Clinical importance of antineutrophil cytoplasmic antibody positivity during propylthiouracil treatment.

BACKGROUND: Propylthiouracil (PTU) is the mainstay of antithyroid drug therapy. Previous studies reported antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis in patients treated for Graves' disease. ANCA has been associated with either PTU or to the disease itself. However, this issue has not been investigated in toxic multinodular goitre (TMNG). The aim of this study was to evaluate the frequency of ANCA positivity in both TMNG and Graves' disease patients treated with PTU, and to investigate the clinical importance of this issue. PATIENTS AND METHODS: We studied the presence of ANCA in 46 patients treated with PTU (30 Graves' disease, 16 TMNG). Two years after the discontinuation of PTU, ANCA was re-evaluated in 29 patients (18 Graves' disease, 11 TMNG). RESULTS: By indirect immunofluorescence, 19 of the 46 patients (41.3%) on PTU treatment were ANCA positive [13 of the 30 patients in Graves disease (43.3%), six of the 16 patients in TMNG (37.5%)]. There was no statistically significant difference between Graves' disease and TMNG patients for ANCA positivity (p = 0.362). ANCA positivity was not related to gender, thyroid autoantibodies, alanine aminotransferase, aspartate aminotransferase, neutrophil count and PTU dose. Two years after withdrawal of PTU treatment, 10.3% of patients continued to have positive ANCA (p < 0.0001). Signs and symptoms of vasculitis could not be detected in any of the ANCA-positive patients. CONCLUSION: Our study suggests that PTU but not Graves' disease itself is the most important factor for ANCA development. The frequency of ANCA positivity is 41.3% in our country which was not different in Graves' disease and TMNG patients. The dose of PTU and ethnic factors are not associated with ANCA positivity. After cessation of PTU, vasculitis did not develop during the 2 years of follow-up despite positive ANCA.

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.

Sheehan's syndrome associated with pancytopenia due to marrow aplasia; full recovery with hormone replacement therapy.

We describe a 52-year-old woman with pancytopenia associated with Sheehan's syndrome, whose presenting feature was severe malaise and syncope after a psychological stress. Hormonal replacement therapy alone (with L-thyroxine and prednisolone) produced clinical and full haematological recovery. This is a very rare case of Sheehan's syndrome because the diagnosis was delayed for 27 years after delivery, and it was associated with pancytopenia.

Graves' disease coexisting with probable autoimmune hypoparathyroidism.

Organ-specific autoimmune endocrine disorders may present as single diseases or may occur together in polyendocrine syndromes. We present a report of 23-year-old female with Graves' disease and concurrent hypocalcemia. As she lacked other specific features of autoimmune polyendocrine syndromes, the most likely diagnosis was Graves' disease coexisting with autoimmune hypoparathyroidism.

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.

Erythrocyte, plasma, and serum antioxidant activities in untreated toxic multinodular goiter patients.

Erythrocyte, plasma, and serum antioxidant activities were studied in patients with newly diagnosed and untreated toxic multinodular hyperthyroid goiter and compared to healthy control subjects. Erythrocyte antioxidant enzyme activities, glutathione, malondialdehyde, and ceruloplasmin levels were significantly increased, whereas serum vitamin E, plasma vitamin C, and selenium levels were decreased in hyperthyroid patients compared to control subjects. The findings show that untreated toxic multinodular goiter causes profound alterations in components of the antioxidant system in erythrocytes indicative of increased oxidative stress. Taken together, these data suggest that hyperthyroid patients may benefit from dietary supplements of antioxidants.

Effects of propylthiouracil treatment on antioxidant activities in blood of toxic multinodular goiter patients.

Erythrocyte, serum and plasma antioxidant activities and the effects of propylthiouracil (PTU) treatment on these activities were studied in patients with toxic multinodular goiter. The activities of the erythrocyte antioxidant enzymes (glucose-6-phosphate dehydrogenase, catalase, Cu/Zn-superoxide dismutase, selenium (Se)-dependent glutathione peroxidase and glutathione reductase) and the levels of erythrocyte Se, serum ceruloplasmin and plasma malondialdehyde were significantly higher while serum vitamin E, plasma vitamin C and plasma Se were lower in hyperthyroid patients. PTU treatment, not for 1 but for 3 months caused a partial reversal of antioxidant activities to euthyroid levels. It is suggested that alterations in blood antioxidant activities following PTU treatment might be due to the antioxidant and/or antithyroid effect of this drug.

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.

The value of Tc-99m tetrofosmin thyroid scintigraphy in patients with nodular goiter.

The aim of this study is to investigate the value of Tc-99m tetrofosmin (Tc-99m-TF) in conjunction with conventional Tc-99m-pertechnetate (Tc-99m-P) scintigraphy in the differentiation of malignant nodules from benign thyroid nodules. Forty-two patients [(32 females, 10 males; mean age 41 +/- 13 years; twenty-two multinodular goiter (MNG) patients with 58 nodules and 20 solitary thyroid nodules (STN)] were included in the study. Thyroid scintigraphy with Tc-99m-P and Tc-99m-TF, thyroid ultrasonography and fine needle aspiration cytology (FNAC) were performed. After i.v. injection of 370-550 MBq Tc-99m-TF, images were obtained at 15 minutes and evaluated semiquantitatively by using a five point (0-4) scoring system. Four patients with a hypoactive STN, and 1 patient with a hypoactive MNG was found to have thyroid malignancy by histopathological examination; 2 of these patients had false negative benign FNAC results. The tetrofosmin uptake score (TUS) was 2-3-3-3 and 3 in these 5 malignant nodules. Five hyperactive (hot or warm) STN with benign FNAC had a TUS of 2-3-3-3-3. All hypoactive (cold) MNG nodules with benign FNAC (n = 21) had TUS < or = 2. Our preliminary results suggest that follicular adenomas and thyroid cancers have higher tetrofosmin uptake than benign colloidal goiter nodules. Mitochondrial sequestration of tetrofosmin in benign or malignant follicular cells that proliferate more rapidly than normal follicular cells and/or hypervascularity may be responsible for this. The use of Tc-99m-TF in conjunction with Tc-99m-P thyroid scintigraphy will be helpful in the evaluation of patients with nodular goiter (NG). In patients with a STN, a hypoactive nodule with a high TUS has a higher probability of malignancy; whereas a hyperactive nodule with a high TUS is a follicular adenoma. In patients with MNG, a hypoactive nodule with a high TUS may be suggestive of malignancy despite a benign FNAC result. We think that further studies with Tc-99m-TF are required to confirm these results.

Transfer of native insulin through the peritoneal membrane during CAPD in non-diabetic and diabetic patients.

Because of its relatively small molecular size of 5800 daltons, insulin is a transperitoneally diffusable substance. Insulin is also known to be a mitogenic coadjuvant for mice fibroblasts, and safety of its long-term intraperitoneal use has been questioned because of the potential risk for peritoneal fibrosis. For similar reasons native insulin content of the peritoneal effluent should also not be neglected. To our knowledge, no sufficient data are available about native insulin transfer to dialysate during continuous ambulatory peritoneal dialysis (CAPD). In this study we measured plasma and dialysate immune-reactive insulin levels during a 4 hour peritoneal exchange in 9 nondiabetic and 4 type II diabetic end-stage renal disease patients on CAPD. In both plasma and dialysate, insulin levels were higher in diabetic patients. At hour 4 of dwell time, plasma insulin was 37.5 +/- 7.9 microU/mL in non-diabetics and 64.2 +/- 34.1 microU/mL in type II diabetics. In both groups, dialysate insulin was 1.5 to 2 x higher than their simultaneous peripheral vein insulin levels and was measured as 88.1 +/- 26.8 microU/mL in nondiabetic group and 101.7 +/- 52.6 microU/mL in the diabetic group at hour 4 (p < 0.005 vs 4 hour plasma level). In conclusion, in both diabetic and nondiabetic CAPD patients, native insulin was present in the dialysate in amounts exceeding simultaneous plasma levels. Equilibration with high portal vein insulin content through hepatic capsule may explain higher insulin concentrations measured in the dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased plasma endothelin levels in Kawasaki disease: a possible marker for Kawasaki disease.

Plasma immunoreactive endothelin (iET) levels were investigated in patients with Kawasaki disease (KD). The iET level was 2.49 +/- 0.13 pg/mL in KD patients and 1.32 +/- 0.06 in age-matched control subjects, showing a significant increase with KD. The iET level was not increased in patients with febrile inflammatory diseases of bacterial origin without KD (non-KD group). Parameters indicating an inflammatory reaction, such as C-reactive protein, platelet count, white blood cell count, and interleukin-6 level, were increased in the KD patients. However, they were similarly increased in the patients with febrile diseases of bacterial origin and showed no significant differences between the two groups. This study is the first to report that plasma iET levels are elevated in a disease mainly involving vasculitis. These results suggest that blood iET levels are increased in KD patients as a result of the associated vascular endothelial damage and that iET can be a useful marker for the diagnosis of KD.

The value of 99mTc-DTPA renal scintigraphy in the evaluation of post-traumatic abdominal fluid collection.

A patient with a post-traumatic retroperitoneal urinoma is presented. On admission, there was a clinical suspicion of retroperitoneal hematoma and ultrasonography (US) was performed which showed a hypoechoic fluid collection suggesting retroperitoneal hematoma. In order to determine the nature of the fluid, radionuclide angiography and renal scan were performed successively with 99mTc-DTPA. Demonstration of urinary leakage into the mass in the delayed renal scintigraphic images suggested a urinoma. At laparotomy, total transection of the left ureter in the uretero-pelvic region was found and the diagnosis of urinoma was confirmed.

Esophageal clearance scintigraphy, in diabetic patients--a preliminary study.

The aim of this preliminary study was to evaluate the predictive value of esophageal clearance scintigraphy (ECS) in the diagnosis of esophageal autonomic neuropathy in diabetic patients without any esophageal symptoms. A single swallow ECS was performed in 12 diabetic patients and 15 normal volunteers, and esophageal transit time (ETT) and esophageal (Es) T 1/2 values were calculated. ETT and Es T 1/2 were found to be significantly prolonged in the diabetic group (p less than 0.01 and p less than 0.05, respectively). In this preliminary study, our results strongly suggest that ECS may be an important noninvasive diagnostic tool in the evaluation of diabetic patients with asymptomatic esophageal autonomic neuropathy.

Tc-99m-HMDP bone uptake quantification and plasma osteocalcin levels in hemodialysis patients--a preliminary study.

In this preliminary study plasma osteocalcin levels and Tc-99m-HMDP (Technetium 99m hydroxymetylene diphosphonate) bone uptake (BU) were measured in 10 chronic end-stage renal failure patients who were on maintenance hemodialysis. The aim of this study was to determine the correlation between bone uptake and osteocalcin-a sensitive and specific marker of osteoblastic activity. There was a statistically significant increase in both 20 and 180 minute uptake in the patient group (36 +/- 2.7 and 39 +/- 3.6) when compared to the normal volunteers (32 +/- 3.1 and 19 +/- 2.7). Plasma osteocalcin levels were also significantly high (24.5 +/- 5.6 ng/ml) when compared with normal values (6.5 +/- 2.3 ng/ml). The correlations between osteocalcin and 20 and 180 min BU were high (r = 0.62 and 0.72 respectively). In conclusion, our preliminary study suggests that, in hemodialysis patients, Tc-99m-HMDP bone uptake quantification is a sensitive and non-invasive method for showing increased osteoblastic activity.

Effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin on urinary 6 beta-hydroxycortisol excretion: a preliminary study.

In this preliminary study, the levels of urinary 6 beta-hydroxycortisol and urinary free cortisol and the 6 beta-hydroxycortisol/free cortisol ratio were determined in normal volunteers and in patients with heterozygous familial hypercholesterolemia before and after Pravastatin administration (10 mg/d for 2 weeks). Urinary 6 beta-hydroxycortisol and 6 beta-hydroxycortisol/free cortisol ratio increased significantly in both groups after Pravastatin administration (P less than 0.05). The percent increase of 6 beta-hydroxycortisol/free cortisol did not differ significantly when the two groups were compared. Our preliminary results suggest that Pravastatin induces hepatic microsomal 6 beta-hydroxylase both in normal volunteers and in patients with heterozygous familial hypercholesterolemia.

Influence of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, on corticosteroid metabolism in patients with heterozygous familial hypercholesterolemia.

The present study examined whether hypolipidemic therapy with a potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, pravastatin, influences corticosteroid metabolism in patients with heterozygous familial hypercholesterolemia (FH). Urinary excretion of tetrahydrocortisone, tetrahydrocortisol, 6 beta-hydroxycortisol and free cortisol were determined in 22 patients with heterozygous FH before and after pravastatin administration (10 mg/day for 2 months). Pravastatin induced a statistically significant decrease in serum total cholesterol in patients with heterozygous FH from 6.9 +/- 0.1 to 5.9 +/- 0.1 mmol/l (p less than 0.05). No significant changes were seen in the urinary tetrahydrocortisone, tetrahydrocortisol and free cortisol levels before and after pravastatin therapy. Urinary excretion of 6 beta-hydroxycortisol was significantly (p less than 0.05) increased after pravastatin administration. These results suggest that the hypolipidemic effect of pravastatin in patients with heterozygous FH does not influence the corticosteroid metabolism. The increase in urinary 6 beta-hydroxycortisol may be caused by pravastatin-induced hepatic microsomal 6 beta-hydroxylase induction.