 kg/m in 2010). There is limited information about the factors that contribute to the changes in these trends. We, as well as other researchers, feel the need to conduct well-designed studies on the criteria or definition including gestational weight Response

Cystatin C as a Predictor for Diabetes according to Glycosylated Hemoglobin Levels in Korean Patients

Cystatin C is entirely filtered by the kidney glomerulus and metabolized by the proximal tubule, and it is mainly used as a biomarker of renal function. It was first proposed by Anders Grubb as a potential alternative to be used as a glomerular filtration rate (GFR) that could overcome the known limitations of serum creatinine [1], and has been investigated for about 30 years. Cystatin C is less influenced by demographic characteristics such age, gender, race, muscle mass, heath status, and drugs than creatinine [2]. Most studies have shown the associations of cystatin C and creatinine with longitudinally adverse outcomes of renal disease such as end-stage renal disease, cardiovascular disease (CVD), heart failure, and death [3]. In addition, three recent researches have reported interesting results regarding cystatin C in kidney function [4,5,6]. These had an impact on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) guideline and led to its widespread clinical use.

Response: Diagnostic Whole-Body Scan May Not Be Necessary for Intermediate-Risk Patients with Differentiated Thyroid Cancer after Low-Dose (30 mCi) Radioactive Iodide Ablation (Endocrinol Metab 2014;29:33-9, Eon Ju Jeon et al.).

We want to thank the editors of Endocrinology and Metabolism for giving us the opportunity to publish our work, and have provided the following response to Prof. Jungs letter. At present, thyroid nodules are common clinical problem. The prevalence of differentiated thyroid cancer (DTC) is dramatically increasing and a large number of clinical studies have been conducted. The American Thyroid Association (ATA) published revised guidelines on practice recommendations [1]. The ATAs long-term management guidelines suggest that diagnostic whole-body scan (WBS) at 6 to 12 months after remnant ablation may be of value in the follow-up of patients with high or intermediate risk of persistent disease. Low-risk patients with undetectable thyroglobulin (Tg) levels with negative anti-Tg antibody, and a negative ultrasonography do not require routine diagnostic WBS. Nevertheless, it is not clear whether diagnostic WBS provides any benefit to patients with intermediate-risk thyroid cancer after a complete surgical resection and initial radioactive iodine ablation. As mentioned in the letter, TSH-stimulated Tg levels alone may not represent thyroid uptake on diagnostic I-131 WBS during short-term follow-up (1.17 to 8.17 years) considering the long-term survival of DTC patients in this study. However, the thyroid bed uptake on diagnostic I-131 WBS showed a statistically significant difference according to TSH-stimulated Tg levels in the absence of anti-Tg antibody (P=0.008). Serum Tg without antibody interference following thyroid hormone withdrawal or stimulation using recombinant human TSH has a high degree of sensitivity and specificity in detecting thyroid cancer after total thyroidectomy and remnant ablation [2]. Based on this evidence, diagnostic WBS may not be necessary for intermediate-risk patients with DTC after low-dose (30 mCi) radioactive iodide ablation. Recently, Rosario et al. [1] reported that diagnostic WBS can be avoided in patients with large tumors or extensions beyond the thyroid capsule or lymph node metastases, but who show no apparent disease upon initial radioactive iodine WBS and ultrasonography and whose serum Tg during levothyroxine therapy of <1 ng/mL and negative anti-Tg antibody after thyroidectomy and ablation for DTC. In addition, cervical ultrasonography is highly sensitive in the detection of cervical metastases even when stimulated Tg remains undetectable [4,5]. In this study, all four patients with recurrent cancer were diagnosed by ultrasonography and three recurrent patients showed stimulated serum Tg level (<2 ng/mL) and no uptake in diagnostic I-131 WBS. As Prof. Jung mentioned, we feel that a prospective, long-term study is needed to further investigate the effect of the presence of thyroid remnant tissue in diagnostic WBS on recurrence and prognosis. We will keep tracing the recurrence of 17 patients with thyroid bed uptake and stimulated Tg below 2 ng/mL during long-term follow-up. Thank you again for your interest and comprehensive comments on our paper.