Health-related quality of life in patients with thyroid disorders.

Limited reports are available on quality of life (HRQL) in thyroid diseases, and no data are available in euthyroid disorders, such as goiter and Hashimoto thyroiditis. Also, asymptomatic patients may suffer a reduction in perceived health status due to distress related to physical appearance and awareness of disease. We measured HRQL by means of Medical Outcome Study Short Form-36 (SF-36) and Nottingham Health Profile (NHP) questionnaires in 368 patients (hypothyroid, 81; hyperthyroid, 45 (for both states including overt and subclinical states); Hashimoto thyroiditis, 51; euthyroid goiter, 191). The final scores of the domains were compared with age- and sex-adjusted Italian normative values, by computing the effect size. All domains of SF-36, except bodily pain, were reduced in thyroid disease; this was mainly the case of role limitation (both physical and emotional), general health and social functioning. The domains of NHP were less severely affected. HRQL was impaired also in the absence of altered hormone levels. Mood/behavior disturbances were present in a large proportion of patients and were significantly associated with poor HRQL. HRQL was significantly reduced in patients with thyroid diseases referred to a secondary level endocrinology unit. Perceived health status may be considered as an additional outcome of management and therapy of thyroid disorders.

The effect of transient intestinal ischemia on inflammatory parameters.

BACKGROUND AND AIMS: To determine the early biological changes occurring in intestinal ischemia in vivo. PATIENTS AND METHODS: We studied the effects of acute transient intestinal ischemia in 15 patients undergoing elective open surgery for the treatment of abdominal subrenal aortic aneurysm induced by clamping of the aorta at subrenal level and above the branching of the inferior mesenteric artery. Blocking the blood flow results in hypoperfusion of the inferior mesenteric artery and then to rectal mucosal ischemia. RESULTS: With the introduction of a mucosal ischemic period the basal intestinal mucosal pH decreased during ischemia, and showed a rapid increase during reperfusion to the level preceding ischemia. Parameters were evaluated in blood taken from inferior mesenteric vein. A rectal dialysis was put into the rectum to evaluate eicosanoid concentrations in rectal fluid collected before and during clamping and after declamping. Significant enhancement in plasma level of xanthine, a marker for tissue damage, was observed during reperfusion. Interleukin-6 levels were significantly elevated from 11.28+/-3.4 pg/ml (preischemic) to 109+/-85.9 pg/ml (ischemic) and to 189.33+/-120.24 pg/ml (reperfusion); and tromboxane B(2) levels from 141.57+/-51.20 pg/ml preoperation to 473.01+/-319.01 pg/ml during the surgical procedure. CONCLUSION: These observations indicate that even transient ischemia modifies the inflammatory pattern.

Relationship between intrathyroid calcifications and thyroglobulin in endemic goiter.

Intrathyroid calcifications represent a common finding within simple or nodular goiters, but, as far as they can be found also inside papillary and medullary thyroid carcinomas, an ultrasonographic detection of intrathyroid calcifications stands as a different diagnosis problem. We have been looking for the presence of parameters associated with thyroid calcifications in patients affected by simple or nodular goiter, either sporadic or endemic. We studied 284 euthyroid subjects, 250 females, ageing from 24 to 90 years, affected by a simple goiter, in the 9.51% of the cases, and by a nodular goiter in the remaining part. 69.37% of the patients came from an endemic goiter area, while the others were affected by sporadic goiter. We tested fT3, fT4, TSH, hTG, Ab-TG, Ab-TPO and performed an ultrasonography in all the subjects, 57.75% of patients shown intrathyroid calcifications in the 57.75% of them. We applied a multistep discriminant analysis taking for the presence/absence of calcifications as dependent variable and we tried to find which variable, by itself or in combination with others, could foretell its presence. We also created a new variable (TG1) to differentiate normal from supraphysiologic concentrations of hTG (< 60 ng/ml). The variable with the highest significance F originated from endemic goiter area (F = 96.36), followed by TG1 (F = 24.46) and age (F = 10.61). On the contrary hTG did not relate to calcifications, due to non-proportionally direct relationship between these two parameters, afterwards we used the multistep logistic regression that gave overlapping significances. This means that supraphysiologic hTG rates are sufficient to predict the possible presence of intrathyroid calcifications. In conclusion, as far as a follicular hyperstimulation can be assumed, especially if long-lasting, the presence of intrathyroid calcifications should rise a clinical suspect toward an old goiter rather than a neoplastic lesion.

Can oxypurines plasma levels classify the type of physical exercise?

BACKGROUND: A laboratory-based model able to describe muscle energy status during physical exercise and changes in myofibrillar composition in response to training would be desirable. Lactate and ammonia concentrations are not sufficient for a comprehensive knowledge of these systems. All muscle fibres, irrespective of the type, show ATP depletion and IMP accumulation following exhausting muscular exercise with quantitative differences due to the different concentrations of deaminase. We studied the plasma concentration of metabolites of oxypurine cascade to test their reliability to classify different exercises. METHODS: We studied 52 athletes, measuring plasma metabolites at the beginning and at the end of their specific field exercise (cycle pursuers, 8 cases; soccer players, 19; marathon runners, 25). K3EDTA-blood samples were assayed for plasma hypoxanthine, xanthine, and inosine, using an HPLC technique, as well as ammonia and lactate by means of enzymatic methods. RESULTS AND CONCLUSIONS: Basal oxypurines levels were not different in relation to any specific physical exercise. Post-exercise oxypurines, namely hypoxanthine, were more precise predictors of muscle energy exhaustion than strain intensity or duration. Plasma levels of hypoxanthine may be elevated also in the presence of normal xanthine and uric acid concentrations, due to an exhaustion of the enzymatic pathway, to a reduced activity of xanthine-oxidase or finally to a substrate-dependent inhibition of the process.

May peripheral and central fatigue be correlated? Can we monitor them by means of clinical laboratory tools?

BACKGROUND: A laboratory-based model which links regional and central fatigue during physical exercise has not yet developed. Today we can assay the oxypurines, a specific and sensible marker of muscle cell-energy exhaustion during strenuous physical exercise, thus allowing us to insight in peripheral fatigue mechanisms. Prolonged physical exercise modifies plasma free amino acids and fatty acids levels, increases plasma free tryptophan (fTrp) and, conversely, probably serotonin, an amine involved in the genesis of central fatigue. We tried to verify if there is a correlation between central and peripheral fatigue. EXPERIMENTAL DESIGN: We studied 29 male marathon runners before marathon, at the arrival, one and three days after the run. MEASURES: Plasma samples were assayed for amino acids, fTrp serotonin, xanthine, hypoxanthine inosine, cortisol. Urine samples were assayed for serotonin and hydroxyin-doleacetic acid (5HIAA). RESULTS: After the competition we observed a decrease in plasma fTrp but an increased ratio fTrp/sum of neutral amino acids with a normalization after 24 hours. No significant changes were observed in plasma and urinary serotonin and 5HIAA. Hypoxanthine and inosine increased at the end of the trial and returned to basal levels the day after. Cortisol increased at the end of the run but was reduced after 24 and 72 hours. CONCLUSIONS: In our athletes we observed only indirect signs of fTrp involvement in the genesis of central fatigue. Oxypurines seem to be a good marker of regional muscular fatigue. Plasma cortisol expresses the stress reaction to the competition and its exhaustion after a prolonged physical exercise.

Effects of beta-blockade on hepatic conversion of amino acid nitrogen and on urea synthesis in cirrhosis.

beta-Blockers are widely used to prevent gastrointestinal hemorrhage in cirrhosis. The metabolic effects of treatment are scarcely studied: hepatic function reportedly does not change significantly, but beta-adrenoceptors have been reported to regulate protein and amino acid metabolism. We studied hepatic nitrogen metabolism in response to constant alanine infusion in seven patients with cirrhosis before and 7 to 10 days after treatment with oral propranolol (60 to 100 mg/d). Beta-blockade was effective: it decreased heart rate by 25%, abolished orthostatic tachycardia, and reduced portal blood flow by 20%. Alanine-stimulated urea nitrogen synthesis rate (UNSR) was higher in patients with propranolol treatment, without any difference in aminonitrogen concentration. The kinetics of hepatic conversion of amino acid nitrogen into urea--ie, functional hepatic nitrogen clearance (FHNC)--increased by 30%, from (mean +/- SD) 17.0 +/- 4.1 to 22.0 +/- 6.6 L/h (P < .01). Increased urea production during alanine infusion resulted in negative nitrogen exchange even at the peak of alpha-aminonitrogen concentration. Basal insulin level was only slightly reduced during propranolol treatment, whereas the insulin response to alanine was significantly blunted. No differences in glucagon and cortisol were demonstrated. Epinephrine and norepinephrine levels were high-normal and did not vary after treatment. Increased urea production and stimulation of hepatic nitrogen clearance during beta-blockade may be mediated by relative hypoinsulinemia or by direct involvement of beta-adrenoceptors in the control of nitrogen metabolism, possibly by regulation of amino acid uptake and release in peripheral tissues.

Thyroid involvement in patients with active inflammatory bowel diseases.

Previous studies have documented an association between systemic diseases and disorders of the thyroid gland, expressed by an enlargement of the thyroid and by the presence of anti-thyroid antibodies. Chronic inflammatory bowel diseases (IBD, ulcerative colitis and Crohn's disease) may also present a multi-organ involvement, including the biliary tree, joints and uvea. To detect a possible subclinical thyroid involvement, thyroid volume and function were assessed in 31 patients with IBD in active phase and in 50 control subjects. Thyroid volume was calculated by ultrasonography on the basis of the three maximum diameters of the 2 lobes. A blood sample was taken to determine free thyroid hormones, TSH, and anti-thyroid antibodies. In patients with IBD, thyroid volume was increased on average by 35%, and the prevalence of thyroid enlargements (antero-posterior diameter > 20 mm) was 3 times higher (45% vs 16%). Free thyroxine was increased by nearly 50%, but only 10% of patients had anti-thyroid antibodies. Alterations of thyroid volume and function are present in IBD, even in the absence of clinically-detectable thyroid disease. The association of IBD with thyroid disorders, as well as the involvement of various organs, confirms the view that IBD is a systemic disease.

Hepatic conversion of amino-nitrogen to urea in thyroid diseases. II. A study in hyperthyroid patients.

Conflicting data have been reported on the influence of thyroid hormones on hepatic nitrogen metabolism and on liver metabolic activity. We studied the urea-nitrogen synthesis rate (UNSR) and the kinetics of the process of hepatic amino-nitrogen to urea-nitrogen conversion in response to constant alanine infusion (ie, the functional hepatic nitrogen clearance [FHNC]) in five hyperthyroid female patients before and after the achievement of a stable euthyroid status. In the same patients, galactose elimination capacity and antipyrine clearance were also measured as quantitative indices of hepatic function. The basal urea synthesis rate was nearly doubled in hyperthyroid patients (35.6 +/- 8.5 mmol.h-1 v 17.6 +/- 7.7 in euthyroid patients, P < .05) and increased linearly with increasing alpha-amino-nitrogen (alpha-AN) concentrations in both conditions. The urea synthesis rate during alanine infusion was still higher by approximately 30 mmol.h-1 in hyperthyroid subjects. The FHNC, calculated as the slope of the linear relation between the UNSR in each time interval and the corresponding average alpha-AN concentration, was not different (hyperthyroidism, 30.6 +/- 7.2 L.h-1; euthyroidism, 28.5 +/- 4.4; normal values > 25). The hepatic microsomal and cytosolic activities (antipyrine clearance and galactose elimination) were normal in hyperthyroid patients and did not change significantly after therapy. Our data show that the hepatic nitrogen metabolism of hyperthyroid patients is characterized by an upregulation of amino-nitrogen catabolism and loss of the sparing mechanism at low plasma amino acid levels, without any change in different metabolic activities.

Reduced ubiquinone plasma levels in patients with liver cirrhosis and in chronic alcoholics.

Ubiquinone (CoQ10 coenzyme) is part of the respiratory chain in mitochondria, and acts as a scavenger in oxidative stress in cell membranes. Ubiquinone is mainly synthesized in the liver and partly derived from the diet; its plasma levels significantly correlate with tissue levels in experimental animals and in pathological states in man. By means of an original high-performance liquid chromatography technique, we measured ubiquinone plasma levels in 10 healthy subjects, in 27 patients with cirrhosis and in 22 chronic alcoholics with normal liver function. Ubiquinone levels were markedly reduced in cirrhosis (0.25 [SD 0.21] microgram/ml vs. 0.92 [0.38] in controls; P < 0.001), without any difference between alcohol- and non-alcohol-related disease. Also, in chronic alcoholics ubiquinone levels were nearly halved (0.49 [0.24]). In cirrhosis, ubiquinone plasma levels significantly correlated with cholesterol (P < 0.05), and with total bilirubin levels (P < 0.01). Our study highlights a remarkable deficiency in ubiquinone levels in patients with cirrhosis and in chronic alcoholics, to which both reduced hepatic synthesis and nutritional defects may contribute.

Lowering effects of a preparation containing fibres and lactulose on glucose and insulin levels in obesity.

The short-term metabolic effects of a dietary supplementation of biscuits containing raw fibre and lactulose (Fiberlac, Bracco) on circadian glucose, insulin and amino acid concentrations were studied in 10 obese patients in a crossover comparison. The biscuits (3 at breakfast, 4 at lunch and 4 at evening meal; approximately 10 g total dietary fibre, 2 g raw fibre, 8.25 g lactulose) were randomly substituted for an equicaloric part of a diet containing 20-22 kcal per kg ideal body weight under strict medical surveillance. Blood glucose in response to meal, as well as mean concentration throughout the day was lower during fibre supplementation. Also mean insulin was halved, and the insulin response to meals was blunted by 100-250 pmol/L. The plasma amino acid response to meals was increased, possibly in relation to decreased insulinemia. The data show a remarkable metabolic effect of the preparation in obese patients, without any further dietary restriction. The clinical effects and compliance remain to be determined in long-term studies, and in other states of glucose-intolerance, e.g. liver cirrhosis.

Model-derived assessment of urea appearance in response to alanine infusion: a quantitative measure of liver function in cirrhosis.

A three compartment mathematical model was used to analyse the urea response to an alanine infusion in six control subjects, and in 15 patients with liver cirrhosis and variable degree of hepatocellular failure. Model-derived coefficients were used to calculate two parameters (Ymax and Tmax), able to describe the theoretical response of the conversion of amino acid derived nitrogen into urea, in response to a unit impulse in alanine concentration. They correspond to the maximum rate of conversion of nitrogen from an intermediary pool into urea and to the time delay between the impulse and Ymax, respectively. In cirrhosis, the apparent volume of distribution of infused alanine was smaller than in controls, while the conversion of alanine nitrogen into an intermediary pool of nitrogen and finally into urea nitrogen were both reduced. Also Ymax was reduced by 50% in cirrhosis, whereas Tmax was increased by 50%, and both significantly correlated with galactose elimination capacity (GEC; R2 = 0.706 and R2 = 0.505, respectively) and with antipyrine clearance (Ap Cl; R2 = 0.823 and R2 = 0.576, respectively). Model-derived assessment of urea appearance in response to alanine infusion is able to quantify the functional liver cell mass, and may prove useful for the study of nitrogen metabolism in cirrhosis, mainly in relation to encephalopathy.

Hepatic conversion of amino nitrogen to urea nitrogen in hypothyroid patients and upon L-thyroxine therapy.

Conflicting studies have been reported regarding the influence of thyroid hormones on hepatic nitrogen metabolism and liver metabolic activity. We studied urea N synthesis rate (UNSR), functional hepatic N clearance (FHNC), galactose elimination capacity, and antipyrine clearance in six hypothyroid female patients before and after achievement of a stable euthyroid status. In both conditions, UNSR measured at intervals in response to constant alanine infusion was linearly related to the average alpha-amino N concentrations. In the hypothyroid state, peak UNSR was decreased by 31% in comparison with values measured in euthyroidism, which were in the normal range. FHNC (ie, the slope of the linear relation between UNSR and blood alpha-amino N concentration) is a measure of the kinetics of the process of hepatic amino N to urea N conversion; it was 19.8 +/- 4.0 L.h-1 in hypothyroid patients and increased to normal values after L-thyroxine replacement (30.4 +/- 3.3 L.h-1, P < .01; normal values > 25 L.h-1). Hepatic microsomal and cytosolic activities (antipyrine clearance and galactose elimination) were normal in hypothyroid patients and did not change significantly after therapy. Our data show a specific defect in hepatic handling of amino acids in hypothyroid patients, leading to reduced alpha-amino N to urea N conversion, in the absence of any detectable impairment in different hepatic metabolic activities.

Vegetable versus animal protein diet in cirrhotic patients with chronic encephalopathy. A randomized cross-over comparison.

In a randomized cross-over comparison, the effects of a mainly vegetable protein diet were compared with an animal protein diet in eight patients with cirrhosis and chronic permanent encephalopathy, under optimum lactulose therapy. After a run-in period, patients were fed two equi-caloric, equi-nitrogenous diets for 7 days (71 g total proteins), containing either 50 g protein of animal origin or 50 g vegetable proteins. In the last 3 days of each period, nitrogen balance was significantly better during the vegetable protein diet (+0.2 (SD 1.4) g vs. -1.7 (2.4); P < 0.01), the difference being entirely due to a reduced urinary nitrogen excretion. Average daytime integrated blood glucose was slightly higher during vegetable proteins, whereas insulin, plasma amino acids and ammonia were lower. The clinical grading of encephalopathy improved slightly on vegetable proteins, and psychometric tests improved significantly, but remained grossly abnormal. Compliance to dietary manipulation was good. The data prove that a mainly vegetable protein diet is worthwhile in cirrhotic patients with chronic encephalopathy under optimum lactulose therapy. Improved nitrogen balance may be related to more effective nitrogen use for protein synthesis, probably due to blunted hormonal response, and largely outweighs the effects on encephalopathy.

Oral BCAA supplementation in cirrhosis with chronic encephalopathy: effects on prolactin and estradiol levels.

The effects of oral BCAA supplementation on fasting levels of prolactin and estradiol were retrospectively analyzed in frozen plasma samples of patients with cirrhosis and chronic hepatic encephalopathy, taking part in a 3-month randomized, double-blind trial. Twenty-five patients had received 0.24g of BCAA per kg body weight, 24 had received an equinitrogenous amount of casein, in addition to a diet providing 0.7-1.0 g/kg of protein. Thirty-eight were males, 11 post-menopausal women. Fasting prolactin did not show any change in the BCAA group, where mental state significantly improved. In the casein group plasma prolactin increased by nearly 50% during the 3-month period. Similarly, estradiol concentrations were unchanged during BCAA supplementation, and increased during casein treatment. The analysis of variance demonstrated significant differences between the 2 treatments. Liver function tests and nutritional parameters (albumin, transferrin, urinary creatinine) supported a superiority of BCAA over casein. These data suggest that the favorable effects of BCAA on mental state are not mediated by changes in cerebral neurotransmission, but are due mainly to maintained liver function, possibly related to improved nutrition.