배재현

204

￭♣

￭

Frequency of germline mutations in apprarently sporadic pheochromocytoma or paraganglioma in Korea

1서울대학교 의과대학 내과학교실, ²충북대학교 의과대학 내과학교실, ³서울대학교 의과대학 진단검사의학교실,

4서울대학교 의과대학 외과학교실

*

배재현

, 김정희

, 최형진

, 김상완

, 최성희

, 신찬수

, 박경수

, 장학철

, 성문우

, 이규언

, 김성연

Background: Germline mutations in the RET, VHL, SDHD, and SDHB gene have been reported in 5-30% in the patients with apparently spora- dic pheochromocytoma (PHEO)/paraganlioma (PGL). However, the necessity for genetic screening of germline mutations in apparently sporadic PHEO/PGL is controversial. This study was conducted to assess the frequency of germline mutation in the patients with apparently sporadic PHEO/PGL in Korean population. Methods: We recruited 33 patients who were diagnosed with non-syndromic and non-familial PHEO/PGL in Seoul National University from 2009 to 2012. Germline DNA was extracted from peripheral leukocytes. Exon 8, 10, 11, and 13 through 16, and intronic flanking region of RET were examined by direct sequencing, and all exons and intronic flanking region of VHL, SDHD, and SDHB by direct sequencing and multiplex ligation-dependent probe amplification. Results: The mean age of onset was 43.1 ± 18.3 years in mutation carrier, and 45.5 ± 13.5 years in non-mutation carrier. The prevalence of germline mutation in apparently sporadic PHEO/PGL was 18.2% (6/33 patients). RET mutations were in 2 cases, all missense mutations (c.1891G > T; p.Asp631Tyr, c.2522C > T; p.Pro841Leu), VHL mutation in 1 case, a missense mutation (c.242C > T; p.Pro81Leu), SDHD mutation in 1 case, a deletion (c.94_95delTC; p.Ala33IlefsX35), and SDHB mutation in 2 cases, all deletions (c.392delC; p.Pro131HisfsX5, c.666_678del13; p.Arg223GlnfsX21). There was 1 novel mutation in VHL (c.242C > T;

p.Pro81Leu), SDHB (c.666_678del13; p.Arg223GlnfsX21), respectively. The patient with SDHD mutation presented with head and neck PGL, and one of the patients with SDHB mutations presented with metastasis to retrocaval lymph node. Conclusion: The frequency of germline mutation in the patients with apparently sporadic PHEO/PGL was 18.2%, similar to previous studies. Patients with PHEO/PGL may be screened for heredi- tary disease, with the considerations of clinical characteristics and cost-effectiveness. Further investigations in a large number of patients are need- ed to provide more strong evidence.

￭♣

￭

Macroalbuminuria Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes Mellitus

Division of Endocrinology & Metabolism, Department of Internal Medicine, The Catholic University of Korea

Hyun A Yu, Sung-Woo Ko, Sun-Hye Ko, Hye-Ji Kim, Seongyul Ryu, Sun-Hee Ko, Yu-Bae Ahn, Seung-Hyun Ko

During strict glycemic control, hypoglycemia is an inevitable clinical problem in both type 1 and type 2 diabetes, and all diabetic patients are exposed to the risk of hypoglycemia as long as they use glucose-lowering treatment. In this ten-year, prospective, longitudinal cohort study, we investigated the factors that might influence the development of severe hypoglycemia in patients with type 2 diabetes. From January 2000 to December 2002, patients with type 2 diabetes aged 25-75 years without chronic kidney disease (estimated glomerular filtration rate [eGFR] ≥ 60 ml/min/1.73 m²) were consecutively recruited (n=1,217) and followed up in January 2011 and May 2012. Severe hypoglycemia (SH) was defined as an event requiring the assistance of another person to actively administer glucose, hospitalization, or medical care in an emergency department. We used Cox proportional hazard regression analysis to test the association between SH episodes and potential explanatory variables.

After a median 10.4 years of follow-up, 111 (12.6%) patients experienced 140 episodes of SH, and the incidence was 1.55 per 100 patient-year.

Mean age and duration of diabetes were 55.7 ± 10.1 and 9.6 ± 6.7 years, respectively. The incidence of SH events was higher in older patients (p<0.001), those with a longer duration of diabetes (p<0.001), those who used insulin (p=0.004) and sulfonylurea (p<0.001), and those who had macroalbuminuria (p<0.001) at baseline. In particular, 24 (22.4%) patients with severe hypoglycemia experienced at least one event of antecedent hypoglycemia within the preceding three months, and 21 (18.9%) patients with severe hypoglycemia experienced severe hypoglycemia previously.

Cox hazard regression analysis revealed that SH was associated with longer diabetes duration and the presence of macroalbuminuria (normoalbuminuria vs. macroalbuminuria, HR 2.71, 95% CI 1.44-5.09; p=0.002). The development of SH was independently associated with diabetic duration and presence of macroalbuminuria, even with normal renal function in patients with type 2 diabetes.