Jae Won Hong

Metabolic Parameters and Nonalcoholic Fatty Liver Disease in Hypopituitary Men

Patients with hypopituitarism have the feature of metabolic syndrome, including central obesity, insulin resistance, and dyslipidemia. Because metabolic syndrome, including insulin resistance, is the main pathogenesis of the development of nonalcoholic fatty liver disease (NAFLD), we considered that patients diagnosed with hypopituitarism have an increased risk of developing NAFLD. We compared control subjects and hypopituitary men in metabolic parameters and the frequency of fatty liver on abdominal ultrasonography, and analyzed associating factors with the severity of the fatty liver in patients with hypopituitarism. 34 male patients with hypopituitarism and 40 age and sex-matched control subjects were included. The frequency of fatty liver on abdominal ultrasonography was significantly higher in hypopituitary men compared to control subjects (32.5% vs. 70.6%, p=0.001). Ln CRP and free fatty acids were significantly elevated in hypopituitary patients with fatty liver compared to patients without fatty liver. Ln GH was significantly lower in hypopituitary patients with fatty liver. The severity of fatty liver on abdominal ultrasonography correlated with negatively Ln GH, after adjusting for the BMI effect (p=0.020). There is a difference only between the severe fatty liver group and normal liver group in the analysis of the mean Ln GH level between 4 groups according to the severity of fatty liver (p=0.036). In conclusion, NAFLD is more common in hypopituitary patients than control subject. Severe growth hormone deficiency in hypopituitarism was associated with the severe degree of hepatic steatosis in NAFLD.

Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy

Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

Clinical management and outcome of 36 invasive prolactinomas treated with dopamine agonist

Treatment of invasive prolactinoma, which has several characteristics including invasive growth into cavernous sinuses and formation of giant adenomas compressing adjacent neural structures, resulting in neurological dysfunction, has been very challenging. There are relatively few reports available describing long-term treatment outcome. Herein, we document the results of bromocriptine administration as initial treatment during average 44xa0months follow-up (up to 12xa0years) period. We retrospectively categorized 36 patients into four groups according to the results of 3xa0months of bromocriptine treatment: groupxa01, tumor volume reduction (TVR) >25% with normalized serum prolactin (NP) (nxa0=xa024); groupxa02, TVR >25% without NP (nxa0=xa04); groupxa03, TVR <25% with NP (nxa0=xa05); and groupxa04, TVR <25% without NP (nxa0=xa03). During follow-up, 22 patients (91.7%) in groupxa01 achieved TVR >50% with NP. Three patients (75%) in groupxa02 achieved TVR >50% with NP after treatment for 8xa0months. In groupxa03, four patients (80.0%) continued medication because of improvement of symptoms and achieved additional TVR (18.8–46.4%). Surgery was performed on five patients (one in groupxa02, one in groupxa03, and all three in groupxa04), and complete resection was achieved in four (80.0%). Overall, 25 (69.4%) of the 36 patients treated with bromocriptine had complete response and 6 (16.7%) had partial response but did not require surgery. Thus, the overall response rate was 86%, with only five patients (14%) requiring surgical debulking. NP was not achieved by surgery alone in all cases, even after total resection of tumor. Patients who achieve TVR >25% with NP with 3xa0months of bromocriptine administration had a high possibility of showing good long-term response (TVR >50% with NP) to bromocriptine. A higher dose of dopamine agonist (DA) or other DA should be considered for patients who achieve TVR >25% without NP.

Clinical predictors of GH deficiency in surgically cured acromegalic patients

OBJECTIVEnEven in patients with cured acromegaly, GH deficiency (GHD) after transsphenoidal adenomectomy (TSA) adversely affects body composition and inflammatory biomarkers of cardiovascular risk. In this study, clinical parameters for predicting GHD after TSA in 123 cured acromegalic patients were investigated.nnnDESIGN AND METHODSnGH levels were measured at 6, 12, 18, 24, 48, and 72u200ah after TSA and serial insulin tolerance tests were conducted at 6 months, 2 years, and then every 2 years after TSA.nnnRESULTSnGHD was found in 12 patients (9.8%) at 4.1 (range: 0.5-4.1) years after TSA. IGF1 levels were significantly lower at 6 months after TSA in GHD group than intact GH group (175.9 vs 316.8u200aμg/l, range: 32.0-425.0 and 96.9-547.3 respectively, P=0.008). Adenomas involving both sides of the pituitary gland were significantly more frequent in GHD patients (29.7 vs 83.3%; P=0.002). Furthermore, immediate postoperative 72-h GH levels after TSA were significantly lower (0.17 vs 0.45, range: 0.02-0.93 and 0.02-5.95 respectively, P=0.019) in GHD patients. In multiple logistic regression analysis, bilaterality of tumor involvement (odds ratio (OR)=10.678, P=0.003; 95% CI=2.248-50.728) and immediate postoperative 72-h GH level (OR=0.079, P=0.047; 95% CI=0.006-0.967) showed significant power for predicting GHD.nnnCONCLUSIONSnThese data suggest that bilateral involvement of a pituitary adenoma and severely decreased immediate postoperative serum GH levels at 72u200ah after TSA may be independent risks factor for accelerated GHD in acromegalic patients.

Discrimination of prolactinoma from hyperprolactinemic non-functioning adenoma

The objective of this study was to evaluate characteristics that discriminate prolactinoma from non-functioning pituitary macroadenoma with hyperprolactinemia. We included 117 patients with hyperprolactinemic pituitary macroadenomas. Patients were divided into three groups according to treatment outcomes and pathologic results: (A) prolactinoma that responded to dopamine agonist (DA) treatment (PRDA); (B) prolactinoma requiring surgical treatment (PRS); and (C) non-functioning pituitary adenoma with hyperprolactinemia (NFPAH). Old age, low serum prolactin levels, and extrasellar extension were associated with NFPAH. Most patients with NFPAH had serum prolactin levels less than 100xa0ng/ml. Visual defects and GH deficiency were more common in patients with NFPAH compared with patients with PRS and PRDA, without difference of tumor size. Galactorrhea and amenorrhea were less frequent in patients with NFPAH than in patients with PRS and PRDA. Post-operative remission of hyperprolactinemia was achieved in 100% of patients with NFPAH and in 72.5% of patients with PRS. DA administration was required in 25.5% of patients with PRS; however, no patients with NFPAH required DA administration. In conclusion, old age, extrasellar tumor extension with relatively low prolactin levels, visual defect, and GH deficiency were considered suggestive of non-functioning pituitary adenoma rather than prolactinoma in hyperprolactinemic pituitary macroadenoma.

Characteristics of Acromegaly in Korea with a Literature Review

Acromegaly is a slowly progressive disease caused by excessive growth hormone (GH), which is related to a GH secreting pituitary tumor in most cases. Herein, we describe the epidemiology, clinical characteristics, and treatment of acromegaly in Korea with a literature review. The average annual incidence of acromegaly in Korea was 3.9 cases per million people, which was within the range of previous Western studies. The primary treatment for acromegaly was also transsphenoidal adenomectomy, which accounted for 90.4% of patients whose primary therapeutic options were known. The overall surgical remission rates were 89%, 87%, 64%, 70%, and 50% for modified Hardy classification I, II, IIIA, IIIB, and IV, respectively. An updated and larger study regarding the treatment outcome of medical/radiotherapy in Korean acromegalic patients is needed.

Association between low-grade albuminuria and cardiovascular risk in Korean adults: the 2011-2012 Korea National Health and Nutrition Examination Survey.

Background Recent studies have indicated that low UACR levels (<30 μg/mg) previously considered to be in the normal range (‘low-grade albuminuria’) are associated with cardiovascular morbidity and mortality in the general population. Methods We studied 9,736 participants with albuminuria in the normal range from the 2011–2012 Korea National Health and Nutrition Examination Survey (KNHANES). Results The weighted prevalences of metabolic syndrome (MS) and the 10-year risk for coronary heart disease measured using the Framingham risk score (FRS) ≥ 20% (high risk) were 22.5 ± 0.7% and 14.5 ± 0.7%, respectively, in males and 23.3 ± 0.8% and 8.5 ± 0.4%, respectively in females. Weighted comparisons among the tertiles of UACR revealed that the prevalences of MS and high-risk FRS increased with increasing UACR (MS: males, 15.9 ± 1.1, 20.2 ± 1.2, 32.4 ± 1.5%, respectively; P < 0.001; and females, 17.6 ± 1.0, 22.7 ± 1.0, 30.2 ± 1.4%, respectively; P < 0.001. High-risk FRS: males, 9.5 ± 0.7, 12.3 ± 0.9, 22.5 ± 1.2, respectively; P < 0.001; and females, 5.8 ± 0.6, 7.9 ± 0.7, 12.0 ± 0.9%, respectively; P < 0.001). The positive association persisted after adjusting for hypertension and diabetes. The weighted comparisons among the deciles of UACR revealed that the prevalences of MS and high-risk FRS began to increase at the ranges of 3.89–5.15 and 5.16–7.36 mg/g Cr, respectively. Conclusion Low-grade albuminuria was significantly associated with estimated cardiovascular risk and MS in a nationally representative sample of Koreans.

The Prevalence and Associated Factors of Periodontitis According to Fasting Plasma Glucose in the Korean Adults: The 2012–2013 Korea National Health and Nutrition Examination Survey

AbstractAlthough the relationship between diabetes and periodontitis is well established, the association between periodontitis and prediabetes has been investigated less extensively. Furthermore, there has been little research on the prevalence of periodontitis among individuals with prediabetes and diabetes as well as in the overall population using nationally representative data.Among 12,406 adults (≥19 years’ old) who participated in the 2012–2013 Korea National Health and Nutrition Examination Survey, a total of 9977 subjects completed oral and laboratory examinations and were included in this analysis. Periodontitis was defined as a community periodontal index score of ≥3 according to the World Health Organization criteria. The fasting plasma glucose level was categorized into the following 5 groups: normal fasting glucose (NFG) 1 (<90u200amg/dL), NFG 2 (90–99u200amg/dL), impaired fasting glucose (IFG) 1 (100–110u200amg/dL), IFG 2 (111–125u200amg/dL), and diabetes (≥126u200amg/dL).Overall, the weighted prevalence of periodontitis among the Korean adult population was 24.8% (23.3–26.4%) (weight nu200a=u200a8,455,952/34,086,014). The unadjusted weighted prevalences of periodontitis were 16.7%, 22.8%, 29.6%, 40.7%, and 46.7% in the NFG 1, NFG 2, IFG 1, IFG 2, and diabetes groups, respectively (Pu200a<u200a0.001). After adjusting for age, sex, smoking history, heavy alcohol drinking, college graduation, household income, waist circumference, serum triglyceride level, serum high-density lipoprotein cholesterol level, and the presence of hypertension, the adjusted weighted prevalence of periodontitis increased to 29.7% in the IFG 2 group (Pu200a=u200a0.045) and 32.5% in the diabetes group (Pu200a<u200a0.001), compared with the NFG 1 group (24%). The odds ratios for periodontitis with the above-mentioned variables as covariates were 1.42 (95% confidence interval [CI] 1.14–1.77, Pu200a=u200a0.002) in the diabetes group and 1.33 (95% CI 1.01–1.75, Pu200a=u200a0.044) in the IFG 2 group, respectively, compared with the NFG1 group.In conclusion, a higher range of IFG levels as well as diabetes, were positively associated with chronic periodontitis in a representative sample of Korean adults. This study suggests that individuals with a higher range of IFG levels before diabetes are at risk of periodontitis, and may benefit from dental screening.

Relationship Between Sarcopenia and Albuminuria: The 2011 Korea National Health and Nutrition Examination Survey

Abstract Studies have shown that albuminuria, obesity, and sarcopenia may share pathophysiological processes related to cardiovascular disease risk. Their direct relationships, however, have not been examined. This study investigated the association between albuminuria and sarcopenia in a representative fraction of the Korean population. Of the 10,589 people who participated in the 2011 Korea National Health and Nutrition Examination Survey, 2158 participants aged over 19 years had been tested for albumin-to-creatinine ratio and for body composition data using dual-energy x-ray absorptiometry. Albuminuria was defined as an albumin-to-creatinine ratio ≥30u200amg/g. Sarcopenia was defined as a skeletal muscle index (SMI) (SMI (%)u200a=u200atotal appendicular skeletal muscle mass [kg]/weight [kg]u200a×u200a100) of less than 1 standard deviation (SD) (grade 1) or 2 SD (grade 2) below the sex-specific mean for a younger reference group. The prevalence of albuminuria was higher in those with grade 2 sarcopenia than in those with a normal SMI or grade 1 sarcopenia (33.3% versus 8.4% and 8.9%; Pu200a<u200a0.001). Conversely, grade 2 sarcopenia was also more prevalent in participants with albuminuria than in those with the upper tertile of normoalbuminuria. In addition, multiple logistic regression analysis showed the odds ratio for albuminuria risk in the grade 2 sarcopenia group was 2.93 (95% confidence interval [CI], 1.46–5.88), compared with normal SMI after adjusting for potential confounding factors, including the presence of obesity, diabetes, and hypertension. Moreover, individuals with albuminuria had an odds ratio of 3.39 (95% [confidence interval], 1.38–8.37) for grade 2 sarcopenia compared with those in the lowest tertile of normoalbuminuria. This is the first study to demonstrate that individuals with sarcopenia exhibited increased risk of albuminuria and vice versa.

Association of the Estimated 24-H Urinary Sodium Excretion with Albuminuria in Adult Koreans: The 2011 Korea National Health and Nutrition Examination Survey

Background Sodium intake and albuminuria have important roles in blood pressure and renal progression. Although their relationship has been reported, the results have not been consistent and all studies have examined small populations. Objective This study investigated the role of the estimated 24-h urinary sodium excretion as a marker of sodium intake and albuminuria. Design This investigation included 5,187 individuals age 19 years and older from a cross-sectional, nationally representative, stratified survey: The Korea National Health and Nutrition Examination Survey (KNHANES V-2), in 2011. Albuminuria was defined as a urinary albumin/creatinine ratio ≥30 mg/g. The 24-h urinary sodium excretion was estimated from a spot urine. Results On classifying our participants into quartiles based on the estimated 24-h urinary sodium excretion, the prevalence of albuminuria increased with the 24-h urinary sodium excretion (5.3, 5.7, 7.5, and 11.8% in the first through fourth quartiles, respectively, p for trend <0.001). Even after adjusting for age, sex, diabetes, obesity, and hypertension, the significance persisted. In a multiple logistic regression analysis, the second and third quartiles of the estimated 24-h urinary sodium excretion were not associated with the presence of albuminuria with the first quartile as a control. However, the fourth quartile was significantly associated with the presence of albuminuria (odds ratio 1.61 [95% confidence interval 1.71–2.21], pu200a=u200a0.003) after adjusting for age, sex, diabetes, obesity, and hypertension. Conclusions These findings suggest that salt intake is associated with the presence of albuminuria in the general Korean adult population.