Disease-free survival and the prognostic factors affecting disease-free survival in patients with medullary thyroid carcinoma: a multicenter cohort study.

PURPOSE: Despite several factors that may have been associated with poor disease-free survival (DFS) in patients with medullary thyroid carcinoma (MTC), only a few studies have evaluated the prognostic factors affecting DFS in MTC patients. Therefore, this study evaluated the prognostic factors affecting DFS, in a large number of patients with MTC. METHODS: Patients treated for MTC were retrospectively analyzed. Patients were stratified as having persistent/recurrent disease and no evidence of disease (NOD) at the last follow-up. The factors affecting DFS after the initial therapy and during the follow-up period were investigated. RESULTS: This study comprised 257 patients [females 160 (62.3%), hereditary disease 48 (18.7%), with a mean follow-up time of 66.8 ± 48.5 months]. Persistent/recurrent disease and NOD were observed in 131 (51%) and 126 (49%) patients, respectively. In multivariate analysis, age > 55 (HR: 1.65, p = 0.033), distant metastasis (HR: 2.41, p = 0.035), CTN doubling time (HR: 2.7, p = 0.031), and stage III vs. stage II disease (HR 3.02, p = 0.048) were independent predictors of persistent/recurrent disease. Although 9 (8%) patients with an excellent response after the initial therapy experienced a structural recurrence, the absence of an excellent response was the strongest predictor of persistent/recurrent disease (HR: 5.74, p < 0.001). CONCLUSIONS: The absence of an excellent response after initial therapy is the strongest predictor of a worse DFS. However, a significant proportion of patients who achieve an excellent response could experience a structural recurrence. Therefore, careful follow-up of patients, including those achieving an excellent response is essential.

Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients.

OBJECTIVE: Thyroid-stimulating hormone (TSH) suppression treatment can induce signs and symptoms of hyperthyroidism and hypothyroidism due to inappropriate treatment or poor compliance to the treatment. The current study aimed to investigate TSH levels, frequency of being on target TSH, adherence to levothyroxine (LT4) suppression treatment in differentiated thyroid cancer (DTC) patients after surgery in a multicentric setting. DESIGN AND PATIENTS: This multicentric cross-sectional study was conducted at 21 medical centres from 12 cities in Turkey. DTC patients followed at least one year in the same center included in the study. Clinical data, serum TSH, free thyroxine (FT4), thyroglobulin (Tg) and anti-Tg levels were recorded during the most recent visit. Body mass index, systolic and diastolic blood pressures, pulse rate were measured. LT4 doses were recorded and doses per kilogram of bodyweight were calculated. Pill ingestion habits recorded and adherence to the therapy were evaluated using the Morisky Medication Adherence Scale and categorized as good, moderate or poor compliant based on their scores. Risk stratification forpredicting the disease persistance and/or reccurence was assessed using the American Joint Committee on Cancer-7th edition thyroid cancer staging calculator. TSH serum concentrations were classified as severe suppression (TSH < 0.01 mU/L), moderate suppression (TSH: 0.01-0.1 mU/L), mild suppression (TSHL 0.1-0.5 mU/L), euthyroid (TSH: 0.5-4 mU/L) and hypothyroid (TSH > 4 mU/L). TSH levels can also be classified as on being on target, under the target, or beyond over the target, according to the American Thyroid Association recommendations. RESULTS: A group of 1125 patients (F/M: 941/184, 50.7 ± 11.7 years) were included in the study. The mean LT4 daily dosage was 132.4 ± 39.6 mcg/day. TSH levels showed severe suppression in 99 (%8.8) patients, moderate suppression in 277 (%24.6) patients and mild suppression in 315 (%28) patients and euthyroid range in 332 (%29.5) patients and hypothyroid range in 97 (8.6%). TSH levels were in target in 29.2% of the patients 20.4% of the patients were undertreated, 50.4% overtreated. The daily LT4 dose and LT4 dose/kg were significantly higher in the severe suppression group (p < .001, p < .001). According to the Morisky scale, 564 patients (50.1%) were good compliant, 368 patients (32.7%) were moderate compliant, and 193 patients (17.1%) were noncompliant. Patients with poor compliance need a higher dose of LT4 compared to the good compliance group (p < .001). TSH levels of patients with good compliance were 0.67 ± 1.96 mU/L and TSH with poor compliance was 2.74 ± 7.47 mU/L (p < .001). TSH levels were similar in patients on fixed and alternating dosages. CONCLUSION: In 29.2% of the DTC patients, serum TSH levels were at target levels. Remaining of the study group have TSH levels under or over treatment range, exposing the patient to medication side effects. Majorty of the study group 82.8% have good or moderate adherence to LT4 therapy. Reaching TSH targets requires simplified and applicable guidelines and following the guideline recommendations.

The Association of Serum Osteocalcin Levels with Metabolic Parameters and Inflammation in Postmenopausal Women with Metabolic Syndrome.

Introduction: Although adipose tissue largely plays a role in the etiopathogenesis of metabolic syndrome (MS), which is an inflammatory process, the skeleton may also contribute to this process through osteocalcin (OC), which is a bone-derived protein. In this study, we aimed to evaluate OC levels in postmenopausal women with MS and to investigate the association of OC levels with the metabolic and inflammatory parameters. Methods: Thirty-five postmenopausal women diagnosed with MS were recruited for the study. Sixteen postmenopausal women without any of the MS criteria formed the control group. Body weight, height, and waist and hip circumference of all of the subjects were measured and body mass indices (BMIs) were calculated. Levels of serum glucose, insulin, C-peptide, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, albumin, creatinine, calcium, phosphorus, total alkaline phosphatase, parathormone, and as inflammatory parameters, erythrocyte sedimentation rate, fibrinogen, and high-sensitive C-reactive protein (hsCRP) were studied from fasting venous blood samples of all the subjects. Homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. Serum total OC levels were studied from all of the subjects. Bone mineral densities were also measured. Results: Serum OC levels of the group with MS median (5.37 ng/mL) were lower than the OC levels of the group without MS (P < 0.01). Serum OC levels significantly and negatively correlated with fasting blood glucose (r = -0.310, P < 0.05), insulin (r = -0.343, P < 0.05), and HOMA-IR (r = -0.384, P < 0.01) values. Serum OC levels showed a significant and negative correlation with body weight (r = -0.293, P < 0.05), BMI (r = -0.333, P < 0.05), and waist-to-hip ratio (r = -0.384, P < 0.05). The inflammatory markers in the patient group were significantly higher than the control group. We found a negative association between serum OC levels and hsCRP levels in all cases (r = -0.283, P < 0.05). Conclusion: In the presence of MS, OC levels are significantly low and display a close association with glucose metabolism and adipose tissue. In addition, OC may play a regulatory role in subclinical systematic inflammatory response.

Effect of hyperparathyroidism on coagulation: a global assessment by modified rotation thromboelastogram (ROTEM)

Background/aim: Hyperparathyroidism is an endocrine disorder characterized by hypercalcemia. Because of calcium's effects on parathyroid glands, bone, intestines, and kidneys, it has an important place in homeostasis. The results of studies regarding hyperparathyroidism hemostasis are conflicting. Thromboelastography helps to evaluate all steps of hemostatic system. Our aim in this study was to investigate the possible role of hemostatic mechanisms in the development of thrombosis in hyperparathyroid patients with the modified rotation thromboelastogram (ROTEM). Materials and methods: Twenty-two patients with primary hyperparathyroidism (PHPT) and 20 healthy controls were involved. This study was conducted in Eskisehir Osmangazi University Faculty of Medicine, Endocrinology and Hematology clinics for 2 years. The complete blood count, fibrinogen, D-dimer levels, prothrombin time, activated prothrombin time, and ROTEM parameters [clot formation time (CFT), clotting time (CT), and maximum clot formation (MCF)] were determined by two activated tests, INTEM and EXTEM analyses. A thromboelastographic evaluation was performed in the preoperative and postoperative (3 months after surgery) periods. Results: In INTEM assay, the CT (p = 0.012) and CFT (p = 0.07) values were increased in preoperative PHPT patients compared with the control group. Although there was a decrease in the postoperative CT and CFT values, no statistical difference was found. Conclusion: The prolongation of the CT and CFT values were consistent with a hypocoagulable state in patients with PHPT. Hyperparathyroidism causes a hypocoagulable state that can be successfully assessed by ROTEM. Hemostatic changes, do not seem to have an effect on increased cardiovascular mortality.

Assessment of fragmented QRS formation and its relationship with left ventricular hypertrophy in nonhypertensive acromegaly patients

Background/aim: It is known that the presence of fragmented QRS (fQRS) on electrocardiography (ECG) is associated with cardiovascular events. The aim of this study was the evaluation of fQRS formation and its relationship with the left ventricular hypertrophy (LVH) parameters in acromegaly patients. Materials and methods: In total, 47 previously diagnosed with non-hypertensive acromegaly patients and 48 control subjects were included in the study. ECG and transthoracic echocardiography (TTE) were performed for each participant. Acromegaly patients were divided into two groups according to the fQRS formation on the ECG. Left ventricular wall thicknesses, and left atrial diameter (LAD), left ventricular mass (LVM), left ventricular mass index (LVMi), and relative wall thickness (RWT) were obtained. Results: In control group 5 (10.4%) and in acromegaly group 17 (36.2%) patients had fQRS on ECG (p = 0.003). LAD [36.0 (34.0­38.0) vs. 38.0 (35.0­41.0) mm, p < 0.001], LVM [155.27 ± 27.00 vs. 173.0 (153.0­235.0) g, p < 0.001], LVMi [83.12 ± 13.19 vs. 92.0 (83.0­118.0) g/m², p < 0.001] and RWT [0.39 ± 0.03 vs. 0.43 (0.41­0.45), p = 0.001] were significantly higher in patients with acromegaly. Disease duration was significantly higher (11.59 ± 1.3 vs. 8.2 ± 1.8 years, p < 0.001) in the fQRS (+) group. LAD [41.0 (39.0­42.5) vs. 37.0 (34.7­38.0) mm, p < 0.001], LVM [219.0 (160.5­254.5) vs. 164.0 (153.0­188.0) g, p = 0.017], LVMi [117.0 (92.5­128.5) vs. 86.0 (82.0­100.2) g/m², p = 0.013] and RWT [0.44 (0.42­0.49) vs. 0.43 (0.40­0.44), p = 0.037] were significantly higher in fQSR (+) acromegaly patients. In multivariate logistic regression analysis, disease duration (odds ratio: 10.05, 95% CI: 1.099­92.012, p = 0.041) and LAD (odds ratio: 2.19, 95% CI: 1.030­4.660, p = 0.042) were found to be the independent predictors of fQRS formation. Conclusion: The results of our study revealed that fQRS (+) acromegaly patients had increased LVH parameters compared to fQRS (-) patients.

Evaluation of exercise capacity using two field tests in patients with metabolic syndrome.

PURPOSE: Field tests are popular for assessing exercise capacity because they are practical and have established validity. The objective of this study was to compare physiological responses and exercise performance of patients with metabolic syndrome in two field tests of exercise capacity. MATERIAL AND METHODS: Forty-seven patients diagnosed with metabolic syndrome participated in this cross-sectional study. Exercise capacity was assessed using incremental shuttle walk test and six-minute walk test. Factors determining exercise capacity and agreement between the two tests were also investigated. RESULTS: Metabolic syndrome patients achieved a significantly greater percentage of predicted maximal heart rate, blood pressure, and longer distance in the incremental shuttle walk test than in the six-minute walk test (p < 0.001). Gender and body mass index explained 48.5% of the variance in six-minute walk test distance (R = 0.697, R2 = 0.485, F(2-46) = 20.737, p < 0.001). Body mass index and fat-free mass explained 55% of the variance in incremental shuttle walk test distance (R = 0.746, R2= 0.557, F(2-46) = 27.623, p < 0.001). CONCLUSIONS: Despite the agreement in the percentages of predicted maximal heart rate during these two field tests, the incremental shuttle walk test may be a better assessment tool than the six-minute walk test because it elicits more pronounced and definitive physiological responses to exercise tolerance in patients with metabolic syndrome.IMPLICATIONS FOR REHABILITATIONThe incremental shuttle walk test can be used to evaluate exercise capacity in metabolic syndrome.The incremental shuttle walk test elicits greater physiological responses than the six-minute walk test.The incremental shuttle walk test may be preferable over the six-minute walk test in investigating exercise capacity.Both tests can guide and assist in the evaluation of this patient population in clinical practice.Body mass index affected distance in both exercise tests.

Effect of teriparatide treatment on endothelial function, glucose metabolism and inflammation markers in patients with postmenopausal osteoporosis.

OBJECTIVE: Teriparatide, an anabolic agent used in the treatment of postmenopausal osteoporosis, can induce effects similar to primary hyperparathyroidism. Our objective was to evaluate the effects of teriparatide on endothelial functions, glucose metabolism and inflammation markers in patients diagnosed with postmenopausal osteoporosis. DESIGN, PATIENTS AND MEASUREMENTS: This was a single-centre, single-arm, 6-month prospective study. Twenty-three postmenopausal women over 65 years old with a lumbar spine or femoral neck T-score of -4·0 or lower and having at least two compression fractures in thoracic or lumbar spine were studied. Low-dose intermittent teriparatide (20 µg/day) was supplemented with calcium carbonate (1000 mg elemental calcium) and 880 IU cholecalciferol for 6 months. The biochemical parameters for glucose metabolism, inflammation and atherosclerosis were determined. For the assessment of vascular endothelial function, carotid intima-media thickness (CIMT), brachial artery intima-media thickness (BIMT), per cent change in flow-mediated dilation (FMD%) and nitroglycerine-induced dilations (NID%) were measured on ultrasonography. RESULTS: The fasting plasma glucose, homoeostatic model assessment of insulin resistance, fibrinogen, homocysteine and high-density lipoprotein cholesterol increased significantly with teriparatide treatment (P < 0·05 for all). Baseline CIMT and BIMT did not change significantly with 6 months of teriparatide treatment (P > 0·05); however, FMD% and NID% showed significant decrease after treatment (P < 0·01 for both). CONCLUSIONS: Intermittent teriparatide treatment may adversely affect some parameters of glucose metabolism, inflammation and endothelial function. On the basis of our findings, further large-scale and controlled studies are needed to clarify the exact effect of teriparatide treatment on glucose metabolism, inflammation and endothelial function.

The Effect of Hyperparathyroid State on Platelet Functions and Bone Loss.

OBJECTIVE: Coagulation and fibrinolysis defects were reported in primary hyperparathyroid patients. However, there are not enough data regarding platelet functions in this group of patients. Our aim was to evaluate the platelet functions in primary and secondary hyperparathyroid patients and to compare them with healthy subjects. MATERIALS AND METHODS: In our study 25 subjects with primary hyperparathyroidism (PHPT), 25 subjects with secondary hyperparathyroidism (SHPT), and 25 healthy controls were included. Platelet functions of the subjects were evaluated by using platelet-rich plasma and platelet aggregation tests induced with epinephrine, adenosine diphosphate (ADP), collagen, and ristocetin. Serum P selectin levels, which indicate platelet activation level, were measured in all subjects. Bone mineral densitometry was performed for all patients. RESULTS: There was no significant difference between the groups with PHPT and SHPT and the control group regarding the platelet aggregation tests and serum P selectin levels. There was also no significant correlation between parathormone levels and aggregation parameters (ristocetin, epinephrine, collagen, and ADP: respectively p=0.446, 0.537, 0.346, and 0.302) and between P selectin (p=0.516) levels. When we separated the patients according to serum calcium levels, there was also no significant difference between aggregation parameters and serum P selectin levels between the patients with hypercalcemia and the patients with normocalcemia. We could not find any significant correlation between aggregation parameters, P selectin levels, and serum calcium levels in this group of patients. Bone loss was greater in patients with PHPT. CONCLUSION: There is no significant effect of PHPT or SHPT and serum calcium levels on platelet functions when evaluated by aggregation tests.

The effects of atorvastatin on antioxidant/antiinflammatory properties of HDLs in hypercholesterolemics.

BACKGROUND/AIM: Hypercholesterolemia is characterized by changes in lipid profile, nitric oxide pathway, and oxidative stress markers, but functions of high-density lipoprotein (HDL) were not well established in hypercholesterolemic subjects treated with atorvastatin. In this study, we aimed to evaluate effects of atorvastatin treatment on functionality of HDL, oxidative stress, and endothelial functions in hypercholesterolemic subjects. MATERIALS AND METHODS: Thirty patients (20 females, 10 males) aged from 40 to 60 years and diagnosed as hypercholesterolemic were included. Patients were treated with 10 mg/day atorvastatin for 3 months. Markers of endothelial functions, namely asymmetric dimethylarginine (ADMA), homocysteine, and nitric oxide (NO), and markers of oxidative status, namely malondialdehyde (MDA), antioxidant potential (AOP), paraoxonase 1 (PON1), and arylesterase, were measured. Before and after atorvastatin treatment, glucose, lipid parameters, and antioxidant/antiinflammatory HDL levels were also measured. RESULTS: ADMA and homocysteine levels were decreased whereas NO levels were increased with atorvastatin therapy. MDA levels were decreased but AOP, PON1, and arylesterase levels and antinflammatory characteristics of HDLs were increased. Furthermore, lipid profiles of the patients improved with atorvastatin therapy. CONCLUSION: Hypercholesterolemia is a cause of oxidative stress, endothelial dysfunction, and proinflammatory HDL levels. Atorvastatin is a beneficial pharmacological modulator of impaired antiinflammatory HDL-C levels, endothelial functions, and oxidative status against atherosclerosis indicating pleiotropic effects of statins.

Investigation on carbohydrate counting method in type 1 diabetic patients.

OBJECTIVE: The results from Diabetes Control and Complications Trial (DCCT) have propounded the importance of the approach of treatment by medical nutrition when treating diabetes mellitus (DM). During this study, we tried to inquire carbohydrate (Kh) count method's positive effects on the type 1 DM treatment's success as well as on the life quality of the patients. METHODS: 22 of 37 type 1 DM patients who applied to Eskisehir Osmangazi University, Faculty of Medicine Hospital, Department of Endocrinology and Metabolism, had been treated by Kh count method and 15 of them are treated by multiple dosage intensive insulin treatment with applying standard diabetic diet as a control group and both of groups were under close follow-up for 6 months. Required approval was taken from the Ethical Committee of Eskisehir Osmangazi University, Medical Faculty, as well as informed consent from the patients. The body weight of patients who are treated by carbohydrate count method and multiple dosage intensive insulin treatment during the study beginning and after 6-month term, body mass index, and body compositions are analyzed. A short life quality and medical research survey applied. At statistical analysis, t-test, chi-squared test, and Mann-Whitney U test were used. RESULTS: There had been no significant change determined at glycemic control indicators between the Kh counting group and the standard diabetic diet and multiple dosage insulin treatment group in our study. CONCLUSION: As a result, Kh counting method which offers a flexible nutrition plan to diabetic individuals is a functional method.

Relation of asymmetric dimethylarginine levels to macrovascular disease and inflammation markers in type 2 diabetic patients.

AIM. We aimed to determine the relation of asymmetric dimethyl arginine (ADMA) levels to atherosclerotic vascular disease and inflammation markers in type 2 diabetes. METHODS. We recruited 50 type 2 diabetic patients with atherosclerosis, 50 type 2 diabetic patients without atherosclerosis, and 31 healthy control patients into our study. We obtained fasting serum and plasma samples and measured HbA1c, fasting blood glucose, C-peptide, creatinine, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, hsCRP, fibrinogen, erythrocyte sedimentation rate, total homocysteine, and ADMA levels. In addition, all of the patients were evaluated for carotid artery intima media thickness by ultrasound. We evaluated ADMA levels in healthy controls, diabetic patients with macrovascular complications, and diabetic patients without macrovascular complications and evaluated the relationship between ADMA levels and total homocysteine, inflammation markers, and macrovascular disease. RESULTS. Mean ADMA values in non-MVD and control groups were significantly lower than in MVD group (0.39 ± 0.16, 0.32 ± 0.13, 0.52 ± 0.23, P < 0.05, resp.). These three variables (carotid intima-media thickness, inflammatory markers, and ADMA levels) were significantly higher in diabetes group than control (P < 0.05). CONCLUSION. There is a relationship between ADMA and macrovascular disease in type 2 diabetes, but further studies are needed to understand whether increased ADMA levels are a cause of macrovascular disease or a result of macrovascular disease.

Cardiovascular risk assessment in patients with type 2 diabetes mellitus and metabolic syndrome: role of biomarkers.

OBJECTIVES: Metabolic syndrome (MetS) and type 2 diabetes mellitus (DM) are associated with a high incidence of cardiovascular diseases. The aim of this study was to determine paraoxonase (PON), total sialic acid (TSA), and nitric oxide (NO) levels in addition to conventional risk markers in patients with DM, MetS and DM plus MetS. MATERIAL AND METHODS: The study has been carried out over 78 subjects which divided into four groups; control (n=18), DM (n=20), newly diagnosed MetS (n=20) and DM plus MetS patient groups (n=20). RESULTS: Both insulin and triglyceride concentrations were significantly higher in DM+MetS group than in control and DM groups and serum HDL-C concentrations were significantly lower in DM+MetS group than other groups. Patients with MetS had higher LDL-C, total cholesterol and hsCRP concentrations than in the other groups. Interestingly, in addition to body mass index and waist circumference values, LDL-C, total cholesterol and hsCRP concentrations were decreased in patients who have both DM and MetS. Serum NO and TSA levels were higher in MetS and DM+MetS groups compared to control subjects. Unexpectedly, PON activity has been found lower in control group when compared to other groups. CONCLUSIONS: Although there is no doubt that association of DM and MetS elevates the risk of cardiovascular disease, occurrence of DM in patients with undiagnosed MetS might be encouraging patients to change their life styles and dietary habits.

Hypokalemic paralysis due to primary hyperaldosteronism simulating Gitelman's syndrome.

Some diseases, such as Gitelman's syndrome, Bartter's syndrome, and primary hyperaldosteronism (Conn's syndrome), may bear some similar clinical and laboratory findings. Their treatment modalities being different from one another, the need for a scrupulous diagnostic evaluation arises as far as clinical practice is concerned. In this report, we present a patient with Conn's syndrome who was initially considered to have Gitelman's syndrome due to displaying a few overlapping features of both diseases. We also give an account of the hardships encountered during the diagnostic evaluation.

Chronic alcohol consumption augments loss of sialic acid residues and alters erythrocyte membrane charge in type II diabetic patients.

In this study, the effects of alcohol consumption on erythrocyte membrane properties in type 2 diabetic patients were investigated. Therefore, we measured total and lipid-bound sialic acid (LSA) levels, sialidase activities, and erythrocyte membrane negative charge. Three groups, including control group (n = 20), alcohol-consuming diabetic patients group (n = 14), and diabetic patients without alcohol consumption group (n = 42), were created. Plasma total sialic acid (TSA) levels of the alcohol-consuming diabetic group were elevated as compared to the healthy control and diabetic group (p < 0.001 and p < 0.01, respectively). TSA levels of the diabetic group were significantly elevated as compared to the healthy control group (p > 0.001). Plasma LSA levels of the alcohol-consuming diabetic group were higher than that in the healthy control and diabetic group (p < 0.05 and p < 0.05, respectively). LSA levels of the diabetic group were found to be high as compared to the healthy control group (p < 0.05). Plasma sialidase activities of the alcohol-consuming diabetic group and diabetic group were significantly elevated as compared to the healthy control group (p < 0.05 and p < 0.05, respectively). Sialidase activities of the alcohol-consuming diabetic group were elevated as compared to the diabetic group, but this was not statistically significant (p > 0.05). Erythrocyte membrane negativity levels of the alcohol-consuming diabetic group and diabetic group were significantly decreased (p < 0.001 and p < 0.001, respectively) as compared to the healthy control group. Erythrocyte membrane negativity levels of the alcohol-consuming diabetic group were decreased as compared to the diabetic group, but this was not statistically significant (p > 0.05). In conclusion, our results indicate that chronic alcohol consumption may augment membrane alterations in type 2 diabetic patients.

Unusual case of calciphylaxis associated with primary hyperparathyroidism without coexistent renal failure.

OBJECTIVE: To report a case of calciphylaxis in a patient with primary hyperparathyroidism without coexistent renal failure. METHODS: The clinical, laboratory, and radiographic details of this case are reviewed, and the pathogenesis of calciphylaxis and the associated prognosis are discussed. RESULTS: A 52-year-old woman had progressive fatigue, cachexia, severe osteoporosis, and necrotizing skin lesions. Her serum calcium level was 16 mg/dL, serum phosphorus level was 2.13 mg/dL, and parathyroid hormone level was 2,257 pg/mL (reference range, 15 to 65). On physical examination, gangrenous skin lesions with black crusts were noted on her legs, abdomen, and gluteal region. A mass lesion was detected in the parathyroid region by both ultrasonography and a parathyroid scan. The patient underwent a bilateral neck exploration, and a parathyroid adenoma measuring 3.5 by 1.5 by 1.2 cm was found on pathologic examination. After the operation, biochemical findings normalized, and the skin lesions progressively improved. CONCLUSION: Severe primary hyperparathyroidism may be a factor leading to calciphylaxis, even in the absence of renal failure and a high calcium-phosphate product. This potentially life-threatening condition should not be left untreated if the levels of serum calcium and parathyroid hormone are severely elevated.

Short term effects of atorvastatin on endothelial functions and oxidized LDL levels in patients with type 2 diabetes.

OBJECTIVE: This study was designed in order to investigate the short term effects of atorvastatin on endothelial function and oxidized LDL (oxLDL) levels and to evaluate the association of endothelial dysfunction to oxLDL levels and inflammatory markers in type 2 diabetic patients. MATERIAL AND METHODS: Thirty type 2 diabetic and 11 healthy subjects with LDL levels between 100-160 mg/dl. without a history of cardiovascular event were included in the study. Both groups were matched with respect to age, gender, body mass indices and lipid levels. Flow- mediated dilatation (endothelium dependent, FMD) and nitroglycerine-induced dilatation (endothelium independent, NID) were measured in the brachial artery using high-resolution ultrasound in all participants and carotid artery intima media thickness (IMT) were also evaluated. OxLDL levels, lipid parameters, blood glucose, C-peptide, HbA1c and inflammatory markers including C-reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR) were studied. Type 2 diabetic patients received 10 mg. Atorvastatin for 6 weeks and FMD and NID were reevaluated and oxLDL levels and inflammatory markers remeasured. RESULTS: Basal FMD, NID, IMT and oxLDL levels besides inflammatory markers were not significantly different between patients and controls. No correlation was found between inflammatory markers and FMD and NID. Only IMT correlated with fibrinogen levels obtained before treatment. In non-diabetics, IMT also correlated with oxLDL levels (p: 0.013). FMD and NID significantly improved after atorvastatin therapy ((7.62 +/- 7.6 vs. 12.65 +/- 7.8, p<0.001 and 18.22 +/- 9.57 vs. 21.43 +/- 9.6, p: 0.007, respectively). Atorvastatin significantly reduced oxLDL levels (57.85 +/- 10.33 vs. 44.36 +/- 6.34, p<0.001). CONCLUSION: Atorvastatin improves endothelial functions and reduces oxLDL levels in type 2 diabetics with average lipid levels in the short term and may have beneficial effects in the prevention of early atherosclerotic changes.

Relation of plasma homocysteine levels to atherosclerotic vascular disease and inflammation markers in type 2 diabetic patients.

OBJECTIVE: Both hyperhomocysteinemia and increased inflammatory activity are shown to be associated with atherosclerosis. The relation of inflammatory activity to homocysteine (Hcy) levels is not well established. In the present study, we aimed to evaluate the relation of plasma Hcy levels to atherosclerotic vascular disease and inflammatory activity in type 2 diabetic patients. DESIGN AND METHODS: In total 90 type 2 diabetic patients were included in the study. Of these patients, 41 had established atherosclerotic vascular disease and 49 had no evidence of atherosclerotic vascular disease. Hcy levels and markers of inflammation, namely C-reactive protein, fibrinogen, erythrocyte sedimentation rate, interleukin-6, and tumor necrosis factor alpha (TNFalpha), were measured. Glucose regulation, C-peptide, lipid parameters, and renal functions were also studied. RESULTS: Both Hcy levels and inflammation markers were all significantly elevated in patients with atherosclerotic vascular disease when compared with patients without vascular disease. Reduced renal functions were responsible for the majority of Hcy elevation in patients with vascular disease. Also, renal functions were significantly associated with both Hcy levels and inflammatory markers. There was no correlation between Hcy levels and inflammation markers except for TNFalpha. CONCLUSIONS: Inflammatory activity and Hcy levels are increased in type 2 diabetic patients with atherosclerotic vascular disease. Impairment of renal functions is the key factor that affects both Hcy levels and inflammation markers. Inflammation is not involved in the process by which Hcy leads atherosclerosis in type 2 diabetes.

Bone remodelling markers and serum cytokines in patients with hyperthyroidism.

OBJECTIVE: This study was designed in order to evaluate bone turnover with bone formation and resorption markers in hyperthyroidism and its possible relationship with serum cytokines interleukin 6 (IL-6) and tumour necrosis-alpha (TNF-alpha), levels of thyroid hormones and thyroid autoantibodies. DESIGN AND PATIENTS: Twenty-six hyperthyroid patients including nine with Graves' disease, 14 with toxic multi-nodular disease and three toxic adenoma were studied. Twenty normal subjects served as the control group. MEASUREMENTS: Serum calcium, phosphorus, total and bone-specific alkaline phosphatase, procollagen type 1-C peptide (PICP), osteocalcin, IL-6 and TNF-alpha measurements were performed and deoxypyridinoline (free DPD), calcium, phosphorus and creatinine levels were measured in fasting morning urine specimens of all hyperthyroid patients and all controls. Also, serum total and free T3 and T4 and TSH were analysed and thyroid antiperoxidase and antithyroglobulin antibodies were determined in sera of hyperthyroid patients. Patients with hyperthyroidism received propylthiouracil treatment until the achievement of euthyroidism and then serum cytokine levels were remeasured. RESULTS: Mean serum values of osteocalcin, total and bone-specific alkaline phosphatase were all significantly higher in hyperthyroid patients than in normal controls. PICP levels were not significantly different between these two groups. Urinary deoxypyridinoline levels were markedly elevated in hyperthyroid patients compared to the control group. There was a significant positive correlation between urinary free DPD levels and serum free T3, free T4 and T4 levels. Serum free T4 levels also correlated with urinary calcium levels. Serum IL-6 values were significantly higher in hyperthyroid patients compared to control group. TNF-alpha levels were slightly lower in patients with hyperthyroidism. No significant correlation was found between bone remodelling markers and serum cytokines. Serum Il-6 levels were correlated positively with age. After the treatment period both IL-6 and TNF-alpha returned to levels comparable with euthyroid controls. CONCLUSION: Bone turnover is increased in favour of resorption and the rate of resorption is associated with the levels of thyroid hormones in hyperthyroidism. The increase in the levels of serum IL-6 in hyperthyroidism is not related directly with bone resorption seen in hyperthyroidism.