Yun Jae Chung

Postoperative-stimulated serum thyroglobulin measured at the time of 131I ablation is useful for the prediction of disease status in patients with differentiated thyroid carcinoma

BACKGROUND This study was conducted to identify the relevant cutoff value and to evaluate the usefulness of postoperative-stimulated serum thyroglobulin (Tg) at the time of (131)I ablation for the prediction of disease status in patients with differentiated thyroid carcinoma (DTC) who received high-dose (131)I ablation therapy after total thyroidectomy. METHODS We analyzed 218 consecutively enrolled patients who were diagnosed with DTC and underwent total thyroidectomy. All patients underwent (131)I ablation at doses of 100-200 mCi, and stimulated serum Tg was measured at the time of (131)I ablation therapy. To assess disease-free status after (131)I ablation therapy, stimulated serum Tg levels, diagnostic whole-body scan (DxWBS) and neck ultrasonography (US) were performed 6-12 months after (131)I ablation. RESULTS The relevant cutoff value of postoperative stimulated Tg for the prediction of disease-free status was 2 ng/mL. A total of 138 patients (63.3%) showed values of <2 ng/mL. Postoperative-stimulated Tg < 2 ng/mL had a negative predictive value of 94.9%, which increased to 97.7% when low Tg was combined with negative neck US findings. CONCLUSION Postoperative-stimulated Tg at the time of (131)I remnant ablation is a useful biochemical marker for the prediction of disease status in patients with DTC. When high-dose (131)I remnant ablation is performed after total thyroidectomy, the stimulated Tg measurement and DxWBS that are usually performed 6-12 months after (131)I ablation therapy may be skipped, at least in low- and intermediate-risk patients with postoperative stimulated Tg of < 2 ng/mL and negative neck US findings.

Clinical significance of the BRAFV600E mutation in multifocal papillary thyroid carcinoma in Korea

BACKGROUND We examined the frequency of the BRAF(V600E) mutation and compared the clinicopathologic features based on the BRAF(V600E) mutation status in multifocal papillary thyroid carcinoma (PTC). METHODS A total 85 patients who were diagnosed with multifocal PTC were enrolled. We confirmed the status of the BRAF(V600E) mutation in each tumor focus by the real-time polymerase chain reaction technique. RESULTS Among the 85 patients, 49 (57.6%), 34 (40.0%), and 2 (2.4%) patients were determined to have all BRAF(V600E)-positive, mixed BRAF(V600E), and all BRAF(V600E)-negative in their tumor foci, respectively. When we compared clinicopathologic features according to the BRAF(V600E) mutation status of the dominant tumor, the BRAF(V600E) -positive group (n = 70) showed more extrathyroidal invasion in the dominant tumor (32.9% vs 6.7%, P = .041) and more lymph node metastasis (67.2% vs 40.0%, P = .049) than the BRAF(V600E) -negative group (n = 15). Considering all tumor foci, the all BRAF(V600E) mutation group exhibited a younger population (P = .039), showed increased extrathyroidal invasion (38.8% vs 14.7%, P = .017) and lymph node metastasis (71.4% vs 48.4%, P = .038), and received more radioactive iodine therapy (79.2% vs 52.9%, P = .012) than the mixed BRAF(V600E) mutation group. A larger tumor size and heavier preoperative body weight was positively correlated with the relative expression of BRAF(V600E) mutation calculated by 2(-△△Ct) method. CONCLUSION Most of the Korean patients with multifocal PTC had the BRAF(V600E) mutation in one or more tumor foci, and all BRAF(V600E)-positive multifocal PTC showed more aggressive features.

Clinicopathologic correlations of the BRAFV600E mutation, BRAF V600E immunohistochemistry, and BRAF RNA in situ hybridization in papillary thyroid carcinoma

BACKGROUND The BRAF(V600E) mutation is the most common genetic alteration in papillary thyroid carcinoma (PTC). The aim of this study is to analyze the clinicopathologic correlations of the BRAF(V600E) mutation, BRAF V600E immunohistochemistry (IHC) and BRAF RNA in situ hybridization (ISH) in PTC. METHODS This study included 467 patients with PTC who underwent surgical resection. We studied the BRAF(V600E) mutation using real-time PCR and BRAF V600E and BRAF RNA ISH using tissue microarray (TMA). RESULTS The frequencies of a positive BRAF(V600E) mutation by real-time PCR, positive BRAF V600E IHC, and high BRAF RNA ISH were 84%, 86%, and 70%, respectively, in PTC. Conventional PTC had higher positive rates in all three tests than other histologic types. The BRAF(V600E) mutation, BRAF V600E IHC, low ΔCt, and high BRAF RNA ISH were significantly associated with lymph node metastasis. The BRAF(V600E) mutation was significantly associated with positive immunostaining for BRAF V600E mutant protein (P<0.001) overall, with high BRAF RNA ISH only in the follicular variant (P=0.035). No significant correlation was noted between BRAF V600E IHC and BRAF RNA ISH. The sensitivity of BRAF V600E IHC for the BRAF(V600E) mutation was 95%, and the specificity was 61% overall, 96% and 54% in the conventional type, and 85% and 70% in the follicular variant. CONCLUSIONS Our results showed that positive BRAF V600E IHC significantly correlated with the BRAF(V600E) mutation. This suggests its clinical utility as a screening tool for the BRAF(V600E) mutation. In addition, a high BRAF RNA ISH score could be a candidate marker of aggressive behavior in BRAF(V600E) mutation-positive cases of PTC.

Anti-proliferative Effect and Action Mechanism of Dexamethasone in Human Medullary Thyroid Cancer Cell Line

Introduction. Dexamethasone is known to inhibit the cell proliferation of certain transformed cell lines. In this study, the effect and action mechanism of dexamethasone were examined in the human medullary thyroid cancer cell line, TT cells. Methods. TT cells were treated with or without dexamethasone. 5-Bromo-2′-deoxyuridine uptake assay was used to evaluate cell proliferation. Cell cycle and its regulatory proteins were assessed by flow cytometry and western blot analysis, respectively. Apoptosis was analyzed by Hoechst staining and Annexin V assay. Results. Dexamethasone significantly reduced TT cell proliferation by 60% (p < 0.01). A substantial portion of cells was arrested at the G1 phase. The expression levels of cyclin D1, cyclin-dependent kinase (CDK)4, and CDK2 were decreased. In addition, the phosphorylation of retinoblastoma protein, which is a critical checkpoint protein in the transition of G1 to S phase, was decreased. On the other hand, the expression level of p27Kip1, which is a cyclin/CDK inhibitor, was enhanced. Hoechst staining showed many fragmented nuclei in the dexamethasone-treated cells. The proportion of early apoptotic cells was also increased in the Annexin V assay. Conclusion. Dexamethasone inhibited the proliferation of TT cells through cell cycle arrest at the G1 phase and increased apoptosis.

Euthyroid Status After Total Thyroidectomy Due to Functioning Lung Metastases from a Clear Cell Variant of Papillary Thyroid Carcinoma

BACKGROUND Although functioning thyroid cancer metastases have been reported, they have almost never been reported for the clear cell variant of papillary thyroid carcinoma (PTC). Here we describe a patient with disseminated lung metastases of the clear cell variant of PTC who presented in the euthyroid state despite discontinuance of levothyroxine after total thyroidectomy. PATIENT FINDINGS A 49-year-old woman underwent total thyroidectomy for the clear cell variant of PTC in March 2002. Levothyroxine replacement was initiated after total thyroidectomy, but the patient was lost to follow-up 5 years after the operation. She did not take any levothyroxine for 4 years. Upon presentation to our institution, her initial thyroid function tests were a serum thyroid-stimulating hormone (TSH) of 4.51 mIU/L (0.30-5.00), total triiodothyronine of 82 ng/dL (60-181), and free thyroxine of 1.21 ng/dL (0.89-1.76). The results of workups, including thyroid ultrasonography, chest computed tomography (CT) scan, and fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET)/CT, revealed that she had multiple metastases in the cervical lymph nodes and both lungs. She received 0.9 mg of recombinant human TSH (rhTSH) for 2 consecutive days followed by administration of 200 mCi 131I. A therapeutic whole body scan after 131I administration demonstrated intense uptake in the whole lung fields, suggesting functioning lung metastases. SUMMARY It is extremely rare for metastatic PTC, even though it is a well-differentiated thyroid carcinoma, to produce a sufficient amount of thyroid hormones to result in euthyroid state after total thyroidectomy. To our knowledge, this is the first report of functioning lung metastases of the clear cell variant of PTC after total thyroidectomy that produced enough thyroid hormone to restore a euthyroid state. CONCLUSION Functioning metastases from recurred PTC, particularly of the clear cell variant, are very rare. When they occur, rhTSH is required to prepare these patients for treatment with ablative doses of radioactive iodine (131I).

Ectopic Intrapulmonary Thyroid Tissue Mimicking Metastatic Tissue

BACKGROUND Ectopic intrapulmonary thyroid is extremely rare, with only about two cases reported in the literature. These cases were found either during the work-up of a solitary pulmonary nodule or at autopsy. Here, we report a case of ectopic intrapulmonary thyroid mimicking multiple pulmonary metastases from an endometrioid adenocarcinoma of the uterus. PATIENT FINDINGS A 50-year-old woman presented with dysmenorrhea and menorrhagia. Endometrial curettage of the uterus revealed an endometrioid adenocarcinoma. During the staging, multiple pulmonary nodules were found. To exclude the possibility of lung metastases of the endometrioid adenocarcinoma from the uterus, video-assisted thoracic surgery (VATS) with wedge resection was performed for the largest nodule. The histopathology for that nodule was entirely consistent with normal thyroid tissue. The patient underwent surgery for uterine cancer and was discharged without further adjuvant chemotherapy. The remaining intrapulmonary nodules were unchanged in size on a serial computed tomography scan. SUMMARY In this patient, pulmonary metastases were initially considered the most likely cause of the multiple pulmonary nodules, but the diagnosis of the ectopic intrapulmonary thyroid was ultimately made based on VATS-wedge resection for the largest pulmonary nodule. The patient was able to avoid any unnecessary systemic chemotherapy. CONCLUSIONS Ectopic intrapulmonary thyroid is extremely rare but can be confused with pulmonary metastases from other sites. We are unaware of similar cases in the literature.

A case of nesidioblastosis causing hypoglycaemia after delivery

Nesidioblastosis is a rare cause of adult-onset hyperinsulinaemic hypoglycaemia. We describe a case of nesidioblastosis during pregnancy in a woman receiving medical nutrition therapy for suspected gestational diabetes. However, nesidioblastosis was undiscovered until the development of hypoglycaemia after delivery, being previously masked by pregnancy-related changes in insulin sensitivity.

Serum 25-hydroxyvitamin D might be an independent prognostic factor for Graves disease recurrence

Abstract Graves disease is the most common cause of thyrotoxicosis. Although medical intervention with antithyroid drugs (ATDs) is commonly the first choice of treatment in Korea, the remission rate associated with this approach is not satisfactory. During ATD therapy, low or undetectable serum levels of thyroid-stimulating hormone (TSH) receptor antibodies (TRAbs) have been reported to affect the incidence of Graves disease remission. This study evaluated the correlation between serum 25-hydroxyvitamin D levels and TRAb levels, as well as the effect of 25-hydroxyvitamin D on the recurrence of Graves disease. A total of 143 patients, who were diagnosed with Graves disease and treated with ATDs, were retrospectively included in our observational study. These patients were followed for more than 1 year after ATD discontinuation. The levels of serum 25-hydroxyvitamin D and TRAb (ie, thyroid-stimulating antibody [TSAb], as detected by bioassay, and TSH-binding inhibitory immunoglobulins [TBIIs]) were measured, and a thyroid function test was performed upon ATD discontinuation. Recurrence was evaluated every 3 months, and was defined as an occurrence of overt thyrotoxicosis during the follow-up period. A total of 95 patients (66.4%) experienced recurrence with a median latency period of 182 days (ranging 28–1219 days). The serum 25-hydroxyvitamin D levels at the time of ATD discontinuation were not correlated with either TBII or TSAb. In the Cox proportional hazard regression analysis, higher free T4 levels (>1.4 ng/dL; hazard ratio [HR], 3.252; 95% confidence interval [CI], 1.022–10.347) and low levels of 25-hydroxyvitamin D (⩽14.23 ng/mL) were associated with a higher probability of Graves disease recurrence (HR, 3.016; 95% CI, 1.163–7.819). Lower serum 25-hydroxyvitamin D levels were associated with a higher incidence of Graves disease recurrence. Therefore, serum 25-hydroxyvitamin D might be an independent risk factor for predicting Graves disease recurrence after ATD discontinuation.