Eui Dal Jung

Free T4 is negatively correlated with body mass index in euthyroid women

Background/Aims Overt thyroid dysfunction is well known to affect weight. However, the influence of normal-range changes in thyroid status on body mass index (BMI) is unclear. We sought to evaluate thyroid function (free T4, TSH) and its possible relationship with BMI and lipid profiles in euthyroid subjects. Methods A total of 1572 euthyroid women (mean age 46.2 years) who visited Daegu Catholic University Medical Centre for primary health screening participated in this cross-sectional study. Women who were not euthyroid and women who took thyroid medication were excluded. TSH, free T4, and lipid profile [total-cholesterol, triglyceride (TG), HDL-C, LDL-C] were evaluated. Results Obese euthyroid women had lower free T4 levels than did lean euthyroid women. After adjustment for age and smoking, free T4, but not TSH, was significantly negatively correlated with BMI. After adjustment for age, smoking, and BMI, free T4 was negatively correlated with TG to a significant degree. Conclusions We demonstrated a negative correlation between free T4 within the normal range and BMI in euthyroid subjects. These findings suggest that low free T4 is associated with obesity in euthyroid subjects.

Microarray Analysis of Papillary Thyroid Cancers in Korean

BACKGROUND/AIMS Papillary thyroid cancer (PTC) is the most common malignancy of the thyroid gland. It involves several molecular mechanisms. The BRAF V600E mutation has been identified as the most common genetic abnormality in PTC. Moreover, it is known to be more prevalent in Korean PTC patients than in patients from other countries. We investigated distinct genetic profiles in Korean PTC through cDNA microarray analysis. METHODS Transcriptional profiles of five PTC samples and five paired normal thyroid tissue samples were generated using cDNA microarrays. The tumors were genotyped for BRAF mutations. The results of the cDNA microarray gene expression analysis were confirmed by real-time PCR and immunohistochemistry analysis of 35 PTC patients. RESULTS Four of the five patients whose PTC tissues were subjected to microarray analysis were found to carry the BRAF V600E mutation. Microarrays analysis of the five PTC tissue samples showed the expression of 96 genes to be increased and that of 16 genes decreased. Real-time reverse transcription-polymerase chain reaction (RT-PCR) confirmed increased expression of SLC34A2, TM7SF4, COMP, KLK7, and KCNJ2 and decreased expression of FOXA2, SLC4A4, LYVE-1, and TFCP2L1 in PTC compared with normal tissue. Of these genes, TFCP2L1, LYVE-1, and KLK7 were previously unidentified in PTC microarray analysis. Notably, Foxa2 activity in PTC was reduced, as shown by its cytoplasmic localization, in immunohistochemical analyses. CONCLUSIONS These findings demonstrate both similarities and differences between our results and previous reports. In Korean cases of PTC, Foxa2 activity was reduced with its cytoplasmic accumulation. Further studies are needed to confirm the relationship between FOXA2 and BRAF mutations in Korean cases of PTC.

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.

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: 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.