EFFECTIVENESS OF UNILATERAL ADRENALECTOMY IN BILATERAL ADRENAL INCIDENTALOMA PATIENTS WITH SUBCLINICAL HYPERCORTISOLEMIA.

Objective: Unilateral adrenalectomy (UA) is an alternative for treatment in bilateral adrenal incidentaloma (AI) to avoid possible long-term risks of bilateral adrenalectomy. In this study, we aimed to evaluate the effectiveness of UA in bilateral AI patients with subclinical hypercortisolemia (SH). Method: A total of 35 patients were included in this study. The patients were divided into two groups; those who underwent UA (n=27) and patients without adrenalectomy (PWA) (n=8). Hormone tests related to cortisol mechanism were reviewed to analyze results at the time of diagnosis compared to the latest available results to figure out any changes in cortisol mechanism and determine whether SH has recovered or not. Results: Median age of PWA group were higher compared to UA group (p=0.03). Median duration of follow-up in groups were similar (p=0.3). In the PWA group, none of the patients recovered from hypercortisolemia during their follow-up. In UA group 92.6% of the patients went into remission, whereas during follow-up 3.3% had recurred and another 3.3% were found to have post-adrenalectomy persistent SH. Patients in UA group had lower final cortisol level following dexamethasone suppression (p=0.003) and higher final adrenocorticotrophic hormone (ACTH) levels (p=0.001) than patients in PWA group. In UA group, final basal cortisol level (p=0.009) and final cortisol level after 1 mg dexamethasone suppression test (DST) (p=0.004) were lower than corresponding levels at the time of diagnosis. Discussion: Our study demonstrates unilateral adrenalectomy targeting the side with the larger lesion is an effective approach to reduce excess cortisol levels in bilateral AI patients with SH.

Using plasma exchange to successfully manage thyrotoxicosis in a patient with possible antithyroid drug-related thrombotic thrombocytopenic purpura.

OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenic purpura, neurologic abnormalities, fever, and renal insufficiency. The association or co-existence of thyrotoxicosis or antithyroid drugs with TTP has not been previously reported. Subject and Results. Herein, we present a 54-year-old female patient newly diagnosed with toxic multinodular goiter accompanying with TTP, possibly triggered by either thyrotoxicosis or antithyroid drugs. CONCLUSIONS: The present report is the first in the literature to demonstrate the co-existence of these two diseases and the use of plasma exchange as a modality to treat both conditions.

Type-2 diabetes down-regulates glucose transporter proteins and genes of the human blood leukocytes.

OBJECTIVE: White blood cells are essential in mediating immune and inflammatory responses. A prominent feature of these cells during activation of the immune function is increased glucose utilization, and this is dependent on the functioning of specific glucose transporter (GLUT) isoforms. The few data available on leukocyte glucose transporter expression are limited to type-2 diabetes mellitus, and nothing is known about its regulation. MATERIAL AND METHODS: Peripheral blood was drawn from 35 healthy controls and 35 diabetic subjects. Expression of GLUT1, GLUT3 and GLUT4 was determined in the leukocytes of healthy individuals and diabetic patients by flow cytometry, Western blot and semi-quantitative RT-PCR. RESULTS: GLUT 3 was decreased in granulocytes, lymphocytes and monocytes from diabetic patients. In monocytes, GLUT3 and GLUT4 were reduced in type-2 diabetic patients. In leukocytes of diabetic patients, GLUT1 and GLUT4, protein and mRNA were unchanged, but GLUT3 protein and mRNA levels were down-regulated compared to those of healthy controls. CONCLUSION: Elevated glucose concentration affects leukocyte GLUT expression. Decreased expression of GLUT isoforms in leukocytes may be responsible for diminished activation of diabetic leukocytes. These situations possibly contribute to a predisposition to infection and to a decreased immune response in diabetes.

Kidney-pancreas transplantation: single-center experience at a university hospital in Turkey.

INTRODUCTION: One treatment option for patients with type 1 diabetes mellitus with end-stage nephropathy is combined pancreas-kidney transplantation, which can be performed either simultaneously (SPK) or following kidney transplantation (PAK). PATIENTS AND METHODS: Between February 2003 and November 2004, 14 patients, including 10 males and 4 females of overall mean age of 31.3 +/- 6.1 years (range, 23-44 years), presented with end-stage renal disease secondary to type 1 diabetes mellitus. Five patients (35.7%) received SPK; 7 patients (50%) received PAK; and 2 patients (14.3%) received simultaneous pancreas and living-related kidney (SPLK) transplantations. RESULTS: Two among 14 pancreas grafts were lost in the early postoperative period secondary to venous thrombosis despite anticoagulation including 1 with poor portal drainage. Insulin therapy was reinitiated in 1 patient after a second rejection episode in the seventh postoperative month. By the ninth median follow-up month (range, 1-21 months), all kidney grafts were functioning. CONCLUSION: Our single-center short-term experience with 14 consecutive kidney-pancreas transplantations suggests that while the pancreas transplant is effective and safe to reestablish normoglycemia, this transplant creates additional surgical and immunosuppressive stresses on the patient.

Insulin resistance in chronic hepatitis C.

Insulin resistance (IR), glucose intolerance and diabetes mellitus are commonly associated with cirrhosis. The exact pathogenetic mechanisms responsible are still unknown; however, they may be related to both hepatitis C virus itself and to liver injury. IR may be the earliest abnormality, which in the following years may progress to clinical diabetes mellitus. The aim of this study was to investigate the presence of IR by euglycaemic hyperinsulinemic clamp technique, in chronic hepatitis C patients. 15 patients and nine healthy controls without any known condition that may affect IR were enrolled to the study. Chronic hepatitis C was diagnosed by liver biopsy (hepatic activity index was also determined in 10 patients) and appropriate viral and biochemical tests. Eight patients were given interferon therapy, which had been stopped for at least 3 months before the study. Euglycaemic hyperinsulinemic clamp technique was performed as previously described and peripheral glucose utilisation rate, M value, was calculated in mg/kg/min by infusion of 40 IU/m2/min regular insulin. M value of the control group was significantly higher than that of chronic hepatitis C patients (M = 5.1+/-1 vs. 3.7+/-1; p = 0.004), which was consistent with IR in the patient group. There was no significant correlation between the M value and alanine aminotransferase, aspartate aminotransferase and hepatic activity index (p = 0.621, 0.549, 0.479, respectively). Our results suggest that IR is present in chronic hepatitis C patients; it is not directly related to hepatic injury, moreover, it may be associated with some component(s) inherent to hepatitis C virus.

Effect of chronic Pseudomonas aeruginosa infection on the development of atherosclerosis in a rat model.

In order to investigate the possible relationship between atherosclerosis and chronic Pseudomonas aeruginosa infection, 66 Wistar rats were given five separate intratracheal inoculations of either P. aeruginosa or sterile saline at 4-week intervals. The rats were divided into four groups: group 1 was infected with P. aeruginosa and fed a diet containing cholesterol 1% w/v; group 2 was infected with P. aeruginosa and fed a normal diet; group 3 was not infected and was fed a diet containing cholesterol 1% w/v; and group 4 (the control group) was not infected and was fed a normal diet. One month after the final inoculation, the rats were killed humanely; computerised image analysis was used to evaluate sections of the aorta and heart, and the maximal wall thickness of the aorta and coronary artery. The aortic wall thickness was significantly greater for group 1 (329.53 +/- 58.06 microm) compared to groups 2 (190.59 +/- 27.81 microm; p < 0.0001), 3 (262.90 +/- 61.12 microm; p < 0.0004) and 4 (158.00 +/- 30.30 microm; p < 0.0001). Similarly, the coronary artery wall thickness was significantly greater for group 1 (72.96 +/- 10.67 microm) compared to groups 2 (35.07 +/- 8.53 microm; p < 0.0001), 3 (41.45 +/- 10.22 microm; p < 0.0001) and 4 (32.30 +/- 5.27 microm; p < 0.0001). These findings strengthen the hypothesis that chronic infection plays a role in the pathogenesis of atherosclerosis.

Severe and prolonged hypoglycemia triggered by long-acting octreotide in a patient with malignant mesenchymal tumor: case report.

Somatostatin analogues are potent growth hormone and glucagon inhibitors and are commonly used in the treatment of several endocrine and non-endocrine disorders. We report severe and longstanding hypoglycemia triggered by long-acting octreotide (Sandostatin LAR) in a 62-year-old women with malignant mesenchymal tumor. Hypoglycemia developed after 6 hours of octreotide injection and she was admitted to the emergency unit with sweating, tremor, palpitation and confusion. On admission, her plasma glucose level was: 17 mg/dl (normal: 65-110), cortisol: 31 microg/dl (normal: 5-25), insulin: 4.32 microIU/ml (normal: 6-27), C-peptide: 2.64 ng/ml (normal: 0.9-4.0), growth hormone: 0.06 ng/ml (normal: 0.06-5.0), insulin-like growth factor-I: 8.5 ng/ml (normal: 101-303), insulin-like growth factor binding protein-3: 1715 ng/ml (normal: 2020-3990). Intravenous dextrose infusion was given for a month to sustain normoglycemia since hypoglycemia recurred following cessation of infusion. Therefore, prednisolone, 35 mg/day was added and the parenteral dextrose infusion rate was decreased gradually and finally stopped. Normoglycemia could be maintained with prednisolone 20 mg/day. In patients prone to tumor hypoglycemia, long-acting octreotide may trigger severe and prolonged hypoglycemia due to suppression of counter-regulatory hormones; clinical trial with short-acting octreotide may be warranted to predict and prevent this life-threating complication.

Asymptomatic acute pancreatitis due to tamoxifen-induced severe hypertriglyceridemia in a patient with diabetes mellitus and breast cancer.

We report tamoxifen-induced hypertriglyceridemia and asymptomatic acute pancreatitis in a 51 year-old women with type 2 diabetes mellitus and stage III-b infiltrative ductal carcinoma, admitted to the hospital with weakness, oliguria and glucose dysregulation. On admission, there was no fever, abdominal or back pain, rebound tenderness, nausea, or vomiting. Following 1 year of tamoxifen treatment, triglycerides increased from 400 to 1344 mg/dl (blood urea nitrogen 52 mg/dl, creatinine 2.0 mg/dl, glucose 341 mg/dl). Hypertriglyceridemia was considered to be due to either diabetic dyslipidemia and/or tamoxifen. On computerized tomography, pancreatic enlargement, heterogenity, hypodensity and a pancreatic pseudocyst (5 x 7.5 cm diameter) were found. Acute pancreatitis was suspected, and serum amylase level was found to be increased (273 IU/L). Tamoxifen was discontinued and gemfibrozil was started. Triglycerides decreased to 301 mg/dl and amylase decreased to 66 IU/L a week later and remained normal thereafter. This case indicates that tamoxifen-induced hypertriglyceridemia may cause acute pancreatitis without classical symptoms which might be due to autonomic neuropathy in diabetic patients. Effects on lipid metabolism should be considered and triglycerides should be closely followed in patients on tamoxifen.

Serum HbA1c levels and exercise capacity in diabetic patients.

It is well known that cardiovascular morbidity and mortality are high in diabetic patients. Cardiac involvement is silent and early and these diabetic patients generally complain of chronic fatigue. This study was designed to evaluate the relation between glycemic control and exercise capacity in 330 diabetic patients who have no cardiac symptoms by sustaining dynamic exercise. After a cardiac examination, patients with coronary heart disease, ECG abnormalities, cardiac failure, valvular disease, cerebrovascular disease, peripheral artery disease, anaemia and peripheral neuropathy were excluded. Plasma HbA1c and lipid levels were obtained and a symptom limited exercise test based on "Bruce Protocol" was performed on all patients. Plasma HbA1c levels were significantly increased in smokers and in hypercholesterolemic patients (p<0.001, p=0.006). A moderate correlation between exercise capacity and HbA1c levels, and a weak correlation between duration of diabetes, age, sex, hypertension and plasma lipids were obtained. Multivariant regression analys is revealed that only HbA1c and hypercholesterolemia affected exercise capacity independently (r=-0.54 r=-0.30). In conclusion, poor glycemic control in diabetic patients causes earlier cellular involvement. Because of the high affinity of HbA1c to oxygen, the energy metabolism of the cell is affected, with a clinical correlation between chronic fatigue and worsening exercise capacity.

EGFR and p53 expression and proliferative activity in parathyroid adenomas; an immunohistochemical study.

EGFR (epidermal growth factor receptor), p53, and proliferative markers provide some clues as to the formation of several tumours. In this study the mechanism of the genesis of parathyroid adenomas was investigated using immunohistochemistry. Sections of parathyroid adenomas from 12 cases were stained using PCNA (proliferating cell nuclear antigen), EGFR, and p53 immunohistochemistry. Correlations between PCNA LI (labelling index), EGFR expression, p53 expression, age, serum parathormone, Ca and P levels, and tumour diameter were investigated. PCNA LI was 45.8+/-33.1 (mean+/-standard deviation) and all the cases were somewhat positive. Five cases (41.67 %) were EGFR positive. Maximum 10 % of the cells were positive in these cases. All the cases were p53 negative. There was a correlation between PCNA LI and serum parathormone level (r=0.607, p=0.036). According to these results, parathormone synthesis is high when the proliferative activity of parathyroid adenoma is high. Four of the five EGFR-positive patients were below 35 years of age. These data may indicate that formation of parathyroid adenoma in young patients is related to a mechanism involving EGFR. Absence of p53 expression suggests that p53 mutation is not a common component of parathyroid adenomas.

Operative management of substernal goiter: analysis of 52 patients.

Thyroid surgery for substernal goiter is an uncommon operation. This study was carried out to evaluate the clinical presentation, workup, surgical complications, and risk of malignancy for substernal goiter. From January 1995 to June 2001, 52 patients [27 men and 25 women (ratio, 1.1:1); average age of 52 years (range, 26-71 years)] underwent thyroid surgery for substernal goiter at Akdeniz University Hospital. All patients were symptomatic at presentation. A chest radiograph was used for most patients with a computed tomography scan being by far the most helpful in the study. A cervical approach was adequate for resection of the lesions in 50 (96%) patients. Two (4%) patients required medial sternotomy for removal of thyroid tissue. There was no perioperative mortality. Transient recurrent laryngeal nerve (RLN) palsy occurred in 2 (4%) patients, and permanent RLN occurred in 2 (4%) patients. The incidence of transient and permanent hypoparathyroidism was 8% and 6%, respectively. Other complications included wound infection in 2 (4%) patients and postoperative bleeding in 1 patient (2%). Histopathologically, 46 (88%) lesions were benign and 6 (12%) were malignant. Because the history of substernal goiter is progressive enlargement, surgical removal of thyroid tissue is always indicated and should be performed as soon as possible, unless there are contraindications for surgery. Cervical collar incision is nearly always adequate, with few exceptions.

Circadian variations in natural coagulation inhibitors protein C, protein S and antithrombin in healthy men: a possible association with interleukin-6.

Recent observations describe an increase in platelet aggregability and a decrease in fibrinolytic activity in the early morning hours. To determine whether anticoagulant proteins also show such a circadian variation we measured protein C (PC), protein S (PS), antithrombin (AT) and heparin cofactor-II (HC-II) levels on venous plasma samples taken from 10 healthy men at three-hour intervals throughout a 24-hour period. To investigate the possible temporal mapping of circadian periodicity, we also measured plasma levels of beta-thromboglobulin (beta-TG) as an indicator of platelet activation, and interleukin-6 (IL-6) as one of the possible regulatory factors that drive this rhythm. Blood samples were drawn at 6 a.m., 9 a.m., noon, 3 p.m., 6 p.m., 9 p.m. and midnight. PC, IL-6 and beta-TG were measured by ELISA, PS and AT by latex immune assay and HC-II by chromogenic substrate method. A significant circadian variation was found in PC, PS, AT, beta-TG and IL-6, but not in HC-II levels. PC, PS, IL-6 and beta-TG were at their peaks at 6 a.m., and nadirs at a time from noon to midnight. AT peak was at 6 p.m. and nadir at noon. The regression of PS on IL-6 was significant. Although the fluctuations of PS and AT were within the normal ranges during the day, some PC levels of two subjects were below the lower normal limit (0.70). These data indicate that PC, PS, and AT show a marked circadian periodicity as the other components of the blood coagulation and fibrinolytic system do. The similar trends in plasma concentrations of PC, PS, beta-TG and IL-6 may be coincidental, but could reflect a common regulatory mechanism or an effect on each other. The clinical implications of these physiological changes in coagulation inhibitors and the role of IL-6 in the anticoagulant response deserve further studies.

The use of recombinant human G-CSF in the treatment of propylthiouracil-induced agranulocytosis.

A 43-year-old female patient with Basedow-Graves' disease developed agranulocytosis in the eighth month of propylthiouracil therapy. After discontinuing the drug, a broad spectrum antibiotic regimen plus recombinant human granulocyte colony-stimulating factor (G-CSF), a human haematopoietic growth factor, were started. Her granulocyte count returned to normal with the second dose of G-CSF, and ulcerating pharyngitis improved rapidly. We think that in patients with propylthiouracil-induced agranulocytosis, G-CSF will reduce the risk and severity of infection, and should be accepted as a part of the standard therapy.

Glycemic control and coagulation inhibitors in diabetic patients.

OBJECTIVE: To investigate the plasma antigenic levels and functional activities of coagulation inhibitors in poorly controlled diabetic patients and the possible effect of good glycemic control on these parameters. RESEARCH DESIGN AND METHODS: Both functional activities and plasma antigenic levels of coagulation inhibitors (antithrombin III, heparin cofactor II, protein C, and protein S) and plasma levels of C4b-binding protein were measured in 28 diabetic patients (13 males, 15 females; 2 IDDM, 26 NIDDM; median age 56.5 years; median duration of diabetes 5.5 years) with poor glycemic control (median HbA(1c) 11.8%). Twenty-three healthy subjects were enrolled as controls. Following a 3-month intensification of antihyperglycemic therapy, good glycemic control (HbA(1c) <8%) was achieved in 17 patients, and the plasma levels of the same parameters during this period were compared with baseline values. RESULTS: Functional activities and plasma antigenic levels of coagulation inhibitors were comparable in poorly controlled diabetic patients and healthy subjects. In patients achieving good control after 3 months, there was a significant reduction in plasma antigenic levels of protein S (p = 0.005) and C4b-binding protein (p = 0.03); however, no difference could be observed in other parameters. HbA(1c) did not show any correlation with plasma antigenic levels or functional activities of coagulation inhibitors either at baseline or at 3 months of good glycemic control. CONCLUSIONS: Our findings suggest that in poorly controlled diabetic patients, coagulation inhibitors are not different from healthy controls. Short-term good glycemic control may not exert a profound effect on coagulation inhibitors except protein S and its binding protein, C4b-binding protein.