BACKGROUND

Caloric restriction (CR) is the only treatment known to substantially prolong both average and maximal life span in experimental animals. Interventions that mimic certain effects of CR could be potential anti-aging treatments in humans. Drugs which reduce appetite (anorexiants) represent one class of candidate treatments. Agents that reduce the glucose utilization by the organism could also represent another class of candidate CR mimetics.

OBJECTIVE

In our study, we addressed the following questions: (1) Does treatment with an anorexiant reduce caloric intake and body weight of experimental animals comparable to that caused by CR? (2) Does treatment with an antidiabetic agent influence caloric intake and body weight? (3) Does treatment with any of these drugs affect metabolic parameters of an organism in the way similar to that observed with CR?

METHODS

One hundred and twenty 6-month-old female Wistar-derived LIO rats were randomly subdivided into four groups and exposed to: (1) ad libitum feeding with placebo (controls); (2) the antidiabetic drug phenformin (2 mg/kg); (3) the anorectic drug phentermine (1 mg/kg), and (4) the same amount of food as the group with the least food intake during the previous week (pair-fed controls). Food and water intake, body weight, and rectal temperature were measured weekly during 16 weeks. At the end of the 16th week of the experiment, serum levels of glucose, total beta-lipoprotein and pre-beta-lipoprotein fractions, cholesterol, triglycerides, insulin, total triiodothyronine, and free thyroxine were estimated. The contents of diene conjugates and Schiff's bases, total antioxidant activity, the activities of Cu/Zn superoxide dismutase, glutathione S-transferase, and glutathione peroxidase, and the generation of reactive oxygen species (ROS) were studied in brain and liver homogenates and in the serum.

RESULTS

The controls exposed to pair feeding had a significantly reduced food consumption (about 20%) as compared with the ad libitum fed controls and thus exhibited a moderate CR. Treatment with phentermine reduced the caloric intake by about 12% as compared with the ad libitum fed controls. Body weight and water intake in this group were only slightly decreased (by about 2 and 5%, respectively) as compared with the controls. The mean rectal temperature in the phentermine group (38 degrees C) was significantly higher than in the ad libitum fed (37.8 degrees C) and pair-fed (37.6 degrees C) controls. Treatment with phentermine also resulted in significantly reduced ROS levels in all tissues studied, while the highest ROS production was found in ad libitum (blood serum) and pair-fed (brain) controls. Treatment with phenformin did not significantly influence food and water consumption, body weight, and temperature when compared with the ad libitum fed controls. Rats treated with this antidiabetic drug showed intermediate values of ROS generation. Differences among the groups in total antioxidant activity were not obvious.

CONCLUSIONS

Treatment with phentermine reduces caloric intake slightly less than is commonly observed in CR studies. CR due to forcibly reduced feeding and CR due to substance-suppressed appetite appear to act through different metabolic mechanisms and thus may affect aging and longevity in different ways.

Sex hormone-binding globulin (SHBG) levels were followed in three groups of female subjects to evaluate interrelationships between its levels and parameters characterizing thyroid function. In the first part of the study the data from 201 patients with thyroid and other endocrine dysfunctions were grouped according to SHBG or basic laboratory parameters of thyroid function (thyrotropin, free thyroxine). Particular attention was paid to the presence of antithyroid antibodies (against thyroglobulin or thyroid peroxidase). Analysis of covariance revealed that SHBG changes were significant only in hyperthyroidism, and were not influenced by the presence of antibodies. Age was a minor factor influencing SHBG levels, in contrast to thyroid status. In a well-defined group of 16 females with severe hypothyroidism after total thyroidectomy because of thyroid cancer the low SHBG levels increased significantly to physiologic values after reaching normal thyroid function, irrespective of contraceptive use. In the final part of the study SHBG levels were correlated with the basic laboratory data, reflecting thyroid function in a sample of normal female population (129 subjects) screened for iodine deficiency in one region of the Czech Republic. After adjustment for age, the only significant positive correlation was between SHBG and free triiodothyronine.

OBJECTIVE

To evaluate the prevalence of chronic autoimmune thyroiditis or Hashimoto's thyroiditis (HT) in a group of patients with spondyloarthritis (SpA).

METHODS

We evaluated serum levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine, and titers of antithyroglobulin and antithyroid peroxidase (anti-TPO) antibodies in 357 consecutive patients with SpA. We also recruited 318 healthy age-matched controls. Ultrasonography of the thyroid gland was performed in all subjects and rheumatic activity was evaluated.

RESULTS

Indices of thyroid autoimmunity were significantly more frequent in patients with SpA than in controls (24.09% vs 10.69%, respectively; p < 0.05). In the SpA group, a higher prevalence of HT was found in patients with an active disease than in those with low-moderate disease levels. Also in the SpA group, patients with a disease duration>> 2 years had a higher prevalence of HT and anti-TPO antibodies positivity than patients with a disease duration ≤ 2 years. Ultrasonography detected a significantly higher frequency of thyroid nodules and hypoechoic pattern in patients with SpA than in controls. Among patients with SpA, HT and anti-TPO antibodies positivity were significantly more frequent in patients with peripheral involvement (68.6%) than in patients with axial involvement (31.4%; p < 0.05).

CONCLUSIONS

Our study shows a significantly higher prevalence of thyroid autoimmunity in patients with SpA as compared to controls. Thyroiditis occurs more frequently in patients with longer disease duration and active rheumatic disease. We suggest that thyroid function tests be part of the clinical evaluation in patients with SpA.

OBJECTIVE

To clarify the relationship between interferon-alpha (IFN-alpha) therapy and autoimmune thyroiditis in chronic hepatitis C virus (HCV) infection, we investigated a selected number of patients without basal thyroid dysfunctions.

METHODS

130 patients (average age: 20-70), with chronic HCV infection and without basal clinical and laboratory signs of autoimmune thyroiditis were divided into two groups: IFN-alpha treated (A) and untreated (B) patients. Group A received IFN-alpha (three million U.I./3 times a week) for six months; group B was followed for the same period. Thyroid peroxidase and thyroglobulin autoantibodies were measured by radioimmunoassay; thyroid function was measured by radioimmunoassay (free thyroxine and triiodothyronine) and immunoradiometric assay (thyroid stimulating hormone).

RESULTS

After a 6-month period, thyroid autoantibodies positivity was documented in 21.1% of group A and in 10.3% of group B patients, both statistically relevant (p<0.001 and p<0.011, respectively). The comparison between the two groups was not statistically relevant (p=0.142).

CONCLUSIONS

Our study showed a prevalence of de novo thyroid autoimmunity in chronic HCV patients treated with IFN-alpha, confirming previous data in literature. The lack of a significant difference between treated and untreated patients strongly suggests that the anti-thyroid autoimmune response is linked to the HCV infection itself. Moreover, IFN-alpha therapy probably does not represent a risk factor in renewing the autoimmune processes of the thyroid gland. Thyroid function and autoantibodies must be systematically monitored in patients with HCV infection, especially in female and IFN-alpha treated population, not only to verify the possible thyroid abnormalities but also to rule out concomitant autoimmune diseases.

Serum thyrotropin (TSH) is considered the single most sensitive and specific measure of thyroid function in the general population owing to its negative logarithmic association with free triiodothyronine and free thyroxine concentrations. It is therefore often the test of choice for screening, diagnosis, and monitoring of primary hypothyroidism. Serum TSH concentrations can be analyzed quantitatively using third-generation immunoassays, whereas its bioactivity can be measured by TSH activity assays in cell culture. Theoretically, if serum TSH concentrations are directly related to TSH activity, the two tests should yield comparable results. However, on occasion, the results are discordant, with serum concentrations being higher than TSH biological activity. This review focuses on the dissociation between the clinical state and serum TSH concentrations and addresses clinically important aspects of TSH analysis.

Previous thaw-mount light microscopic autoradiographic studies have shown that intravenously administered [125I] triiodothyronine is saturably concentrated and retained for at least 10 hours in discrete neural systems in the rat brain. To survey the brain more completely and to gain information about the time course of labeling, serial thaw-mount film autoradiograms were prepared from rat brains obtained at intervals through 48 hours after intravenous injection of high specific activity [125I] triiodothyronine. Parallel biochemical studies of whole brain homogenate extracts revealed that, at all time intervals, the label in the brain was mainly due to triiodothyronine itself (80%), or other organic iodocompounds (15%), but probably not due to free [125I] iodide (3%), which is rapidly transported out of the brain. The highly reproducible, well-defined labeling patterns seen on film indicated a widespread but selective localization of the hormone. At early times after intravenous injection of [125I] triiodothyronine, label was nonuniformly and prominently concentrated in selected regions of gray matter; evidence for saturability of hormone processing was obtained in competition studies with unlabeled triiodothyronine. Discrete labeling of fiber tracts (usually after 10 hours) left some regions of white matter conspicuously unlabeled. At 48 hours, many originally labeled gray regions showed markedly diminished or virtually complete loss of radioactivity, whereas others became newly or more prominently labeled. At that time, certain fiber tracts were also conspicuously labeled. The observed changing profiles of regional labeling over time are best explained by movement of the hormone from original sites of saturable incorporation in specific nuclei, to terminal fields, through the mechanism of axonal transport.

To determine the effect of oral administration of prednisolone on thyroid function, 12 healthy Beagles were given 1.1 mg of prednisolone/kg of body weight every 12 hours for 22 days after 8 days of diagnostic testing of the dogs before treatment with prednisolone. Thyroid-stimulating hormone (TSH) and thyrotropin-releasing hormone (TRH) response tests were performed before treatment (days 1 and 8 of the study) and during treatment (days 21 and 28 of the study). Blood samples were collected daily at 8 AM and 2 and 8 PM to rule out normal daily hormone fluctuations as the cause of a potential decrease in serum triiodothyronine (T3), thyroxine (T4), and free T4 (fT4) concentrations. Serum T3, T4, and fT4 concentrations before treatment and 1 day and 21 days after the first prednisolone dose were compared by analyses of variance. Post-TSH and -TRH serum T3 and T4 concentrations before and during treatment were compared, using the Student t test for paired data. Oral administration of prednisolone significantly (P less than 0.005) decreased serum T3, T4, and fT4 concentrations in the 8 AM and 2 and 8 PM samples obtained 1 day and 21 days after the first prednisolone dose. Serum T4 and fT4 concentrations in 8 AM and 2 PM samples were significantly (P less than 0.05) lower 21 days after the first prednisolone dose than they were at 1 day after the first dose. Before treatment, serum T4 concentration in the 2 PM samples was significantly (P less than 0.05) higher than serum T4 concentration in 8 AM and 8 PM samples.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND

The thyroid hormone milieu is of crucial importance for the developing fetus. Pregnancy induces physiological changes in thyroid homeostasis that are influenced by the iodine status. However, longitudinal studies addressing thyroid function during pregnancy and after delivery are still lacking in mild-to-moderate iodine-deficient populations. Here we characterize the serum parameters of thyroid function throughout pregnancy, and until 1 year after delivery, in a population of pregnant women whom we have previously reported to be iodine deficient (median urinary iodine levels below 75 microg/L).

METHODS

One hundred eighteen pregnant women were studied. Clinical data were recorded and serum was collected. Serum total and free thyroxine (T(4)) and triiodothyronine (T(3)), thyroid-stimulating hormone, thyroxine-binding globulin, and thyroglobulin were measured.

RESULTS

Mean total T(4) ranged from 159 at the start of gestation to 127 nmol/L at 1 year after delivery, free T(4) from 14.2 to 17.8 pmol/L, total T(3) from 2.4 to 2.1 nmol/L, free T(3) from 6.7 pmol/L to 6.4 pmol/L, thyroid-stimulating hormone from 1.2 to 1.4 mIU/L, T(4)-binding globulin from 62.0 to 26.9 mg/L, and thyroglobulin from 11 to 10 microg/L.

CONCLUSIONS

The pregnant women in this study had an absence of the usual free T(4) spike and a smaller than expected increment in total T(4), described during pregnancy in iodine-sufficient populations. A greater number of women had subclinical hypothyroidism compared with iodine-sufficient populations. This hormonal profile, most likely due to iodine insufficiency, may result in inadequate thyroid hormone supply to the developing fetus. We conclude that care should be taken when reviewing the results of thyroid hormone tests in iodine-insufficient populations and when no gestation-specific reference values have been established. In addition, we recommend iodine supplementation in our population and populations with similar iodine status, particularly during pregnancy and lactation.

Indices of thyroid function were measured in 97 preterm infants at birth and at 5, 10, and 15 days of age. Triiodothyronine uptake, free thyroxine index, thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, and thyroxine binding globulin values at birth correlated with gestational age, whereas thyroid stimulating hormone values did not. Treatment with steroids prenatally had no apparent effect on thyroid function at birth or postnatally. Infants developing respiratory distress syndrome had normal values for all indices at birth. These infants had significantly lower thyroxine, free thyroxine index, free thyroxine, and triiodothyronine values at 5 days of age, while thyroid stimulating hormone values remained normal. This alteration in thyroid function was interpreted as being secondary to respiratory distress syndrome. Gestational maturity and respiratory distress syndrome, if present, must be taken into account when evaluating thyroxine variables in preterm infants, whereas measurement of thyroid stimulating hormone as the screen for congenital hypothyroidism circumvents these considerations.

Definitive confirmation or denial of the hypothesis that thyrotoxic hearts are supersensitive to catecholamines has been difficult to obtain, largely because secondary alterations in neural and humoral factors that occur after thyroid administration in vivo may obscure the primary changes induced by the hormone on the myocardium itself. To study the direct action of thyroid hormone apart from secondary factors, thyrotoxicosis should be induced in isolated hearts in vitro, but the slow onset of thyroid action plus the rapid deterioration of conventional in vitro preparations have precluded such experiments.Recen'ly a method was developed for maintaining intact, spontaneously-beating hearts from late-fetal mice in organ culture for several weeks. When 5 x 10(-7) to 5 x 10(-6)m l-triiodothyronine is added to the culture medium arrhythmias and or tachycardia gradually appear, just as in thyrotoxicosis in vivo. Accordingly, these "thyrotoxic" hearts were used in the present experiments to test for altered responsiveness to norepinephrine. Dose-response curves to norepinephrine were identical for hearts maintained for 3 hr in triiodothyro-nine-treated or control medium. After 2 days, however, the curve was shifted to the left in triiodothyronine-treated hearts. Thus, 10(-8)m norepinephrine increased the atrial rate by 20+/-6.1 (sem) beats/min in hearts exposed to 5 x 10(-6)m triiodothyronine and by 1+/-3.0 in control hearts (P < 0.02); 10(-7)m norepinephrine raised the rate by 79+/-22.3 in treated hearts vs. 17+/-9.8 in controls (P < 0.05). At maximal doses (10(-6)m norepinephrine), increases were identical. In addition, norepinephrine (10(-8)-10(-6)m) induced arrhythmias in 56% of treated hearts vs. 14% of controls (P < 0.01). Thus, in a precisely controlled environment free of differences in neural and humoral factors, triiodothyronine can act directly on the fetal mouse heart to enhance sensitivity to norepinephrine.

BACKGROUND

Insufficient iodine in children's diets is of concern because thyroid hormones are needed for normal growth and development, particularly of the brain. This study aimed to carry out a comprehensive assessment of the iodine status of New Zealand schoolchildren using a range of biochemical indices suitable for populations (i.e. urinary iodine concentration) and individuals (i.e. thyroid hormones).

METHODS

The New Zealand National Children's Nutrition Survey was a cross-‒sectional survey of a representative sample of schoolchildren aged 5-‒14 years. Children were asked to provide a casual urine sample for the determination of urinary iodine concentration (UIC) and a blood sample for the determination of thyroglobulin (Tg), Thyroid Stimulating Hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3).

RESULTS

The median UIC was 68 μg/L (n = 1153), which falls between 50-‒99 μg/L indicative of mild iodine deficiency. Furthermore, 29% of children had an UIC <50 μg/L and 82% had an UIC <100 μg/L. The median Tg concentration was 12.9 μg/L, which also falls between 10.0-‒19.9 μg/L indicative of mild iodine deficiency. The Tg concentration of children with an UIC <100 μg/L was 13.9 μg/L, higher than the 10.3 μg/L in children with an UIC >100 μg/L (P = 0.001). The mean TSH (1.7 mU/L), fT4 (14.9 pmol/L), and fT3 (6.0 pmol/L) concentrations for these mildly iodine deficient New Zealand children fell within normal reference ranges.

CONCLUSIONS

The UIC and Tg concentration indicate that New Zealand schoolchildren were mildly iodine deficient according to WHO/UNICEF/ICCIDD, and both are suitable indices to assess iodine status in populations or groups. The normal concentrations of TSH, fT4 and fT3 of these children suggest that these thyroid hormones are not useful indices of mild iodine deficiency.

Patients receiving exogenous levothyroxine are reported to have higher total and free serum thyroxine levels than euthyroid controls. This may be an artifact of the serum collection time. We explored the effect of collection time on serum levels of thyroid hormones in outpatients receiving levothyroxine for replacement therapy (26 patients) or suppression of thyrotropin (25 patients). Blood samples, obtained during regular clinic visits (random samples) and at more than 22 h from ingestion of levothyroxine (trough samples), were assayed for total and free thyroxine, triiodothyronine, and thyrotropin. Four athyreotic patients on levothyroxine therapy had serial blood sampling over 24 h. Compared to corresponding trough samples, random samples had elevated total thyroxine levels in patients receiving replacement (8.1 +/- 1.2%, mean +/- SE, p = 0.0001) and in patients undergoing suppression (8.8 +/- 1.6%, p = 0.0001). Free thyroxine was increased by 12.7 +/- 2.6% (p = 0.0003) and 14.5 +/- 2.3% (p = 0.0001), respectively, compared with trough samples. Thyrotropin levels were 18.9 +/- 6.8% (p = 0.003) lower in patients receiving replacement and triiodothyronine levels showed small or no changes. Time-course analysis showed that free and total thyroxine levels remained significantly elevated above baseline for 9 and 5 h, respectively, after a levothyroxine dose. In conclusion, there is a transient increase in thyroid hormone levels for 9 h after an oral levothyroxine dose. Accurate assessment of thyroid hormone levels in patients receiving levothyroxine therapy should take this into account. This has greatest significance in selecting minimal levothyroxine dosages for suppression of thyrotropin.

Serum thyrotropin (TSH), free thyroxine (T4), and free triiodothyronine (T3) levels illustrate the thyroid function set point, but the interrelations between these have never been characterized in detail. The aim of this study was to examine the associations between TSH and thyroid hormone levels in healthy euthyroid twins and to determine the extent to which the same genes influence more than one of these biochemical traits; 1,380 healthy euthyroid Danish twins (284 monozygotic, 286 dizygotic, 120 opposite-sex twin pairs) were recruited. Genetic and environmental associations between thyroid function measurements were examined using quantitative genetic modeling. In bivariate genetic models, the phenotypic relation between two measurements was divided into genetic and environmental correlations. Free T4 and free T3 levels were positively correlated (r=0.32, P<0.0001). The genetic correlation between serum free T4 and free T3 levels was rg=0.25 (95% CI 0.14-0.35), suggesting that a set of common genes affect both phenotypes (pleiotropy). The correlation between the environmental effects was re=0.41 (0.32-0.50). From this we calculated that the proportion of the correlation between free T4 and free T3 levels mediated by common genetic factors was 48%. Only 7% of the genetic component of serum free T3 levels is shared with serum free T4. Serum TSH and thyroid hormone levels did not share any genetic influences. In conclusion, thyroid hormone levels are partly genetically correlated genes that affect free T4 levels and exert pleiotropic effects on free T3 levels, although most of the genetic variance for these measurements is trait specific.

This study investigated Anguilla anguilla (European eel) physiological and genotoxic responses to copper (Cu) and their relation with metallothionein (MT) protection. Eels were exposed during 7 days to Cu 0.2 micromol/L. MT induction was assessed in gill and liver, revealing significant response only in liver. Endocrine responses displayed a plasma free triiodothyronine (T3) and cortisol significant decrease, though the thyroid-stimulating hormone (TSH) and free thyroxine (T4) concentrations were unaltered. A significant plasma glucose increase was observed whereas lactate was significantly decreased. Despite the absence of DNA integrity decrease in blood, gill, liver and kidney, erythrocytic nuclear abnormalities (ENA) frequency significantly increased in Cu exposed group. MT induction was insufficient to prevent endocrine and metabolic alterations as well as genotoxicity/clastogenicity in blood. However, MT protection was evident in liver by preventing DNA integrity loss. Globally, it was demonstrated that Cu environmentally realistic levels may pose a serious ecological risk to fish.

The effect of an in ovo infection with a Dutch isolate of avian leukosis virus subgroup J (ALV-J) on the growth of specific pathogen free (SPF) broiler chickens was analysed. During this study, possible immune suppressive effects of ALV-J were assessed by measuring delayed-type hypersensitivity with keyhole limpet haemocyanin (KLH), natural killer (NK) cell activity, the production of radicals of nitric oxide (NO) by macrophages, humoral immune response against Newcastle and infectious bursal disease vaccine viruses, and automated total and differential leukocyte counts. In an attempt to elucidate the underlying causal mechanisms of the induced growth retardation, 3,3',5-triiodothyronine (T3) concentrations in serum were measured. Four experiments were conducted. In experiment 1, ALV-J-injected birds were compared with ALV subgroup A (ALV-A)-injected and negative control chickens. In experiment 2, ALV-J-injected birds were only compared with negative controls. Finally, in experiments 3a and 3b, ALV-J-injected chickens were compared with negative controls and a group of chickens in which only 10% of birds had been injected with ALV-J. Birds were injected in ovo at day 7 of incubation with 10(4) median tissue culture infectious dose (TCID(50)) ALV-J or ALV-A, except in experiment 3a where 10(2) TCID(50) ALV-J was injected. Significant growth suppression was found in all 100% of ALV-J-infected groups. The average growth retardation of ALV-J-infected birds compared with negative controls at 6 weeks of age was approximately 8, 11, 2.5 and 6% for the four successive experiments performed. The delayed-type hypersensitivity test against KLH of ALV-J-infected birds showed a tendency towards lower wattle thickness; however, the difference with controls was not significant (P>> 0.05). The same was true for NK cell activity and NO production by macrophages, although the difference was not significant. The total and differential leukocyte counts performed on blood samples from birds at 3, 4 and 6 weeks of age as well as the humoral immune response against Newcastle and infectious bursal disease vaccine viruses did not show significant differences between treatment groups either. Only the number of basophils were significantly higher (P = 0.02) in ALV-J-infected birds at 3 weeks of age. No significant lower T(3) levels were found in ALV-J-infected birds in weeks 2 and 3 (experiment 2) and weeks 3 and 5 (experiment 3b); however, at 4 weeks (experiment 2) and 6 weeks (experiment 3b) of age, T(3) levels were significantly lower suggesting mild hypothyroidism in these broilers. In conclusion, the present experiments show the occurrence of significant growth retardation in SPF broilers after an ALV-J in ovo infection. The various studies performed to assess the immune competence of ALV-J-infected chickens did not show significant differences in immune responsiveness. The assays on cellular immunity showed a tendency to a lower response in ALV-J-infected birds, but these differences were not statistically significant.

Disturbances of thyroid function occur more often in the elderly than in the young. This short review gives an up-to-date overview of this topic. After discussing the difference in epidemiology of thyroid dysfunction in elderly persons in areas with different iodine nutrient status, the physiologic age-induced changes of the hypothalamic-pituitary-thyroid axis are discussed, especially with regard to their consequences on normal ranges of thyroid hormones. Although slight decreases in thyrotropin (TSH) and free triiodothyronine (T3) have been described as occurring in healthy elderly persons, it is concluded from the available data that abnormal values of thyroid hormones in serum of old people should be further investigated, since none of the described changes lead to values outside the normal range. Special emphasis is given to the fact that disturbances of thyroid function are oligosymptomatic or may even be asymptomatic in old persons. Therefore, laboratory screening for thyroid dysfunction in patients over 65 years of age seems to be justified. Lastly, differences of treatment in comparison with younger patients with hyper- or hypothyroidism are presented. The impact of subclinical disturbances of thyroid function in the elderly and their possible therapeutic consequences are also included in this discussion.

Overt hypothyroidism is known to be associated with increased serum creatine kinase (CK) levels. However, there is little information on CK levels in subclinical hypothyroidism. The aim of the study was to assess the relationship between CK levels and thyroid function in overt and subclinical hypothyroidism. Thyroid function tests (thyrotropin [TSH], free thyroxine [FT4], free triiodothyronine [FT3]) and the serum levels of CK were obtained from 23 patients admitted to a general hospital for illnesses other than thyroid or muscular diseases, myocardial ischemia, or brain damage. Overt hypothyroidism, based on thyroid function tests, was present in 10 patients, whereas hypothyroidism could be classified as subclinical in the other 13. A positive correlation was observed between CK and thyrotropin, and to a lesser extent between CK and thyroid hormones. Moreover, the correlation between CK and TSH and between CK and FT4 was detectable in subclinical hypothyroidism. Our data suggest that even in subclinical hypothyroidism there is some degree of dysfunction in skeletal muscle metabolism.

The objective of this study was to establish optimal conditions for the primary culture of pig preadipocytes. We cultured pig preadipocytes for 10 d and studied the effects of insulin, hydrocortisone, and triiodothyronine (T3) added to serum-free basal medium on differentiation and gene expression of lipoprotein lipase an early marker, and adipsin, a late marker of preadipocyte differentiation. Insulin alone and hydrocortisone alone stimulated a low level of cell differentiation, as indicated by an increase in glycerol-3-phosphate dehydrogenase activity. When added together, insulin and hydrocortisone had a synergistic effect on cell differentiation. When combined with insulin or hydrocortisone, T3 had no effect on cell differentiation, indicating that T3 is not required in porcine preadipocyte culture. Gene expression studies also showed that removal of insulin or hydrocortisone from complete serum-free medium reduced both early and late marker mRNA. As expected, removal of T3 had no effect on the gene expression of early and late marker mRNA. We conclude that insulin and hydrocortisone, but not T3, are required for the differentiation of pig preadipocytes in primary culture.

The secretion of lutenizing hormone (LH), follicle-stimulating hormone (FSH), thyrotrophin (TSH) and prolactin (PRL, was studied in 17 women suffering from anorexia nervosa. The mean basal serum LH was reduced (8.4 +/- 0.8 SE mIU/ml; P less than 0.001 vs normal controls), while LH increase after gonadotrophin-releasing hormone (LH-RH) appeared to be normal in 9 cases and impaired in 6 cases. The mean basal FSH did not significantly differ from normal subjects (3.9 +/- 0.5 mIU/ml), while LH-RH administration elicited an exaggerated increase in 7 cases and a normal increase in 8 cases: the mean FSH response was significantly higher than in controls (P less than 0.02). Plasma oestradiol-17beta was reduced (20.4 +/- 0.4 pg/ml; P less than 0.001) while the serum testosterone levels were normal (0.73 +/- 0.09 ng/ml). Clomiphene administration induced an increase in gonadotrophins in only 1 out of 7 patients. The mean serum TSH concentration was normal (2.3 +/- 0.4 muU/ml), while serum thyroxine and triiodothyronine and free thyroxine index, thought generally in the normal range, were significantly lower than values obtained in a control group (6.1 +/- 0.4 mug/100 ml, P less than 0.005; 102.3 +/- 7.7 ng/100 ml, P less than 0.005; 3.8 +/- 0.3, P less than 0.05). Though the mean serum TSH increase after thyrotrophin-releasing hormone (TRH) was normal (12.0 +/- 2.3 muU/ml), there were 4 impaired and 1 exaggerated increases, and 8 patients showed a delayed and frequently prolonged response. The increase in serum T3 after TRH appeared lower than in normal subjects (36.3 +/- 1.8 ng/100 ml, P less than 0.001). Serum PRL levels in basal conditions were higher than in the controls (19.4 +/- 4.1 ng/ml, P less than 0.001) while the increase in PRL after TRH was exaggerated in only 2 patients. The present data suggest that the primary failure in gonadotrophin secretion in anorexia nervosa occurs at hypothalamic level; moreover the data on TSH and PRL secretion also point to the existence of a hypothalamic disorder in this disease.

In human thyroid, caveolin-1 is localized at the apex of thyrocytes, but its role there remains unknown. Using immunohistochemistry, (127)I imaging, transmission electron microscopy, immunogold electron microscopy, and quantification of H(2)O(2), we found that in caveolin-1 knockout mice thyroid cell homeostasis was disrupted, with evidence of oxidative stress, cell damage, and apoptosis. An even more striking phenotype was the absence of thyroglobulin and iodine in one-half of the follicular lumina and their presence in the cytosol, suggesting that the iodide organification and binding to thyroglobulin were intracellular rather than at the apical membrane/extracellular colloid interface. The latter abnormality may be secondary to the observed mislocalization of the thyroid hormone synthesis machinery (dual oxidases, thyroperoxidase) in the cytosol. Nevertheless, the overall uptake of radioiodide, its organification, and secretion as thyroid hormones were comparable to those of wild-type mice, suggesting adequate compensation by the normal TSH retrocontrol. Accordingly, the levels of free thyroxine and TSH were normal. Only the levels of free triiodothyronine showed a slight decrease in caveolin-1 knockout mice. However, when TSH levels were increased through low-iodine chow and sodium perchlorate, the induced goiter was more prominent in caveolin-1 knockout mice. We conclude that caveolin-1 plays a role in proper thyroid hormone synthesis as well as in cell number homeostasis. Our study demonstrates for the first time a physiological function of caveolin-1 in the thyroid gland. Because the expression and subcellular localization of caveolin-1 were similar between normal human and murine thyroids, our findings in caveolin-1 knockout mice may have direct relevance to the human counterpart.

One hundred and eighty patients had serum thyrotropin, total triiodothyronine and free thyroxine concentrations measured within 3 h of admission to the Intensive Therapy Unit to assess whether thyroid function tests could predict outcome in critical illness. Overall mortality was 30.6%. Nonsurvivors were older (p = 0.001), and had higher APACHE II scores (p < 0.001) and predicted mortalities (p < 0.001). There was no difference in the median values of thyrotropin, total triiodothyronine and free thyroxine concentrations between survivors and nonsurvivors. Thyrotropin concentration was subnormal in 15 patients, normal in 152 and elevated in 13 patients. In contrast, 80 patients had subnormal triiodothyronine concentration. Free thyroxine was subnormal in five patients. Thyrotropin, total triiodothyronine and free thyroxine concentrations were not related to outcome (p = 0.360, p = 0.622, p = 0.726, respectively). No variable independently predicted death. Total triiodothyronine concentrations were lower in patients who received dopamine before admission to the intensive therapy unit than those who did not (p = 0.008); thyrotropin and free thyroxine concentrations were not influenced by dopamine administration. Serum concentrations of thyrotropin, total triiodothyronine and free thyroxine measured within 3 h of admission to the intensive therapy unit are not predictive of outcome.

The circadian rhythm of hormones (N = 10) and mental performance (N = 18) was investigated in male cadets during a 5-day military training course with continuous heavy physical activities corresponding to 35% of the maximal oxygen uptake, with almost total lack of food and sleep. The 24-h means for androstenedione, dihydroepiandrosterone (DHEA), 17 alpha-hydroxyprogesterone, testosterone and thyroid-stimulating hormone decreased strongly during the course, and the circadian rhythm was extinguished below the minimum levels measured during the control experiment. The 24-h means for cortisol, dihydroepiandrosterone sulfate (DHEA-S) and progesterone increased during the course, and the circadian rhythm was abolished above the maximum levels of the control experiment. A gradual increase was found in thyroxine, free thyroxine and triiodothyronine during the first 12 h of activities, followed by a constant decrease for the rest of the course. Mental performance decreased during the course and the amplitude of its circadian rhythm increased from +/- 10% to +/- 30% of the 24-h mean. The circadian rhythms investigated were almost normalized after 4-5 days of rest. However, the nocturnal rise for cortisol, androstenedione and DHEA appeared earlier, and the plasma levels of thyroid hormones, estradiol and DHEA-S were lower during the recovery experiment than in the control experiment. The responses to stress of the circadian rhythm for mental performance and steroid hormones during the course indicate a differential regulation.

Hexachlorobenzene (HCB) residue levels in dosed rats (50.0 mg kg-1 body wt.day-1, n = 9) were significantly (P < 0.05) greater in the periovarian fat compared to the thyroid gland. Hexachlorobenzene residue levels were significantly (P < 0.05) greater in the thyroid versus the adrenal and ovary. Ovarian HCB residue levels were greater than those found in the thymus, liver and lung. Serum thyroxin (T4) and the free T4 index (FTI) were significantly (P < 0.05) suppressed in HCB-treated rats compared to the control group (n = 8). In contrast, no significant differences in serum concentrations of oestradiol (E2), progesterone (P4) or percentage triiodothyronine uptake (%T3) were observed, thus suggesting an HCB-induced hypothyroid-like state. In a second experiment, adult female Sprague Dawley rats (n = 16) were dosed as above and superovulated with pregnant mare serum gonadotrophin (PMSG, 10 IU s.c.) and human chorionic gonadotrophin (hCG, 20 IU s.c.). Circulating levels of P4 were significantly (P < 0.05) elevated compared to the control group (n = 8). The %T3 uptake and serum T4 levels were significantly (P = 0.05) suppressed compared to controls. Hexachlorobenzene treatment had no effect on circulating levels of E2 or on the FTI. These results suggest that HCB-induced changes found in the spontaneously cycling rat are augmented by ovulation induction strategies. We also conclude that HCB concentrates in the endocrine tissues in addition to the fat.

In parallel with industrial advancements, number of the occupational diseases secondary to chemical exposure is increasing. The chemical agents in the work places affect various organ and tissue systems, leading to chronic diseases. In this study, the cases diagnosed with occupational disease due to exposure to lead were studied and importance of the environmental forensic sciences on this issue was emphasized. A hundred and ninety patients diagnosed with occupational disease related to lead intoxication in Ankara Occupational Diseases Hospital between 01/01/2009 and 31/12/2009 were included in the study. Twenty cases were used as the controls. Sociodemographic characteristics, serum chemical parameters and hematological parameters of the patients were retrospectively assessed. Mean age of the cases included in the study was 35.3±8.69. Hemoglobin (Hb) (p=0.018) and Mean corpuscular volume (MCV) (p<0.001) values were found significantly lower in the patients with lead exposure than in the controls. Gamma glutamyl transferase (GGT) was significantly lower in the patients with lead exposure than in the controls (p=0.002), whereas alkaline phosphatase (ALP) was found higher (p<0.001). In thyroid function test (TFTs) panel, free triiodothyronine (fT3) levels were found significantly higher in the patients with lead exposure than in the control group (p=0.01), while Thyrotrophin-stimulating hormone (TSH) levels were lower (p<0.001). No significant difference was found in terms of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values. In the correlation analysis; serum level of serum lead (Pb) was correlated positively with ALP values and negatively with Hb, MCV and TSH. Considering its effects on the biochemical and hematological parameters, a detailed investigation should be carried out in the cases with lead exposure, which occupies an important place among the occupational diseases.