Impaired Cortisol and Growth Hormone Counterregulatory Responses among Severe Hypoglycemic Patients with Type 2 Diabetes Mellitus

BACKGROUND: Elevated levels of cortisol and growth hormone are critical counterregulatory responses to severe hypoglycemia. However, the proportion and clinical characteristics of patients with type 2 diabetes mellitus (DM) who fail to show appropriate cortisol and/or growth hormone secretion in response to severe hypoglycemia have not been investigated. METHODS: We measured plasma cortisol and growth hormone levels in type 2 DM patients with severe hypoglycemia who visited the emergency department between 2006 and 2015. RESULTS: Of 112 hypoglycemic patients, 23 (20.5%) had an impaired cortisol response (<18 µg/dL) and 82 patients (73.2%) had an impaired growth hormone response (<5 ng/mL). Nineteen patients (17.0%) had impaired responses to both cortisol and growth hormone. The patients with impaired responses of cortisol, growth hormone, and both hormones were significantly older and more likely to be female, and had higher admission rates, lower growth hormone levels, and lower adrenocorticotropic hormone levels than the patients with a normal hormonal response. Multivariate logistic regression analysis indicated that an impaired growth hormone response was significantly associated with advanced age, shorter DM duration, a higher admission rate, and a higher body mass index (BMI). An impaired cortisol response was significantly associated with growth hormone levels. Patients with an impaired growth hormone response had higher admission rates than patients with a normal response. CONCLUSION: A considerable number of type 2 DM patients had impaired cortisol and/or growth hormone responses to severe hypoglycemia. Advanced age, shorter DM duration, and higher BMI were independently associated with an abnormal growth hormone response.

Determinants of Long-Term Durable Glycemic Control in New-Onset Type 2 Diabetes Mellitus

BACKGROUND: Long-term durable glycemic control is a difficult goal in the management of type 2 diabetes mellitus (T2DM). We evaluated the factors associated with durable glycemic control in a real clinical setting. METHODS: We retrospectively reviewed the medical records of 194 new-onset, drug-naïve patients with T2DM who were diagnosed between January 2011 and March 2013, and were followed up for >2 years. Glycemic durability was defined as the maintenance of optimal glycemic control (glycosylated hemoglobin [HbA1c] <7.0%) for 2 years without substitution or adding other glucose-lowering agents. Clinical factors and glycemic markers associated with glycemic durability were compared between two groups: a durability group and a non-durability group. RESULTS: Patients in the durability group had a higher baseline body mass index (26.1 kg/m² vs. 24.9 kg/m²) and lower HbA1c (8.6% vs. 9.7%) than the non-durability group. The initial choice of glucose-lowering agents was similar in both groups, except for insulin and sulfonylureas, which were more frequently prescribed in the non-durability group. In multiple logistic regression analyses, higher levels of education, physical activity, and homeostasis model assessment of β-cell function (HOMA-β) were associated with glycemic durability. Notably, lower HbA1c (<7.0%) at baseline and first follow-up were significantly associated with glycemic durability (adjusted odds ratio [OR], 7.48; 95% confidence interval [CI], 2.51 to 22.3) (adjusted OR, 9.27; 95% CI, 1.62 to 53.1, respectively), after adjusting for confounding variables including the types of glucose-lowering agents. CONCLUSION: Early achievement of HbA1c level within the glycemic target was a determinant of long-term glycemic durability in new-onset T2DM, as were higher levels of education, physical activity, and HOMA-β.

Predicting Extrathyroidal Extension in Patients With Papillary Thyroid Microcarcinoma According to a BRAF Mutation

OBJECTIVES: The aim of this study was to evaluate the association between preoperative parameters and extrathyroidal extension (ETE) of papillary thyroid microcarcinoma (PTMC) according to the BRAF mutation and to evaluate the preoperative predictability of ETE. METHODS: We analyzed the medical records of 332 patients with PTMC (140 in the BRAF– group and 192 in the BRAF+ group). The presence of ETE was subjected to a correlation analysis with age, sex, tumor size, clinical nodal status, and ultrasonography (US) findings. Among the US findings, the correlation between tumors and the thyroid capsule was categorized into four groups; US group A, intraparechymal; US group B, tumor abutting the capsule 50% of diameter; and US group D, tumor destroyed the capsule. The predictive value of ETE, including sensitivity, specificity, and positive and negative predictive values were evaluated. RESULTS: Tumor size and US group were significantly correlated with gross ETE in the BRAF– and BRAF+ groups. Tumor size of 0.5 cm and US groups B and C in the BRAF– group were cutoff values for gross ETE, with a negative predictive value of 100%, whereas tumor size of 0.7 cm and US groups A and B in the BRAF+ group had negative predictive values of 92.4% and 100%, respectively. CONCLUSION: Excluding of ETE by US was categorized according to tumor size and US findings. A different categorization to exclude ETE is needed according to the BRAF mutation.

Metastatic papillary thyroid cancers with malignant pleural effusion aggravated during thyroid hormone withdrawal for radioiodine therapy / 영남의대학술지

L-thyroxine (LT4) withdrawal prior to radioactive iodine (RAI) ablation therapy is a commonly used method for successful treatment of patients with papillary thyroid cancer (PTC). However, a prolonged period of hypothyroidism induced by LT4 withdrawal is sometimes associated with impaired quality of life and cardiopulmonary dysfunction in PTC patients. Furthermore, LT4 withdrawal may have a trophic effect on residual cancer by means of increased thyrotropin. We report on 2 cases of metastatic PTC patients with malignant pleural effusion (MPE) whose disease showed rapid worsening after LT4 withdrawal and RAI therapy. The first case is a 65-year-old woman who had PTC with multiple distant metastases and MPE. During LT4 withdrawal for RAI therapy, MPE showed rapid worsening, and the patient required repetitive therapeutic thoracentesis. The second case is a 49-year-old woman with PTC who underwent 3 additional operations for cancer recurrence in the neck lymph nodes and 6 times of RAI treatments. While preparing for the 7th RAI treatment by withdrawing LT4, she developed MPE which became progressively aggravated after RAI therapy. Both patients experienced increased pleural effusion during the LT4 withdrawal period and a rise in the thyroglobulin level was observed after RAI therapy. MPE was not controlled with therapeutic thoracentesis and pleurodesis. Eventually, both patients died of rapid disease progression after RAI therapy. In summary, LT4 withdrawal may have an adverse effect on metastatic PTC patients, particularly those with MPE.

Interferon-Alpha Induced Severe Hypothyroidism Followed by Graves' Disease in a Patient Infected with Hepatitis C Virus

Interferon-alpha (IFN-alpha) is an important therapeutic agent for hepatitis C virus (HCV) infection, but has various side effects including thyroiditis. We report a case of interferon-induced non-autoimmune hypothyroidism followed by autoimmune-medicated Graves' disease. A 59-year-old woman was diagnosed with chronic active hepatitis C; she had been treated with IFN-alpha and ribavirin for 24 weeks. Before starting the IFN-alpha, her thyroid function was normal and she was negative for autoantibodies. Severe hypothyroidism developed 5 weeks after halting the IFN-alpha, with the Graves' disease phase arising at 32 weeks. For accurate diagnosis and appropriate treatment of thyroid dysfunction during treatment with IFN-alpha, we need to understand and consider rare cases of multiphasic disorder involving both non-autoimmune and autoimmune thyroiditis induced by IFN-alpha.

Current Status of Glycemic Control of Patients with Diabetes in Korea: The Fifth Korea National Health and Nutrition Examination Survey

BACKGROUND: The Korea National Health and Nutrition Examination Survey (KNHANES) III (2005) reported that 22.9% of individuals with diabetes have a glycated hemoglobin (HbA1c) or =30 years with diabetes, we excluded 157 individuals who were missing HbA1c data. A total of 1,341 subjects were included in the final analysis. RESULTS: The prevalence of known diabetes was 7.7% (n=1,498, estimated to be 2.32 million people). The proportions of well-controlled diabetes meeting a HbA1c goal of 5 years. HbA1c in the group taking only oral hypoglycemic agents (OHAs) was significantly lower than that in the group administered only insulin or OHA and insulin in combination. In logistic regression analysis, a longer duration of diabetes, insulin use and the absence of chronic renal failure were associated with HbA1c levels >6.5%. CONCLUSION: The level of adequate glycemic control was similar to but slightly improved compared with previous levels. The glycemic control of long-standing diabetes patients is more difficult even though they receive insulin treatment.

Association of the Parathyroid Adenoma Volume and the Biochemical Parameters in Primary Hyperparathyroidism

BACKGROUND: The objective of this study is to demonstrate the relationship between the volume of a parathyroid adenoma and the preoperative biochemical parameters in patients undergoing surgery for primary hyperparathyroidism. METHODS: The medical records of 68 patients who underwent a parathyroidectomy for a single parathyroid adenoma were retrospectively reviewed. The volume of the adenoma was estimated using its measured size and a mathematical formula. The correlation between the volume of the parathyroid adenoma and the preoperative laboratory data was assessed. RESULTS: There were no correlations between the estimated volume of the adenoma and the serum calcium, alkaline phosphatase and parathyroid hormone levels. However, the volume of the adenoma was associated with the preoperative level of serum phosphorus. After excluding 5 adenomas with cystic degeneration, a positive correlation was noted between the adenoma volume and the preoperative levels of alkaline phosphatase and parathyroid hormone. CONCLUSION: The preoperative serum levels of calcium, alkaline phosphatase and parathyroid hormone are of limited use to predict the volume of the parathyroid adenoma in patients with a single parathyroid adenoma. We suggest that the absence of a correlation between the volume of the adenoma and the biochemical parameters can be attributed to the cystic degeneration of the adenomas.

The Clinical Characteristics of Normoalbuminuric Renal Insufficiency in Korean Type 2 Diabetic Patients: A Possible Early Stage Renal Complication

It has been recently reported that a considerable portion of diabetic patients with renal insufficiency show normoalbuminuria. As little is known about normoalbuminuric renal insufficiency in the Asian population, we examined its prevalence and clinical characteristics in Korean type 2 diabetic patients. We studied 562 patients with type 2 diabetes from Seoul National University Hospital. The estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease formula and the degree of albuminuria was evaluated by spot urine albumin-creatinine ratio. Of 562 patients, 151 (26.9%) patients had renal insufficiency (eGFR <60 mL/min/ 1.73m(2)). Among them, 44 (29.1%) patients had normoalbuminuria. After excluding the patients using renin-angiotensin system (RAS) inhibitors, the prevalence of normoalbuminuric renal insufficiency was 35.3% (18 of 51 patients). Compared with microand macroalbuminuric renal insufficiency, normoalbuminuric renal insufficiency was associated with the female predominance, shorter duration of diabetes, lower prevalence of diabetic retinopathy, and lower prevalence of using antihypertensive drugs except RAS inhibitors. The prevalence decreased progressively with an increase in the duration of diabetes and an increase in the severity of retinopathy. Normoalbuminuric renal insufficiency was prevalent in Korean type 2 diabetic patients. The association with a shorter duration of the diabetes and a lower prevalence of retinopathy suggests that it might be an early stage renal complication.

Discovery of an inta-atrial extension of hepatocellular carcinoma in a patient presenting with right-heart failure / 대한내과학회지

A primary right atrial (RA) mass is not common; instead, most tumors in the right atrium originate from metastasis through the caval route. Here we describe a patient with a huge RA tumor that showed contiguous spread from the inferior vena cava. This 60-year-old patient, positive for hepatitis B surface antigen, visited the emergency department of our institution due to recently aggravated dyspnea. Transthoracic and transesophageal echocardiography clearly demonstrated a huge RA mass, 6.5x6.0 cm, causing flow disturbance. Cardiac magnetic resonance imaging and dynamic computed tomography of the liver showed multiple large hepatic masses that extended into the right atrium, with tumor thrombi in the inferior vena cava. Given the enhancement pattern in dynamic computed tomography of the liver, the hepatic mass was diagnosed as hepatocellular carcinoma. Due to the risk of spontaneous rupture of the mass, emergency transarterial chemoembolization was performed, without complications. Thereafter, thalidomide, which has been shown to have anti-angiogenic effects, was prescribed to the patient.

Prevalence and Clinical Characteristics of Aspirin Resistance in the Patients with Type 2 Diabetes Mellitus / 당뇨병

BACKGROUND: We examined the prevalence and clinical characteristics of aspirin resistance in the Korean patients with type 2 diabetes mellitus. METHODS: We studied 181 Korean patients with type 2 diabetes mellitus who were taking aspirin (100 mg/day for > or = 3 months) and no other antiplatelet agents. The VerifyNow System was used to determine aspirin responsiveness. Aspirin resistance was defined as an aspirin reaction unit (ARU) > or = 550. We measured the cardio-ankle vascular index (CAVI) and ankle-brachial index (ABI) to evaluate arteriosclerosis. The anthropometric parameters, electrocardiogram, blood pressure, fasting plasma glucose, lipid profiles, hemoglobin A1c, highly sensitive C-reactive protein (hsCRP), homocysteine, and microalbuminuria were measured in each patient. RESULTS: The prevalence of aspirin resistance in type 2 diabetic patients was 9.4% (17 of 181). Those who had aspirin resistance were older than those without aspirin resistance (64.6 +/- 10.6 vs. 59.8 +/- 8.1, P = 0.024). Aspirin resistance was not associated with fasting plasma glucose, total cholesterol, triglyceride, LDL-cholesterol, HDL-cholesterol, hemoglobin A1c, hsCRP, homocysteine, microalbuminuria, ABI, CAVI, and body mass index. CONCLUSION: Prevalence of aspirin resistance in the Korean patients with type 2 diabetes mellitus was 9.4%. Although aspirin resistance was associated with old age, we could not find any good clinical parameter to predict it. Therefore, aspirin resistance should be evaluated in diabetic patients taking aspirin for prevention of cardiovascular complications.

Mosaic Pattern of Lung Attenuation on Thin-Section CT: Review of 31 Cases

PURPOSE: To correlate radiologic findings with clinical findings in patients with a mosaic patten of lungattenuation, as seen on thin-section CT. MATERIALS AND METHODS: Thirty-one cases in which a mosaic pattern oflung attenuation was detected on combined expiratory and inspiratory scans of thin-section CT were retrospectivelyanalyzed. Cases involving infiltrative lung disease were excluded. Both thin-section CT and clinical findings wereanalyzed and the relationship between the extent of the area of hyperlucency -as seen on expiratory scan- andphysiologic parameters was evaluated. The subjects were 10 men and 21 women ranged in age from 25 to 76 (mean 50)years. RESULT: Twenty-nine patients with small airway disease, [chronic bronchitis and/or bronchiolitis(n=11),bronchiectasis(n=8), bronchial asthma(n=8), mycoplasmic pneumonitis(n=1) and hypersensitive pneumonitis(n=1),] andtwo patients with pulmonary vascular disease, [chronic pulmonary thromboembolism(n=1) and stenosis of the leftupper pulmonary artery(n=1)] were included in our study. Commonly associated thin-section CT findings in the casesinvolving small airway disease(n=29) were bronchial wall thickening(n=25), nodular opacity(n=25), bronchial andbronchiolar dilatation(n=20) and small branching opacity(n=16). These findings were not observed in two patientswith pulmonary vascular disease, though bronchial wall thickening was seen in the patient with chronic pulmonarythromboembolism. At expiratory scan level, there was statistical correlation between FEV1/FVC and the number ofpulmonary segments(r= 0.982, p0.05). CONCLUSION: The mosaic pattern of lung attenuation seen on thin-section CT isindicative of various diseases, involving small airways such as bronchiolitis, bronchitis, bronchiectasis andbronchial asthma, and vascular lung disease. Bronchial wall thickening and nodular opacity can be associated withsmall airway diseases.