OBJECTIVE

Results of cohort studies on the association between decreased serum TSH levels and mortality are conflicting. Some studies demonstrated an increased mortality risk in subjects with decreased serum TSH levels, others did not. Even meta-analyses revealed contradictory results. We undertook the present study to investigate the association between decreased serum TSH levels and mortality in the large population-based Study of Health in Pomerania (SHIP).

METHODS

Data from 3651 individuals from SHIP without known thyroid disorders or thyroid treatment were analyzed. Serum TSH, free triiodothyronine, and free thyroxine levels were determined by immunochemiluminescent procedures. Decreased TSH was defined as serum TSH levels below 0.25 mIU/l. Cox regression was used to associate decreased TSH levels with mortality.

RESULTS

The median duration of follow-up was 8.5 years (30 126 person years). During follow-up, 299 individuals (6.9%) died corresponding to a death rate of 9.92 deaths per 1000 person years. Survival time was shorter in subjects with decreased serum TSH levels compared to euthyroid individuals. After adjustment for age and sex, however, there was no association between decreased serum TSH levels and all-cause mortality (hazard ratio: 0.95; 95% confidence interval: 0.67; 1.36). Likewise, decreased serum TSH levels were neither associated with cardiovascular nor with cancer mortality.

CONCLUSIONS

There is no independent association of decreased serum TSH levels with all-cause, cardiovascular, and cancer mortality in the adult northeast German population. Although our study has some strengths, we cannot finally conclude on therapeutical implications in individuals with subclinical thyroid diseases.

The sensitivity and specificity of two sensitive thyrotropin assays were compared with those of other standard thyroid function tests in 544 ambulatory subjects who were clinically euthyroid, thyrotoxic, or hypothyroid. Both sensitive thyrotropin assays had the highest sensitivity and specificity (95%/89% and 92%/95%), following by estimated free thyroxine (T4) level (82% and 94%), calculated free T4 index (78% and 93%), and free triiodothyronine index (86% and 88%). Sensitivity of the two thyrotropin assay kits in the diagnosis of thyrotoxicosis was 86% and 95%, and that in the diagnosis of hypothyroidism was 92% and 94%. Other tests were nearly as sensitive in the diagnosis of thyrotoxicosis but not hypothyroidism. A cost analysis of a testing strategy that used either total T4, free T4 index, or sensitive thyrotropin assay alone as the first-line thyroid test disclosed that to establish the patient's thyroid metabolic status would have cost $11,093, $14,536, and $24,902, respectively, using each test first. We suggest that, at current prices, routine use of the thyrotropin assay as a first-line test in ambulatory patients is not as cost-effective as the free T4 index.

Hypothyroidism is associated with a disturbance of behaviour and mood. There are also individuals, not classified as hypothyroid, with low to 'low normal' thyroid hormone levels and normal thyroid-stimulating hormone (TSH) levels who have mood and behavioural changes. As the peripheral thyroid hormones decrease, TSH is expected to increase. However, there are a number of physiological mechanisms known to suppress TSH. In the present study, we report on thyroid hormone regulation in a rat model of neuropathic pain and altered social behaviour that is usually transient, but is persistent in a sub-group of the population. Following ligation of the sciatic nerve, male Sprague-Dawley rats were assessed for social dominance towards an intruder: 20% showed persistently decreased social dominance. Plasma levels of thyroid hormones, TSH and corticosterone were measured before and on days 2, 3, 4, 5 and 6 after injury in 21 rats. The mean plasma thyroxine (T4), free thyroxine (fT4) and triiodothyronine (T3) levels decreased significantly post-injury in rats with persistently changed behaviour compared to rats with unchanged behaviour (P < or = 0.002). There was no significant difference between groups for mean change in free triiodothyronine (fT3) or TSH. There was a correlation between decreased dominance behaviour and decrease in both T4 (r = 0.62, P = 0.009) and fT4 (r = 0.71, P = 0.001), but no correlation with TSH. In a sub-population of rats, decreased thyroid hormones did not result in the expected increased levels of TSH to restore pre-injury levels, nor did they show increased hypothalamic thyrotrophin-releasing hormone mRNA expression, indicating altered hypothalamic-pituitary-thyroid axis regulation. Because T3 availability to the brain is dependent on both circulating T3 and T4, decreased peripheral thyroid hormones may result in changed neural function, as expressed in altered complex behaviours in this sub-population of rats.

BACKGROUND

Biological variation of an analyte is an important determinant of its usefulness. Intraindividual variation in serum thyroid hormones, parathyroid hormone (PTH) and insulin-like growth factor-1 (IGF-1) in healthy subjects was determined in this study.

METHODS

Blood samples were taken at weekly intervals for six weeks from 10 healthy subjects and analysed for serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), PTH and IGF-1.

RESULTS

Intraindividual variations for serum FT4 and FT3 were <5.0%, IGF-1 9.4% and TSH and PTH 25.1% and 25.9%, respectively. Index of individuality was lowest for FT4 (0.42) and FT3 (0.38), and highest for PTH (1.09).

CONCLUSIONS

Intraindividual variation for FT4, FT3 and IGF-1 are low.

Serum levels of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) were studied in 80 patients with endogenous depression before and after electroconvulsive treatment (ECT). Compared to the values found after recovery, the patients when depressed had significant increased serum levels of T4, rT3, 3,3'-T2 and 3',5'-T2. Serum concentrations of T3 and 3,5-T2 were not significantly altered. Similarly the free T4 index (FT4I) was increased, while the free T3 index (FT3I) was unaffected. Previous studies have shown a reduced TSH response to TRH in patients with endogenous depression and that the long-term outcome after ECT is strongly related to changes in the TSH response. However, patients with increased TSH response to TRH (n = 23) had a pattern of serum iodothyronine concentrations similar to those (n = 57) with an unchanged TSH response. A similar pattern was also found in 7 patients with nonendogenous psychosis, in whom the TSH response to TRH was unchanged after recovery. It is concluded that the alterations of the TSH response to TRH found in endogenous depression cannot be explained by changes of FT4I or FT3I.

The effect of early feed restriction on metabolic programming and compensatory growth was studied in broiler chickens. A total of 480 female 1-d-old broiler birds (Aconred) were randomly allocated to ad libitum and feed-restricted groups, each of which was replicated 6 times with 40 birds per replicate. Broilers were provided commercial diets. Feed-restricted broilers were deprived of feed for 4 h per day from 1 to 21 d of age. Effects of treatments were determined at 21 and 63 d of age. In feed-restricted birds at 21 d of age, BW, average daily gain and average daily feed intake, breast muscle (P < 0.01), carcass yield (P < 0.05), and abdominal fat (P < 0.05) were decreased. Ether extract content in breast muscle was increased (P < 0.01), whereas CP content was slightly decreased. Triiodothyronine (P < 0.01) and thyroxine (P < 0.05) were decreased in serum. Free fatty acid and very low density lipoprotein were slightly increased in serum, whereas triglyceride and glucose were decreased (P < 0.01). Activities of NADPH-generating enzymes in liver including malic dehydrogenase, isocitrate dehydrogenase, and glucose-6-phosphate remained unchanged in ad libitum birds, whereas hormone-sensitive lipase activity was increased (P < 0.01). In feed-restricted birds at 63 d of age, BW, average daily gain, average daily feed intake, carcass yield, breast muscle yield, and serum triiodothyronine and thyroxine remained as ad libitum birds, whereas abdominal fat yield was increased (P < 0.05). Ether extract content in breast muscle was decreased (P < 0.01), whereas CP content was increased (P < 0.05). Activities of NADPH-generating enzymes were significantly increased, except abdominal malic dehydrogenase and hormone-sensitive lipase activity was decreased (P < 0.01) in liver and abdominal fat. Lipoprotein lipase activity was increased (P < 0.05) in abdominal fat. In summary, feed restriction severely affected growth performance and lipid metabolism in broilers in the early period. Because there was no statistical difference among the final BW, near full compensatory growth was achieved. In addition, early feed restriction might have induced prolonged metabolic programming in chicks and led to adult obesity.

A reciprocal relationship between the endocrine and immune system has been demonstrated under pathophysiological conditions. However, few studies have assessed the relationship between thyroid hormones and immune function in apparently healthy individuals. Therefore, to clarify our understanding of normal physiological endocrine-immune interactions this study aimed to examine the interrelationships between thyroid hormones and immunity in healthy individuals. Total <em>triiodothyronine</em> (T(3)), total thyroxine (T(4)) and markers of immune status were assessed in 93 <em>free</em>-living and apparently healthy individuals aged 55-70 years. T(3) and T(4) concentrations were determined by commercially available kits. Immune status was assessed using flow cytometry and biochemical markers. Statistical analysis was performed by partial correlation, controlling for age. Thyroid hormone concentration was positively associated with markers of inflammation (P<or=0.05), natural killer-like T cells (P<or=0.001), expression of interleukin-6 (IL6) by activated monocytes (P<or=0.05); percentage expression of memory T-lymphocytes (P<or=0.01), memory T-helper lymphocytes (P<or=0.05) and memory T-cytotoxic lymphocytes (P<or=0.05), and higher IL2 receptor density on CD3+T-lymphocytes (P<or=0.05). Thyroid hormone concentration was inversely associated with early lymphocyte apoptosis (P<or=0.05) and the ratio of naïve- to memory T-cytotoxic lymphocytes (P<or=0.05). The current study provides preliminary evidence of a role for T(3) and T(4), within normal physiological ranges, in the maintenance of lymphocyte subpopulations, and in mediating the inflammatory response. In conclusion, these findings highlight the potential implications of altered thyroid function in older individuals and the importance of future research examining thyroid-immune interactions.

BACKGROUND

Neuroendocrine changes are important processes which accompany critical illness, however, the number of clinical studies concentrating on the role of thyroid gland hormones in stroke pathogenesis is relatively small. The aim of this prospective study was to investigate the relation between free triiodothyronine (fT3) levels and the prognosis of patients with stroke.

METHODS

The prospective study included 387 patients with acute (<24 h of symptoms onset) ischemic stroke consecutively admitted to Stroke Units. The subjects with known conditions that could interfere with thyroid gland metabolism were excluded. We analyzed: the routine blood tests, fT3, free thyroxine (fT4), thyroid-stimulating hormone (TSH) levels, unenhanced CT scans, initial clinical status (NIH Stroke Scale, NIHSS), 30- and 360- days outcome (modified Rankin Scale-mRS) and calculated the survival rate.

RESULTS

A higher NIHSS score was in the 1 (st) fT3 levels tertile, whereas a lower in the 3 (rd) fT3 levels tertile (p=0.006). The 30- and 360-days mRS scores showed that patients in the lowest fT3 tertile had more severe neurological impairment than those in the highest tertile (p=0.001 and p=0.03, respectively). A 1-year mortality of the patients with the first tertile fT3 levels was significantly higher than that of the patients with the third tertile hormone levels (p=0.008). Additionally, subjects with fT3 level in the lowest tertile demonstrated higher WBC counts and the ventricular system on Computed Tomography of head performed on admission to hospital was statistically more frequent compressed than that in the patients with fT3 level in the highest tertile (p=0.02 and p=0.03, respectively).

CONCLUSIONS

In acute stroke patients lower free T3 levels are an important factor related to unfavorable outcome, i. e., severe disability and death.

Various aetiopathological mechanisms have been postulated to be at the root of Menière's disease (MD), and some data suggest that there may be also an underlying autoimmune factor. In fact, Menière patients manifest certain characteristics that are typical of autoimmune involvement association of particular human leucocyte antigen haplotypes, the presence of antibodies against internal ear antigens. In this study, we evaluated the association between thyroid autoimmunity and MD in a non-selected group of patients. We recruited 50 consecutive MD patients and two groups as controls: group A, 82 healthy volunteers; and group B, 50 subjects suffering from acute unilateral peripheral vestibulopathy. All subjects were submitted to instrumental assessment of cochlear-vestibular function and analysis of thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, anti-TSH receptor antibody (TR-Ab), anti-thyroperoxidase antibody (TPO-Ab) and anti-thyroglobulin antibody (Tg-Ab) in the blood. The prevalence of autoimmune thyroiditis in group B [6/50 (12%); 66.7% TPO-Ab and 33.3% Tg-Ab] was superimposable with the healthy controls [6/82 (7%); 66.7% TPO-Ab and 33.3% Tg-Ab]. In contrast, 38% of the MD patients (P = 0.0001 versus group A and group B) had significant autoantibody levels (68.4% TPO-Ab; 15.8% TPO-Ab + TR-Ab; 10.5% Tg-Ab; 5.2% TPO-Ab + Tg-Ab). Furthermore, 14% of the MD patients were hyperthyroid under l-thyroxine therapy, while no dysfunction was seen in the control groups. Overall, our data demonstrate a significant association between MD and thyroid autoimmunity, which suggests that an autoimmune factor is involved in the aetiopathogenesis of this disease. These findings suggest that it should be useful to submit MD patients to multi-disciplinary clinical investigation.

A nontender goiter rapidly developed in a 54-year-old patient with suspected disseminated carcinoma. Thyroid function tests showed increased thyroxine, triiodothyronine resin uptake, free thyroxine index, and free thyroxine. Radioactive iodine uptake by the gland was near zero, and thyroid-stimulating hormone (TSH) was undetectable. Histologic examination of the thyroid before and after death showed invasion and disruption of the thyroid follicles by adenocarcinoma (pancreatic primary). Release of thyroglobulin by follicular disruption probably resulted in hyperthyroxinemia and suppression of TSH and radioactive iodine uptake, as occurs in subacute thyroiditis.

Of 27 patients with ophthalmic Graves's disease (OGD) who had been clinically euthyroid three years previously, one became clinically hyperthyroid and seven overtly hypothyroid. Improvement in eye signs was associated with a return to normal of thyroidal suppression by triiodothyronine (T3) and of the response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). Of a further 30 patients with OGD who had not been studied previously, three were overtly hypothyroid. Of the combined series, 46 patients were euthyroid, 18 (40%) of whom had an impaired or absent TSH response to TRH, and 3(6-7%) an exaggerated response. Eleven out of 37 patients (29-7%) had abnormal results in the T3 suppression test. There was a significant correlation between thyroidal suppression by T3 and the TSH response to TRH. Total serum concentrations of both T3 and thyroxine (T4) were closely correlated with T3 suppressibility and TRH responsiveness. Free T4 and T3 (fT3) concentrations were normal in all but three patients, in whom raised fT3 was accompanied by abnormal TSH responses and thyroidal suppression. The presence of normal free thyroid hormone concentrations in patients with impaired or absent TSH responses to TRH is interesting and challenges the concept that free thyroid hormones are the major controlling factors in the feedback control of TSH.

The long term effects of usage of triclosan-containing toothpaste on thyroid function are currently unknown. Triclosan is structurally similar to thyroid hormones and reductions in serum thyroid hormone levels have been observed in animal studies following oral administration of triclosan. Therefore, an assessment of thyroid function over 4 years was undertaken in a subset of individuals in a randomised, placebo controlled clinical trial comparing the effects of 0.3% triclosan toothpaste with placebo toothpaste in subjects with coronary heart disease. Thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), antithyroglobulin antibody (anti-TGab) and antithyroid peroxidase antibody (TPOab) were measured. Paired serum samples at year 1 and year 5 from 132 subjects (64 triclosan group, 68 placebo group) were analysed. At year 1 there were no significant differences in thyroid function between the groups: mean (SD) TSH 1.4 (0.8) and 1.6 (0.9) mU/L, triclosan and placebo groups respectively, fT4 15.8 (2.2) and 15.2 (2.1) pmol/L; fT3 4.8 (0.5) and 4.8 (0.5) pmol/L. Similarly, for antithyroid antibodies there were no group differences at year 1. Median (25th, 75th percentile) for anti-TGab, 38 (34, 42) and 37 (30, 42) U/mL triclosan and placebo groups respectively; anti-TPOab, 15 (10, 22) and 18 (10, 24) U/mL. At year 5, fT4 was the only measure to show a significant difference between groups (mean and 95% Confidence Interval) 15.6 (15.1, 16.1) and 14.7 (14.2, 15.1) pmol/L triclosan and placebo respectively (p=0.01). This reflects reduced levels in the placebo group but no change in the triclosan group. In conclusion, over 4 years triclosan toothpaste had no detectable effect on thyroid function. The data support the view that 0.3% triclosan in toothpaste is safe and free of significant thyroid adverse effects.

Despite improved hematologic care, multiendocrine dysfunction is a common complication of homozygous transfusion-dependent beta-thalassemia. In this study our goal was to estimate the prevalence of thyroid dysfunction in a large homogenous group of thalassemic patients. Two hundred patients with beta-thalassemia major (100 males and 100 females; mean age, 23.2 +/- 6.7 years; age range 11-43 years), regularly transfused and desferioxamine chelated, were randomly selected from a pool of approximately 800 patients with beta-thalassemia followed in our department. Thyroid function and iron-load status were evaluated by measurements of free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH), and serum ferritin levels. Of the subgroup of patients who proved to have normal thyroid hormone values, 26 (12 males, 14 females; mean age, 23.6 +/- 6.8 years; age range, 15-36 years) were randomly selected and underwent a standard TRH stimulation test. Thyroid dysfunction was defined as follows: overt hypothyroidism: low FT4 and/or FT3, increased TSH levels; subclinical hypothyroidism: normal FT4, FT3, increased TSH levels; exaggerated TSH response: normal FT4, FT3, normal basal TSH, deltaTSH>> or = 21 microIU/mL (TSH levels measured prior and 30 minutes after intravenous TRH administration). Normal thyroid hormone values were found in 167 (83.5%) of the 200 patients studied. Eight (4%) of the remaining patients had overt hypothyroidisim, and 25 (12.5%) had subclinical hypothyroidism. Exaggerated TSH response to TRH was revealed in 7 of the 26 patients with normal hormone values tested (26.9%). Antithyroglobulin and anti-thyroid peroxidase (TPO) antibody titers were negative in 191 patients (95.5%). Mean ferritin levels in hypothyroid and euthyroid patients were 2707.66 +/- 1990.5 mg/L and 2902.9 +/- 1997.3 mg/L, respectively, (p = 0.61), indicating no correlation between ferritin levels and thyroid functional status. Mean ferritin levels in the patients who responded normally to TRH stimulation and in those who overresponded, were 2,586 +/- 1791 mg/L and 3,228 +/- 2473 mg/L, respectively (p = 0.46; NS). Thyroid failure is a rather rare endocrine complication in patients with beta-thalassemic from Greece. In our series, no case of central hypothyroidism was observed. No correlation was found between thyroid functional status and ferritin plasma levels. Approximately 1 of 5 beta-thalassemic patients with normal thyroid hormone values showed an exaggerated TSH response to TRH test. It is to be investigated how many of these patients will establish overt or subclinical hypothyroidism in the future.

Serum total and free thyroid hormone concentrations were estimated in 42 patients with epilepsy taking anticonvulsants (phenytoin, phenobarbitone, and carbamazepine either singly or in combination). There was a significant reduction in total thyroxine (TT4), free thyroxine (FT4), and free triiodothyronine (FT3) in the treated group compared with controls. Free hormone concentrations were lower than total hormone concentrations, suggesting that increased clearance of thyroid hormones occurs in patients receiving anticonvulsants. Detailed analysis indicated that phenytoin had a significant depressant effect on TT4, FT4, FT3, and reverse T3 (rT3). Phenobarbitone and carbamazepine had no significant main effects, but there were significant interactions between phenytoin and carbamazepine for TT4 and FT4. phenobarbitone and carbamazepine for FT3, and phenytoin and phenobarbitone for rT3.

A growing body of evidence indicates that hormones play an important role in learning and memory functions as well as in mood modulation. During the acute stage of anorexia nervosa (AN), weight loss has a significant effect on serum levels of estrogen, thyroid hormones, and cortisol. Furthermore deficits in learning and memory functions are evident in patients with eating disorders during emaciation. Hormonal and neuropsychological alterations at least partly remit during weight restoration. We investigated the association between learning and memory functions as well as mood and neuroendocrinological parameters before and after weight gain in adolescent AN. Twenty-eight female subjects with AN, diagnosed according to DSM-IV, were examined before and after weight recovery. Both investigations took place while the patients were receiving hospital treatment, and the results were compared to a control group consisting of 18 age- and IQ-matched normal-weight female adolescents also tested twice within 4 months. Verbal memory and learning were assessed by a German paper-pencil-test (LGT). We performed correlation calculations between neuropsychological functions and depressive symptoms and estrogen, cortisol and free triiodothyronine (fT₃) in the plasma at both time points. Compared to normal controls adolescents with AN performed worse in one subtest of the LGT which requires the verbal reproduction of figural material across both time points. Verbal learning was positively correlated with estrogen levels after weight recovery. Depressive symptoms of AN patients significantly decreased during weight rehabilitation and correlated negatively with fT₃ at T₁. We did not find a relationship between cortisol levels and neuropsychological functions. We observed subtle memory impairments and depressive symptoms in subjects with adolescent AN associated with starvation-induced estrogen and triiodothyronine deficits, respectively. Normalization of body weight and resuming of menses is needed to restore learning and memory functions as well as to alleviate depressive symptoms.

The uptake of 2-deoxy-D-[1-3H]glucose ([1-3H]DOG)by cultured chick embryo heart cells was stimulated by exposure to triiodothyronine (T3). The concentration of free T3 for half maximal stimulation of [1-3H]DOG uptake was 8.7 x 10(-10)M. Nuclear binding studies revealed that the Kd for T3 was 4.2 x 10(-10)M. The molar potencies of other thyroactive compounds in stimulating [1-3H]DOG uptake, relative to L-T3, were: 500% for 3'-isopropyl-3,5-diiodo-L-thyronine, 20% for L-thyroxine (T4), 17% for D-T3, 2.2% for D-T4, 0.6% for 3,5-diiodo-L-thyronine and less than 0.1% for 3',5',3-triiodo-L-thyronine and L-thyronine. These data suggest that cultured chick embryo heart cells may serve in the study of the mode of action of thyroid hormones.

BACKGROUND

Severe iodine deficiency disorders have been eradicated in many parts of the world, but milder forms still exist and may escape detection. Turkey has long been known to be a mild to moderate iodine deficiency area.

OBJECTIVE

The aim of this study was to assess the iodine nutritional status and the thyroid function of pregnant women and their neonates in the region of Kayseri (central Anatolia of Turkey) that appeared to be iodine deficient in previous studies performed before the introduction of mandatory salt iodization.

METHODS

A cross-sectional voluntary screening study was performed in the Maternity Unit of a university hospital. A total of 70 mothers and their healthy full-term neonates were included in this study. Urinary iodine concentration was estimated in spot urine samples obtained from mothers and their neonates on day 5. All the neonates were breastfed. The iodine content was determined in the breast milk of all mothers on day 5. Serum concentrations of TSH, thyroglobulin (Tg), free triiodothyronine (FT3) and free thyroxine (FT4) were investigated in the cord serum of neonates and compared to those of mothers immediately after parturition

RESULTS

The median urinary iodine on day 5 in mothers and their babies were 30.20 and 23.80 microg/l, respectively. These figures are much lower than normal for these age groups (150-200 microg/l). The median iodine content of breast-milk was 73 microg/l. It is again much lower than in iodine sufficient areas, indicating that the status of iodine nutrition of pregnant and lactating women is clearly insufficient. The median concentrations (and ranges) of neonatal TSH, Tg, FT3 and FT4 were 7.44 mU/l, 71.62 ng/ml, 1.30 pg/ml and 1.34 ng/dl respectively. The corresponding levels for the mothers during labor were 2.19 mU/l, 25.65 ng/ml, 1.31 pg/ml and 1.23 ng/dl respectively. The median neonatal serum concentrations of TSH and Tg were significantly higher than the corresponding maternal levels (P < 0.0001, P < 0.0001, respectively) and 27.1% of the neonates had serum TSH concentrations above 10 mU/l and 57.1 % had cord blood serum Tg concentrations above 54 ng/ml. None of the mothers showed TSH concentrations above 5 mU/l and 41.4% had serum Tg concentrations above 30 ng/ml.

CONCLUSIONS

Iodine deficiency with low urinary iodine excretion and high serum Tg and TSH concentrations were recognized among pregnant women and their babies in Kayseri in spite of the program of salt iodization. National measures are urgently required for improving the correction of iodine deficiency in Turkey. This includes regular supplementation with iodine, starting at preconception or in early pregnancy and continuing during the period of nursing in this region.

BACKGROUND

Our objective was to determine the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) in documenting both group and individual relationships between thyroid hormone and thyroid-stimulating hormone (TSH) concentrations.

METHODS

This was a prospective analysis of 50 euthyroid patients undergoing thyroidectomy. Thyroxine (T(4)), triiodothyronine (T(3)), free T(4) (FT(4)), and TSH levels were documented on two occasions before thyroidectomy. After thyroidectomy, patients were treated with levothyroxine (LT(4)) to achieve either a normal or low serum TSH concentration. All laboratory evaluations were repeated twice while patients were taking LT(4). Thyroid hormone concentrations were documented by both immunoassay and LC-MS/MS, and their relationship with TSH was studied both in the entire group and in individual patients pre- and postthyroidectomy.

RESULTS

FT(4) and total T(3) correlated better with the log-transformed TSH when measured by LC-MS/MS. Postthyroidectomy the closest correlation was between log TSH and FT(4) (r = 0.86, p < 0.001). The next best correlation was between log TSH and total T(3) (r = 0.71, p < 0.001). When all data points were combined, the slope of the relationship between log TSH and total T(3) was relatively blunted compared with the log TSH-FT(4) slope (slope - 0.39 vs. - 1.38; p < 0.001), perhaps suggesting autoregulation of T(3) in response to the altered conditions postthyroidectomy.

CONCLUSIONS

LC-MS/MS is an excellent tool for documenting the known physiological phenomenon of a log-linear relationship between TSH and thyroid hormone concentrations. In a group of patients studied pre- and postthyroidectomy, both FT(4) and total T(3) measured by tandem mass spectrometry correlate well with TSH. However, T(3) correlates slightly less well and has a relatively blunted relationship with the log-transformed TSH. These paired data suggest that in LT(4)-replaced patients T(3) concentrations are held stable in the face of fluctuating T(4) concentrations.

Our study investigated body composition and body fat distribution in healthy centenarians. Body composition, body fat distribution, and resting metabolic rate (RMR) were studied in 40 adult subjects aged < 50 y, 35 aged subjects>> 75 y, and 15 healthy centenarians aged>> 100 y. Body composition was determined by bioimpedance analysis, body fat distribution was calculated as waist-hip ratio (WHR), and RMR was calculated by using the Arciero-Poehlman formula. Healthy centenarians had a cognitive impairment and degree of disability greater than aged subjects. Despite such differences, fat-free mass (FFM) and RMR were not different in centenarians compared with aged subjects but were lower than in adult subjects. In contrast, healthy centenarians had a WHR lower than that of aged subjects but not different from that of the adult subjects. After the level of physical activity and degree of disability were adjusted for, FFM (44 +/- 2.7 and 40 +/- 1.1 kg; P < 0.05) and RMR (6757 +/- 761 and 5891 +/- 723 kJ/24 h; P < 0.05) were significantly higher in healthy centenarians than in aged subjects, respectively. Independent of age, sex, body weight, degree of disability, level of physical activity, and fasting plasma triiodothyronine, there was a strong correlation between RMR and FFM (r = 0.50, P < 0.05) in healthy centenarians. In conclusion, healthy centenarians had a lower FFM and higher body fat content than aged subjects. Level of physical activity and degree of disability seem to be the major determinants for explaining such differences.

Recently, we demonstrated that 3,3',5-triiodothyronine (T3) induces oxidative stress in rat liver, with enhancement in the DNA binding of nuclear factor-kappaB (NF-kappaB) and the NF-kappaB-dependent expression of tumor necrosis factor-alpha (TNF-alpha). In this study, we show that T3 administration (daily doses of 0.1 mg/kg i.p. for three consecutive days) elicited a calorigenic response and higher liver O2 consumption rates, with increased serum levels of TNF-alpha (ELISA), liver inhibitor of kappaB (IkappaB-alpha) phosphorylation (Western blot analysis), and hepatic NF-kappaB DNA binding (EMSA) at 56-72 h after treatment. Within this time interval, liver manganese superoxide dismutase (MnSOD) activity and the protein expression of MnSOD and Bcl-2 are enhanced. These changes are abrogated by the administration of alpha-tocopherol (100 mg/kg i.p.) prior to T3. It is concluded that T3 treatment leads to the redox upregulation of MnSOD and Bcl-2 in rat liver, in association with TNF-alpha release and activation of the IkappaB-alpha kinase/NF-kappaB cascade, which may constitute a protective mechanism against free radical toxicity involving cell death signaling.

The present study examined whether oral short-term administration of salbutamol (Sal) modifies performance and selected hormonal and metabolic variables during submaximal exercise. Eight recreational male athletes completed two cycling trials at 80-85% peak O(2) consumption until exhaustion after either gelatin placebo (Pla) or oral Sal (12 mg/day for 3 wk) treatment, according to a double-blind and randomized protocol. Blood samples were collected at rest, after 5, 10, and 15 min, and at exhaustion to determine growth hormone (GH), cortisol, testosterone, triiodothyronine (T(3)), C peptide, free fatty acid (FFA), blood glucose, lactate, and blood urea values. Time of cycling was significantly increased after chronic Sal intake (Sal: 30.5 +/- 3.1 vs. Pla: 23.7 +/- 1.6 min, P < 0.05). No change in any variable was found before cycling except a decrease in blood urea concentration and an increase in T(3) after Sal that remained significant throughout the exercise test (P < 0.05). Compared with rest, exercise resulted in a significant increase in GH, cortisol, testosterone, T(3), FFAs, and lactate and a decrease in C peptide after both treatments with higher exercise FFA levels and exhaustion GH concentrations after Sal (P < 0.05). Sal but not Pla significantly decreased exercise blood glucose levels. From these data, short-term Sal intake did appear to improve performance during intense submaximal exercise with concomitant increase in substrate availability and utilization, but the exact mechanisms involved need further investigation.

BACKGROUND

Blood samples collected in rural and remote areas of Australasia are often exposed to a range of environmental conditions prior to analysis in a laboratory. The aim of this study was to determine analyte stability of venous blood specimens in serum gel tubes exposed to a range of storage temperatures and times prior to centrifugation.

METHODS

Thirty healthy adult volunteers were enrolled in the study. Blood was collected into 11 serum gel separator tubes. All samples were allowed to clot at room temperature for 30 min. Two samples were centrifuged and analysed as controls. Nine samples were stored at 15, 25 or 35 degrees C for 4, 8 or 24 h, respectively, before centrifugation. Thirty-five biochemical analytes were measured on each sample.

RESULTS

Most analytes remained stable in all storage conditions including sodium, total protein, albumin, bilirubin, alanine transferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase, creatinine kinase, lipase, cholesterol, triglycerides, transferrin, urate, C-reactive protein, vitamin B(12), thyroid-stimulating hormone, free thyroxine, free triiodothyronine, follicle-stimulating hormone, oestradiol, prostate-specific antigen, cortisol and vitamin D. Potassium, glucose, phosphate, creatinine, urea, ferritin, iron, lactate dehydrogenase, magnesium and calcium were not stable in at least one of the storage conditions.

CONCLUSIONS

These results can be used to determine which analytes produce valid results despite exposure to variable storage conditions for up to 24 h prior to centrifugation. The majority of analytes were unaffected by a delay in centrifugation at a variety of temperatures, however, some important analytes were significantly affected.

A significant reduction in plasma free triiodothyronine (T3) (P less than 0.0001) has been observed in patients undergoing open heart surgery. The beneficial effect of T3 would appear to be associated with increased synthesis and utilization of myocardial high energy stores. We have therefore administered T3 (4-10 micrograms iv) to 10 patients either when difficulty was being experienced in weaning from cardiopulmonary bypass (CPB) support (n = 5), or when myocardial function remained extremely poor (n = 5), despite inotropic and intraaortic balloon pump support. Mean preoperative NYHA functional class of the 10 patients was 3.2, left ventricular enddiastolic pressure (LVEDP) 20 mm Hg and ejection fraction (EF) 40%. The mean myocardial ischaemia time was 72 min (range 40-120 min). Within 1 h of T3 administration the mean plasma free T3 level had risen from 1.03 to 3.56 micrograms/ml and CPB was discontinued in all 5 cases. Balloon pump support (n = 2) was no longer essential within 3 h. At 1 h, the mean arterial pressure (MAP) had risen from 42 to 78 mm Hg, and heart rate (HR) from 90 to 104 beats/min; the left atrial pressure (LAP) had fallen from 30 to 14 mm Hg, and the central venous pressure (CVP) from 20 to 11 cm H2O. (All changes significant at P less than 0.0001.) Inotropic support had been significantly reduced or discontinued. To our knowledge, T3 has not been administered previously as an inotropic agent to patients who have undergone cardiac surgery. We believe that T3 may have an important role in the rescue of failing hearts following a period of myocardial ischaemia in patients who have undergone open heart surgery.

Indices of thyroid function were measured in 108 infants born at 23-31 weeks gestation, after birth, at 24 and 72 h, and at 1, 3, 4, 5 and 6 weeks of age. This group was characterised by low serum thyroxine (T4), normal thyroid stimulating hormone (TSH), low-normal thyroid binding globulin (TBG), low free thyroxine index (FTI) and low triiodothyronine (T3). The incidence of hypothyroxinaemia defined as a serum T4 value of less than 65 nmol/l was 58% after birth, increasing to 84% at 1 week, after which there was progressive reduction to 36% by 6 weeks of age. Mean T4 values were inversely proportional to gestational age during this study period. Infants of 23-28 weeks gestation had significantly lower T4, TBG, FTI and T3 values compared to those of 29-31 weeks gestation. Infants who had hyaline membrane disease (HMD) had significantly lower T4 and FTI values compared to those without HMD for up to 3 weeks of age. Similar differences were found between deaths and survivors in the first week after birth. This study suggests that there is increasing delay in maturation of the hypothalamic-pituitary-thyroid axis control with increasing prematurity. In addition, the data suggest that infants who were extremely preterm or those with HMD had worse and more persistent abnormalities of thyroid function secondary to their illness and metabolic stress. The significance of our findings, in particular that of prolonged hypothyroxinaemia, is uncertain. The role of thyroid replacement therapy in these very preterm infants therefore need to be assessed with a randomised clinical trial.