Genetic and Clinical Characteristics of Korean Patients with Isolated Hypoparathyroidism: From the Korean Hypopara Registry Study

Isolated hypoparathyroidism (IH) shows heterogeneous phenotypes and can be caused by defects in a variety of genes. The goal of our study was to determine the clinical features and to analyze gene mutations in a large cohort of Korean patients with sporadic or familial IH. We recruited 23 patients. They showed a broad range of onset age and various values of biochemical data. Whole exome sequencing was performed on two affected cases and one unaffected individual in a family. All coding exons and exon-intron borders of GCMB, CASR, and prepro-PTH were sequenced using PCR-amplified DNA. In one family who underwent the whole exome sequencing analysis, approximately 300 single nucleotide changes emerged as candidates for genetic alteration. Among them, we identified a functional mutation in exon 2 of GCMB (C106R) in two affected cases. Besides, heterozygous gain-of-function mutations in the CASR gene were found in other subjects; D410E and P221L. We also found one single nucleotide polymorphism (SNP) in the prepro-PTH gene, five SNPs in the CASR gene, and four SNPs in the GCMB gene. The current study represents a variety of biochemical phenotypes in IH patients with the molecular genetic diagnosis of IH.

Delayed Surgery for Parathyroid Adenoma Misdiagnosed as a Thyroid Nodule and Treated with Radiofrequency Ablation

Primary hyperparathyroidism occurs as a result of isolated parathyroid adenoma in 80% to 85% of all cases. A 99mtechnetium (99mTc) sestamibi scan or neck ultrasonography is used to localize the neoplasm prior to surgical intervention. A 53-year-old female was referred for the exclusion of metabolic bone disease. She presented with low back pain that had persisted for the past 6 months and elevated serum alkaline phosphatase (1,253 IU/L). Four years previously, she had been diagnosed at a local hospital with a 2.3-cm thyroid nodule, which was determined to be pathologically benign. Radiofrequency ablation was performed at the same hospital because the nodule was still growing during the follow-up period 2 years before the visit to our hospital, and the procedure was unsuccessful in reducing the size of the nodule. The results of the laboratory tests in our hospital were as follows: serum calcium, 14.6 mg/dL; phosphorus, 3.5 mg/dL; and intact parathyroid hormone (iPTH), 1,911 pg/mL. Neck ultrasonography and 99mTc sestamibi scan detected a 5-cm parathyroid neoplasm in the left lower lobe of the patient's thyroid; left parathyroidectomy was performed. This case indicated that thyroid ultrasonographers and pathologists need to be experienced enough to differentiate a parathyroid neoplasm from a thyroid nodule; 99mTc sestamibi scan, serum calcium, and iPTH levels can help to establish the diagnosis of parathyroid neoplasm.

Improvement of Glycemic Control after Re-Emphasis of Lifestyle Modification in Type 2 Diabetic Patients Reluctant to Additional Medication

PURPOSE: The aim of this study is to observe glycemic changes after emphasizing the importance of lifestyle modification in patients with mild or moderately uncontrolled type 2 diabetes. MATERIALS AND METHODS: We examined 51 type 2 diabetic patients with 7.0-9.0% hemoglobin A1c (HbA1c) who preferred to change their lifestyle rather than followed the recommendation of medication change. At the enrollment, the study subjects completed questionnaires about diet and exercise. After 3 months, HbA1c levels were determined and questionnaires on the change of lifestyle were accomplished. We divided the study subjects into 3 groups: improved (more than 0.3% decrease of HbA1c), aggravated (more than 0.3% increase of HbA1c) and not changed (-0.3%

Concurrent Presence of Sjogren's Syndrome, Warthin Tumor, and MALT Lymphoma in a Parotid Gland and Hashimoto's Thyroiditis / 대한갑상선학회지

A 54-year-old female patient was referred due to a mass in the left salivary gland. A neck CT was performed and surgery was agreed due to a suspected Warthin tumor. The patient was also diagnosed with Sjogren's syndrome and Hashimoto's thyroiditis and treated. Warthin tumor and extranodal marginal zone B-cell lymphoma were also diagnosed after parotidectomy. The coexistence of the two autoimmune diseases, Hashimoto's thyroiditis and Sjogren's syndrome, has been reported, as has the coexistence of Warthin tumor and malignant tumor within a single salivary gland. However, these four diseases have not previously been reported in an individual patient. The authors treated a patient who was first diagnosed with Sjogren's syndrome and Hashimoto's thyroiditis, and subsequently also with Warthin tumor and extranodal marginal zone B-cell lymphoma after superficial parotidectomy. Therefore, this case is reported together with a related literature review.

Spurious Elevation of Glucose Concentration during Administration of High Dose of Ascorbic Acid in a Patient with Type 2 Diabetes on Hemodialysis

We describe herein a case of life-threatening hypoglycemia due to spurious elevation of glucose concentration during the administration of ascorbic acid in a type 2 diabetic patient. A 31-year-old female was admitted for proliferative diabetic retinopathy treatment and prescribed high dose ascorbic acid. During hospitalization, she suddenly lost her consciousness and her glucose concentration was 291 mg/dL, measured using self-monitoring blood glucose (SMBG) device, while venous blood glucose concentration was 12 mg/dL. After intravenous injection of 50% glucose solution, the patient became alert. We reasoned that glucose measurement by SMBG device was interfered by ascorbic acid. Physicians should be aware of this interference; high dose ascorbic acid may cause spurious elevation of glucose concentration when measuring with SMBG devices.

Clinical Significance of the Presence of Autonomic and Vestibular Dysfunction in Diabetic Patients with Peripheral Neuropathy

BACKGROUND: We investigated the prevalence of diabetic autonomic neuropathy (DAN) and vestibular dysfunction (VD) in diabetic patients with peripheral neuropathy. METHODS: Thirty-five diabetic patients with peripheral neuropathy were enrolled from August 2008 to July 2009. All subjects underwent autonomic function tests. Nineteen of the patients (54.3%) underwent videonystagmography. RESULTS: Diabetic autonomic neuropathy was observed in 28 patients (80%). A mild degree of autonomic failure was observed in 18 patients (64.3%), and a moderate degree of autonomic failure was observed in ten patients (35.7%). Factors related to DAN included diabetic nephropathy (P=0.032), degree of chronic kidney disease (P=0.003), and duration of diabetes (P=0.044). Vestibular dysfunction was observed in 11 of 19 patients (57.9%). There was no significant association between DAN and VD. CONCLUSION: Diabetic autonomic neuropathy was observed in 28 diabetic patients (80%) with peripheral neuropathy. Vestibular dysfunction was observed in nearly 60% of diabetic patients with peripheral neuropathy who complained of dizziness but showed no significant association with DAN. Diabetic patients who complained of dizziness need to examine both autonomic function and vestibular function.

Differential Diagnostic Value of Total T3/Free T4 Ratio in Graves' Disease and Painless Thyroiditis Presenting Thyrotoxicosis

BACKGROUND: It is important to differentiate Graves' disease from that of painless thyroiditis in patients with thyrotoxicosis. In this study, we evaluated the usefulness of total T3 to free T4 ratio in making a differential diagnosis between Graves' disease and painless thyroiditis. METHODS: We reviewed medical records of thyrotoxic patients, who had been diagnosed with Graves' disease or painless thyroiditis, from October 2009 to July 2011. We assessed clinical characteristics, serum levels of total T3, free T4, thyroid stimulating hormone, thyrotropin-binding inhibitory immunoglobulin, and findings of 99mTechnetium thyroid scan. We analyzed the total T3/free T4 ratios between Graves' disease and painless thyroiditis patients. RESULTS: A total of 76 untreated thyrotoxic patients "49 Graves' disease and 27 painless thyroiditis" were examined. The total T3, free T4 levels and the total T3/free T4 ratios were significantly higher in patients with Graves' disease than in those with painless thyroiditis (P 73, the possibility of Graves' disease was significantly higher than in painless thyroiditis (sensitivity, 75.5%; specificity, 70.3%). The sensitivity and specificity of the total T3/free T4 ratio in patients with free T4 < 3.6 ng/dL have been increased (sensitivity, 100%; specificity, 71.4%). CONCLUSION: The total T3/free T4 ratios was useful for making a differential diagnosis between Graves' disease and painless thyroiditis.

A Case of Mixed Papillary Thyroid Tumor and Squamous-Cell Carcinoma / 영남의대학술지

The occurrence of a mixed tumor containing papillary thyroid carcinoma (PTC) and primary squamous-cell carcinoma (SCC) is rare because there is no squamous epithelium in the thyroid gland. Reported herein is a 30-year-old female with mixed PTC and primary SCC of the thyroid presented as thyroid incidentaloma. Fine-needle aspiration biopsy of the thyroid nodule revealed the presence of malignant thyroid cells. The histopathological examination following total thyroidectomy yielded two mixed, morphologically distinct histotypes that included PTC and SCC. After total thyroidectomy, the patient underwent radioactive iodine therapy. No recurrence or metastasis occurred during the 20-month follow-up period after the operation.

Tumor Size Is Still a Useful Prognostic Factor for the Therapeutic Plan of Papillary Thyroid Carcinoma / 대한갑상선학회지

BACKGROUND AND OBJECTIVES: Papillary thyroid microcarcinoma (PTMC) was regarded as early-stage carcinoma, but its aggressiveness has been frequently reported. We performed this study to compare the clinicopathologic characteristics of PTMC with those of papillary thyroid carcinoma (PTC) >1 cm. We evaluated the association of clinicopathologic parameters of PTMC with tumor size divided by each millimeter. MATERIALS AND METHODS: We retrospectively analyzed the medical records of 1,139 patients with PTMC and 1,296 patients with PTC >1 cm who underwent thyroidectomy from 1995 to 2004 at Samsung Medical Center. The aggressive variants of PTC were excluded in the subjects. RESULTS: Multifocality, extrathyroidal invasion (ETI), lymph node invasion (LNI), and distant metastasis (DM) were significantly less frequent in PTMC than PTC >1 cm (p1 cm (recurrence 2.9% vs. 8.1%, p<0.001; mortality 0.5% vs. 1.5%, p<0.05). Tumor size was correlated with the rates of multifocality, ETI, LNI, and DM in all PTC (p<0.01). All patients with DM had the tumor size 0.6 cm in diameter or more. Among PTMC, the rates of LNI, multifocality, and N1b significantly increased when tumor size exceeded 0.3 cm, 0.4 cm, and 0.6 cm, respectively (p<0.05). CONCLUSION: Recurrence and mortality rates of PTMC were extremely low, although local invasion was detected on the level of subcentimeter. Tumor size was well correlated with the aggressiveness of PTC. We suggest that tumor size is still a useful prognostic factor for the therapeutic plan of PTC.

Clinical Characteristics of Patients with Hyperglycemic Emergency State Accompanying Rhabdomyolysis

BACKGROUND: The purpose of this study was to investigate the prevalence of rhabdomyolysis and its association with both clinical course and prognosis and to evaluate the factors associated with rhabdomyolysis in patients with hyperglycemic emergencies. METHODS: We reviewed the medical records of patients with hyperglycemic emergencies who visited our hospital from May 2003 to April 2010. We assessed the clinical characteristics, biochemical profiles and clinical course of patients and analyzed these data according to the presence of rhabdomyolysis. RESULTS: The prevalence of rhabdomyolysis was 29 patients (28.4%) among 102 patients. Mean serum osmolarity, glucose and serum creatinine levels were higher in patients with rhabdomyolysis than those without rhabdomyolysis. Patients with rhabdomyolysis had higher rates of hemodialysis and mortality than those without the condition. The factors associated with rhabdomyolysis in the hyperglycemic emergency state were increased serum osmolarity and APACHE II score on admission (P < 0.05). CONCLUSION: Rhabdomyolysis commonly occurred in patients with hyperglycemic emergencies and this could aggravate their clinical course and increase mortality.

A Case of 36-Year-Old Man with Normokalemic Thyrotoxic Periodic Paralysis / 대한갑상선학회지

Thyrotoxic periodic paralysis is not a rare complication of hyperthyroidism in Asian people, but the cases of paralysis with normal serum potassium levels are very rare. A 36-year-old Korean man who had been diagnosed with Graves' disease had experienced recurrent paralysis for 9 months in spite of normokalemia. We measured the patient's serum potassium levels nine times at the time of paralysis. All measurements fell in the range 3.3~4.7 mmol/L. We treated the patient with methimazole, Lugol's solution, beta-blockers, and radioactive iodine. Thyroid function was normalized after anti-thyroid treatment and then no further paralytic attacks have occurred.

Comparison of Bone Mineral Density in Postmenopausal Women Aged Over 50: Mountain and Seaside Villagers in Gyeongnam / 대한골다공증학회지

OBJECTIVES: The purpose of this study was to compare the differences in bone mineral density (BMD), T-scores, and the prevalence of osteopenia and osteoporosis between mountain villagers and seaside villagers. MATERIALS & METHODS: Four hundred fifty-one postmenopausal women (138 women in mountain villagers and 313 women in seaside villagers) were examined, including women > 50 years of age. The study subjects were recruited from the women who had received care at the health examination center of our hospital between January 2005 and September 2009. The BMD was measured at lumbar 1-4 by dual-energy X-ray absorptiometry.

Streptozotocin-induced Diabetes Increases the Adiponectin-mediated AMP-activated Protein Kinase Cascade in the Hippocampus of Mice / 대한해부학회지

Adiponectin is an adipocyte-derived protein with anti-diabetic and anti-angiogenesis properties that improves both glucose metabolism and insulin resistance via the adenosine monophosphate-activated protein kinase (AMPK) cascade. Diabetic cognitive deficits are correlated with dysregulation of energy metabolism in the hippocampus. In the present study, we investigated the expression of adiponectin-mediated AMPK cascade proteins in the hippocampus of streptozotocin (STZ)-induced diabetic mice. Diabetes was induced by STZ (55 mg/kg) injection intraperitoneally. Twenty-four weeks after induction of diabetes, mice were sacrificed. Results showed that decreased serum adiponectin levels and increased expression of hippocampal adiponectin receptor 1 (AdipoR1) was expressed in diabetic mice. Phosphorylated AMPK, acetyl CoA carboxylase (ACC), and eNOS expression levels were increased in the hippocampus of diabetic mice. The immunoreactivity of glucose transporter 1 in the endothelium of hippocampal blood vessels was also increased. These results indicate that adiponectin-mediated AMPK cascade activation may play a role in catabolic process that is involved in diabetic neurodegeneration.

The Classification of Diabetic Patients Presenting Diabetic Ketoacidosis: The Characteristics of Fulminant Type 1 Diabetes / 당뇨병

No abstract available.

A Case of Cushing's Syndrome Presenting as Endometrial Hyperplasia

We describe here the case of a 39-year-old woman with a cortisol-producing adrenal adenoma and she presented with endometrial hyperplasia and hypertension without the specific characteristics of Cushing's syndrome. The patient had consulted a gynecologist for menometrorrhagia 2 years prior to her referral and she was diagnosed with endometrial hyperplasia and hypertension. Her blood pressure and the endometrial lesion were refractory despite taking multiple antihypertensives and repetitive dilation and curettage and progestin treatment. On admission, the clinical examination revealed mild central obesity (a body mass index of 22.9 kg/m2, a waist circumference of 85 cm and a hip circumference of 94cm), but there was no hirsutism and myopathy. She showed impaired glucose tolerance on an oral glucose tolerance test. The biochemical hypercortisolemia together with the prolactin and androgen levels were evaluated to explore the cause of her anovulation. Adrenal Cushing's syndrome was confirmed on the basis of the elevated urinary free cortisol (454 microgram/24h, normal range: 20-70) with a suppressed ACTH level (2.0 pg/mL, normal range: 6.0-76.0) and the loss of circadian cortisol secretion. A CT scan revealed a 3.1 cm, hyperechoic, well-marginated mass in the left adrenal gland. Ten months post-adrenalectomy, the patient had unintentionally lost 9 kg of body weight, had regained a regular menstrual cycle and had normal thickness of her endometrium.

Overexpression of USF Increases TGF-beta1 Protein Levels, But G1 Phase Arrest was not Induced in FRTL-5 Cells

Transforming growth factor-beta1 (TGF-beta1) is a potent inhibitor of cellular growth and proliferation by G1 phase arrest or apoptosis. We investigated the association of TGF-beta1 with the anti-proliferative effect of upstream stimulatory factor (USF) in Fischer rat thyroid cell line (FRTL-5) cells. [Methyl-(3)H] thymidine uptake was measured after treatment of FRTL-5 cells with TGF-beta1 to identify its anti-proliferative effect. USF-1 and USF-2 proteins were in vitro translated, and an electrophoretic mobility shift assay was performed to identify the interaction between USF and the TGF-beta1 promoter. FRTL-5 cells were transfected with USF cDNA, and then the expression of TGF-beta1 was examined with Northern and Western blotting. The cell cycle-regulating proteins associated with TGF-beta1 were also measured. TGF-beta1 significantly inhibited [methyl-(3)H] thymidine uptake in FRTL-5 cells. Two specific binding sites for USF were found in the TGF-beta1 promoter: -1,846~-1,841 (CACATG) and -621~-616 (CATGTG). Overexpression of USF increased both the mRNA levels and protein levels of TGF-beta1. However, the expression of cyclin D1, CDK4, cyclin E, and CDK2, and the phosphorylation of retinoblastoma protein remained unchanged. Overexpression of USF in FRTL-5 cells increased the expression of TGF-beta10 through specific binding to TGF-beta1 promoter. However, the USF-induced expression of TGF-beta1 did not cause G1 arrest.

Analysis of Clinical Features of Korean Patients with Adrenocortical Carcinoma / 대한내분비학회지

BACKGROUND: Adrenocortical carcinoma (ACC) is an extremely rare tumor. Its early detection is difficult and its prognosis is poor. METHOD: We retrospectively analyzed the medical records of 13 patients with ACC between 1995 and 2005 at Samsung Medical Center. Their clinical features and prognosis were evaluated. RESULTS: The average age of the patients with ACC was 40 years (2~75 years). Eight patients were men and five were women. On the first visit, eight of 13 patients (62%) complained abdominal pain, and abdominal mass was palpable in five of 13 patients (38%). Urinary concentration of 17-ketosteroid collected for 24 hours was increased in two of eight patients (25%). Three out of 13 patients were identified as having functioning adrenal tumors (1 Cushing's syndrome and 2 androgen-producing tumors), and the other 10 patients had hormonally inactive adrenal tumors. Ten patients had tumors in left adrenal gland, and three had in right adrenal gland. At the time of diagnosis, four patients were classified as having stage II, seven as stage III, and two as stage IV. Twelve patients underwent adrenalectomy. One of them received additional chemotherapy, and two patients were treated with external radiation therapy after surgery. The other one patient was treated only with chemotherapy due to the presence of liver metastasis. It was possible to continue the regular follow-up in eight of 13 patients. The median duration of follow-up was 39 months (7~114 months). Six of them are still alive (three have no evidence of disease, one had persistence of disease, and two had recurrence of disease during follow-up period). Two patients died of multiple metastases and lung metastasis, respectively. CONCLUSION: Radical surgery is the only curative approach and is recommended for all patients with resectable tumors, even though in those patients with recurrent disease. There is no consensus concerning adjuvant therapy.

A Case of Hyperglycemic Hyperosmolar State Associated with Graves' Hyperthyroidism: A Case Report

Hyperglycemic hyperosmolar state (HHS) is an acute complication mostly occurring in elderly type 2 diabetes mellitus (DM). Thyrotoxicosis causes dramatic increase of glycogen degradation and/or gluconeogenesis and enhances breakdown of triglyc-erides. Thus, in general, it augments glucose intolerance in diabetic patients. A 23-yr-old female patient with Graves' disease and type 2 DM, complying with methimazole and insulin injection, had symptoms of nausea, polyuria and generalized weakness. Her serum glucose and osmolarity were 32.7 mM/L, and 321 mosm/kg, respectively. Thyroid function tests revealed that she had more aggravated hyperthyroid status; 0.01 mU/L TSH and 2.78 pM/L free T3 (reference range, 0.17-4.05, 0.31-0.62, respectively) than when she was discharged two weeks before (0.12 mU/L TSH and 1.41 pM/L free T3). Being diagnosed as HHS and refractory Graves' hyperthyroidism, she was treated successfully with intravenous fluids, insulin and high doses of methimazole (90 mg daily). Here, we described the case of a woman with Graves' disease and type 2 DM developing to HHS.

Clinical Characteristics of Poorly Differentiated Carcinoma of the Thyroid and Comparison of Its Survival to the Tall Cell and Columnar Cell Variants of Papillary Carcinoma / 대한내분비학회지

BACKGROUND: Poorly differentiated carcinoma (PDC) of the thyroid includes tall and columnar cell variants (TCV) of the papillary carcinoma as well as the thyroid carcinoma with trabecular, insular and solid (TIS) growth patterns. There have been a few clinical studies on the PDC of the thyroid. We evaluated the clinical characteristics and the outcome of the PDC. METHODS: We investigated the clinicopathologic features of the thyroid carcinoma with TIS growth patterns (n = 46) and TCV of the papillary carcinoma (n = 14). We investigated the clinical features of ten patients diagnosed as PDC of the thyroid who had been undergone thyroidectomy for well differentiated carcinoma previously and compared these outcome with those of patients primarily diagnosed as PDC of the thyroid (n = 60). RESULTS: The clinical course of the thyroid carcinoma with TIS growth patterns was slightly more aggressive than that of TCV of the papillary carcinoma. However, disease-specific survivals of both cancers were not significantly different. Disease-specific survival was independently correlated with the presence of distant metastasis at diagnosis and high dose radioiodine therapy. The clinical features and outcome of the patients with PDC detected at recurred sites after operation for well-differentiated carcinoma were more aggressive than those diagnosed as PDC of the thyroid. CONCLUSION: The prognosis of the thyroid carcinoma with TIS growth patterns and TCV of the papillary carcinoma were similar. The PDC which was detected after thyroidectomy for well-differentiated carcinoma had worse prognosis than primarily diagnosed as PDC of the thyroid.

A 20-Year-Old Woman with Hashimoto's Thyroiditis and Evans' Syndrome

Here we report the case of a 20-year-old female patient previously diagnosed with Hashimoto's thyroiditis and overt hypothyroidism, and who had been taking synthetic thyroxine (100micro/day) for eight months. She experienced intermittent dizziness and generalized weakness, and was diagnosed as having severe autoimmune hemolytic anemia (AIHA). We prescribed prednisolone treatment and continued synthetic thyroxine administration. Two years and five months later, she developed idiopathic thrombocytopenic purpura (ITP) and was diagnosed with Evans' syndrome. Thereafter, laparoscopic splenectomy was performed because her autoimmune hemolytic anemia was refractory and dependent on steroid therapy. The HLA genotypes of the patient were HLA-A*020101/A*2602, HLA-B*270502/B*5401, HLA-Cw*0102/Cw*020202, HLA-DRB1*0404/DRB1*0405, and HLA-DQB1*0302/DQ B1*0401. Hashimoto's thyroiditis is often associated with other nonendocrine autoimmune diseases, and antithyroid antibodies are frequently observed in Evans' syndrome (coexistence of AIHA and ITP). However, there is no report of Evans' syndrome developing in patients with overt hypothyroidism and Hashimoto's thyroiditis. This case suggests that three autoimmune diseases (AIHA, ITP, and Hashimoto's thyroiditis) might share a common immunogenetic pathway in pathogenesis.