Relationship between metabolic syndrome and multinodular non-toxic goiter in an inpatient population from a geographic area with moderate iodine deficiency.

BACKGROUND: Obesity and insulin resistance predispose individuals to the development of both metabolic syndrome and non-toxic nodular thyroid diseases. AIM: The aim of this observational, cross-sectional study is to evaluate the relationship between metabolic syndrome and multinodular nontoxic goiter in an inpatient population from a geographic area with moderate iodine deficiency. SUBJECTS AND METHODS: We examined 1422 Caucasian euthyroid inpatients. Thyroid volume was determined by ultrasound of the neck. A fine-needle aspiration biopsy was performed to evaluate single thyroid nodules and dominant nodules ≥15 mm in euthyroid multinodular goiter. The diagnosis of metabolic syndrome was made according to the criteria of the American Heart Association/ National Heart, Lung, and Blood Institute. RESULTS: Of the sample, 277 patients had clinical evidence of multinodular nontoxic goiter, 461 met the criteria for the diagnosis of metabolic syndrome, and 132 were found to have both conditions. After adjusting for age, gender, body mass index, nicotinism, parity, alcohol intake, thyroid function, and metabolic syndrome- related pharmacological treatment, metabolic syndrome was found to be an independent risk factor for the occurrence of multinodular non-toxic goiter. The relationship between metabolic syndrome and multi nodular non-toxic goiter was apparent in both men and women. CONCLUSIONS: In this study of euthyroid inpatients, we demonstrate that metabolic syndrome is an independent risk factor for the occurrence of multinodular non-toxic goiter in a geographic area with moderate iodine deficiency. We propose that patients meeting the criteria for metabolic syndrome should be screened for the presence of multinodular non-toxic goiter.

Epidemiological, clinical, and genetic characteristics of Paget's disease of bone in a rural area of Calabria, Southern Italy.

BACKGROUND: The prevalence of Paget's disease of bone (PDB) is unknown in peninsular Southern Italy, although an elevated clinical severity of the disease was reported in patients from Campania. AIM: This study was performed to evaluate the epidemiological and genetic characteristics of PDB in a rural area of Calabria, the southernmost region in the Italian peninsula. SUBJECTS AND METHODS: We examined 1068 consecutive pelvic radiographs of patients older than 40 yr referred for any reason to the "Spinelli" Hospital, Belvedere Marittimo, from January 1st 2004 to December 31st 2006. In subjects with radiological findings of pelvic PDB, a 99m Technetium methylene diphosphonate bone scan and the sequence analysis of the sequestosome 1 (SQSTM1) gene were subsequently performed. RESULTS: In the examined geographic area, the crude radiographic prevalence of pelvic PDB was 0.74% (8/1068; male:female 5:3, mean age 71.6 ± 13.1 yr) whereas the estimated overall prevalence of PDB between 0.82% and 1.21%. PDB patients from Calabria showed clinical characteristics similar to those reported in patients from Campania. The disease was also frequently complicated by osteoarthritis and the right side of the body was more affected than the left. The SQSTM1 gene analysis revealed the presence of a novel missense mutation (M401V) in exon 8 in one subject with a familial and aggressive form of PDB. CONCLUSION: The study results confirmed that patients with PDB from rural districts of Southern Italy show an earlier onset and an increased clinical severity of the disease that appears mostly independent from the presence of germinal SQSTM1 mutations.

[Phosphatonins: novel insights and clinical perspectives]. / Le fosfatine: recenti acquisizioni e possibili evoluzioni nella clinica.

Phosphate plays a vital role in several biological processes including energy and nucleic acid metabolism, cell signaling and bone mineralization. Several endocrine factors coordinately act on the intestine, kidney and bone to maintain their physiological homeostasis. A number of peptides, collectively known as phosphatonins, have recently been identified as regulators of phosphate metabolism in physiological and pathological conditions. These factors--fibroblast growth factors (FGF) 23 and 7, secreted frizzled related protein 4 (sFRP-4), and matrix extracellular phosphoglycoprotein (MEPE)--primarily regulate tubular phosphate reabsorption by acting on the transmembrane expression of SLC34 sodium-phosphate cotransporters. FGF- 23, FGF-7 and sFRP-4 also inhibit the biosynthesis of 1,25(OH)2D3, leading to decreased intestinal phosphate absorption. In this review, we discuss the biological properties of these peptides, their physiological roles, and the alterations in their concentrations in various hypophosphatemic and hyperphosphatemic clinical disorders.

Interleukin (IL)-6 and receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) are increased in the serum of a patient with primary pachydermoperiostosis.

Primary pachydermoperiostosis (PDP) is a rare syndrome, characterized by digital clubbing, periostosis, and pachydermia. We have evaluated biochemical bone turnover markers, including components of interleukin-6 (IL-6) and osteoprotegerin/receptor activator of nuclear factor (NF)-kappaB ligand (OPG/RANKL) systems, in an 18-year-old man affected by primary PDP. The acute phase of the disease was characterized in our patient by high serum levels of IL-6 and RANKL. The observed high serum levels of these parameters are associated with increased values in markers of bone resorption (degradation products of C-terminal telopeptides of type-I collagen and urinary hydroxyproline/creatinine ratio) and reduced serum levels of bone alkaline phosphatase, a marker of bone formation. Serum levels of osteotrophic hormones were in the normal range. Our data suggest that, despite the radiographic findings, the acute phase of primary PDP is characterized by increased bone resorption, probably mediated by IL-6 and RANKL.

Risedronate and pamidronate treatment in the clinical management of patients with severe Paget's disease of bone and acquired resistance to bisphosphonates.

The aim of this study was to evaluate the efficacy and safety of risedronate and pamidronate in 30 patients (mean age = 57.86 +/- 8.90 years) with severe Paget's disease of bone (PDB), showing acquired resistance to intravenous (IV) clodronate treatment. Fifteen patients were treated with oral risedronate (30 mg/day for 8 weeks). Treatment was repeated in patients without evidence of PDB remission [total alkaline phosphatase (tALP) serum levels in the normal range] at day 120. Fifteen patients were treated with IV pamidronate (30 mg/day for 3 days). Pamidronate treatment (60 mg/day for 3 days) was repeated in patients without evidence of PDB remission at day 120. At day 60, a significant decrease in tALP serum levels was obtained in all pagetic patients. At day 360, 13 (86.6%) patients treated with risedronate achieved PDB remission, 9 patients during the initial treatment and 4 after retreatment. Two patients showed a significant decrease in tALP serum levels without clinical remission after two risedronate treatments. At the same time, 12 (80%) patients treated with pamidronate achieved PDB remission, 6 patients during the first treatment and 6 after retreatment. Three patients showed a significant decrease in tALP serum levels but no clinical remission after two pamidronate courses. Two of these patients showed a relapse during the study. The incidence of minor side effects and transient hyperparathyroidism related to bisphosphonate treatment was significantly lower after risedronate therapy. In patients with resistant PDB, oral risedronate therapy has comparable efficacy to IV pamidronate with a lower incidence of treatment-related side effects.

Biochemical markers of bone turnover, serum levels of interleukin-6/interleukin-6 soluble receptor and bisphosphonate treatment in Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare non-Langherans form of histiocytosis characterized radiologically by symmetrical sclerosis of the metaphysis and the diaphysis of long tubular bones. Macrophages are potent interleukin-6 (IL-6) producers and elevated IL-6 serum levels have been described in pathological conditions characterized by increased bone resorption. In a patient with ECD, during the acute phase of the disease we found high serum levels of IL-6 and IL-6 soluble receptor (sIL-6R) and high levels of bone turnover markers. After 5 years of combination therapy with oral prednisone and intravenous clodronate a significant reduction in the above mentioned biological parameters was seen. We suggest that the systemic disorders present in ECD could be related to the high serum levels of IL-6 and sIL-6R. We also propose the use of bisphosphonates in the clinical management of ECD.

Association between vitamin D receptor gene polymorphisms and tubular citrate handling in calcium nephrolithiasis.

OBJECTIVES: Hypocitraturia is a risk factor for calcium nephrolithiasis. 1,25(OH)2D3 influences renal citrate handling and enhances citraturia. The aim of this study was to evaluate the relationship between vitamin D receptor (VDR) allelic variant and urinary citrate excretion in recurrent stone formers (SF) patients. DESIGN: Case-control study. SUBJECTS: A total of 220 recurrent calcium oxalate SF patients and 114 healthy control (C) subjects were enrolled for this study. Subjects with urinary tract infections, hyperparathyroidism, cystinuria >70 micromol/24 h, gouty diathesis, renal tubular acidosis, renal failure, chronic diarrhoeal states, intake of thiazide diuretics, angiotensin-converting enzyme (ACE)-inhibitors, glucocorticoids or oestrogens were excluded. A standard constant diet was given for 7 days. The 24-h urinary citrate excretion and the active tubular reabsorption of filtered citrate (Rcit) were evaluated. Hypocitraturia was defined as a urinary citrate excretion lower than 1.7 mmol day-1. Stone formers patients and C were genotyped for BsmI and TaqI VDR alleles. Contingency table chi-square tests were used to compare genotype frequencies in hypocitraturic SF patients, normocitraturic SF and C. RESULTS: The prevalence of hypocitraturia in SF patients was 32.7% (72 of 200). Hypocitraturia in these patients resulted from excessive Rcit of a normal load of citrate. We found a different distribution (P < 0.05) of BsmI and TaqI VDR genotypes in hypocitraturic SF patients compared with normocitraturic SF and C. In particular, the prevalence of bb and TT VDR genotypes in hypocitraturic SF was significantly higher than in normocitraturic SF and C. CONCLUSIONS: These results point to a genetic association between BsmI and TaqI VDR polymorphisms and idiopathic hypocitraturia in calcium-oxalate recurrent SF patients.

Clodronate treatment reduces serum levels of interleukin-6 soluble receptor in Paget's disease of bone.

OBJECTIVE: Interleukin-6 (IL-6) and its soluble receptor (sIL-6R) stimulate osteoclast formation and activity. The primary cell abnormality in Paget's disease of bone (PDB) involves osteoclasts. Pagetic osteoclasts overproduce IL-6 and IL-6 receptor in vitro. In vivo, IL-6 serum levels are very high in the acute phase of PDB. The aim of this study was to evaluate the modification in the serum levels of IL-6, sIL-6R and osteotropic hormones (parathormone, 25OHD3 and 1,25(OH)2D3) as a in long-term response to clodronate treatment in patients with PDB. METHODS: 16 patients (8 females) with polyostotic PDB were studied. IL-6, sIL-6R and osteotropic hormones serum levels were evaluated in active PDB and after clodronate treatment (300 mg injected intravenously for 5 consecutive days). The sequential changes in total alkaline phosphatase (tALP) serum levels were used to assess the maximal pharmacological response to treatment. RESULTS: In untreated pagetic patients, mean serum levels of IL-6 (3.20+/-1.18 pg/ml) and sIL-6R (35.02+/-8.33 ng/ml) were significantly increased. Serum osteotropic hormone levels fell within the normal range. Eight weeks after treatment, the maximal pharmacological response to clodronate was associated with a significant reduction of sIL-6R serum levels in all patients, without a significant variation in serum IL-6 and osteotropic hormone levels. Moreover, we observed a correlation between lower sIL-6R serum levels before clodronate therapy and complete remission of PBD, defined as a decrease of tALP serum levels within the normal range. CONCLUSION: The decrease in serum sIL-6R levels could be one of the molecular mechanisms that play a role in the clinical response to clodronate treatment in PDB.

Cirrhosis negatively affects the efficiency of serologic diagnosis of Helicobacter pylori infection.

In cirrhosis, Helicobacter pylori infection may be implicated, together with portal hypertension, bile reflux and alcohol abuse, in damage to gastric mucosa. Aim of this study was to define the influence of non-alcoholic liver disease on the incidence of Helicobacter pylori infection and on the diagnostic accuracy of specific serology. Enrolled in the study were 232 individuals, 105 also had cirrhosis. Infection by Helicobacter pylori, diagnosed by a positive concordance of quick urease test and histology, was detected in 97 (48 with cirrhosis) out of 184 patients. Severe gastritis was more frequent in patients with Helicobacter pylori infection than in patients without. Cirrhosis did not significantly affect the prevalence of Helicobacter pylori infection or the histological features of gastritis. Specific anti-Helicobacter pylori IgG and IgA assay (Bio-Rad GAP test) was used for serological diagnosis. Anti-Helicobacter pylori IgG showed a high sensitivity (85% in cirrhotics, 89% in non-cirrhotics) and low specificity being more evident in cirrhotics (38% vs 56% non-cirrhotics). Serum specific IgA showed low sensitivity (approximately 25% in both groups) and specificity of 79% in cirrhotics vs 84% in non-cirrhotics. In conclusion, non-alcoholic cirrhosis does not affect the incidence of Helicobacter pylori infection and the histological features of chronic gastritis but does decrease diagnostic efficiency of serological tests for Helicobacter pylori.

Adenosquamous carcinoma of the colon. Case report of an unusual type.

Primary adenosquamous carcinoma of the colon is a rare entity. Its prevalent site of origin is at the level of the proximal portion of the large bowel. The tumor presents in young patients and follows a highly aggressive course. We present an extremely unusual case of adenosquamous carcinoma in which the classical mucinous and signet-ring cell adenocarcinoma was associated with the squamous component. The prognosis of this rare neoplasm is very poor.

XbaI polymorphism of the apolipoprotein B gene in patients with hyperlipidemia and echo-Doppler evidence of arterial lesions.

This study was designed to assess whether the XbaI restriction fragment length polymorphism (RFLP) for apolipoprotein B (apo B) gene could be related with a genetic predisposition to develop hyperlipidemia and atherosclerosis. Relationships between XbaI RFLP and serum cholesterol were evaluated by comparing hyperlipidemic patients with healthy controls. Statistical analysis (chi-square test) showed no significant difference in either genotype distribution or allele frequencies. Hyperlipidemic patients were then divided according to triglycerides, either above or below 200 mg/dl and XbaI genotype frequencies were measured. No significant differences in genotype distribution or allele frequencies were found. The hyperlipidemic patients were tested for the presence of arterial disease by echo-Doppler and angina questionnaire. The XbaI genotype frequencies were determined in patients with arterial disease and compared to those without evidence of disease. No significant differences were found between the two groups.

[Morphological and biochemical study of the lipid components of the fetal aorta]. / Studio morfologico e biochimico della componente lipidica della aorta fetale.

We made a biochemical and histochemical study of the lipidic component of intima of fetal aortas on 8 autopsy cases (7 +/- 2 months aged) arrived at our observation in the Pathology's Institute of II Faculty of Naples. We made a study with freeze-sections stained with Oil-Red 0 and after dissociation of the intima by the adventitia, it is valued biochemically the lipidic peroxidation studying the levels of malonyldialdehyde (MDA) like indirect marker of peroxidation. It is known that is present a lipidic component in the intima of fetal aorta whether intracellular or extracellular (Fig. 1, 2). Sometimes this component can accumulate until to determinate true lipidic striae. The aim of this study is a detection of MDA in lipids extracted from human fetal aortas. MDA levels was measured by Thiobarbituric method (TBA): lipids were extracted both intima and adventitia by Chloroform/methanol method, after surgery immediately. The results are expressed in nMoles/mg of lipids +/- Standard Deviation. Controls of spontaneous lipid peroxidation was take at a different times. It is known that in vitro incubation of LDL with cultured endothelial cells, smooth muscle cells or macrophages leads to peroxidation of LDL phospholipids and oxidatively modified LDL become atherogenic via foam cells production. In addition lipid peroxidation was formed by the direct peroxidation of unsaturated fatty acids and their esters are capable of further lipoperoxide production by oxygen free radical; chain reactions. In this context lipid peroxidation could be an important factor in the first stage of human pathophysiological development and this phenomenon may be related by an early free radical production.

Left ventricular hypertrophy, compliance and ventricular filling.

A total of 20 untreated hypertensive patients were divided into two equal groups matched for sex, age and blood pressure but with [mean diastolic wall thickness (MDWT) greater than 1.2 cm] or without (MDWT greater than 1.2 cm) left ventricular hypertrophy (LVH). All patients underwent pulsed doppler echocardiography and 99Tc radionuclide ventriculography at rest to assess diastolic and systolic abnormalities. In hypertensives with LVH the interventricular wall thickness, posterior wall thickness and relative diastolic wall thickness were significantly (P less than 0.01) higher and peak filling rate was significantly (P less than 0.01) lower than in hypertensives without LVH. The indices of systolic function, however, were not significantly different in the two patient groups. In hypertensives without LVH peak filling rate directly correlated with heart rate, whereas in those with LVH peak filling rate directly correlated with heart rate and the ratio of peak velocity of early left ventricular filling : peak velocity of late left ventricular filling due to atrial contraction. It is concluded that diastolic parameters may be useful tools for assessing myocardial compliance and may be effective markers of diastolic dysfunction.

[Heart function (angioscintigraphic evaluation) and sympathetic tone in insulin-dependent diabetes mellitus]. / Funzione cardiaca (valutazione angioscintigrafica) e tono simpatico nel diabete mellito insulino-dipendente.

Cardiac failure is a frequent feature in diabetic patients and it often causes their death. But how and when cardiac disease begins in this kind of patient is still debatable. For example, cardiac failure can be present even in the absence of atherosclerotic involvement of coronary arteries in young diabetics. The aims of our study were to evaluate the cardiac function and sympathetic tone of 16 young type 1 diabetic patients (8 M and 8 F, mean age: 27 years, SD +/- 5) in comparison with 10 normal subjects (4 M and 6 F, mean age: 30 years, SD +/- 7). Diabetic patients were choose from a large population because of the following features young age, absence of clinical and instrumental evidence of micro- or macroangiopathy, clinical evidence of diabetic autonomic neuropathy, proteinuria or arterial hypertension. They were in good metabolic control on daily insulin therapy of two or three administrations. Cardiac function was evaluated at rest and during submaximal exercise on a cycloergometer in supine position using radionuclide ventriculography with technetium 99m. Sympathetic tone was checked using the five clinical tests according to Ewing and the plasmatic level of catecholamines at rest was evaluated using high pressure chromatography. The ejection fraction, cardiac output, stroke volume of diabetics were comparable with those of normal subjects even in the presence of comparable systemic vascular resistance. The increase in ejection fraction during effort was normal. Only in one diabetic patient (incidentally the oldest one) did ejection fraction decrease (7%) during effort. The peak ejection and filling rates were significantly higher (p less than 0.001) in diabetic patients compared to those of normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cardioscintigraphic evaluation of obese subjects with or without arterial hypertension]. / Valutazione cardioscintigrafica dell'obeso con o senza ipertensione arteriosa.

A group of normotensive obese subjects (group A), a group of hypertensive obese subjects (group B) and a group of control subjects (group C) were submitted to radionuclide ventriculography using 99mTc to investigate cardiac function and haemodynamic situation in the presence of an increased preload (group A), preload and afterload (group B). Results show a significant reduction in ejection fraction and systolic blood pressure/end systolic volume in group A. Group B shows better cardiac function probably for the presence of cardiac concentric hypertrophy. Left ventricle work either in a minute and for each beat is greatest in patients of group B. Thus the simultaneous presence of obesity and hypertension can cause a worse prognosis in such patients for cardiac ischaemia and/or sudden death.

Cardiac function and sympathetic activity in young diabetics.

This study was aimed at evaluating cardiac function, both systolic and diastolic, in young type 1 diabetics with a mean duration of the disease of 10.9 +/- 6 years and without evidence of cardiac autonomic neuropathy and micro- or macroangiopathy. Thirteen diabetics, with good metabolic control, and 10 normal matched subjects were studied by echocardiography at rest and by radionuclide ventriculography both at rest and during effort. The level of plasma catecholamines was also determined. The echocardiographic data were comparable in the two groups. Scintigraphic data showed an increased peak ejection and peak filling rate (P less than 0.001) in diabetics while the other indices of cardiac function were comparable. Norepinephrine (P less than 0.01) and epinephrine (P less than 0.001) were higher in diabetics. A hypothesis is formulated that the higher indices of flow velocities in type 1 diabetics are supported by a sympathetic overactivity.

[Hemodynamic adaptation in severe obesity with or without arterial hypertension]. / L'adattamento emodinamico nell'obesità di grado elevato associata o meno ad ipertensione arteriosa.

Hypertension and obesity are 2 common pathological conditions that have been directly related. The incidence of hypertension in an obese population is far greater than in otherwise normal people. Nevertheless, a causal relationship between the 2 disorders has not been established. But their coincidence in the same patient carries increased risk of cardiovascular morbidity and mortality. In the present study we have studied a group of normotensive obese patients (21 patients, Group A), a group of hypertensive obese patients (19 patients, Group B) and a group of normal subjects (11 patients, Group C) by radionuclide ventriculography with Tc 99m to visualize the different hemodynamic adaptation to these different conditions. Overweight causes an increased preload while hypertension causes an increased afterload. In response to the increase in preload the heart of obese patient undergoes eccentric hypertrophy; when an increase in afterload is present at the same time, the left ventricle develops concentric hypertrophy. We found an increased preload in both the obese groups (A and B) testified by increased blood volume and end diastolic volume. Heart rate was higher in the 2 populations of obese patients. As a result, cardiac output was significantly increased in Group A and B. But the stroke index is decreased in Group A and B with respect to Group C. The ejection fraction is reduced in Group A with respect to Group B and C. The contractility index (systolic blood pressure/end systolic volume) is higher in Group B in comparison with Group A. Thus, hypertensive obese patients seem to have a better cardiac performance respect to the normotensive obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Plasma prorenin as an index of prognostic evaluation in diabetes]. / La prorenina plasmatica quale indice di valutazione prognostica nella malattia diabetica.

Plasma renin exists in an active form or as an inactive zymogen (P.P.) which is converted into active enzyme by exposure to trypsin. Inactive renin was first shown to be increased in patients with diabetes mellitus by Bye et al. The relationship between microalbuminuria (M.A.) in diabetic patients and the level of plasma inactive renin activated by trypsin was examined. The patients were divided into two groups: 1st group (Albustix+) and 2nd group (Albustix-). In the 1st group the inactive renin was greatly increased. In the patients with Albustix- albuminuria was measured by the R.I.A. method and two subgroups were identified. In the patients with albumin excretion over 40 mg/24 hr, prorenin was increased and correlated directly (r = 0.60) with M.A. In the group with albumin excretion below 40 mg/24 hr prorenin was normal except in three patients with increased M.A. These findings suggest that increased plasma prorenin levels in uncomplicated diabetes could anticipate the development of overt nephropathies.

Effects of nicardipine on chronic stable effort angina: a non-invasive assessment.

The effects of 60 mg/day nicardipine hydrochloride were evaluated in a 4-week single-blind study on 12 patients with chronic stable effort angina. All patients completed the treatment with few reports of adverse effects. Nicardipine hydrochloride was effective in reducing the incidence of anginal attacks and consumption of glyceryl trinitrate. Treadmill exercise time, angina onset time and the time to 1 mm ST-segment depression were increased. The extent of ST-segment depression was reduced at maximum comparable exercise, with a reduced rate-pressure product and, at maximum exercise, with an increased rate-pressure product. Myocardial stress 201Tl scintillography was carried out in eight of the patients and showed improved washout in antero-septal, infero-apical and postero-lateral segments. Echocardiographic measures of left ventricular function were enhanced because of reduction of afterload. Systemic vascular resistance and end-systolic stress were also decreased and a significant correlation was found between the increase in ejection fraction and reduction of systolic blood pressure. It is concluded that nicardipine hydrochloride is effective in the control of stable effort angina by reducing myocardial oxygen consumption and enhancing coronary blood flow thereby improving left ventricular function.