갑상선유두암의 병인에 근거한 치료제의 개발과 문제점

이민희 ( Min Hee Lee ),조영석 ( Young Suk Jo ),송민호 ( Minho Shong ) 대한갑상선학회 2010 International Journal of Thyroidology Vol.3 No.2

Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The prognosis of PTC is defined primarily by the principal clinical features such as patient’s age, tumor size, histological subtypes, regional nodal metastasis, extra-thyroidal invasion and distant metastasis. Although PTC prognosis is excellent, adverse clinical features increase the probability of recurrence and progression. To improve patients’ survival and reduce recurrence and progression, advances in molecular biological insights for principal clinical features will beneeded. It has been recognized for years that aberrant kinase activation can induce cellular transformation, carcinogenesis and disease progression. Based on this concept, many investigators have been focusing on the development of new small molecules to inhibit the aberrant kinase activation and conducted clinical trials. In this review article, we describe the background for development of new targeted therapy and define molecular biological insights into the carcinogenesis of PTC.

갑상선 유두암에서 BRAF^V600E 돌연변이와 초음파 소견과의 연관성

조영석 ( Young Suk Jo ),김윤정 ( Yun Jeung Kim ),김성수 ( Song-soo Kim ),김진만 ( Jin-man Kim ),노흥규 ( Heung-kyu Ro ),송민호 ( Minho Shong ) 대한갑상선학회 2008 International Journal of Thyroidology Vol.1 No.1

Background and Objectives: According to wide use of thyroid ultrasound (US), the incidence of thyroid cancer has been increased. Interestingly, a number of studies have reported specific sonographic findings might predict papillary thyroid carcinoma (PTC). However, there was no study which investigated the relation between oncogene and sonographic findings. In this study, we have investigated the effect of BRAF^V600E mutation on sonographic findings. Materials and Methods: We included 141 nodules from patients who underwent US-guided fine-needle aspiration biopsy (FNAB) and compared sonographic findings between PTC (n=55) and benign nodules (n=86). And then we have also compared sonographic findings according to presence or absence of BRAF^V600E mutation. Results: Expectedly, PTCs have frequently showed irregular shape, solid content, hypoechogenicity (29.1% vs 46.3%, p=0.04) and microcalcification (54.5% vs 26.7%, p=0.01) compared to benign nodules. In the case of PTC, 36 cases of 53 PTCs posed BRAFV600E mutation (BRAF^V600E (+) PTC) and 17 cases did not (BRAF^V600E (-) PTC). Lymph node enlargement, multifocality, solidity, poorly defined margin, irregular shape, hypoechogenicity and bilaterality were not significantly different between two groups. But, interestingly, microcalcification was more frequently detected in BRAF^V600E (-) PTC (76.5%, p=0.03). Conclusion: Compared with BRAF^V600E (-) PTC, BRAFV600E mutation did not relate to malignant sonographic findings. This might represent that malignant sonographic findings were not BRAF^V600E induced specific phenomenon.

산후 갑상선염의 경과에 관한 임상적 고찰

노흥규,송치운,송민호 충남대학교 의과대학 지역사회의학연구소 1994 충남의대잡지 Vol.21 No.2

Postpartum thyroiditis is a disease with transient changes of thyroid function as hyperthyroidism, hypothyroidism and normal recovery 2-4 months after delivery. It occurs in 7-9% of postpartum women, is needed careful differential diagnosis from Graves' disease or Hashimoto's thyroiditis because of quite different clinical course. In order to establish the points for differentiation, we evaluated 30 cases of postpartum thyroiditis patients with the following results. 1. 14 patients were diagnosed as hyperthyroidism 4.4±1.6 months after delivery with mild degree of thyrotoxic symptoms. The anti-thyroglobulin antibody and anti-microsomal antibody were positive but thyrotropin receptor antibody were negative. 2. 16 cases were diagnosed as hypothyroidism with enlarged goiter 6.1±0.9 months after delivery and the ATA and AMA were positive both but TBII was negative in all cases. 3. The thyroid function of 71.4% of hyperthyroid patients became hypothyroidism in 1-3 months and recovered to normal in 1-3.5 months thereafter. In 68.8% of hypothyroid patients became euthyroidism within 1-8 months and 21.4% 1(3 cases) of the patients remained as hypothroidism untill 12 months' observation. In conclusion, the thyroid function changes as hyperthyroidism, hypothyroidism and euthyroidism stepwise in most cases of pospartum thyroiditis and serum TBII is negative, which are the most important features in differentiating from other autoimmune thyroid disease.

갑상선 악성결절에 대한 미세침흡인검사와 침생검의 진단적 의의

노흥규,신재규,주원찬,한희정,송민호 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.2

To evaluate the usefulness. of fine needle aspiration (FNA) cytology and biopsy for the detection of malignant thyroid nodules in nodular nontoxic goiter. We retropsectively analyzed 70 patients who had the nodular nontoxic goiter which is highly suspicious by the cytological and biopsy findings. The results were as follows: 1) Out of 70 patients who were thyroidectomized for malignant nodules, 63 (88.6%) patients were women and 7 (11.4%) men. 2) Sensitivity and specificity of FNA cytology for the detection of malignant thyroid nodule were 72% and 15.4% respectively. 3) Sensitivity and specificity of biopsy for the detection of malignant thyroid nodule were 97.4% and 33.3%, respectively. 4) Sensitivity and specificity of combination of FNA cytology and biopsy for detection of malignant thyroid nodule were 95% and 100%m respectively. 5) Malignant thyroid nodules were almost (93.4%) cold nodules in ^99m-Tc thyroid scan single nodule (72.7%) was more common than multiple nodules, location of lesion was 1.99 times more common in right lobe than in left lobe in malignant thyroid nodule. 6) Regional lymph node and distant metastasis were identified in 43%, 3.7% of malignant thyroid nodules, respectively. We concluded that preoperative biopsy may increased detection rate of malignant thyroid nodule with benign findings in FAN cytology.

폐경후 여성에서 에스트로겐, 이프리플라본, 칼시토닌 투여에 따른 골대사 표지자의 변화

노흥규,주원찬,한희정,채수흥,송민호 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.2

The measurements of metabolic bone markers are important for assesment of risks of osteoporotic fractures and efficacy of anti-osteoporotic treatment in postmenopausal women. We measured bone mineral densites, serum total alkaline phosphatases, and osteocalcin levels in estrogen replacement group(n=13), lpriflavone group(n=8), Calcitonin gruop(n=8) and untreated group(n=50). We used the dual energy X-ray absorptiometry for measurement of bone mineral densities in vertebra, used the p-nitrophenylphosphate and radioimmunoassay for serum alkaline phosphatase and serum osteocalcin, repectively. We compared the metablic hone markers, serum alkaline phosphatase, and osteocalcin between differrent treatment groups and analyzed the correlation between bone mineral densities with above metahlic bone markers. The treatment groups; estrogen, ipriflavone, and calcitonin groups showed significant low osteocalcin (p<0.05) levels but total alkaline phosphatase levels showed no significant difference compare to untreated group (p>0.05). There were no statistical significance of serum osteocalcin and alkaline phosphatase levels beween Ipriflavonc and untreated control group. Calcitonin group showed significant high alkaline phoshatase levels compare to untreated group(p<0.05) but osteocalcin levels showed no significant difference to untreated group. In conclusion, The biochemical bone markers such total alkaline phosphatase and serum osteocalcin are useful markers for the assesment of anti-osteoporotic treatment efficacy in postmenopausal women and reflect the high bone turnover in untreated postmenopausal women

만성 신부전증에서 혈청 1,25-디하이드록시 비타민 D농도와 부갑상선 호르몬, 혈청 칼슘과 25-하이드록시 비타민 D치의 상관관계

노흥규,신재규,주원찬,송민호 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.1

Objectives : Low production of 1,25-dihydroxyvitamin D_3 due to decreased 1-hydroxylation in patients with chronic renal failure causes reduction of gastrointestinal calcium absorption, secondary hyperparathyroidism and development of renal osteodystrophy. The measurement of serum 1,25-dihydroxyvitamin D_3 concentration is important as a marker of renal osteodystrophy. We measured the serum 1,25-dihydroxyvitamin D_3 and evaluated the inerrelationship between 25-hydroxyvitamin D_3, PTH and calcium level in the patients with chronic renal failure. Methods : 23 patients with chronic renal failure were measured the serum level of 25-hydroxyvitamin D_3, and 1,25-dihydroxyvitamin D_3 with radioreceptorassay. We also measured the parathyroid hormone and calcium level simultaneously in same patients and analyzed the relationship of those hormones in the patients with chronic renal failure. Results : The mean level of 25-hydroxyvitamin D_3 and 1,25-dihydroxyvitamin D_3 in the patients with chronic renal failure were lower (11.8±8.3ng/ml, 6.3±8.3pg/ml,repectively)than those of normal control (20.7±9.1ng/ml, 38.8±18.7pg.ml, p<.0001,repectively). The mean level of parathyroid hormone in the patients with chronic renal failure (135.3±160.8pg/ml) was higher than that of normal control (33.9±35.9pg/ml, p<0.01). The mean PTH concentraion in the CRF patient who showed the normocalcemia was lower than hypocalcemic (Ca <8.5mg/dl) CRF patients (44.8±49.1 vs 160.5±172.7 pg/ml, p<0.05 repectively). Old aged (above 60yrs) CRF patients showed significantly less 1,25-dihydroxyvitamin D_3 level than younger patients (4.05±3.53 vs 8.83±11.5, repectively p>0.05). we could not find any statistically significant correlations between 1,25-dihydroxyvitamin D_3, 25-hydroxyvitamin D_3, parathyroid hormone levels in both groups of chronic renal failure and normal control Conclusion : We could confirm the low 1.25-dihydroxyvitamin D_3 level in patients with chronic renal failure, this decreased 1-alpha hydroxylation were causing secondary hyperparathyroidism and aggravation of renal osteodystrophy. In near future, the therapeutic correction of low 1,25-dihydroxyvitamin D_3 level might be helpful for the prevention of metabolic bone abnormalities associated with chronic renal failure.

비외상성 척추 압박골절환자에서 척추 골밀도의 변화

주원찬,신재규,한희정,송민호,노흥규 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.2

The measurement of bone mineral density(BMD) is important for diagnosis of osteoporosis and prediction of fracture risk in postmenopausal women. We measured bone mineral density in patients with osteoporotic spinal compression fracture group and control group. Here we described clinical changes of bone mineral densities and fracture threshold in postmenopausal women who had the nontraumatic spinal compression fracture. The measurement of BMD were performed by dual energy X-ray absortiometry in 36 postmenopausal patients who had the spinal compression fracture which were evident in simple spine X-ray. The control group (fourteen postmenopausal women) had no back pain and no evident in simple spine X-ray. The mean bone mineral densities from L2-L4 in the pateinets with spinal fracture (0.630±0.114g/㎠) were significantly lower than the control group (0.969±0.156 g/㎠) (p<0.0001). The bone mineral densities were positively correlated with age (n=36, r=36, p<0.05). The number of spine fracture were increased with in patents who showed low bone mineral densities, high T score, low body mass index and early menopause. The most frequent site of compression fracture were noted at L1, T12, L2 and L4, L3, The fracture threshold definded by Riggs was 0.793 g/㎠ in theses patients. In conclusion, the patients with nontraumatic spinal compression fracture showed signifcantly low bone mineral densitie and T score and the fracture threshold was 0.793 g/㎠.

급·만성 간질환 환자에서 혈청 25-하이드록시 비타민 D_3 농도의 변화에 대한 연구

신재규,한희정,주원찬,송민호,이헌영,노흥규 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

The liver plays a central role in the vitamin D metabolism; it determines the overall efficiency of vitamin D₃utilization through the 25-hydroxylation of vitamin D. The abnormalities of vitamin D metabolism in acute and chronic liver diseases result from multiple causes such as defects in synthesis of vitamin D binding protein and decreased metabolic activities in 25-hydroxylation of vitamin D. Presumably the severity of liver disease may be related to the low level of vitamin D₃,especially 25-hydroxylated vitamin D₃. We measured the serum 25-hydroxyvitamin D₃in the patients with acute and chronic liver diseases and analyzed their levels according to the severity of liver disease. The patients with acute hepatitis(n=9, M/F;7/2, age 32.3±16.2) and with liver cirrhosis (n=30, M/F;22/8, 55.8±10.5) were subjected to measure serum concentrations of 25-hydroxylated or 1,25-dihydroxylated forms of vitamin D3. Simultaneously we measured serum albumin, serum calcium, parathyroid hormone (PTH) to assess calcium metabolism and the severity of liver disease in those patients. 1) The level of serum 25-hydroxyvitamin D, concentrations in the patients with liver disease (acute hepatitis 12.4±6.4 ng/ml and liver cirrhosis 8.5±4.7 ng/ml, p<0.05) showed significant lower levels compared to normal controls (21.6±9.3 ng/ml) but there was no significant differences in the groups between acute hepatitis and liver cirrhosis. 2) The serum calcium concentrations were not significantly changed in the patients with acute hepatitis (9.06±0.33 mg/dl, p>0.05) but in the patients with liver cirrhosis showed significant decrease in serum calcium levels (8.22±0.57 mg/dl, p<0.05) than those of normal controls (8.76±0.5 mg/dl). 3) The level of serum 1,25-dihydroxyvitamin D₃ concentrations in the patients with liver, cirrhosis showed significant decrease (12.1±10.3 pg/ml, p<0.05) than those of normal controls (35.1±16.2 pg/ml). 4) We could observe the significant positive correlations between serum 25hydroxyvitamin D₃concentrations and serum albumin concentrations in both groups of acute hepatitis (r=0.757, p<0.05, n=9) and liver cirrhosis (r=0.431, p<0.05, n=30). We could observe low serum 25-hydroxyvitamin D, concentrations in patients with acute and chronic liver diseases. This finding suggest that the 25-hydroxylation of vitamin D showed a defect in the early course of liver disease and this is progressively deranged during the course of chronic liver disease. This finding support the causal relationship between liver disease and its metatolic derangement.

인슐린 비의존형 당뇨병 환자에서 아카보스의 혈당조절 효과

박소영,구본정,신재규,윤상임,노흥규,김영건,송민호 충남대학교 의과대학 지역사회의학연구소 1997 충남의대잡지 Vol.24 No.1

Acarbose is an oral alpha-glucosidase inhibitor for use in the management of noninsulin dependent diabetes mellitus. We tried to detemined to efficacy of Acrabose monotherapy on glycemic control in patients with nonisulin dependent diabetes mellitus who were not adequately controlled with diet and exercise. Thirty four patients with noninsulin dependent diabetes mellitus who showed unacceptable range of glycemic control were treated with oral Acarbose. Acarbose reduced the level of mean fasting blood glucose, postprandial blood glucose after 4 and 8 weeks of the trial. The lipids, triglyceride and cholesterol level were significantly reduced by along with Acarbose treatment. Acarbose, through its unique mechanism of action, appears to bo a safe and effective adjuvant agent to diet and exercise therapy for treatment of noninsulin dependent diabetes mellitus.

제2형 당뇨병에서 Rosiglitazone과 Sulfonylurea 병합요법의 혈당 개선 효과의 후향적 연구

김군순,나소영,이효진,홍우정,조영석,구본정,송민호,노흥규,김영건 대한당뇨병학회 2002 임상당뇨병 Vol.3 No.4

연구배경: 혈당조절이 잘 되지 않는 제2형 당뇨병 환자에게 설폰요소제와 rosiglitazone의 병합요법을 하였을 때의 혈당 개선 효과와 이에 영향을 미치는 인자에 대해서 평가하고자 하였다. 방법: 식사요법, 운동요법, 약물요법에도 혈당조절이 악화된 총 52명의 제2형 당뇨병 환자들을 대상으로 후향적으로 연구하였고, 설폰요소제와 최소 6개월이상 Rosiglitazone (4 mg/day)을 병용투여하였다. 치료 전 및 치료 6개월 후에 당화 혈색소, 공복시 혈당, 식후 2시간 혈당의 변화를 측정하여 치료 효과를 판정하였다. 치료 효과에 영향을 미치는 인자들은 체질량지수, 당뇨병의 유병기간, c-peptide, 나이 등으로 정의하였다. 결과: Rosiglitazone과 설폰요소제의 병합 요법으로 평균 당화 혈색소는 치료전보다 1.5% (p<0.05)의 감소가 있었다. 또한 반응군과 비 반응군에서 각각 체질량지수, 당뇨병의 유병기간, c-peptide, 나이 등의 인자에 따른 당화 혈색소의 감소치를 비교하였을 때 통계학적으로 유의한 차이는 없었다. 결론: 혈당 조절이 잘 되지 않는 제2형 당뇨병환자에게 설폰요소제와 Rosiglitazone 4 mg/day의 병합 요법을 시행했을 때 유의한 혈당 강하 효과가 있었다. Background: This study was designed to evaluate the blood glucose lowering effects of rosiglitazone combination therapy with sulfonylurea in poor glycaemic controlled, type 2 diabetes. The factors affecting the response to rosiglitazone combination therapy with sulfonylurea were also evaluated on the basis of the degree of glycaemic control. Method: The 52 patients with type 2 diabetes who participated in this retrospective study had poor glycaemic control in spite of proper diet (30 kcal/kg), exercise (1hour walking/day) or antidiabetic medications; FBS ≥140 mg/dL, PP2 ≥ 200 mg/dL or HbA1C ≥8%. They received rosiglitazone 4 mg once daily with sulfonylurea for 6 months or more. We evaluated the change of hemoglobin A1c (HbA1C), fasting blood glucose, and post prandial blood sugar level, relative to baseline levels. The factors affecting response of rosiglitazone combination therapy with sulfonylurea were defined as body mass index (BMI), duration of diabetes, c-peptide and age. The patients with a decrement of HbA1C level more than 1% were defined as responders. Results: Rosiglitazone combination therapy with sulfonylurea significantly improved glycaemic control. The mean HbA1C reduction from the baseline was 1.5%. The factors (BMI, duration of diabetes, c-peptide and age) between non-responder and responder in HbA1c reduction were not statistically different. Conclusion: Rosiglitazone (4 mg/day) combination therapy with sulfonylurea resulted in a significant improvement in glycaemic control with type 2 diabetic patients who had poor glycaemic control.