Although the association between low free triiodothyronine (FT3) and poor outcome has been extensively reported in literature, the degree of peripheral thyroxin deiodination and its relationship with frailty and survival in hospitalized older patients has not yet been fully established. The aim of the current study was to evaluate the possible correlation between FT3/free thyroxine (FT4) ratio reduction, an indirect marker of thyroxin deiodination impairment, and frailty status and survival in hospitalized older patients.

We consecutively enrolled older patients, hospitalized in the geriatrics ward of the University of Pisa. At admission, Multidimensional Geriatric Assessment (MGA) and Multi Prognostic Index (MPI), an indirect measure of frailty, were obtained from all the patients. Causes of hospitalization and prevalence of delirium were recorded. Blood samples for FT3, FT4, and thyrotropin value evaluation were drawn after an overnight fast.

A total of 643 patients (83.8 ± 7.4 years, 53% women) were studied. FT3 was inversely and strongly correlated, whereas FT4 was moderately positively correlated with MGA parameters, MPI score (P < 0.001 and P < 0.05, respectively), and survival (P < 0.001 and P = 0.09, respectively). FT3/FT4 ratio reduction was highly associated with worse MGA (P < 0.001) and MPI scores (P < 0.0001), even in patients without low FT3. The inclusion of FT3 in the final model of multivariate Cox regression confirmed the independent role of FT3/FT4 ratio in predicting survival (P = 0.005).

Overall, our study documented a strong association between FT3/FT4 ratio reduction, a surrogate marker of peripheral thyroxin deiodination, and frailty. Moreover, FT3/FT4 ratio value emerged as independent marker of survival, even in patients with normal FT3 values.

Thyroid hormone disorders have long been linked to depression, but the causal relationship between them remains controversial. To address this question, we established rat models of hypothyroidism using (131)iodine ((131)I) and hyperthyroidism using levothyroxine (LT4). Serum free thyroxine (FT4) and triiodothyronine (FT3) significantly decreased in the hypothyroid of rats with single injections of (131)I (5mCi/kg). These rats exhibited decreased depression-like behaviors in forced swimming test and sucrose preference tests, as well as decreased anxiety-like behaviors in an elevated plus maze. Diminished levels of brain serotonin (5-HT) and increased levels of hippocampal brain-derived neurotrophic factor (BDNF) were found in the hypothyroid rats compared to the control saline-vehicle administered rats. LT4 treatment reversed the decrease in thyroid hormones and depression-like behaviors. In contrast, hyperthyroidism induced by weekly injections of LT4 (15μg/kg) caused a greater than 10-fold increase in serum FT4 and FT3 levels. The hyperthyroid rats exhibited higher anxiety- and depression-like behaviors, higher brain 5-HT level, and lower hippocampal BDNF levels than the controls. Treatment with the antidepressant imipramine (15mg/kg) diminished serum FT4 levels as well as anxiety- and depression-like behaviors in the hyperthyroid rats but led to a further increase in brain 5-HT levels, compared with the controls or the hypothyroid rats. Together, our results suggest that hypothyroidism and hyperthyroidism have bidirectional effects on anxiety- and depression-like behaviors in rats, possibly by modulating hippocampal BDNF levels.

OBJECTIVE

To illustrate that severe primary hypothyroidism alone may not be enough to cause hyponatremia in the otherwise healthy ambulatory patient.

METHODS

A retrospective chart review was conducted using an academic health center enterprise-wide electronic health record to identify 10 patients with primary hypothyroidism and same-day serum thyroid-stimulating hormone (TSH), sodium, creatinine, and calculated glomerular filtration rate (GFR). Same-day free triiodothyronine or free thyroxine was also recorded if tested. Patients were included in our case series if they met the following inclusion criteria: TSH level >100 μU/mL and same-day sodium and creatinine levels. All laboratory tests were collected on an outpatient basis.

RESULTS

The 10 subjects (2 men and 8 women) were ages 19 to 97 years (median, 51.5 years). Median TSH was 193 μU/mL (range, 104.2 to 515.6 μU/mL; normal, 0.40 to 5.50 μU/mL) with median sodium of 138 mmol/L (range, 136 to 142 mmol/L; normal, 135 to 146 mmol/L). The lowest sodium was 136 mmol/L with concurrent TSH of 469.7 μU/mL, free triiodothyronine of 1.0 pg/mL (normal, 1.8 to 4.6 pg/mL), and free thyroxine of 0.2 ng/dL (normal, 0.7 to 1.8 ng/dL). Median GFR was 67.5 mL/min/1.73 m2 (range, 44 to 114 mL/min/1.73 m2; normal, 90 to 120 mL/min/1.73 m2).

CONCLUSIONS

In our small series of patients with extreme TSH elevations, none had a serum sodium level below normal (<135 mmol/L), even in the presence of a reduced GFR. Hyponatremia can be a common occurrence in hospitalized and/or chronically ill patients; however, in an otherwise relatively healthy ambulatory patient, hypothyroidism, even when severely undertreated, may be a less clinically relevant cause of hyponatremia.

BACKGROUND

Many molecular epidemiology studies focusing on high prevalent diseases, such as metabolic disorders and cancer, investigate metabolic and hormonal markers. In general, sampling for these markers can occur at any time-point during the day or after an overnight fast. However, environmental factors, such as light exposure and food intake might affect the levels of these markers, since they provide input for the internal time-keeping system. When diurnal variation is larger than the inter-individual variation, time of day should be taken into account. Importantly, heterogeneity in diurnal variation and disturbance of circadian rhythms among a study population might increasingly occur as a result of our increasing 24/7 economy and related variation in exposure to environmental factors (such as light and food).

OBJECTIVE

The aim of the present study was to determine whether a set of often used biomarkers shows diurnal variation in a setting resembling large molecular epidemiology studies, i.e., non-fasted and limited control possibilities for other environmental influences.

RESULTS

We show that markers for which diurnal variation is not an issue are adrenocorticotropic hormone, follicle stimulating hormone, estradiol and high-density lipoprotein. For all other tested markers diurnal variation was observed in at least one gender (cholesterol, cortisol, dehydroepiandrosterone sulfate, free fatty acids, low-density lipoprotein, luteinizing hormone, prolactin, progesterone, testosterone, triglycerides, total triiodothyronine and thyroid-stimulating hormone) or could not reliably be detected (human growth hormone).

CONCLUSIONS

Thus, studies investigating these markers should take diurnal variation into account, for which we provide some options. Furthermore, our study indicates the need for investigating diurnal variation (in literature or experimentally) before setting up studies measuring markers in routine and controlled settings, especially since time-of-day likely matters for many more markers than the ones investigated in the present study.

We sought to ascertain how high the success rates of radioiodine therapy are for Graves' disease patients with large diffuse goiters when aiming for a constant absorbed dose of 250 Gy. Thirty-six patients with a thyroid volume of 50-110 mL were evaluated for changes in thyroid function and appearance 3, 6, and 12 months after radioiodine therapy. Success was defined as definitive elimination of hyperthyroidism following therapy (hypothyroidism corrected with thyroxine on diagnosis); failure as persistent/recurrent hyperthyroidism after 12 months. Overall success rate was 50%. However, a subgroup of 20 patients without simultaneous carbimazole (carbimazole-off) showed a highly significantly larger success rate (85%) than the 16 patients with simultaneous carbimazole (carbimazole-on) at the time of radioiodine therapy (6.3%, p < 0.000005). Successful cases showed a significantly higher volume reduction after radioiodine than failures (75.5% vs. 35.4%, p < 0.00005). Stepwise logistic regression showed that therapy failure was related to administration of carbimazole during radioiodine therapy (p < 0.0250 and absorbed dose (p < 0.05), but not thyroid function (free triiodothyronine [FT3] and free thyroxine [FT4]), initial thyroid volume or thyrotropin-receptor antibody (TRAb) value. However, a significant correlation of therapy success to absorbed dose (r = 0.69, p < 0.005) could be shown only for carbimazole-off patients, but not for the others. Finally, multivariate factor analysis consistently showed that therapy success was correlated only to absorbed dose and antithyroid drugs, not to initial thyroid volume, TRAb value, or thyroid function. Thyroid volume per se is not responsible for the lower success rate in Graves' disease patients with large goiters because even a comparable group of 32 Graves' disease patients with small thyroid glands (< or =20 mL) and without simultaneous carbimazole showed a success rate of 87.5%. The high failure rate in the carbimazole-on patients (absorbed dose comparable to carbimazole-off) is due to the simultaneous administration of carbimazole. Therefore, if clinically feasible, we recommend discontinuing carbimazole at least one day before beginning radioiodine therapy.

Triiodothyronine (T3) and triiodothyroacetic acid (TA3) are thyroid compounds that similarly protect low-density lipoprotein (LDL) against oxidation induced by the free radical generator 2,2'-azobis-[2-amidinopropane] dihydrochloride (AAPH). However, TA3 is more antioxidant than T3 on LDL oxidation induced by copper ions (Cu2+), suggesting that these compounds act by different mechanisms. Here we measured conjugated diene production kinetics during in vitro human LDL (50 mg LDL-protein per l) oxidation induced by various Cu2+ (0.5-4 microM) or AAPH (0.25-2 mM) concentrations in the presence of T3, TA3, butylated hydroxytoluene (BHT) (a free radical scavenger) or ethylenediaminetetracetic acid (EDTA) (a metal chelator). From the kinetics were estimated: length of the lag phase (Tlag), maximum velocity of conjugated diene production (Vmax), and maximum amount of generated dienes (Dmax). Thyroid compound effects on these oxidation parameters were compared to those of the controls BHT and EDTA. In addition we measured by atomic absorption spectrometry copper remaining in LDL after a 30 min incubation of LDL with Cu2+ and the compounds followed by extensive dialysis, i.e. copper bound to LDL. As expected, LDL-copper was decreased by EDTA in a concentration-dependent manner, whereas it was not affected by BHT. T3 increased LDL-copper whereas TA3 slightly decreased it. The whole data suggest that T3 and TA3 are free radical scavengers that also differently disturb LDL-copper binding, an essential step for LDL lipid peroxidation. The most likely mechanisms are that T3 induces new copper binding sites inside the LDL particle, increasing the LDL-copper amount but in a redox-inactive form, whereas TA3 blocks some redox-active copper binding sites highly implicated in the initiation and the propagation of lipid peroxidation. Alternatively, we also found that a little amount of copper is tightly bound in LDL, which may be essential for the propagation of lipid peroxidation induced by free radical generators.

Antithyroid drugs and phenobarbital (PB) have been shown to promote thyroid tumors in rats. It has been proposed that increased thyroid-stimulating hormone (TSH) mediates the thyroid tumor-promoting effect of antithyroid drugs and PB, and is increased because of decreased thyroxine (T4) concentration. However, PB is much less effective than antithyroid drugs at increasing TSH. It has been proposed that small increases in serum TSH produced by PB treatment is sufficient to promote thyroid tumors. However, the level to which TSH must be increased to stimulate the thyroid gland has not been reported. Therefore, we have examined the effect of increasing serum TSH concentration on thyroid growth by measuring thyroid gland weight and thyroid follicular cell proliferation. Serum TSH concentrations were increased by feeding rats various concentrations of propylthiouracil (PTU) or methimazole (MMI) for 21 days. Serum total T4, free T4, total T3 (triiodothyronine), free T3, and TSH concentrations were measured by radioimmunoassay. Thyroid follicular cell proliferation was measured by autoradiography and expressed as a labeling index (LI). PTU and MMI treatments reduced total and free T4 more than 95% by day 21, whereas total and free T3 were reduced 60%. TSH, thyroid follicular cell proliferation and thyroid weight were increased 560%, 1400%, and 200%, respectively, by day 21. TSH was significantly correlated with thyroid weight and LI. Moderate increases in serum TSH of between 10 and 20 ng/ml increased the number of proliferating thyroid follicular cells, but had no effect on thyroid weight. These results support that small increases in serum TSH can be sufficient to stimulate thyroid follicular cell proliferation. Furthermore, thyroid follicular cell proliferation may be more useful than thyroid weight alone for assessing alterations in thyroid growth in rats treated with chemicals that produce only small to moderate increases in serum TSH.

OBJECTIVE

We investigated the clinical usefulness of thyroid blood-flow measurement in predicting relapse of Graves' disease (GD) in comparison with known risk factors for GD relapse.

METHODS

Thyroid blood flow was measured in pulsed Doppler mode at the inferior thyroid artery (ITA), and the peak systolic velocity (PSV) calculated.

METHODS

ITA-PSV was measured in euthyroid GD patients (n = 79) immediately before withdrawal of anti-thyroid drug (ATD) and in healthy subjects (n = 17).

RESULTS

In the 79 euthyroid GD patients, the values of free triiodothyronine (FT3), TSH receptor autoantibody (TRAb), ITA-PSV and thyroid volume were significantly higher in the relapse group (n = 40) than in the nonrelapse group (n = 39) and the Youden index of ITA-PSV was significantly higher than that of FT3, TSH, TRAb and vascular endothelial growth factor (VEGF).

CONCLUSIONS

ITA-PSV may assist in the prediction of early GD relapse after ATD withdrawal.

A novel interference with measurements of serum free thyroxine (FT4) caused by rheumatoid factor (RhF) is described. We found misleading, sometimes gross, increases of FT4 results in 5 clinically euthyroid elderly female patients with high RhF concentrations. All 5 patients had high FT4 on Abbott AxSYM or IMx analyzers. "NETRIA" immunoassays gave misleading results in 4 of the 5 patients; Amerlex-MAB in 2 of 4 patients; AutoDELFIA in 2 of the 5; and Corning ACS-180 and Bayer Diagnostics Immuno 1 in 1 of the 5. BM-ES700 system results for FT4 in these women remained within the reference range. Results for serum T4, thyroid-stimulating hormone, free triiodothyronine, thyroid-hormone-binding globulin, and FT4 measured by equilibrium dialysis were normal in all 5 patients. Drugs, albumin-binding variants, and anti-thyroid-hormone antibodies were excluded as interferences. Addition to normal serum of the RhF isolated from each of the 5 patients increased the apparent FT4 (Abbott AxSYM). Screening of 83 unselected patients demonstrated a highly significant positive correlation between FT4 (Abbott AxSYM) and RhF concentrations. Discrepant, apparently increased FT4 with a normal result for thyroid-stimulating hormone should lead to measurement of the patient's RhF concentration.

BACKGROUND

Recent evidence has suggested an association between subclinical hypothyroidism (SCH) and microalbuminuria in patients with type 2 diabetes. However, whether SCH is related to microalbuminuria among subjects with prediabetes has not been studied. Thus, we evaluated the association between SCH and microalbuminuria in a cohort of prediabetic Egyptian adults.

METHODS

A total of 147 prediabetic subjects and 150 healthy controls matched for age and sex were enrolled in this study. Anthropometric measurements, plasma glucose, lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR), thyroid stimulating hormone (TSH), free thyroxine, triiodothyronine levels, and urinary albumin-creatinine ratio (UACR) were assessed.

RESULTS

The prevalence of SCH and microalbuminuria in the prediabetic subjects was higher than that in the healthy controls (16.3% vs. 4%, P<0.001; and 12.9% vs. 5.3%, P=0.02, respectively). Prediabetic subjects with SCH were characterized by significantly higher HOMA-IR, TSH levels, UACR, and prevalence of microalbuminuria than those with euthyroidism. TSH level was associated with total cholesterol (P=0.05), fasting insulin (P=0.01), HOMA-IR (P=0.01), and UACR (P=0.005). UACR was associated with waist circumference (P=0.01), fasting insulin (P=0.05), and HOMA-IR (P=0.02). With multiple logistic regression analysis, SCH was associated with microalbuminuria independent of confounding variables (β=2.59; P=0.01).

CONCLUSIONS

Our findings suggest that prediabetic subjects with SCH demonstrate higher prevalence of microalbuminuria than their non-SCH counterparts. SCH is also independently associated with microalbuminuria in prediabetic subjects. Screening and treatment for SCH may be warranted in those patients.

OBJECTIVE

To determine the usefulness of measuring serum free thyroxine (T4) concentration as a diagnostic test for hyperthyroidism in cats, and to determine the influence of nonthyroidal disease on free T4 concentration in cats without hyperthyroidism.

METHODS

Prospective case series.

METHODS

917 cats with untreated hyperthyroidism, 221 cats with nonthyroidal disease, and 172 clinically normal cats.

METHODS

Serum free T4, total T4, and total triiodothyronine (T3) concentrations were measured in cats with untreated hyperthyroidism and cats with nonthyroidal disease. Serum total T4 and T3 concentrations were determined by use of radioimmunoassay, and free T4 concentration was measured by use of direct equilibrium dialysis. Reference ranges for hormone concentrations were established on the basis of results from the 172 clinically normal cats.

RESULTS

Sensitivity of serum free T4 concentration as a diagnostic test for hyperthyroidism was significantly higher than the test sensitivity of either total T4 or T3 concentration. Of the 221 cats with nonthyroidal disease, 14 had a high free T4 concentration (ie, false-positive result). Therefore, calculated specificity of measuring serum free T4 concentration as a diagnostic test for hyperthyroidism was significantly lower than test specificity of measuring either the total T4 or T3 concentration.

CONCLUSIONS

Results indicate that determination of free T4 concentration is useful in the diagnosis of hyperthyroidism, especially in cats in which hyperthyroidism is suspected but total T4 and T3 concentrations are within reference ranges. However, because some cats with nonthyroidal disease have high serum free T4 concentrations, hyperthyroidism should not be diagnosed solely on the finding of high free T4 concentration.

The aims of this study were to: 1) determine the prevalence of hyperprolactinaemia in patients with newly diagnosed subclinical and overt hypothyroidism, and 2) investigate the change in PRL levels with treatment. In this observational study, patients with a new diagnosis of hypothyroidism in our endocrinology clinic were approached for participation, as were healthy controls. Patients with medical reasons for having elevated PRL levels, lactating and pregnant women were excluded from the study. No patient had kidney or liver disease. After examination to determine if clinical causes of PRL elevation were present, serum levels of thyrotropin (TSH), free thyroxine, free triiodothyronine and PRL were measured and correlation of PRL levels with the severity of hypothyroidism (overt or subclinical) was performed. Fifty-three patients (45 women, 8 men, mean age 45.3 ± 12.2 years) had overt hypothyroidism. One hundred forty-seven patients (131 women, 16 men, mean age 42.9 ± 12.6 years) had subclinical hypothyroidism. One hundred healthy persons (85 women, 15 men, mean age 43.9 ± 11.4 years) participated as controls. The same blood tests were repeated in patients after normalization of TSH levels with L-thyroxine treatment. PRL elevation was found in 36% of patients with overt hypothyroidism, and in 22% of patients with subclinical hypothyroidism. PRL levels decreased to normal in all patients after thyroid functions normalized with L-thyroxine treatment. In the hypothyroid patients (overt and subclinical) a positive correlation was found between TSH and PRL levels (r=0.208, p=0.003). PRL regulation is altered in overt and subclinical hypothyroidism, and PRL levels normalize with appropriate L-thyroxine treatment.

Thyroid hormone has numerous effects on cardiovascular function in the adult. The present study was undertaken to evaluate the effects of cardiopulmonary bypass and deep hypothermia on thyroid function in the neonate. Ten newborns were studied preoperatively and postoperatively. The total and free triiodothyronine, total and free thyroxine, thyroid-stimulating hormone, and thyroglobulin levels were measured by immunoassays. The data demonstrated a transient rise in the free thyroxine level associated with and followed by significant reductions in the free and total triiodothyronine, total thyroxine, thyroid-stimulating hormone, and thyroglobulin levels in the early postoperative period. By the fifth postoperative day, the free and total triiodothyronine and total thyroxine levels were returning toward the preoperative levels under the influence of an elevated thyroid-stimulating hormone level. These results suggest that the combination of cardiopulmonary bypass and deep hypothermia can result in a transient suppression of the pituitary-thyroid axis in the neonate.

Autoantibodies against complement C1q (anti-C1q) have been well described in patients with systemic lupus erythematosus, where they correlate with the occurrence of severe lupus nephritis. However, data on anti-C1q in organ-specific autoimmune diseases are scarce. In order to determine the prevalence of anti-C1q in patients with autoimmune thyroid disorders (AITD) and a possible association with thyroid function, we measured prospectively anti-C1q in 23 patients with Graves' disease (GD) and 52 patients with Hashimoto's thyroiditis (HT). Anti-C1q levels were correlated with parameters of thyroid function and autoantibodies against thyroperoxidase, thyroglobulin and thyroid stimulating hormone (TSH) receptor. Twenty-one patients with multi-nodular goitre and 72 normal blood donors served as controls. We found elevated concentrations of anti-C1q more frequently in patients with AITD than in controls: seven of 23 (30%) patients with GD and 11 of 52 (21%) patients with HT, compared with one of 21 (5%) patients with multi-nodular goitre and six of 72 (8%) normal controls. Anti-C1q levels did not correlate with thyroid autoantibodies. However, in GD absolute levels of anti-C1q correlated negatively with TSH and positively with free thyroxine (FT4) and triiodothyronine (FT3). In contrast, in HT, anti-C1q correlated positively with TSH levels. No correlation between TSH and thyroid autoantibodies was found. In conclusion, we found an increased prevalence of anti-C1q in patients with AITD and their levels correlated with the thyroid function in both GD and HT. This correlation seems to be independent of thyroid autoantibodies. Therefore, anti-C1q might point to a pathogenic mechanism involved in the development of AITD that is independent of classical thyroid autoantibodies.

This study was conducted to evaluate the effect of γ-aminobutyric acid (GABA) on laying performance, egg quality, digestive enzyme activity, hormone level and immune activities in Roman hens under heat stress. Roman hens (320 days old) were fed with 0, 25, 50, 75 and 100 mg/kg GABA, respectively during a 60-day experiment. Compared with control, supplementation of 50 mg/kg GABA improved the laying performance and egg quality by significantly increasing egg production, average egg weight and shell strength (P < 0.05), while decreasing the feed-egg ratio and cholesterol level. Anti-oxidation activity was improved by significantly increasing the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), but decreasing malondialdehyde level in serum (P < 0.05), while significantly increasing the glucose and total protein (TP) level, follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E(2) ), insulin, triiodothyronine (T(3) ) and free triiodothyronine (FT(3) ) levels, and IgG, IgA and complement (C3)activity in serum (P < 0.05). The results indicated that oral GABA improved laying performance and physical condition mainly by modulating hormone secretion, enhancing anti-oxidation and immune activity, and maintaining electrolyte balance. Fifty mg/kg was the optimum level for laying hens under heat stress in the present study.

Thyroid hormone levels and thyrotrophin (TSH) were measured in 45 alcohol-dependent patients before detoxification and 8 days, 3 months and 6 months after detoxification, and compared to levels in healthy controls. Before detoxification, levels of thyroxine (T4) and thyroxine-binding globulin (TBG) were significantly reduced in patients compared with healthy controls, while triiodothyronine (T3), reverse T3, and TSH levels did not differ from those in healthy controls. During the entire observation period, free T4 (fT4) and free T3 (fT3) levels were slightly elevated compared with those in healthy controls. T4 and TBG levels increased significantly during the first week of abstinence. Severity of withdrawal symptoms was negatively correlated with the total T4 levels after 8 days of abstinence. Three months after detoxification, relapsers displayed significantly lower T4 and TBG levels compared with abstinent patients. The increase in T3 levels was most pronounced between 8 days and 3 months of abstinence in both relapsing and abstinent patients. Six months after detoxification, only abstinent patients could be assessed, and they displayed increased TBG and T3 levels compared to healthy controls. Our findings suggest a different time-course for T3 and T4 levels after detoxification in alcohol-dependent patients, and indicate that T4 levels after detoxification interact with withdrawal symptoms.

OBJECTIVE

The present study was performed to investigate the contribution of ultrasonographic (US) findings to diagnosis in anti-thyroid marker-positive patients with normal hormone levels among euthyroid subjects with Hashimoto's thyroiditis (HT).

METHODS

Forty premenopausal euthyroid patients with a median age of 32 years (range, 20-44 years) with normal levels of free triiodothyronine (FT3) and free thyroxine (FT4), and elevated anti-thyroid peroxidase (TPO) antibodies were enrolled in this study. A control group of 46 healthy individuals with a median age of 29 years (range, 18-43 years) was composed of randomly selected volunteers. The examinations included basic morphometric (measurement of thyroid gland dimensions in three axes, the volume of each thyroid lobe, and the total thyroid volume), morphological grayscale imaging (echogenicity, nodularity, septations, undulation of the margins, and reactive lymph nodes), and thyroid gland vascularity.

RESULTS

There were no statistically significant differences in morphometric parameters of the thyroid gland between the study and control groups. There were significant differences in the presence of nodularity, undulation of the gland margins, septations inside the glands, infrathyroidal and/or pretracheal reactive lymph nodes, and increased vascularity on power Doppler imaging between the groups. The use of all parameters together yielded a sensitivity of 90%, specificity of 84.8%, positive predictive value (PPV) of 83.7%, negative predictive value (NPV) of 90.7%, and accuracy of 87.2% for diagnosis of HT.

CONCLUSIONS

US and power Doppler US are helpful for the diagnosis of HT in anti-thyroid marker-positive patients with normal thyroid hormone levels.

The effects of a 4-day isocaloric isoprotenic dietary replacement of carbohydrate by fats were studied in six healthy subjects, the experimental diet being preceded and followed by a 3-day period of balanced diet. During the ketogenic regimen, the concentrations of fat derived substrates (free fatty acids, glycerol and 3-hydroxybutyrate) rose significantly and glucose levels decreased by 16.5 +/- 3.2% (mean +/- SEM). The hormonal pattern switched towards a catabolic mode with a fall in insulin levels (-44.0 +/- 6.3%) and a rise in glucagon concentration (+39.0 +/- 10.4%). A significant fall in triiodothyronine and rise in reverse triiodothyronine were observed, while thyroxine levels remained unchanged. The average levels of the most important gluconeogenic amino acids (alanine, glutamine, glycine, serine and threonine) were reduced by 8-34% while those of the branched chain amino acids increased by more than 50%. Since these changes reproduce those observed after a few days of total fasting, we suggest that it is the carbohydrate restriction itself which is responsible for the metabolic and hormonal adaptations of brief fasting.

Alterations of circulating thyroid hormones are frequently present in chronic nonthyroidal illnesses and may predict prognosis. Pulmonary tuberculosis, a common treatable debilitating disease, may provide a useful model for detailed evaluation of changes of thyroid hormones in relation to subsequent recovery or mortality. Over a period of 12 months, we performed a prospective study of 40 consecutive Chinese patients aged over 50 years and admitted with newly diagnosed pulmonary tuberculosis. Blood samples were drawn for serial thyroid function tests [free thyroxine (T4), free triiodothyronine (T3) and thyroid-stimulating hormone] before treatment and at 1, 2 and 4 months afterwards. Mortality was determined up to 12 months of follow-up. The euthyroid sick syndrome occurred in 63% of patients at presentation. Twelve of 25 euthyroid sick patients died as compared to one of 15 patients with normal baseline thyroid function tests (P < 0.02). Among euthyroid sick patients, those who died had significantly lower free T3 concentration at presentation than those who survived (P < 0.05). An undetectable free T3 concentration at presentation was associated with a subsequent mortality of 75% (9 of 12). Of the survivors, all patients demonstrated a significant rise in serum free T4 concentrations following treatment, which was apparent by 1 month. These data suggest that an undetectable free T3 concentration at presentation reflects severity of illness and predicts a subsequent high mortality.

We examined the contribution of hypothyroidism to streptozotocin diabetes-induced alterations in the arrhythmia susceptibility of ex vivo hearts to regional zero-flow ischaemia. Diabetic rats received either protamine zinc insulin (10 IU/kg/day, s.c.) or triiodothyronine (10 microg/kg/day, s.c.) for 8 weeks commencing 72 h after injection of streptozotocin (60 mg/kg, i.p.). Arrhythmias were determined in ex vivo Langendorff-perfused hearts, subjected to a 30-min main left coronary artery occlusion, followed by 30-min reperfusion. Serum free thyroxine concentrations, rectal temperature and ex vivo heart rate were significantly decreased in the 8-week diabetic group (P<0.001). These changes were prevented by administration of triiodothyronine or insulin. Ventricular fibrillation during reperfusion was abolished in hearts from diabetic rats. This protection was prevented by treatment with either triiodothyronine or insulin. Hearts from methimazole-hypothyroid rats also showed no ventricular fibrillation during reperfusion. The protection against ischaemia-reperfusion-arrhythmias observed in hearts from streptozotocin-diabetic rats may be due to diabetes-induced hypothyroidism.

BACKGROUND

Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH).

METHODS

The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels.

RESULTS

During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years.

CONCLUSIONS

We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.

Subclinical hypothyroidism (SCH) is defined as elevated thyroid stimulating hormone (TSH) with normal levels of free triiodothyronine (FT3) and free thyroxine (FT4). SCH is further classified into a milder condition with TSH levels between 4.0 and 10.0 milli-international units (mIU)/l (mild-SCH) and a severe form with TSH >10.0 mIU/l (severe-SCH). SCH is a common problem (prevalence is greater in women than men), which increases further with increasing age and TSH levels. Even though the risk of progression to overt hypothyroidism is higher in patients with severe-SCH, the risk is also significant in patients having mild-SCH; it has been suggested that every twofold rise in serum TSH would increase the risk from 1 to 4%, which further increases to 38% if thyroid antibodies are positive. Current data have shown increased cardiovascular risk in patients with mild-SCH and have demonstrated some benefits of levothyroxine treatment in reducing these events. However, evidence on the association of mild-SCH and musculoskeletal system, cognitive dysfunction, mood disorders, dyslipidaemia, diabetes and goitre is conflicting. Similarly, the discussion regarding the exact upper limit of normal for serum TSH remains controversial. The data have also shown increased risk of adverse pregnancy outcomes in patient with mild-SCH, with some benefits of thyroxine treatment. The recent available guidelines related to management of patients with serum TSH <10 mIU/l have suggested decisions should be made taking into account the age of the patient, associated risk factors and comorbid conditions. This chronicle review assesses current evidence regarding the risks associated and the recommendations related to benefits of levothyroxine treatment in patients having mild-SCH.

OBJECTIVE

We investigated the clinical significance of incidental diffuse thyroid uptake (DTU) on (18)F-FDG PET in subjects without a history of cancer.

METHODS

This study included 2062 studies from adults who underwent (18)F-FDG PET as a cancer screening program. Subjects were divided into the following two groups: with (group I) or without (group II) DTU. The presence of DTU and the thyroid visual grading score were compared with thyroid function tests, serum anti-microsomal antibody (AMA) levels, and the presence of diffuse parenchymal change (DPC) on ultrasonography (USG).

RESULTS

DTU was found in 6.6% of the scans (137/2062). Serum thyroid stimulating hormone (TSH) and AMA levels were significantly higher in group I than in group II. Increased AMA level (55.1%) and DPC (48.7%) were more frequently found in group I (p < 0.001). The proportion of subjects with any abnormal results in serum free thyroxine, triiodothyronine, TSH, or AMA levels or DPC on USG was significantly higher in group I than in group II (71.5% vs. 10.6%, p < 0.001), and was significantly and gradually increased according to the visual grading score group (0 vs. 1-2 vs. 3-4 = 10.6% vs. 58.5% vs. 90.9%, p < 0.001). TSH and is AMA levels were significantly increased according to the visual grading score.

CONCLUSIONS

The presence or degree of incidental DTU on (18)F-FDG PET is closely correlated with increased serum AMA and TSH levels, and the presence of DPC on USG. Therefore, the most plausible pathological cause of DTU may be cell damage by an autoimmune mechanism.

Delay in access to feed for 1-d-old chicks impairs posthatch growth. It is a standard practice that 1-d-old chicks are deprived of feed for about 48 h before they are placed on farms. During incubation, there is a spread of 24 to 48 h for late versus early hatching. As spread of hatch increases, number of chicks that are feed-deprived for a longer time before free access (IA) to feed and water increases. In this current study, we investigated the effects of time delay in feed access on chick juvenile relative growth (RG: a measure of speed of growth) up to d 7, taking into consideration the duration of egg storage and spread of hatch. Our results confirmed that delay in feed access caused weight loss during holding time and depressed growth rate after access to feed. The magnitude of the effect depended on the hatching period within the hatching window. It also depended on whether the biological age (BA) or the chronological age (CA) of the chick was considered. Immediate access to feed produced significantly different results depending on CA or BA. Both ways, the method seemed to benefit the late hatchers. This finding contrasts with the effect of delayed feeding in which early hatchers benefited more. Long duration of egg storage depressed RG not only of chicks with immediate access to feed but also in those denied access after hatch. Delay in feed access significantly aggravated the effects of long egg storage duration on RG. Triiodothyronine levels were lower in feed-deprived chicks, and the effect was greater in late hatchers. It is concluded that the beginning of delay in feed access should be determined from the time of hatch not at the end of hatch. It is suggested that the adverse effects of delay in feed access can be reduced by providing a source of energy in hatching baskets or during transportation.