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Malignant pheochromocytoma (PCC) is a rare condition. Although the liver is the second most frequent site of metastasis in malignant PCC, no definite treatments have been established. Herein, we report a case of liver metastasis of PCC that was successfully treated by transcatheter arterial chemoembolization (TACE). A 69-year-old man was admitted to the Department of Gastroenterology for evaluation of an incidental hepatic mass in August 2013. He had undergone right adrenalectomy in May 2005 and PCC had been confirmed on the basis of histopathological findings. Liver biopsy was performed, and metastatic PCC was diagnosed. The lesion appeared inoperable because of invasion of the portal vein and metastases in the lymph nodes along the hepatoduodenal ligament. Thus, TACE was performed instead. After TACE, symptoms including dizziness and cold sweating improved, and the patient's serum catecholamine levels decreased. On the basis of this case, we believe that TACE may be a useful treatment for liver metastasis in malignant PCC.
Adrenalectomy ; Aged ; Biopsy ; Dizziness ; Gastroenterology ; Humans ; Ligaments ; Liver ; Lymph Nodes ; Neoplasm Metastasis* ; Pheochromocytoma* ; Portal Vein ; Sweat ; Sweating

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Solitary Skin Metastasis of Papillary Thyroid Carcinoma.

Hyemi KWON ; Hyojung KIM ; Sojung PARK ; Dong Eun SONG ; Won Gu KIM ; Tae Yong KIM ; Young Kee SHONG ; Won Bae KIM

Endocrinology and Metabolism.2014;29(4):579-583. doi:10.3803/EnM.2014.29.4.579

A solitary skin metastasis is a rare manifestation of papillary thyroid carcinoma (PTC). A 55-year-old woman presented with a movable subcutaneous nodule in her anterior neck for several months. Three years ago, she underwent total thyroidectomy and remnant ablation for classical PTC (pT3N0M0) and was under thyroxine suppression therapy without any evidence of recurrent disease. The subcutaneous nodule was 0.4 cm in size, firm, and movable without any change in the overlying skin. Recurrent PTC was confirmed after excision biopsy. Eight months after, she got a new nodule along the previous excision site. After punch biopsy, metastatic PTC was confirmed in the deep dermis and was re-excised with a clear resection margin. This is the first report of a case of solitary skin metastasis of PTC in Korea. Although solitary skin metastasis of PTC is rare, it should be considered in patients with a skin nodule.
Biopsy ; Dermis ; Female ; Humans ; Korea ; Middle Aged ; Neck ; Neoplasm Metastasis* ; Skin* ; Thyroid Neoplasms* ; Thyroidectomy ; Thyroxine

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Low Serum Testosterone Concentrations in Hospitalized Men with Poorly Controlled Type 2 Diabetes.

Kyung Soo KIM ; San Ha KANG ; Moon Jong KIM ; Soo Kyung KIM ; Yoo Lee KIM ; Won Keun PARK ; Seok Won PARK ; Yong Wook CHO

Endocrinology and Metabolism.2014;29(4):574-578. doi:10.3803/EnM.2014.29.4.574

Our aim was to examine whether serum testosterone concentrations are in fact low in hospitalized men with poorly controlled type 2 diabetes compared with healthy men. In this study, 79 men aged 40 years or older (41 healthy men and 38 men with type 2 diabetes) were included. Total testosterone and sex hormone-binding globulin levels were measured. The average duration of diagnosed diabetes was 10.8 years and the mean glycated hemoglobin value was 10.8%. Total testosterone concentrations were lower in men with type 2 diabetes than in healthy men, after adjusting for age and body mass index (3.83+/-0.32 ng/mL vs. 5.63+/-0.31 ng/mL, P<0.001). In conclusion, this study shows that serum testosterone concentrations are lower in hospitalized men with poorly controlled type 2 diabetes than in healthy men. Therefore, men with poorly controlled type 2 diabetes should undergo further assessment for hypogonadism.
Body Mass Index ; Diabetes Mellitus, Type 2 ; Hemoglobin A, Glycosylated ; Humans ; Hypogonadism ; Male ; Sex Hormone-Binding Globulin ; Testosterone*

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Expression of Glucagon-Like Peptide 1 Receptor during Osteogenic Differentiation of Adipose-Derived Stem Cells.

Yun Kyung JEON ; Min Jung BAE ; Ju In KIM ; Joo Hyoung KIM ; Soo Jong CHOI ; Su Kyoung KWON ; Joon Hyop AN ; Sang Soo KIM ; Bo Hyun KIM ; Yong Ki KIM ; In Joo KIM

Endocrinology and Metabolism.2014;29(4):567-573. doi:10.3803/EnM.2014.29.4.567

BACKGROUND: Glucagon-like peptide 1 (GLP-1), an incretin hormone well known for its glucose-lowering effect, was recently reported to exert an anabolic effect on bone. Although the exact mechanism is not known, it likely involves the GLP-1 receptor (GLP-1R), which is expressed in some osteoblastic cell lines. Adipose-derived stem cells (ADSCs) have mesenchymal stem cell-specific characteristics, including osteoblastic differentiation potential. We evaluated the expression of GLP-1R during osteogenic differentiation of ADSCs. METHODS: ADSCs were isolated from subcutaneous adipose tissue obtained from three male donors during plastic surgery and were subjected to osteogenic induction. Mineralization was assessed by Alizarin Red staining on day 21. Expression of alkaline phosphatase (ALP), osteocalcin (OC), and GLP-1R was measured by real-time polymerase chain reaction in triplicate for each patient on days 0, 7, 14, and 21. Target mRNA expression levels were normalized to that of beta-actin. RESULTS: ADSCs were fibroblast-like in morphology, adhered to plastic, and had multipotent differentiation potential, as assessed using specific antigen markers. The osteogenic markers ALP and OC were notably upregulated at 21 days. Osteogenic differentiation resulted in a time-dependent increase in the expression of GLP-1R (P=0.013). CONCLUSION: We demonstrated upregulation of GLP-1R gene expression during osteogenic differentiation of ADSCs. This finding suggests that GLP-1 may induce osteogenic differentiation in bone tissue.
Actins ; Alkaline Phosphatase ; Anabolic Agents ; Bone and Bones ; Cell Line ; Gene Expression ; Glucagon-Like Peptide 1* ; Humans ; Incretins ; Male ; Osteoblasts ; Osteocalcin ; Osteogenesis ; Real-Time Polymerase Chain Reaction ; RNA, Messenger ; Stem Cells* ; Subcutaneous Fat ; Surgery, Plastic ; Tissue Donors ; Up-Regulation ; Glucagon-Like Peptide-1 Receptor

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Partial Hepatectomy in Acetylation-Deficient BubR1 Mice Corroborates that Chromosome Missegregation Initiates Tumorigenesis.

Yoo Kyung LEE ; Inai PARK ; Hyunsook LEE

Endocrinology and Metabolism.2014;29(4):561-566. doi:10.3803/EnM.2014.29.4.561

BACKGROUND: Aneuploidy has been suggested as one of the major causes of cancer from the time of Boveri. In support of this notion, many studies have shown that cancer cells exhibit aneuploidy. However, there are evidences that do not support the aneuploidy hypothesis. We have previously reported that the spindle assembly checkpoint protein BubR1 is acetylated in mitosis and that the acetylation of BubR1 is crucial for checkpoint maintenance and chromosome-spindle attachment. Mice heterozygous for acetylation-deficient BubR1 (K243R/+) spontaneously develop cancer with chromosome instability. As K243R/+ mice develop hepatocellular carcinoma, we set out to test if chromosome mis-segregation was the cause of their liver cancer. METHODS: Primary hepatocytes in the regenerating liver after partial hepatectomy (PH) were analyzed and compared for various mitotic parameters. RESULTS: Primary hepatocytes isolated from K243R/+ mice after PH displayed a marked increase of chromosome misalignment, accompanied by an increase of micronuclei. In comparison, the number of nuclei per cell and the centrosome numbers were not different between wild-type and K243R/+ mice. Taken together, chromosome mis-segregation provokes tumorigenesis in mouse liver. CONCLUSION: Our results corroborate that PH provides a reliable tool for assessing mitotic infidelity and cancer in mice.
Acetylation ; Aneuploidy ; Animals ; Carcinogenesis* ; Carcinoma, Hepatocellular ; Centrosome ; Chromosomal Instability ; Hepatectomy* ; Hepatocytes ; Hydrogen-Ion Concentration ; Liver ; Liver Neoplasms ; M Phase Cell Cycle Checkpoints ; Mice* ; Mitosis

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Activation of AMP-Activated Protein Kinase Attenuates Tumor Necrosis Factor-alpha-Induced Lipolysis via Protection of Perilipin in 3T3-L1 Adipocytes.

Seok Woo HONG ; Jinmi LEE ; Se Eun PARK ; Eun Jung RHEE ; Cheol Young PARK ; Ki Won OH ; Sung Woo PARK ; Won Young LEE

Endocrinology and Metabolism.2014;29(4):553-560. doi:10.3803/EnM.2014.29.4.553

BACKGROUND: Tumor necrosis factor (TNF)-alpha and AMP-activated protein kinase (AMPK) are known to stimulate and repress lipolysis in adipocytes, respectively; however, the mechanisms regulating these processes have not been completely elucidated. METHODS: The key factors and mechanism of action of TNF-alpha and AMPK in lipolysis were investigated by evaluating perilipin expression and activity of protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2 alpha (eIF2alpha) by Western blot and an immunofluorescence assay in 24-hour TNF-alpha-treated 3T3-L1 adipocytes with artificial manipulation of AMPK activation. RESULTS: Enhancement of AMPK activity by the addition of activator minoimidazole carboxamide ribonucleotide (AICAR) suppressed TNF-alpha-induced lipolysis, whereas the addition of compound C, an inhibitor of AMPK phosphorylation, enhanced lipolysis. Perilipin, a lipid droplet-associated protein, was decreased by TNF-alpha and recovered following treatment with AICAR, showing a correlation with the antilipolytic effect of AICAR. Significant activation of PERK/eIF2alpha, a component of the unfolded protein response signaling pathway, was observed in TNF-alpha or vesicle-treated 3T3-L1 adipocytes. The antilipolytic effect and recovery of perilipin expression by AICAR in TNF-alpha-treated 3T3-L1 adipocytes were significantly diminished by treatment with 2-aminopurine, a specific inhibitor of eIF2alpha. CONCLUSION: These data indicated that AICAR-induced AMPK activation attenuates TNF-alpha-induced lipolysis via preservation of perilipin in 3T3-L1 adipocytes. In addition, PERK/eIF2alpha activity is a novel mechanism of the anti-lipolytic effect of AICAR.
2-Aminopurine ; Adipocytes* ; AMP-Activated Protein Kinases* ; Blotting, Western ; Endoplasmic Reticulum ; Fluorescent Antibody Technique ; Lipolysis* ; Necrosis* ; Phosphorylation ; Phosphotransferases ; Prokaryotic Initiation Factor-2 ; Protein Kinases ; Tumor Necrosis Factor-alpha ; Unfolded Protein Response

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The Validity of Ultrasonography-Guided Fine Needle Aspiration Biopsy in Thyroid Nodules 4 cm or Larger Depends on Ultrasonography Characteristics.

Jin Hwa KIM ; Na Kyung KIM ; Young Lyun OH ; Hye Jeong KIM ; Sang Yong KIM ; Jae Hoon CHUNG ; Sun Wook KIM

Endocrinology and Metabolism.2014;29(4):545-552. doi:10.3803/EnM.2014.29.4.545

BACKGROUND: The objective of this study was to evaluate the validity of fine needle aspiration biopsy (FNAB) according to ultrasonography (US) characteristics in thyroid nodules 4 cm and larger. METHODS: We retrospectively reviewed the cases of 263 patients who underwent thyroid surgery for thyroid nodules larger than 4 cm between January 2001 and December 2010. RESULTS: The sensitivity of US-FNAB was significantly higher in nodules with calcifications (micro- or macro-) than those without (97.9% vs. 87.% P<0.05). The accuracy of US-FNAB was higher in large thyroid nodules with US features suspicious of malignancy, such as a solid component, ill-defined margin, hypoechogenicity or marked hypoechogenicity, or any calcifications (micro- or macro-) compared to thyroid nodules with none of these features. Furthermore, the accuracy improved as the number of these features increased. The overall false negative rate (FNR) was 11.9%. The FNR of thyroid nodules that appeared benign on US, such as mixed nodules (7.7%) or nodules without calcification (9.8%), trended toward being lower than that of solid nodules (17.9%) or nodules with any microcalcification or macrocalcification (33.3%). In nodules without suspicious features of malignancy, the FNR of US-FNAB was 0% (0/15). CONCLUSION: We suggest individualized strategies for large thyroid nodules according to US features. Patients with benign FNAB can be followed in the absence of any malignant features in US. However, if patients exhibit any suspicious features, potential false negative results of FNAB should be kept in mind and surgery may be considered.
Biopsy* ; Biopsy, Fine-Needle* ; Humans ; Retrospective Studies ; Thyroid Gland ; Thyroid Nodule* ; Ultrasonography*

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Expression of Glucagon-Like Peptide-1 Receptor in Papillary Thyroid Carcinoma and Its Clinicopathologic Significance.

Min Jung JUNG ; Su Kyoung KWON

Endocrinology and Metabolism.2014;29(4):536-544. doi:10.3803/EnM.2014.29.4.536

BACKGROUND: Incretin-based therapies are rapidly becoming one of the main glycemic control strategies in diabetes. Considering the large numbers of papillary thyroid carcinomas (PTCs) and possible effects of glucagon-like peptide-1 (GLP-1) on cell proliferation, the expression of GLP-1 receptor (GLP-1R) in PTC is likely to have clinical significance. We performed this study to evaluate the expression of GLP-1R in PTC and the clinical meaning of GLP-1R expression in PTC. METHODS: Fifty-six cases of PTC, four cases of medullary thyroid cancer (MTC), seven cases of nodular hyperplasia and 56 normal thyroid tissue samples were selected for immunostaining for GLP-1R. Clinical parameters were obtained by retrospective review of medical records. RESULTS: Immunohistochemical staining for GLP-1R showed immunoreactivity in 18 of 56 cases of PTC (32.1%). All four cases of MTC exhibited cytoplasmic GLP-1R expression. Nodular hyperplasia exhibited immunoreactivity in two of seven cases (28.6%). All normal thyroid follicular cells showed negative immunoreactivity. In univariable and multivariable analyses, tumor multifocality was negatively correlated with GLP-1R expression. Extrathyroidal extension showed positive association with GLP-1R expression that was almost significant. Sex, age, tumor size, and lymph node metastasis were not significantly associated with GLP-1R expression. CONCLUSION: Some parts of PTC tissues express GLP-1R, and GLP-1R expression in PTC was negatively correlated with tumor multifocality. The long-term influence of pharmacologically increased GLP-1 on thyroid follicular cells and development and progression of tumors originating from thyroid follicular cells should be investigated.
Cell Proliferation ; Cytoplasm ; Glucagon-Like Peptide 1* ; Hyperplasia ; Lymph Nodes ; Medical Records ; Neoplasm Metastasis ; Retrospective Studies ; Thyroid Gland ; Thyroid Neoplasms* ; Glucagon-Like Peptide-1 Receptor

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