The relative contributions of menopause and aging to postmenopausal reduction in intervertebral disk height.

AIM: To evaluate, in a population of normal women, the effects of aging and menopause on the height of intervertebral discs by measuring the intervertebral disk space, between the 12th thoracic and 4th lumbar vertebrae, by dual-energy X-ray absorptiometry (DXA). MATERIALS AND METHODS: The study was conducted on 2455 consecutive women attending our Department, from whom 464 normal women were selected. The measurement was validated utilizing a spine phantom. RESULTS: The phantom mean intervertebral disk space was 0.44 cm, with a coefficient of variation of 1.4%. The coefficients of variation in premenopausal, early postmenopausal and elderly women were 2.2, 2.0 and 6.0%, respectively. Values of intervertebral disk space were stable from age 20 to 50 years, thereafter showing a significant (p < 0.05) decrease, negatively correlated with both age and years since menopause (p < 0.0001). In postmenopausal women younger than 60 years, a correlation (p = 0.042) was evident between intervertebral disk space and years since menopause, but no correlation was evident with age. In women over 60 years, no correlations were found between intervertebral disk space and either age or years since menopause. In three groups of age-matched women (47.5 +/- 1.5 years, n = 39 in each group), intervertebral disk space was significantly (p < 0.0001) lower in postmenopausal than in both premenopausal and perimenopausal women. CONCLUSION: The DXA measurement of intervertebral disk space is precise. After menopause, intervertebral disk space shows a progressive decrease that almost entirely occurs in the first 5 - 10 years since menopause, suggesting that the estrogen decrease may rapidly change connective tissue metabolism in the intervertebral disks.

Accumulation of p27(kip1) is associated with cyclin D3 overexpression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma.

BACKGROUND: The down regulation of protein p27(kip1) (p27) in most cases of thyroid cancer has relevant diagnostic and prognostic implications. However, the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma expresses more p27 than benign oxyphilic lesions do. AIM: To evaluate the mechanism underlying this difference in expression of p27. METHODS: Because high levels of cyclin D3 lead to p27 accumulation in cell lines and clinical samples of thyroid cancer, the immunocytochemical pattern of cyclin D3 in oxyphilic (n = 47) and non-oxyphilic (n = 70) thyroid neoplasms was investigated. RESULTS: In the whole study sample, there was a significant correlation between p27 and cyclin D3 expression (Spearman's r: 0.64; p<0.001). The expression of cyclin D3 and p27 was significantly higher in the oxyphilic variant of follicular carcinomas than in non-oxyphilic carcinomas (p<0.001). In the former, cyclin D3 overexpression and p27 accumulation were observed in a median of 75% and 55% of cells, respectively. In co-immunoprecipitation experiments, the level of p27-bound cyclin D3 was much higher in oxyphilic neoplasias than in normal thyroids and other thyroid tumours. CONCLUSION: These results show that increased p27 expression in the oxyphilic (Hurthle cell) variant of follicular thyroid carcinoma results from cyclin D3 overexpression.

Pain relief in early rehabilitation of rotator cuff tendinitis: any role for indirect suprascapular nerve block?

AIM: The purpose of the trial was to evaluate the efficacy of suprascapular nerve block (SSNB) to relieve the shoulder pain, ameliorate recovery after physiotherapy and reduce disability due to a rotator cuff tendinitis (RCT). A prospective, randomized, comparison cross over investigation was performed in the setting of a large inpatient rehabilitation unit with more than 200 admissions annually. METHODS: A total of 40 potential study subjects, who complained of shoulder pain from a RCT, were enrolled and randomly assigned to standard rehabilitation treatment plus SSNB (Group A) or to standard rehabilitation treatment alone (Group B). The UCLA shoulder rating scale was used to assess the shoulder mobility on admission and discharge, and to calculate the percentage of potential improvement achieved during rehabilitation (effectiveness). A pain visual analogic scale was used to serially assess pain. At the end of the trial, a self-report questionnaire evaluated whether patients could sleep and achieve activity of day life carry out everyday activities better than they could before treatment. RESULTS: Forty patients suffering from RCT entered the study. Those receiving nerve block from the beginning of the treatment in addition to standard rehabilitation therapy reported significantly less pain during physiotherapy and better final outcomes. During treatment with SSNBs, patients reported a more significant reduction in the intensity of pain and a better reduction of pain during sleep and rehabilitation exercises in comparison to with the standard therapy alone. A statistically significant inverse correlation was found between shoulder pain and mobility. CONCLUSIONS: The results indicate that combining nerve block with standard rehabilitative therapy may improve the final outcome of painful RCT. It decreased the severity and frequency of the perceived pain, improved the compliance with physiotherapy, restored more normal sleep patterns, and increased compliance with the rehabilitation program. This result proves to be an effective, safe and inexpensive therapeutic option for patients suffering from painful disabling shoulder tendinitis.

New limit on the neutrinoless betabeta decay of 130Te.

We report the present results of CUORICINO, a search for neutrinoless double-beta (0nu betabeta) decay of 130Te. The detector is an array of 62 TeO2 bolometers with a total active mass of 40.7 kg. The array is cooled by a dilution refrigerator shielded from environmental radioactivity and energetic neutrons, operated at approximately 8 mK in the Gran Sasso Underground Laboratory. No evidence for (0nu betabeta) decay was found and a new lower limit, T(1/2)(0nu) > or = 1.8 x 10(24) yr (90% C.L.) is set, corresponding to [m(nu)] < or = 0.2 to 1.1 eV, depending on the theoretical nuclear matrix elements used in the analysis.

Myocardial contractility and total arterial stiffness in patients with overt hyperthyroidism: acute effects of beta1-adrenergic blockade.

OBJECTIVES: To ascertain whether myocardial contractility and total arterial stiffness are significantly altered in human thyrotoxicosis, and to what extent they are affected by acute beta(1)-adrenergic blockade. METHODS: Doppler-echocardiography was used to assess left ventricular (LV) structure and function, hemodynamics and total arterial stiffness in untreated overt hyperthyroid patients before and 2 h after 5 mg bisoprolol given orally compared with age- and sex-matched healthy euthyroid controls. RESULTS: Compared with controls, untreated patients (n=20) had a higher heart rate (HR) and LV stroke index (SI), which were associated with higher pulse pressure (PP), larger LV end-diastolic volume index (EDVI, an index of preload,+11%, P<0.05), marginally increased stress-corrected LV midwall fractional shortening (MWS, an index of myocardial contractility,+5%; P=0.066), and shorter isovolumic relaxation time (IVRT). These changes resulted in a higher cardiac index (CI) and a lower systemic vascular resistance (SVR), which were associated with fairly normal mean blood pressure (BP) but higher PP/stroke volume (an index of total arterial stiffness,+29%; P<0.01). After bisoprolol, compared with controls, the randomly treated patients (n=10) had comparable HR but additionally increased SI; PP remained enhanced, EDVI was further enlarged (+26%, P<0.001), stress-corrected MWS was substantially unchanged, and IVRT remained shorter. Overall, these effects attenuated the high-output state, which was associated with normalization of PP/stroke volume without changes of mean BP. CONCLUSIONS: In human overt hyperthyroidism, myocardial contractility does not play a major role in increasing LV performance, which is instead predominantly sustained by increased preload with enhanced LV diastolic function. In addition, human thyrotoxicosis is associated with increased total arterial stiffness despite fairly normal mean BP. In this scenario, acute beta(1)-adrenergic blockade blunts the cardiovascular hyperkinesia predominantly by slowing HR - a process that is associated with normalization of total arterial stiffness.

Long-term efficacy of doxazosin plus atenolol in the management of severe and sustained arterial hypertension and reversibility of the cardiac damage induced by chronic cathecolamine excess. A case report in a young girl with recurrent, functioning paraganglioma.

Herein we report on a young girl with recurrent, functioning paraganglioma of the organ of Zuckerkandl and severe and sustained arterial hypertension (systolic pressure >200, diastolic pressure >120 mmHg); with evidence of cardiac damage induced by chronic cathecolamine excess. She promptly and steadily improved after the institution of doxazosin (6 mg/day) plus atenolol (50 mg bid) treatment. This case demonstrates that a correct therapeutic strategy in the long-term management of patients with inoperable catecholamine-producing neuroendocrine tumors (pheochromocytomas and paragangliomas) can maintain arterial pressure in the normal range and reverse the cardiac damage induced by chronic cathecolamine excess.

Improvement of left ventricular hypertrophy and arrhythmias after lanreotide-induced GH and IGF-I decrease in acromegaly. A prospective multi-center study.

We report the results of a prospective Italian multi-center study of the effects of lanreotide, a slow-release somatostatin analog, on left ventricular morphology and function and on the prevalence of ventricular arrhythmic events in 19 patients with active, newly diagnosed, uncomplicated acromegaly. Cardiac features were evaluated with Doppler-echocardiography and 24-h Holter ECG monitoring at baseline and after 6 months of lanreotide therapy. Fifteen patients (78.9%) had left ventricular hypertrophy. Lanreotide treatment significantly decreased the left ventricular mass (127.8+/-6.9 vs 140.7+/-7.1 g/m2, p<0.001) and left ventricular hypertrophy significantly disappeared in 6 of these patients. Treatment did not significantly affect systolic function, whereas it increased the Doppler-derived early-to-late mitral flow velocity, (E/A) ratio, of early-to-late trans-mitral flow velocity (1.34+/-0.1 vs 1.09+/-0.06, p=0.001). Stroke volume was slightly but not significantly increased after treatment, whereas systolic BP was significantly higher (134+/-14 vs 129+/-13 mmHg, p<0.05). The 24-h mean heart rate was significantly reduced after treatment (66.5+/-11 vs 71.5+/-20 beats/min, p<0.05). Supra-ventricular premature beats (>50/24 h) occurred in 16.6% of patients and were unaffected by treatment. Differently, ventricular premature beats (>50/24 h) occurred in 33.3% of patients before treatment vs 16.5%, after treatment. In conclusion, lanreotide reduced the left ventricular mass, and improved ventricular filling and ventricular arrhythmic profile.

Plasma and urinary GH following a standardized exercise protocol to assess GH production in short children.

Plasma and urinary GH responses following acute physical exercise were evaluated in 19 short-statured children (12 males, 7 females, median age: 11.4 yr, age range: 6.1-14.5 yr, Tanner stage I-III, height < or = 3rd centile for age; 7 with familial short stature, FSS; 8 with constitutional growth delay, CGD; 4 with GH deficiency, GHD) and 7 normally growing, age- and sex-matched control children (4 males, 3 females, median age 11.0 yr, range: 7.2-13.1 yr, Tanner stage I-III). All patients and controls underwent a standardized exercise protocol (consisting of jogging up and down a corridor for 15 min, strongly encouraged to produce the maximum possible effort, corresponding to 70-80% of the maximal heart rate) after an overnight fasting. Samples for plasma GH determinations were drawn at 0 time (baseline), at 20 min (5 min after the end of exercise) and at 35 min (after 20 min of rest); urine samples were collected before (0 time) and at 40, 80 and 120 min after exercise. The distance covered by children with GHD during the test was significantly lower (p<0.05) than in the other groups of patients and controls. No differences in the pattern of plasma GH responses after physical exercise were found between children with FSS, CGD and healthy controls, the maximum percent increase (vs baseline) being evident at 20 min (median, FSS: +1125%; CGD: +1271%; controls: +571%). Children with GHD showed a smaller percent increase (+94%) of plasma GH, significantly lower (p<0.01) than those recorded in the other groups. A significant percent increase (p<0.01) of baseline urinary GH following exercise was found in children with FSS (median: +34%), CGD (+18%) and controls (+44%). Children with FSS and CGD showed a gradual increase of urinary GH, reaching the maximum at 80 min, while healthy controls had a more evident and precocious increase (maximum at 40 min). Urinary median GH levels did not change following physical exercise in children with GHD (-5%, not significant). A significant correlation was found between the maximal percent increase (vs baseline) of plasma and urinary GH following physical exercise (r=0.7, p<0.001). In conclusion, our results show that: 1) plasma and urinary GH responses (as well as the distance covered and the number of steps, i.e. the physical performance) to a standardized exercise protocol are similar in children with FSS, CGD and in normal-statured controls, being unable to differentiate among the "normal variants" of growth; 2) children with GHD, unable to accomplish the same performance of the other three groups, show significantly reduced plasma and urinary GH responses following physical exercise. Although the determination of GH responses to pharmacological stimuli remains the definitive tool for the diagnosis of GHD, these preliminary results seem to suggest a potential role of urinary (and plasma) GH response to a standardized exercise protocol as a safe, acceptable first screening test for GH sufficiency also in children, as previously reported in adults.

Quantitative assessment of oxyphilic cell lesions of the thyroid gland on fine needle aspiration samples.

OBJECTIVE: To assess the possible contribution by a multiparametric quantitative approach to the cytologic diagnosis of oxyphilic cell (OC) thyroid lesions. STUDY DESIGN: Ten cases of chronic lymphocytic (Hashimoto) thyroiditis and 10 nodular goiters containing oxyphilic cells plus 20 cases of tumors subsequently classified as oxyphilic cell adenomas (10 cases) or oxyphilic cell well-differentiated carcinomas (10 cases) were evaluated. The study was performed on May-Grünwald-Giemsa-stained smears for planimetric measurements. The same smears were destained and Feulgen restained for densitometric measurements. The latter were performed using static cytometry equipment measuring 100 and 20-30 lymphocytes per case for the determination of integrated optical density (IOD). The following parameters were considered: nuclear area, perimeter, maximum diameter, form ELL, form PE, IOD, 5c exceeding rate (5cER) and visual classification of histograms as euploid, polyploid and aneuploid. RESULTS: Mean nuclear area of carcinomas was smaller than that of adenomas, goiter and thyroiditis. Nuclear area was larger in adenomas than in other benign lesions and carcinomas. All the other planimetric parameters were similar in the lesions examined. Four carcinomas and three adenomas were aneuploid, and all the rest were euploid. All the cases of thyroiditis and goiter were euploid or polyploid; four thyroiditis cases showed polyploid histograms and 5cER values > 1. CONCLUSION: Morphometric and densitometric procedures have a limited role in the discrimination of OC lesions, but small nuclear area values may be useful in distinguishing OC carcinoma from other lesions. The role of densitometry seems even more limited because aneuploid histograms may be found among adenomas and carcinomas. Further studies are needed to explain polyploidy and 5cER > 1 in Hashimoto thyroiditis.

The inverse association between age and cholesterol level among older patients: the role of poor health status.

BACKGROUND: The total cholesterol concentration decreases with age in older people. The reasons for this phenomenon are controversial. This study investigated the hypothesis that poor health status is a determinant of the inverse association between age and cholesterol in older persons. METHODS: Cross-sectional study of 2,486 (53% women) older medical patients (> or =65 years) admitted at 35 centers of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA) study in Italy. Total cholesterol was measured on the first day after admission to the hospital. Disease burden and comorbidity were assessed by the Charlson index; low serum albumin and iron were considered markers of frailty and poor health. RESULTS: In men there was a significant, inverse age-cholesterol relationship (-0.97 mg/dl per year, p<0.001). In women the association was nonlinear and cholesterol significantly decreased after the age of 75 (-0.95 mg/dl per year, p<0.005). In multiple linear regression analysis, indicators of poor health accounted for almost two thirds of the crude effect of age on the cholesterol level in both men and women (adjusted coefficients for age were: for men, -0.38 mg/dl per year, p = 0.044; for women after the age of 75, -0.37 mg/dl per year, p = 0.205). The unadjusted probability of having low cholesterol significantly increased with age among men (p for trend <0.005). In multiple logistic regression, indicators of poor health were strongly associated with low cholesterol in both men and women. After adjusting for indicators of poor health, the association between age and low cholesterol in men was no longer present. CONCLUSION: These findings suggest that the age-dependent reduction of cholesterol often observed in clinical and epidemiologic studies is substantially explained by the effect of poor health status. Low cholesterol in older persons may be a marker of poor health.

Efficient T cell activation requires an optimal dwell-time of interaction between the TCR and the pMHC complex.

Cytotoxic T cell (CTL) activation by antigen requires the specific detection of peptide-major histocompatibility class I (pMHC) molecules on the target-cell surface by the T cell receptor (TCR). We examined the effect of mutations in the antigen-binding site of a Kb-restricted TCR on T cell activation, antigen binding and dissociation from antigen.These parameters were also examined for variants derived from a Kd-restricted peptide that was recognized by a CTL clone. Using these two independent systems, we show that T cell activation can be impaired by mutations that either decrease or increase the binding half-life of the TCR-pMHC interaction. Our data indicate that efficient T cell activation occurs within an optimal dwell-time range of TCR-pMHC interaction. This restricted dwell-time range is consistent with the exclusion of either extremely low or high affinity T cells from the expanded population during immune responses.

White blood cell count is associated with some features of metabolic syndrome in a very old population.

BACKGROUND AND AIMS: Although the association between white blood cell (WBC) counts and the risk of cardiovascular disease has been repeatedly described, its biological mechanism is still unclear. A significant correlation has been demonstrated in adults between WBC counts and some risk factors for coronary heart disease (CHD), including insulin resistance. The aims of this study were: 1) to investigate the association between WBC count and some risk factors for atherosclerosis in a sample of octo-nonagenarians; and 2) to test the hypothesis of an association between WBC count and "metabolic syndrome", a clinical condition mediated by insulin resistance. METHODS AND RESULTS: The study involved 160 free-living healthy octo-nonagenarians participating in the Val Vibrata Aging Project, whose WBC count, and anthropometric and metabolic parameters were measured using standardised methods. WBC count correlated positively with the logarithm of triglyceride, apoprotein B and glucose levels, and negatively with high-density lipoprotein cholesterol: the subjects with low high-density lipoprotein and high triglyceride levels had higher WBC count than normal subjects. The WBC count were significantly higher in the subjects with four or more of six features of metabolic syndrome than in those with three or less. CONCLUSIONS: The results of this study support the existence of a significant association between WBC count and some of the typical features of metabolic syndrome in very old subjects.

Acute phase markers are associated with reduced plasma lipid levels in a population of hospitalized elderly patients.

BACKGROUND: Several epidemiological studies have documented the presence of a 'J' or 'U' association between total cholesterol levels and total mortality. Not only the mechanism underlying the association between increased mortality and low total cholesterol values is not completely clear, but the relationship itself also appears to be complex in the elderly. OBJECTIVE: The aim of the study was to evaluate the possible association between some biohumoral markers of the acute phase, comorbidity, disability, and reduced levels of some lipoprotein parameters in a sample of hospitalized elderly subjects. METHODS: 341 patients over 65 years of age (185 males, 156 females; mean age 76.2 years), consecutively admitted to our department from 1994 to 1995, were studied. Acute phase was defined as the simultaneous presence of: (1) increased alpha2-plasma protein on electrophoresis (>12%); (2) high fibrinogen concentration (>450 mg/dl), and (3) increased blood sedimentation rate (>15 and >20 mm 1 h in males and females, respectively). RESULTS: The prevalence of signs of acute phase was higher in males and in the youngest patients, but did not change with the level of comorbidity. Patients with signs of acute phase were characterized by lower total, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol levels compared to subjects without signs of acute phase; this difference was significant even after adjustment for indicators of comorbidity, disability, and nutritional status. Multivariate logistic regression analysis evidenced that the simultaneous presence of these three markers of acute phase was independently associated with low levels of total cholesterol [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.1 - 3.9], and HDL-cholesterol (OR 2.3, 95% CI 1.2 - 4.2), considered as the sex-specific first quintile. CONCLUSION: The findings of this study demonstrate an independent association between acute phase markers and low levels of total and HDL-cholesterol, suggesting that recognized or subclinical diseases in elderly patients may determine a reduction in these plasma lipids. Low level of total and HDL-cholesterol should be considered as possible clinical markers of an underlying state of acute phase rather than a sign of malnutrition. Given the high prevalence of chronic diseases in the elderly, epidemiological studies addressing the lipid profile in this age group should take into account the possible confounding effect of the presence of signs of acute phase.

Alzheimer disease and vascular dementia: relationships with fasting glucose and insulin levels.

Cerebrovascular disease and Alzheimer disease are the leading causes of dementia in elderly subjects. In spite of it, relatively little is known about the pathogenesis and risk factors for dementia. We evaluated fasting plasma glucose and insulin, albumin, lipids, Lp(a) and uric acid levels in nondiabetic patients of both sexes affected by vascular dementia (VD) and senile dementia of the Alzheimer type (SDAT) as well as in a control group of age-matched nondemented subjects. Following a covariance analysis by gender, body mass index, albumin levels and prevalence of arterial hypertension, total and LDL cholesterol as well as HDL cholesterol levels were not significantly different among the three groups. Fasting glucose (p < 0.001 and p < 0.005, respectively) and insulin levels (p < 0.05 for both differences) were higher in patients with VD and SDAT than in control subjects. Our data show that nondiabetic patients with VD or SDAT have higher fasting glucose and insulin levels than healthy control subjects. These metabolic characteristics were not influenced by differences in gender, adiposity, nutritional status, lipids or presence of arterial hypertension.

A simplified procedure for the preparation of MHC/peptide tetramers: chemical biotinylation of an unpaired cysteine engineered at the C-terminus of MHC-I.

Recently, a powerful approach for the detection of MHC/peptide-specific T cells has been made possible by the engineering of soluble-tetrameric MHC/peptide complexes, consisting of singly biotinylated MHC/peptide molecules bound to fluorescent-labeled streptavidin. These tetrameric molecules are thought to compensate for the low affinity and relative fast dissociation rate of the TCR/MHC-peptide interaction by increasing the avidity of this interaction, thus allowing the stable binding of MHC/peptide tetramers to TCR expressing cells. Here we describe a new more simplified procedure for obtaining MHC/peptide tetramers using the well-characterized H-2K(b)/VSV system. This procedure consists of the incorporation of an unpaired cysteine residue at the C-terminus of the H-2K(b) molecule, allowing site-specific biotinylation by a -SH-specific biotinylating reagent. The H-2K(b)/VSV tetramers bound only to hybridomas expressing H-2K(b)/VSV-specific TCRs. When coated on a plate, these tetramers were able to induce IL-2 release by those hybridomas. Furthermore, H-2K(b)/VSV tetramers bound to CTL populations obtained from mice immunized with VSV-peptide. The specificity of the binding was further refined by studying cross-recognition of VSV by CTL populations obtained from mice immunized with single amino acid substituted VSV peptide variants. H-2K(b)/VSV tetramers bound only to those CTL populations that cross-reacted with the wild-type VSV peptide. Our method provides a simple, efficient and inexpensive procedure for making MHC/peptide tetramers, a highly specific and very useful reagent with a number of important applications in basic and clinical T cell research.

Cardiovascular effects of short-term growth hormone hypersecretion.

Many studies have shown that acromegaly has relevant effects on cardiovascular system, but few data are available regarding the effects of short-term acromegaly on heart morphology and function. These data would help to clarify the natural history of acromegalic disease and could provide new insight into the mechanisms of GH action on the human heart. Therefore, we studied by Doppler echocardiography a group of 10 young subjects strictly selected as having short-term (<5 yr) uncomplicated acromegaly. The results of this study have shown that shortterm acromegaly is characterized by significantly increased left ventricular mass (P<0.005), with normal relative wall thickness, associated with Doppler indices of diastolic function in the normal range. Furthermore, stroke index and cardiac index were significantly enhanced in the patient group (P<0.01 and P<0.001, respectively), whereas systemic vascular resistance was significantly reduced (P<0.001). In conclusion, our study shows that short-term acromegaly significantly affects the heart, but, at variance with long-term disease, it is characterized by increased left ventricular mass, with eccentric remodeling and normal diastolic function. Moreover, short-term acromegaly induces a high cardiac output state with reduction of systemic vascular resistance.

Endogenous subclinical hyperthyroidism affects quality of life and cardiac morphology and function in young and middle-aged patients.

To determine the clinical impact of endogenous subclinical hyperthyroidism, specific symptoms and signs of thyroid hormone excess and quality of life were assessed in 23 patients (3 males and 20 females; mean age, 43 +/- 9 yr) and 23 age-, sex-, and lifestyle-matched normal subjects by using the Symptoms Rating Scale and the Short Form 36 Health Survey questionnaires. Because the heart is one of the main target organs of the thyroid hormone, cardiac morphology and function were also investigated by means of standard 12-lead electrocardiogram (ECG), 24-h Holter ECG, and complete Doppler echocardiography. Stable endogenous subclinical hyperthyroidism had been diagnosed in all patients at least 6 months before the study (TSH, 0.15 +/- 0.1 mU/L; free T(3), 6.9 +/- 1.1, pmol/L; free T(4), 17.2 +/- 2.3, pmol/L). Fifteen patients were affected by multinodular goiter, and eight patients by autonomously functioning thyroid nodule. The mean Symptoms Rating Scale score (9. 8 +/- 5.5 vs. 4.3 +/- 2.2, P: < 0.001) and both the mental (36.1 +/- 9.5 vs. 50.0 +/- 8.5, P: < 0.001) and physical (42.6 +/- 8.0 vs. 55. 6 +/- 4.1, P: < 0.001) component scores of Short Form 36 Health Survey documented a significant prevalence of specific symptoms and signs of thyroid hormone excess and notable impairment of quality of life in patients. Holter ECG showed a higher prevalence of atrial premature beats in endogenous subclinical hyperthyroid patients than in the controls, but the difference was not statistically significant, although the average heart rate was significantly increased in the patients (P: < 0.001). An increase of left ventricular mass (162 +/- 24 vs. 132 +/- 22 g, P: < 0.001) due to the increase of septal (P: = 0.025) and posterior wall (P: = 0.004) thickness was observed in patients. Systolic function was enhanced in patients as shown by the significant increase of both fractional shortening (P: = 0.005) and mean velocity of heart rate-adjusted circumferential fiber shortening (P: = 0.036). The Doppler parameters of diastolic function were significantly impaired in the patients as documented by the reduced early to late ratio of the transmitral flow velocities (P: < 0.001) and the prolonged isovolumic relaxation time (P: = 0.006). These data indicate that endogenous subclinical hyperthyroidism has a relevant clinical impact and that it affects cardiac morphology and function. Moreover, they suggest that treatment of persistent endogenous subclinical hyperthyroidism should be considered also in young and middle-aged patients to attenuate specific symptoms and signs of thyroid hormone excess, ameliorate the quality of life, and avoid the consequences to the heart of long exposure to a mild excess of thyroid hormone.