Tomris Erbas

Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease

One of the most overlooked of all serious complications of diabetes is cardiovascular autonomic neuropathy. There is now clear evidence that suggests activation of inflammatory cytokines in diabetic patients and that these correlate with abnormalities in sympathovagal balance. Dysfunction of the autonomic system predicts cardiovascular risk and sudden death in patients with type 2 diabetes. It also occurs in prediabetes, providing opportunities for early intervention. Simple tests that can be carried out at the bedside with real‐time output of information – within the scope of the practicing physician – facilitate diagnosis and allow the application of sound strategies for management. The window of opportunity for aggressive control of all the traditional risk factors for cardiovascular events or sudden death with intensification of therapy is with short duration diabetes, the absence of cardiovascular disease and a history of severe hypoglycemic events. To this list we can now add autonomic dysfunction and neuropathy, which have become the most powerful predictors of risk for mortality. It seems prudent that practitioners should be encouraged to become familiar with this information and apply risk stratification in clinical practice. Several agents have become available for the correction of functional defects in the autonomic nervous system, and restoration of autonomic balance is now possible.

Comparison of Metoclopramide and Erythromycin in the Treatment of Diabetic Gastroparesis

OBJECTIVE To compare the effects of erythromycin and metoclopramide on gastric emptying and symptoms of gastroparesis in diabetic patients with delayed gastric emptying. RESEARCH DESIGN AND METHODS The study group consisted of 13 patients with symptoms of severe gastroparesis and delayed gastric emptying. Gastric emptying was evaluated using a radionuclide method, and gastrointestinal symptoms were scored. The patients were given either erythromycin (250 mg 3 times/day) or metoclopramide (10 mg 3 times/day) in random order for 3 wk, and after a washout period of 3 wk they were crossed-over to the other medication for another 3 wk. Parameters of gastric emptying were assessed before treatment and after both erythromycin and metoclopramide administration. RESULTS The half-time of gastric emptying in diabetic subjects was 110 (77–120) min before treatment. At 60 and 90 min, the median value of residual isotope activity was 66.5 (55–83.5) and 55% (43–74.3), respectively. The half-time decreased to 55 min (28.6–115) after 3 wk of treatment with erythromycin and percentages of meal retention in the stomach at 60 and 90 min were 49.9 (38.4–70) and 40.5% (29.7–60), respectively. After taking metoclopramide, the median value of half-time was 67 min (15–115) and percentages of meal retention at 60 and 90 min were 51 (34.5–93.9) and 42% (24–71.2), respectively. When compared with baseline values a significant difference in gastric emptying parameters was found after both erythromycin and metoclopramide. A significant improvement of the total score for gastrointestinal symptoms was observed with both drugs, but this improvement was more pronounced with erythromycin. CONCLUSIONS Erythromycin, a macrolide antibiotic and a motilin receptor agonist, appears to stimulate intestinal motility and seems to be an alternative agent for the treatment of gastroparesis caused by diabetic autonomic neuropathy.

Melatonin levels decrease in type 2 diabetic patients with cardiac autonomic neuropathy

Abstract:  The present study has been designed to determine melatonin levels in type 2 diabetic patients and test the relationship between the autonomic nervous system and melatonin dynamics. Thirty‐six type 2 diabetic patients and 13 age‐matched healthy subjects were recruited for the study. Circadian rhythm of melatonin secretion was assessed by measuring serum melatonin concentrations between 02:00–04:00 and 16:00–18:00 hr. Melatonin dynamics were re‐evaluated with respect to autonomic nervous system in diabetic patients with autonomic neuropathy who were diagnosed by the cardiovascular reflex tests, heart rate variability (HRV), and 24‐hr blood pressure monitoring. Nocturnal melatonin levels and the nocturnal melatonin surge were low in the diabetic group (P = 0.027 and 0.008 respectively). Patients with autonomic neuropathy revealed decreased melatonin levels both at night and during day when compared with healthy controls (P < 0.001 and 0.004 respectively) while the melatonin dynamics were similar to controls in patients without autonomic neuropathy. Nocturnal melatonin level was positively correlated with nocturnal high and low frequency components of HRV (P = 0.005 and 0.011 respectively) and systolic and diastolic blood pressures at night (P = 0.002 and 0.004 respectively) in patients with autonomic neuropathy. We found a negative correlation between nocturnal melatonin levels and the degree of systolic blood pressure decrease at night (r = −0.478, P = 0.045). As a conclusion this study has shown that circadian rhythm of melatonin secretion is blunted in type 2 diabetic patients and there is a complex relationship between various components of autonomic nervous system and melatonin secretion at night. Among the patients with autonomic neuropathy those with more preserved HRV and the systolic nondippers (<10% reduction in blood pressure during the night relative to daytime values) have more pronounced melatonin surge at night.

Endocrine involvement in systemic amyloidosis.

OBJECTIVE To present an overview of the published data on endocrine involvement and endocrine dysfunction in patients with systemic amyloidosis. METHODS We conducted a review of the medical literature using MEDLINE data sources, including clinical trials, in vitro studies, and case reports on pituitary, thyroid, parathyroid, pancreatic, adrenal, and gonadal involvement in systemic amyloidosis. RESULTS Reports of endocrine involvement in systemic amyloidosis seem to consist primarily of small-samplesize clinical trials or case reports, probably because of the rarity of the disease itself. Systemic amyloidosis mainly involves and causes functional impairment in the thyroid and testes in the endocrine system. Evaluation of adrenal function necessitates special consideration because amyloid infiltration of the adrenal glands resulting in failure may be a life-threatening condition. Amyloid deposition commonly seen in the pituitary gland and the pancreas of patients with Alzheimer disease and type 2 diabetes mellitus, respectively, is generally classified as local amyloidosis and should not be confused with systemic involvement. Additionally, detection of amyloid deposition in the thyroid and testes may have a diagnostic role in patients with suspected systemic or renal amyloidosis. CONCLUSION Published data suggest that systemic amyloidosis frequently involves the endocrine system, and endocrine dysfunction seems to be not as rare as previously thought. A rapidly growing goiter or symptoms and signs of adrenal or gonadal dysfunction should raise suspicion of amyloid infiltration. Involvement of pituitary, parathyroid, and pancreatic sites in systemic amyloidosis still remains to be clarified. Further studies with larger sample sizes are needed for complete characterization of the effect of systemic amyloidosis on the endocrine system.

Thermolabile methylenetetrahydrofolate reductase enzyme genotype is frequent in type 2 diabetic patients with normal fasting homocysteine levels

Objective.  To investigate the plasma homocysteine concentrations with regard to nutritional, metabolic and genetic factors and to find out the frequency and impact of thermolabile methylenetetrahydrofolate reductase (T‐MTHFR) polymorphism in patients with type 2 diabetes mellitus.

Scintigraphic evaluation of left ventricular function and correlation with autonomic cardiac neuropathy in diabetic patients

Left ventricular function of 20 diabetic patients was investigated at rest and during hand-grip test using radionuclide ventriculography. The aim of the study was to discuss the correlation of cardiac function with autonomic cardiac neuropathy (ACN) in diabetic subjects. ACN was tested using heart rate response to valsalva maneuver, standing up, deep breathing; blood pressure response to standing up, sustained hand-grip, and additionally corrected QT (QTc) measurements. Plasma glucose regulation was screened with fructosamine levels. Ejection fraction (EF), peak ejection (PER) and filling rates (PFR), times to peak ejection (TPE) and filling (TPF), time to endsystole (TES), TES/T, TPE/T, TPF/T, 1/3 PER, 1/3 PFR, 1/3 EF, 1/3 FF (filling fraction) we calculated. Thirteen patients had ACN. Six patients (30%) had a low EF at rest. As a response to hand-grip, 14 patients (70%) showed a decrease in EF (9 ACN). PFR was low in 10 patients (50%) at rest and in 12 (60%) during hand-grip. The mean rest PER value of ACN+ patients (4.4 +/- 1.3) was significantly higher than that of controls (2.9 +/- 0.5) and patients without ACN (3.4 +/- 0.4; p < 0.05) as well as the mean 1/3 PER value (1.7 +/- 0.5 vs. 1.3 +/- 0.5; p < 0.05). Fourteen patients (70%) had a fall in PER 10 ACN) as a response to hand-grip. The mean TES/T value of patients with ACN (0.44 +/- 0.05) was significantly higher than of those without ACN (0.38 +/- 0.05; p < 0.05). In conclusion, diastolic dysfunction was detected frequently at rest. Systolic parameters were markedly impaired as a response to hand-grip in patients with ACN. Sympathetic overactivity was noted in ACN+ group at rest. Our results indicated that the patients with diabetes and ACN have subclinical left ventricular diastolic dysfunction and symphatic overactivity.

Short-term effects of somatostatin analogue (SMS 201–995) on left ventricular function in healthy persons: A scintigraphic study

Since somatostatin has been reported to have a negative inotropic and chronotropic effect on atria and positive inotropic effect on ventricle, present study was designed to investigate the acute effects of somatostatin analogue SMS 201–995 infusion on the left ventricular function in healthy volunteers. After labeling the autologous red blood cells with 750–1000 MBq 99mTc-perthecnetate, ECG-gated radionuclide ventriculography was performed. Using Fourier analysis of the left ventricular time-activity curve, ejection fraction (EF), peak ejection rate (PER), peak filling rate (PFR), time to endsystole (TES) and normalized TES/T values were calculated. Study group consisted of 12 healthy volunteers. Somatostatin analogue SMS 201–995 infusion was given at a rate of 100 μg/h during 2h. Baseline, 1st, 2nd h and 4th h imagings were done using the same protocol. Simultaneously heart rate and blood pressure were recorded. The difference between parameters was tested using Kruskall-Wallis test. The mean heart rate, systolic and diastolic blood pressures and did not show any statistically significant change during the somatostatin analogue infusion and 2h later in comparison to baseline values. The mean PER and PFR had a slight decrease at the first hour of infusion, but the change was not significant. However, the significant correlation of PER values with heart rate, EF and TES observed at baseline study were disappeared during the infusion. These results indicate that somatostatin analogue infusion does not appear to change the left ventricular systolic and diastolic function in healthy persons significantly.

Amyloid goiter and hypopituitarism in a patient with systemic amyloidosis

Systemic amyloidosis may infiltrate the thyroid or other endocrine glands but rarely causes endocrine dysfunction. We describe a 45 years old female patient with diffusely enlarged goiter and hypopituitarism secondary to amyloid infiltration of the thyroid gland and possibly pituitary gland, respectively. She was on chronic haemodialysis for 3 years due to systemic amyloidosis. While she was being prepared for thyroidectomy, adrenal failure developed. Her anterior pituitary hormone levels were low and magnetic resonance imaging of the hypophysis showed low signal intensity in right part of the adenohypophysis. She improved with corticosteroid replacement therapy and underwent subtotal thyroidectomy without any complication. Histopathologically, amyloid deposition was demonstrated in the thyroid gland. To our knowledge, this is the first case with amyloid goiter and hypopituitarism secondary to systemic amyloidosis. Amyloid infiltration should be considered in a systemic amyloidosis patient presenting with rapidly enlarged thyroid gland and signs of hypopituitarism.

Pituitary adenoma with gangliocytic component: report of 5 cases with focus on immunoprofile of gangliocytic component

IntroductionPituitary adenomas with gangliocytic component are rare tumors of the sellar region that are composed of pituitary adenoma cells and a ganglion cell component. Their histogenesis and hence nosology is not yet resolved because of the small number of cases reported and lack of large series in the literature.MethodsHerein we report five cases of pituitary adenoma with gangliocytic component to add knowledge to this rare neoplasm.ResultsThree cases are functional mammosomatotroph adenomas, one case is functional sparsely granulated somatotroph adenoma and the other is functional corticotroph adenoma. Gangliocytic component showed immunohistochemical expression of hormones in three cases. The ganglion cells were prolactin immunoreactive in case 1, GH and TSH immunoreactive in case 5 and showed expression of prolactin, TSH, ACTH and FSH in case 4. Three cases had undergone more than one surgery of which two had gangliocytic cells only in the recurrent tumors whereas the third case showed gangliocytic cells only in the initial tumor.DiscussionThe cases are discussed with clinical and histological features and a brief review of the literature considering the histogenesis is included.

Assessment of Left Ventricular Dysfunction in Acromegalic Patients Using Radionuclide Ventriculography Parameters

The left ventricular function of 14 acromegalic patients was investigated using radionuclide ventriculography. After labeling the red blood cells with 750-1,000 MBq 99mTc-pertechnetate, ECG-triggered left anterior oblique images were recorded. Fourier analysis was then performed on the time-activity curve of the left ventricle. The ejection fraction (EF), peak ejection rate, time to peak ejection (TPE), time to end-systole (TES), peak filling rate (PFR), time to peak filling (TPF), 1/3 EF, 1/3 filling fraction (FF), TPE/T, TPF/T and TES/T values (T: time interval for one heart beat) were calculated for each patient. Five patients (35.7%) had clinical cardiovascular symptoms. A decreased EF was observed in 28.5% of the patients. In comparison to the control group, the EF (53.5 +/- 5.5 vs. 60.8 +/- 5% p less than 0.009), 1/3 EF (14.45 +/- 3 vs. 20 +/- 4%, p less than 0.001), 1/3 FF (28.5 +/- 10.6 vs. 41 +/- 11%, p less than 0.02), TPE (158 +/- 33 vs. 132 +/- 35 ms, p less than 0.01), TPE/T (20.2 +/- 5 vs. 16 +/- 3.7, p less than 0.01) and PFR (2.4 +/- 0.5 vs. 2.9 +/- 0.4 EDC/s, p less than 0.005) were significantly different. It was found that TPE was prolonged and the early ejection function was decreased. Diastolic dysfunction was found in 5 (35.7%) patients; 21.4% of the patients had decreased PFR values although they had no cardiac symptom, hypertension and/or cardiomegaly. Scintigraphic parameters did not correlate with the presence of hypertension, cardiomegaly or cardiovascular symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)