Nusret Yilmaz

Acquired partial lipodystrophy is associated with increased risk for developing metabolic abnormalities

OBJECTIVE Acquired partial lipodystrophy (APL) is a rare disorder characterized by progressive selective fat loss. In previous studies, metabolic abnormalities were reported to be relatively rare in APL, whilst they were quite common in other types of lipodystrophy syndromes. METHODS In this nationwide cohort study, we evaluated 21 Turkish patients with APL who were enrolled in a prospective follow-up protocol. Subjects were investigated for metabolic abnormalities. Fat distribution was assessed by whole body MRI. Hepatic steatosis was evaluated by ultrasound, MRI and MR spectroscopy. Patients with diabetes underwent a mix meal stimulated C-peptide/insulin test to investigate pancreatic beta cell functions. Leptin and adiponectin levels were measured. RESULTS Fifteen individuals (71.4%) had at least one metabolic abnormality. Six patients (28.6%) had diabetes, 12 (57.1%) hypertrigylceridemia, 10 (47.6%) low HDL cholesterol, and 11 (52.4%) hepatic steatosis. Steatohepatitis was further confirmed in 2 patients with liver biopsy. Anti-GAD was negative in all APL patients with diabetes. APL patients with diabetes had lower leptin and adiponectin levels compared to patients with type 2 diabetes and healthy controls. However, contrary to what we observed in patients with congenital generalized lipodystrophy (CGL), we did not detect consistently very low leptin levels in APL patients. The mix meal test suggested that APL patients with diabetes had a significant amount of functional pancreatic beta cells, and their diabetes was apparently associated with insulin resistance. CONCLUSIONS Our results show that APL is associated with increased risk for developing metabolic abnormalities. We suggest that close long-term follow-up is required to identify and manage metabolic abnormalities in APL.

Parathyroidectomy in asymptomatic primary hyperparathyroidism reduces carotid intima‐media thickness and arterial stiffness

Although an International Workshop has suggested that cardiovascular assessment in asymptomatic primary hyperparathyroidism (PHPT) patients is not necessary, improvements in risk factors of subclinical atherosclerosis have been shown following parathyroidectomy. The objectives of this study were to determine whether parathyroidectomy in asymptomatic PHPT patients causes any change in carotid intima‐media thickness (CIMT), arterial stiffness [pulse wave velocity (PWV)] and soluble CD40 ligand (sCD40L) levels.

ASSESSMENT OF DIASTOLIC DYSFUNCTION, ARTERIAL STIFFNESS, AND CAROTID INTIMA-MEDIA THICKNESS IN PATIENTS WITH ACROMEGALY

OBJECTIVE Early diagnosis and treatment of cardiovascular diseases, the most frequent cause of morbidity and mortality in acromegaly, may be an efficient approach to extending the lifespan of affected patients. Therefore, it is crucial to determine any cardiovascular diseases in the subclinical period. The study objectives were to determine markers of subclinical atherosclerosis and asses heart structure and function. METHODS This was a cross-sectional, single-center study of 53 patients with acromegaly and 22 age- and sex-matched healthy individuals. Carotid intima-media thickness (CIMT), pulse-wave velocity (PWV), and echocardiographic data were compared between these groups. RESULTS CIMT and PWV were higher in the acromegaly group than in the healthy group (P = .008 and P = .002, respectively). Echocardiography showed that left ventricular diastolic dysfunction was present in 11.3% of patients. Left ventricular mass index and left atrial volume index were higher in the patients (P = .016 and P<.001, respectively). No differences in the CIMT, PWV, or echocardiographic measurements were identified between the patients with biochemically controlled and uncontrolled acromegaly and the control group. CONCLUSION Our results showed that subclinical atherosclerosis (i.e., CIMT and PWV markers) and heart structure and function were worse in patients with acromegaly than in healthy individuals. Because there were no differences in these parameters between patients with controlled and uncontrolled acromegaly, our results suggest that the structural and functional changes do not reverse with biochemical control. ABBREVIATIONS AA = active acromegaly BSA = body surface area CA = biochemically controlled acromegaly CH = concentric hypertrophy CIMT = carotid intima-media thickness DBP = diastolic blood pressure DM = diabetes mellitus ECHO = echocardiography EDV = enddiastolic volume EF = ejection fraction ESV = endsystolic volume GH = growth hormone HC = healthy control HL = hyperlipidemia HT = hypertension IGF-1 = insulin-like growth factor 1 LA = left atrial LAV = left atrial volume LAVI = left atrial volume index LV = left ventricular LVDD = left ventricular diastolic dysfunction LVEF = left ventricular ejection fraction LVH = left ventricular hypertrophy LVMI = left ventricular mass index PWV = pulse-wave velocity RWT = relative wall thickness.

Markers of Subclinical Cardiovascular Disease in Nonfunctional Adrenal Incidentaloma Patients without Traditional Cardiovascular Risk Factors.

Introduction: Data regarding cardiovascular risk in patients with non-functional adrenal incidentaloma (NFAI) are limited. The objectives of this study are to investigate markers of subclinical cardiovascular disease like carotid intima media thickness (CIMT), pulse wave velocity (PWV), augmentation index (AIx), soluble CD40 ligand (sCD40L) and leptin levels in NFAI patients without traditional cardiovascular risk factors and healthy control group. Methods: This study involved 35 patients with NFAI (11 males, 24 females; mean age, 52.4±7.7 years) and 35 healthy subjects as control group (11 males, 24 females; mean age, 51.8±7.2 years). CIMT was evaluated by ultrasonographical methods. PWV and AIx were measured with TensioClinic arteriograph system. Serum leptin and sCD40L levels were measured by ELISA. Results: In NFAI patients group; CIMT (p<0.001), PWV (p<0.001), AIx brachial (p<0.001) and AIx aorta (p=0.008) were found higher than the control group. Cortisol levels after 1mg dexamethasone suppression test (DST) were higher (p=0.006) and DHEASO4 levels were lower (p=0.008) in NFAI patients than control group. We found that CIMT had positive correlation with age (r=0.484, p<0.005), triglycerides (r=0.378, p<0.005) and cortisol level after 1 mg DST (r=0.346, p<0.005); PWV had positive correlation with total cholesterol (r=0.338, p<0.005) triglycerides (r=0.335, p<0.05) and insulin levels (r=0.426, p<0.005); AIx brachial had a positive correlation with triglycerides (r=0414, p<0.05) and negative correlation with DHEASO4 (r=-0.380, p<0.005); leptin levels had a positive correlation with body mass index (r=0.541, p<0.001) and HOMA-IR index. Conclusion: We showed that subjects with NFAI without traditional cardiovascular risk factors featured several disturbances (CIMT, PWV and AIx) compared to the control group that could be attributable to increased cardiovascular risk.

Diagnostic value of the late-night salivary cortisol in the diagnosis of clinical and subclinical Cushing’s syndrome: results of a single-center 7-year experience

Late-night salivary cortisol (LNSaC) is an easy-to-use test reflecting the free cortisol level in the serum and does not require hospitalization. Controlled studies reported that LNSaC has a high sensitivity and specificity, but have not set a clearly defined cut-off value to be used in the diagnosis of Cushing’s syndrome. In this study, we aimed to evaluate the diagnostic performance of LNSaC in patients with clinical Cushing’s syndrome (CCS) and subclinical Cushing’s syndrome (SCS). The data of 543 patients, whose LNSaC levels were assessed using electrochemiluminescence immunoassay method, were retrospectively evaluated. The study included a total of 324 patients: 58 patients with CCS, 53 patients with SCS, and 213 patients without Cushing’s syndrome (NoCS). The cause of the Cushing’s syndrome was hypophyseal in 26 patients (45%), adrenal in 24 patients (41%), and ectopic in 8 patients (14%) in the CCS group. Median LNSaC levels were 0.724 (0.107–33) µg/dL in CCS group, 0.398 (0.16–1.02) µg/dL in SCS group, and 0.18 (0.043–0.481) µg/dL in NoCS group (p=0.001). Accordingly, LNSaC had 89.6% sensitivity and 81.6% specificity at a cut-off value of 0.288 µg/dL in the diagnosis of CCS; and had 80.7% sensitivity and 85.1% specificity at a cut-off value of 0.273 µg/dL in the diagnosis of SCS. In the present study, a lower sensitivity and specificity than previously reported was found for LNSaC in the diagnosis of CCS. Moreover, the diagnostic performance of LNSaC in patients with SCS was close to its diagnostic performance in patients with CCS. Each center should determine its own cut-off value based on the method adopted for LNSaC measurement, and apply that cut-off value in the diagnosis of Cushing’s syndrome.

Evaluation of Incidental Thyroid Nodules in Cancer Patients

OBJECTIVE Frequency of thyroid cancer in incidental thyroid nodules identified by imaging techniques in cancer patients is higher than that in the normal population. In the retrospective study, we have both investigated the incidence of thyroid cancer in incidentally identified nodules and compared the imaging techniques to determine whether there is any difference between them in detection of malign nodules. METHODS A total of 7319 patients who underwent thyroid fine-needle aspiration biopsy (FNAB) were included in the study. The data of 174 patients who had previously been diagnosed with a hematologic or solid malignancy prior to the FNAB procedure and had incidentally identified thyroid nodules were evaluated retrospectively. RESULTS Eighty-six (49.5%) of the incidental nodules were identified with ultrasonography (USG), 62 (35.6%) with positron emission tomography (PET) or PET/computed tomography (PET/CT), and 26 (14.9%) with CT. As a result of thyroidectomy, papillary carcinoma was identified in 8 (4.6%) patients, and metastasis to the thyroid of a primary cancer was found in 3 (1.7%) patients. While the papillary carcinoma proportion in the nodules identified by USG was 3.4%, PET/CT was 8.9%. A cut-off maximal standardized uptake value of 11.6 in PET/CT indicated malignancy achieving a sensitivity of 83.3% and a specificity of 91.1%. CONCLUSION Whether the nodule in the incidental thyroid nodules of cancer patients is identified using USG or PET/CT, the risk of thyroid cancer is similar. However, cancer risk is higher in the event of a higher focal uptake in the nodules identified by PET/CT.

GLP-1 and GIP Levels in Patients With Hyperthyroidism: The Effect of Antithyroid Treatment:

Background:Incretin hormones (glucagon-like peptide-1 [GLP-1] and gastric inhibitory polypeptide [GIP]) may play a role in the development of glucose intolerance and hyperglycemia in patients with hyperthyroidism. Objective: We aimed to assess both incretin levels and treatment-induced changes in incretin levels in those with hyperthyroidism. Methods: A total of 24 subjects (12 with hyperthyroidism and 12 healthy) were enrolled in the study. Oral glucose tolerance test was performed and serum glucose, insulin GLP1, and GIP levels were evaluated at 0 (baseline), 30, 60, 90, and 120 minutes using ELISA. Measurements were repeated after euthyroidism was reached in subjects with hyperthyroidism. Results: The baseline glucose level was higher in those with hyperthyroidism compared with controls (P = 0.03). GLP-1 and GIP responses to oral glucose load did not differ significantly between those with hyperthyroidism and controls. Peak GLP-1 and GIP levels were reached in both groups at 60 and 90 minutes, respectively. Areas under the curve (AUCs) for GLP1 and GIP were similar in those with hyperthyroidism and controls. Although GLP-1 and GIP levels did not change before and after antithyroid treatment in subjects with hyperthyroidism, time to peak GLP-1 and GIP levels were reached at 30 minutes after euthyroid state was achieved. Reversal of hyperthyroid to euthyroid status did not induce significant changes in AUCs for incretins. Conclusion: The findings of the present study suggest that the total incretin response to oral glucose load is preserved in patients with hypertyhroidism, but peak incretin responses may change after achieving euthyroid state.

Subcutaneous NPH Insulin for Severe Hypertriglyceridemia in a Pregnant Patient with Type V Hyperlipoproteinemia: a Case Report

An increase in triglyceride levels in familial hyperlipidemia during pregnancy has been reported. Severe hypertriglyceridemia can lead to complications such as acute pancreatitis, preeclampsia, maternal and fetal complications. Because of the teratogenic effects associated with fibrate therapy in pregnancy, alternative treatment strategies such as insulin as a rapid and potent activator of lipoprotein lipase are required during pregnancy. We report a case of hypertriglyceridemia in a 33-year-old pregnant woman in whom treatment with merely single one time administration of Neutral Protamine Hagedorn insulin was accompanied by a reduction in the serum triglyceride level; to the best of our knowledge, this has never been reported in the literature. Her triglyceride level was 3616 mg/dL before insulin treatment and 1246 mg/dL after insulin treatment. Although this regimen was used safely and effectively in our patient, comprehensive studies are required to evaluate the effectiveness and safety of subcutaneously intermediate-acting Neutral Protamine Hagedorn insulin for the treatment of severe hypertriglyceridemia in non-diabetic pregnant women.