The purpose of this prospective study was to define the effect of cardiopulmonary bypass on the concentrations of thyroid hormones and metabolites. Blood samples were obtained from 14 patients preoperatively, at specific times throughout cardiopulmonary bypass, and serially to 24 hours postoperatively. Thyroid-stimulating hormone, thyroid-binding globulin, total thyroxine, triiodothyronine (T3), and reverse T3, an inactive metabolite of thyroxine, were measured by radioimmunoassay. Free T3 was assayed by equilibrium dialysis. Values of total T3 and free T3, the active hormone, were significantly depressed (75% and 50%, respectively) up to 24 hours after bypass (p less than 0.05). Reverse T3 demonstrated a greater than fourfold rise at 8 and 24 hours postoperatively (p less than 0.05). Thyroid-binding globulin was decreased at all sampling times (p less than 0.05). Thyroid-stimulating hormone, thyroxine, and free thyroxine levels remained within normal ranges at all sampling times. These results indicate that cardiopulmonary bypass simulates the "euthyroid sick syndrome" as seen in severely burned patients and critically ill patients, which is characterized by depression of T3 and free T3 concentrations with a concomitant increase in reverse T3 levels and normal concentrations of thyroid-stimulating hormone, thyroxine, and free thyroxine. The hemodynamic effects of primary hypothyroidism are well established. These data provide further support for investigational trials of intravenous administration of T3 in the prevention or treatment of low cardiac output syndrome after cardiopulmonary bypass.

OBJECTIVE

Low free plasma triiodothyronine (fT3) is associated with inflammation and cardiovascular damage in patients with end-stage renal disease (ESRD). We investigated the relationship between fT3, left ventricular systolic function and left ventricular mass in a group of 234 dialysis patients, and modelled the association between fT3 and cardiomyopathy in statistical analyses including both direct (interleukin-6 and C-reactive protein) and inverse (serum albumin) acute phase inflammation markers.

RESULTS

Plasma fT3 concentration in dialysis patients was significantly (P < 0.001) reduced in comparison with healthy participants and clinically euthyroid patients with normal renal function. Left ventricular systolic function was depressed (P <or= 0.003) and left ventricular mass increased (P < 0.001) in patients in the first fT3 quartile as compared with patients in other quartiles. In multiple regression analyses these associations remained significant also after adjustment for Framingham risk factors and antihypertensive therapy (P </= 0.01), and for risk factors peculiar to ESRD (P = 0.03). Adjustments for interleukin-6 or for albumin, however, abrogated these relationships.

CONCLUSIONS

Low triiodothyronine is associated with left ventricular dysfunction and left ventricular hypertrophy in ESRD patients. These associations appear largely mediated by inflammation. Low fT3 may be an intermediate mechanism implicated in the adverse cardiac effects of inflammation in patients with ESRD.

Studies in animal models of spontaneous Hashimoto's autoimmune thyroiditis (HT) show that prophylactic treatment with levothyroxine (LT4) can reduce incidence and degree of lymphocytic infiltration in HT. The aim of the present study was to clarify whether there is a benefit of prophylactic treatment with LT4 in patients with euthyroid HT with respect to the progression of the autoimmune process. Twenty-one patients with euthyroid HT were checked for thyroid function (thyrotropin [TSH], free triiodothyronine [FT3], free thyroxine [FT4]), thyroid volume, antibodies (thyroglobulin [Tg-Ab], thyroid peroxidase [TPO-Ab]), and lymphocyte subsets. Peripheral (PBL) and thyroid-derived lymphocytes (TL) were analyzed by triple color flow cytometry. One-half of the patients with euthyroid HT were treated with LT4 for 1 year (n = 10). The other half (n = 11) were never treated with LT4. TL were obtained by fine-needle aspiration biopsy (FNAB). Thirteen healthy subjects (C) without medical history of thyroid disease served as controls concerning PBL, and patients with non-toxic nodular goiter (NG; n = 10) served as controls concerning TL. Thyroid-derived T-helper cells were found more frequently in euthyroid patients with HT compared to patients with NG (p < 0.01). After 1 year of therapy with LT4, TPO-Abs and B lymphocytes decreased significantly only in the treated group of euthyroid patients with HT (p < 0.05). In contrast, TPO-Abs levels did not change or even increased in untreated euthyroid patients with HT. Thyroid volume did not differ before and after therapy. Prophylactic treatment of euthyroid patients with HT reduced both serological and cellular markers of autoimmune thyroiditis. Therefore, prophylactic LT4 treatment might be useful to stop the progression or even manifestation of the disease. However, the long-term clinical benefit of prophylactic LT4 therapy in euthyroid patients with HT is yet to be established.

OBJECTIVE

To test the hypothesis that during the natural history of sporadic nontoxic goiter (SNG), a diffuse goiter precedes a multinodular goiter with gradual development of autonomous thyroid function.

METHODS

A cross-sectional survey of 102 consecutive patients with SNG (seven male, 95 female) was performed. Thyroid volume was measured by ultrasonography, and plasma thyroid-stimulating hormone (TSH) by a sensitive assay (TSH immunoradiometric assay).

RESULTS

Patients with a multinodular goiter were older and had a larger thyroid volume than patients with a diffuse or uninodular goiter. Plasma free thyroxine (T4) and total triiodothyronine (T3) were higher and plasma TSH was lower in patients than in normal subjects. Free T4 was higher in the subgroup of patients with a multinodular goiter and a decreased TSH response to thyrotropin-releasing hormone. Plasma TSH (y, in mU/L) was negatively related to thyroid volume (x, in mL): y = 8.2x-0.667 (r = 0.578, p less than 0.001). Thyroid volume (y, in mL) was positively related to age (x, in years): y = -21.8 + 2.0x (r = 0.455, p less than 0.001); and to duration of goiter (x, in years): y = 40.6 + 2.1x (r = 0.505, p less than 0.001). The annual increase in thyroid volume was calculated at 4.5%.

CONCLUSIONS

The data suggest a continuous growth of SNG and provide support for the concept of increasing thyroid nodularity and autonomy of thyroid function--related to increasing thyroid volume--during the natural history of this disorder.

Changes in thyroid function are often described in elderly subjects; however, their pathophysiologic significance and the possible contributory role of both malnutrition and nonthyroidal illness are still debated. The aim of this cross-sectional study was to investigate thyroid function in relationship to some markers of the nutritional status in a group of healthy old subjects and in some centenarians living in nursing homes. Patients included 24 clinically healthy elderly women (age, 71 to 93 years), 24 clinically healthy centenarian women (age, 100 to 106 years), and 20 healthy young subjects (age, 22 to 33 years). Blood samples were drawn from each subject for the evaluation of thyroid-stimulating hormone (TSH), free triiodothyronine (FT(3)), free thyroxine (FT(4),) reverseT(3) (rT3), autoantibodies against thyroglobulin (AbTg) and against thyroid peroxidase (AbTPO), and for the main humoral nutritional markers. TSH and thyroid hormones were assayed by fluoroimmunometric method; rT3 and thyroid autoantibodies by radioimmunoassay (RIA) and enzyme chemiluminescent immunometric assay, respectively. The mean values of TSH, FT(3) and FT(4) fell within the normal range in both groups. However, by comparison to old controls, in centenarian subjects, TSH levels were significantly lower, whereas rT(3) concentrations were slightly, but significantly, increased. Autoantibodies positivity was found in 4.16% of centenarians and in 10.4% and 13.6% of old and young controls. Thus, the incidence of thyroid autoantibodies was lower in centenarians than in old controls. Except for transferrin, lower than the normal range in centenarians, all of the other nutritional markers evaluated fell within the laboratory range of normality. Total cholesterol levels were significantly reduced in centenarians by comparison to old controls. Our results showed an age-related decline of the TSH levels and a significant increase of the rT(3) concentrations in centenarians by comparison to old controls. These findings may be related to an age-dependent reduction of the 5'-deiodinase activity rather than to important changes of nutritional markers.

We investigated 15 euthyroid patients from eight families with a recently recognized syndrome, familial dysalbuminemic hyperthyroxinemia (FDH), that could be mistaken for thyrotoxicosis. The syndrome is characterized by elevations in serum thyroxine and the free-thyroxine index (FT4l), which are due to an abnormal serum albumin that preferentially binds thyroxine. This albumin has an abnormal binding site with a much greater affinity for thyroxine (relative to its affinity for triiodothyronine) than that of the hormone-binding site on thyroxine-binding globulin. Results of thyrotropin-releasing hormone and thyroid-suppression tests, as well as direct measurements of the free-thyroxine concentration by equilibrium dialysis, are normal in these patients, although the serum triiodothyronine concentration may be slightly elevated. Although its prevalence is uncertain, FDH may be more common than suspected; we have seen 26 cases within the past year.

To study the spectrum of thyroid disorders in systemic lupus erythematosus (SLE). Hundred SLE patients as per American Rheumatology Association(ARA) classification criteria underwent clinical examination, including assessment of disease activity (SLEDAI) and laboratory evaluation for serum triiodothyronine (T3),free thyroxine (FT4), thyroid stimulating hormone (TSH), antithyroperoxidase (TPO) antibody and antithyroglobulin (TG) antibody. Hundred age- and sex-matched apparently healthy individuals served as control. Thirty-six (36%) lupus patients had thyroid dysfunction when compared to 8 (8%) of controls and all of them were women. Primary hypothyroidism was the commonest dysfunction in 14 (14%), while subclinical hypothyroidism and subclinical hyperthyroidism was seen in 12 (12%) and 2 (2%), respectively. Eight (8%) had isolated low T3 consistent with sick euthyroid syndrome. Eighteen (50%) of thyroid dysfunction were autoimmune in nature (autoantibody positive) and rest 18 (50%) were non-autoimmune. Euthyroid state with the elevation of antibodies alone was seen in 12 (12%) of the lupus patients. In contrast, only 5 (5%) of controls had primary hypothyroidism and 3 (3%) had subclinical hypothyroidism, while none had hyperthyroidism. SLEDAI score and disease duration were compared between lupus patients with thyroid dysfunction to those with normal thyroid function. A statistically significant association was found between SLEDAI and thyroid dysfunction of sick euthyroid type.SLE disease duration had no statistically significant association with thyroid dysfunction. Prevalence of thyroid autoantibodies in lupus patients was 30% when compared to 10% of controls. Ninety-six (96%) of the SLE patients were ANA positive, while 4 (4%) of them were ANA negative but were anti-Sm antibody positive. There were no suggestions of any other autoimmune endocrine diseases like diabetes or Addison's disease (clinically and on baseline investigations) in our lupus cohort and hence no further work up was done for these diseases. Thyroid disorders are frequent in SLE and are multifactorial with a definite higher prevalence of hypothyroidism as well as thyroid autoantibodies.

BACKGROUND

Obesity and metabolic syndrome are major health problems worldwide, including Turkey. Recent studies have shown an association between thyroid function tests and metabolic syndrome parameters. In this study, we aimed to determine the frequency of metabolic syndrome in an obese Turkish population and the relationship between metabolic syndrome and thyroid functions.

METHODS

We recruited 211 patients (187 females/24 males; mean age, 39.7±11.7 years) with body mass index (BMI) >30 kg/m(2) and no other hormonal pathology that could cause obesity. Anthropometric evaluation was followed by measurement of fasting blood glucose (FBG), insulin, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total thyroxine (TT4), free T3 (FT3), and free T4 (FT4). Metabolic syndrome was defined according to the 2005 revision of the National Cholesterol Education Program Adult Panel III (NCEP ATP III) criteria. Insulin resistance was calculated from homeostasis model assessment of insulin resistance (HOMA-IR) formula. The TSH cutoff value was set at 2.5 mU/L.

RESULTS

Metabolic syndrome was diagnosed in 122 patients (58%). Metabolic syndrome positive patients had significantly higher FBG, triglycerides, FT4, systolic (SBP) and diastolic blood pressure (DBP), and statistically lower HDL-C and FT3/FT4 ratio than metabolic syndrome negative patients. TSH decreased with age and was not related with any metabolic syndrome parameters. The FT3/FT4 ratio negatively correlated with FBG, triglycerides, SBP, and DBP (P=0.003, r=-38; P=0.02, r=-0.28; P=0.005, r=-0.35; and P=0.007, r=-0.34, respectively); TT3 positively correlated with HOMA-IR (P=0.006, r=0.40), FBG (P=0.009, r=0.38), and waist circumference (P=0.02, r=0.34).

CONCLUSIONS

Metabolic syndrome frequency was increased in our study population compared to the general population. Metabolic syndrome parameters (except HDL) correlated with TT3, FT4, and the FT3/FT4 ratio. FT4 levels were associated with obesity and metabolic syndrome independently of insulin resistance, whereas TT3 levels were associated with both insulin resistance and metabolic syndrome. This relationship can be explained by compensatory effects of TT3, and probably FT4, on energy expenditure and thermogenesis in obese people.

OBJECTIVE

Several studies have reported the association of systemic sclerosis (SSc) with thyroid autoimmune disorders, but most of them have neither an appropriate control group nor include a complete thyroid work-up.

METHODS

The aim of our study was to evaluate the prevalence of thyroid disorders in a large number of patients with SSc using a complete clinical evaluation.

METHODS

Thyroid-stimulating hormone (TSH), free triiodothyronine, free thyroxine, antithyroglobulin and antithyroid-peroxidase (AbTPO) autoantibodies, thyroid ultrasonography and blood flow and fine needle aspiration were performed in 202 SSc patients versus 404 gender- and age-matched controls from the general population, with similar iodine intake, to evaluate the prevalence of clinical and subclinical thyroid disorders.

RESULTS

Odds ratio (OR) for female SSc versus controls was: for subclinical hypothyroidism, 3.2 (95% CI)=1.8-5.7); for clinical hypothyroidism, 14.5 (95% CI=2.3-90.9); for AbTPO positivity, 2.7 (95% CI=1.8-4.1); for hypoechoic pattern, 3.2 (95% CI=2.2-4.7); for thyroid autoimmunity, 3.7 (95% CI=2.6-5.4); for thyroid volume <6 ml, 1.8 (95% CI=1.2-2.7). OR for thyroid autoimmunity in male SSc versus controls was 10.8 (95% CI=2.2-52.4). Mean values of TSH in female SSc, and of AbTPO in female and male SSc were higher (P<0.01) than in controls. We observed three cases of Graves' disease in female SSc versus zero in controls (P=0.0140), and two cases of papillary thyroid cancer in SSc patients.

CONCLUSIONS

Thyroid function, AbTPO and ultrasonography should be tested as part of the clinical profile in SSc patients. Females, subjects with positive AbTPO and hypoechoic and small thyroid should have thyroid function follow-up and appropriate treatment in due course.

The potential toxicity of perfluorooctane sulfonate (PFOS), an environmentally persistent organic pollutant, is of great concern. The present study examines the ability of PFOS to disturb thyroid function and the possible mechanisms involved in PFOS-induced thyroid hormone alteration. Male Sprague-Dawley rats were exposed to 1.7, 5.0, and 15.0 mg/L of PFOS in drinking water for 91 consecutive days. Serum was collected for analysis of total and free thyroxine (T4), total triiodothyronine (T3), and thyrotrophin (TSH). Thyroid and liver were removed for the measurement of endpoints closely related to thyroid hormone biosynthesis and metabolism following PFOS exposure. Determined endpoints were the messenger RNA (mRNA) levels for two isoforms of uridine diphosphoglucuronosyl transferases (UGT1A6 and UGT1A1) and type 1 deiodinase (DIO1) in liver, sodium iodide symporter (NIS), TSH receptor (TSHR), and DIO1 in thyroid as well as the activity of thyroid peroxidase (TPO). Serum total T4 level decreased significantly at all applied dosages, whereas total T3 level increased markedly only at 1.7 mg/L of PFOS. No statistically significant toxic effects of PFOS on serum TSH were observed. Hepatic UGTIA1, but not UGT1A6, mRNA was up-regulated at 5.0 and 15.0 mg/L of PFOS. Treatment with PFOS lowered hepatic DIO1 mRNA at 15.0 mg/L but increased thyroidal DIO1 mRNA dose dependently. The activity of TPO, NIS, and TSHR mRNA in thyroid were unaffected by PFOS treatment. These results indicate that increased hepatic T4 glucuronidation via UGT1A1 and increased thyroidal conversion of T4 to T3 via DIO1 were responsible in part for PFOS-induced hypothyroxinemia in rats.

BACKGROUND

A number of studies show that the serum levels of antithyroid peroxidase antibodies (TPO-Ab) in patients with Hashimoto's thyroiditis decline during levothyroxine treatment, but do not provide quantitative data or report the fraction of patients in whom test for TPO-Ab became negative ("normalization percentage"). The objective of the present study was to provide this information.

METHODS

This was a retrospective study of TPO-Ab concentrations in 36 women and 2 men (mean age 51 +/- 16 years; range 19-81 years) with Hashimoto's thyroiditis as defined by the following criteria: elevated plasma TPO-Ab and typical hypoechogenicity of the thyroid in high-resolution sonography at first presentation or during follow-up and low pertechnetate uptake in thyroid scintigraphy. When first studied 17 women and 1 man were not yet taking levothyroxine. The remaining 20 patients were receiving levothyroxine. At initial examination 18 patients had serum thyroid-stimulating hormone (TSH) concentrations above normal. Results of up to eight (mean = 5.8) measurements obtained over a mean period of 50 months while patients were receiving levothyroxine were analyzed. In addition, serum TSH, free triiodothyronine (fT3), and free thyroxine (fT4) were measured, and ultrasound of the neck was performed at each follow-up examination.

RESULTS

In terms of TPO-Ab levels, 35 of 38 patients (92%) had a decrease, 2 patients had undulating levels, and 1 patient had an inverse hyperbolic increase in her TPO-Ab levels. In the 35 patients in whom there were decreasing TPO-Ab values, the mean of the first value was 4779 IU/mL with an SD of 4099 IU/mL. The mean decrease after 3 months was 8%, and after 1 year it was 45%. Five years after the first value, TPO-Ab levels were 1456 +/- 1219 IU/mL, a decrease of 70%. TPO-Ab levels became negative, < 100 IU/mL, in only six patients, a normalization percentage of 16%. There were no correlations between changes in thyroid volume and changes in TPO-Ab.

CONCLUSIONS

Serum TPO-Ab levels decline in most patients with Hashimoto's thyroiditis who are taking levothyroxine, but after a mean of 50 months, TPO-Ab became negative in only a minority of patients.

BACKGROUND

Interleukin-37 (IL-37), a member of IL-1 family, is primarily an anti-inflammatory cytokine, which reduces systemic and local inflammation. However, the expression and role of IL-37 in Graves' disease (GD) remains unknown. This study aims to measure the levels of serum and peripheral blood mononuclear cells (PBMCs) IL-37 in patients with Graves' disease and to examine its association with disease activity. Furthermore, we investigate the effect of IL-37 on proinflammatory cytokines involved in the pathogenesis of GD.

METHODS

The expressions of IL-37, TNF-α, IL-6, and IL-17 mRNA in peripheral blood mononuclear cells (PBMCs) of 40 patients with Graves' disease were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the levels of IL-37, TNF-α, IL-6, and IL-17 in serum were detected by enzyme-linked immunoassay (ELISA). The correlation of serum IL-37 levels with cytokines and disease activity in Graves' disease patients were investigated. The expressions of cytokines TNF-α, IL-6, and IL-17 in PBMCs under recombinant IL-37 stimulation were determined by RT-PCR and ELISA respectively.

RESULTS

The levels of IL-37, TNF-α, IL-6, and IL-17 in PBMCs and serum were significantly increased in patients with GD compared with healthy controls (HC). Serum IL-37 were closely correlated with TNF-α, IL-6, IL-17, thyrotropin (TSH), free thyroxine (FT4),free triiodothyronine (FT3) and thyrotropin receptor antibody (TRAB). GD patients with active disease showed higher IL-37 mRNA and serum protein levels compared with those with inactive disease as well as HC. Moreover, IL-37 suppressed the production of IL-6, IL-17 and TNF-α in PBMCs of patients with GD.

CONCLUSIONS

Increased level of IL-37 in patients with GD are associated with TNF-α, IL-6, IL-17 and disease activity, and it plays a protective role against inflammatory effect in GD by inhibiting the production of proinflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of GD.

The aim of this study is to evaluate biological factors associated with recent suicidal attempts in a naturalistic sample. A total of 439 patients suffering from major depression disorder (MDD), bipolar disorder (BD) and psychotic disorders (schizophrenia, schizoaffective disorder and psychosis not otherwise specified), who were consecutively assessed in the Emergency Department of an Italian Hospital (January 2008-December 2009), were included. In the whole sample, suicide attempters and non-attempters differed with regard to free triiodothyronine (FT3) and prolactin values only. A univariate general linear model indicated significant effects of sex (F(1;379)=9.29; P=0.002), suicidal status (F(1;379)=4.49; P=0.04) and the interaction between sex and suicidal status (F(1;379)=5.17; P=0.02) on prolactin levels. A multinomial logistic regression model indicated that suicidal attempters were 2.27 times (odds ratio (OR)=0.44; 95% confidence interval (95%CI): 0.23/0.82; P=0.01) less likely to have higher FT3 values than non-attempters; while prolactin values failed to reach statistical significance (OR=0.99; 95%CI: 0.98/1.00; P=0.051). Both prolactin and thyroid hormones may be involved in a complex compensatory mechanism to correct reduced central serotonin activity. Further studies may help in understanding how these findings can be used by clinicians in assessing suicide risk.

OBJECTIVE

Childhood Graves' disease has been reported to be rare but preliminary epidemiological data on its incidence appeared to be high in Hong Kong Chinese children. The aim of this study is to determine the incidence of childhood Graves' disease in Hong Kong and to analyse whether there is an increasing trend of the incidence.

METHODS

We established a registry of childhood Graves' disease at our centre to collect cases from four districts in Hong Kong. The diagnosis of Graves' disease was based on clinical features, diffused enlargement of thyroid gland, raised free thyroxine or triiodothyronine levels, suppressed TSH levels, and the presence of thyroid receptor antibodies. Confirmed cases of Graves' disease who resided in any of the four districts were used to calculate the incidence for the study period between 1989 and 1998.

RESULTS

One hundred and eighteen Chinese children under 15 years of age had a confirmed diagnosis of Graves' disease during the study period from January 1989 to December 1998. There were 11 boys and 107 girls giving a male to female ratio of 1 : 9.7. The overall incidence rates were 3.2/100 000/year and 6.5/100 000/year for the two periods 1989-93 and 1994-98, respectively. The incidence rates for girls have increased significantly (P < 0.001) from 3.8/100 000/year in 1989 to 14.1/100 000/year in 1998. The current incidence of childhood Graves' disease in our population is about eight times that reported in Danish children.

CONCLUSIONS

This study confirms the high incidence of childhood Graves' disease in Hong Kong and documents an increasing trend for girls. Further studies are required to reveal possible genetic or environmental factors responsible for such epidemiology in Hong Kong Chinese children.

BACKGROUND

In a relatively short period of time, therapeutic laparoscopy has become an everyday part of the general surgeon's life. Although laparoscopy provides distinct clinical advantages, it is not yet clear that it lessens the stress response typical of elective surgical procedures, and as such, the morbidity of surgery. The hypothesis that laparoscopic cholecystectomy produces less of a metabolic and stress hormonal response than open cholecystectomy was tested in a prospective randomized trial.

METHODS

Twenty otherwise healthy women between 18 and 45 years of age with a history of uncomplicated symptomatic cholelithiasis undergoing either laparoscopic (n = 10) or open cholecystectomy (n = 10) were studied. The hormonal response of the adrenocortical (serum adrenocorticotropic hormone, cortisol, and urinary free cortisol), adrenomedullary (plasma and urinary epinephrine and norepinephrine), thyroid (thyroid-stimulating hormone, thyroxine, and triiodothyronine), pituitary (antidiuretic hormone and growth hormone), and glucose (serum glucose, glucagon, and insulin) homeostatic axes were measured serially over a 24-hour period.

RESULTS

No difference was seen between the laparoscopic and open groups in operative time (mean plus or minus standard error of the mean, 70 +/- 6 minutes compared with 77 +/- 6.3 minutes) or hospital stay 1.3 +/- 0.2 compared with 1.1 +/- 0.1 days). Assessment of postoperative pain using an analog pain score was less in the laparoscopic group (4.9 +/- 1.3 compared with 12.3 +/- 2.5, p = 0.01). The response of the adrenocortical, adrenomedullary, thyroid, and glucose axes were similar or identical in both groups. Antidiuretic hormone levels were greater in the laparoscopic group at one hour intraoperatively (281 +/- 79 pg/mL compared with 54 +/- 18 pg/mL, p < 0.01), and at extubation (122 +/- 18 pg/mL compared with 36 +/- 7 pg/mL, p < 0.01). Serum glucose levels were greater immediately following laparoscopic cholecystectomy. Glucose and insulin levels were greater at four, 12, and 24 hours after open cholecystectomy.

CONCLUSIONS

Elective laparoscopic and open cholecystectomy for uncomplicated cholelithiasis result in similar degrees of perioperative hormonal stimulation. The different hormonal responses in the immediate and later postoperative periods after laparoscopic and open cholecystectomy suggest differential stressful stimuli between the two procedures.

BACKGROUND

Accurate assessment of thyroid status during pregnancy is vital for maternal and fetal health. Because free thyroxine (FT4) values in pregnancy vary widely between methods, assessment of total T4 (TT4) and FT4 index (FT4I) may be superior to FT4 in pregnant women. However, trimester-specific reference intervals for FT4I have not yet been established. In this longitudinal self-sequential survey, we aimed at determining the trimester-specific reference range for FT4I in healthy Iranian women with singleton pregnancies.

METHODS

A total of 466 healthy pregnant women were evaluated. After exclusion of women with history, ultrasonographic, or laboratory evidence of any thyroid disorder or iodine deficiency and those who were positive for thyroid autoantibodies, 152 women entered the study. Serum thyrotropin (TSH), TT4, and triiodothyronine-resine uptake were measured by an immunoassay method. Reference intervals were defined as 5th and 95th percentiles, using the bootstrap-based procedure.

RESULTS

Mean values in the first, second, and third trimesters were 1.7±1.5, 1.9±1.8, and 1.9±1.8 mIU/L for TSH; 12.9±3, 14.4±3.1, and 13.6±3.3 μg/dL for TT4; and 12.8±3.5, 14.2±3.3, and 13.5±3.8 for FT4I, respectively. Reference intervals in the first, second, and third trimesters were as follows (respectively): TSH-0.2-3.9, 0.5-4.1, and 0.6-4.1 mIU/L; TT4-8.2-18.5, 10.1-20.6, and 9-19.4 μg/dL; and FT4I-8.5-19, 9.7-21, and 8.7-20.4. Serum TSH had no significant correlation with TT4. Serum TSH had a significant but weak correlation with FT4I only in the first trimester (r=-0.24, p=0.006).

CONCLUSIONS

This study, for the first time, establishes the trimester-specific reference intervals for FT4I in a reference population of normal iodine-sufficient pregnant Iranian women.

BACKGROUND

The common Thr92Ala D2 polymorphism has been associated with changes in pituitary-thyroid axis homeostasis, but published results are conflicting. To investigate the effects of the Thr92Ala polymorphism on intrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion, we designed prospective pharmacogenomic intervention aimed to detect differences in T3 levels after thyrotropin (TSH)-releasing hormone (TRH)-mediated TSH stimulation of the thyroid gland.

METHODS

Eighty-three healthy volunteers were screened and genotyped for the Thr92Ala polymorphism. Fifteen volunteers of each genotype (Thr/Thr, Thr/Ala, and Ala/Ala) underwent a 500 mcg intravenous TRH stimulation test with serial measurements of serum total T3 (TT3), free T4, and TSH over 180 minutes.

RESULTS

No differences in baseline thyroid hormone levels were seen among the study groups. Compared to the Thr/Thr group, the Ala/Ala group showed a significantly lower TRH-stimulated increase in serum TT3 at 60 minutes (12.07 ± 2.67 vs. 21.07 ± 2.86 ng/dL, p = 0.029). Thr/Ala subjects showed an intermediate response. Compared to Thr/Thr subjects, the Ala/Ala group showed a blunted rate of rise in serum TT3 as measured by mean time to 50% maximum delta serum TT3 (88.42 ± 6.84 vs. 69.56 ± 6.06 minutes, p = 0.028). Subjects attained similar maximal (180 minutes) TRH-stimulated TT3 levels. TRH-stimulated TSH and free T4 levels were not significantly different among the three genotype groups.

CONCLUSIONS

The commonly occurring Thr92Ala D2 variant is associated with a decreased rate of acute TSH-stimulated T3 release from the thyroid consistent with a decrease in intrathyroidal deiodination. These data provide a proof of concept that the Thr92Ala polymorphism is associated with subtle changes in thyroid hormone homeostasis.

Aerobic exercise in addition to severe caloric restriction was studied for its effects on resting energy expenditure (REE), weight loss, and lean tissue preservation in adult women. A formula diet providing 1.5 g protein and 0.5 g carbohydrate (CHO) per kilogram of ideal body weight daily (mean intake 720 kcal/d) was given to 12 overweight inpatients for 4 to 5 weeks. Six subjects remained sedentary (group 1), while the other six subjects (group 2) performed supervised endurance exercise (a total of 27 hours at 50% of maximal oxygen uptake (VO2max) over 4 weeks). Lean tissue preservation was excellent in both groups and was unaffected by the group 2 exercise regimen. Weight loss over 4 weeks in the two groups did not differ (group 1, 6.9 +/- 0.7 kg; group 2, 6.5 +/- 0.7 kg). The VO2max was not increased after 4 weeks of exercise compared with controls. The resting oxygen consumption (rVO2) of both groups declined 10% (P less than .001) in the first seven days of dieting. Thereafter the rVO2 in group 1 remained stable, but a further 17% reduction occurred in group 2 (P less than .03) by the third week of exercise. The free triiodothyronine (fT3) concentration also fell more in group 2 (P less than .05), suggesting a relationship between fT3 and energy expenditure during severe caloric restriction. The ergometer exercise for up to two hours daily was well tolerated. The absence of either a training effect or accelerated weight loss in group 2 may be due to the limited duration (4 weeks) or intensity of the exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND

In dialysis patients, the prevalence of thyroid disorders and their impact on specific cardiovascular (CV) events and mortality are largely unknown. The aim of the present study was to analyze whether subclinical thyroid disorders were associated with CV events and mortality.

METHODS

Prospective multicenter cohort study.

METHODS

Thyroid status and clinical outcomes were explored in 1,000 diabetic hemodialysis patients from 178 centers in Germany.

METHODS

Thyroid status, defined by the following cutoff values: euthyroidism (thyrotropin [TSH], 0.30-4.0 mIU/L; free triiodothyronine [T3], 2.7-7.6 pmol/L; and free thyroxine [T4], 11.0-24.0 pmol/L), subclinical hyperthyroidism (TSH<0.3 mIU/L and free T3/free T4 within reference ranges), subclinical hypothyroidism (TSH, 4.1-15.0 mIU/L and free T3/free T4 within reference ranges), euthyroid sick syndrome (free T3<2.7 pmol/L and TSH/free T4 low or within reference ranges).

RESULTS

During 4 years' follow-up, prespecified adjudicated end points were determined: sudden cardiac death, myocardial infarction, stroke, combined CV events, and overall mortality. Short-term effects within the first 12 months were contrasted to long-term effects (years 2-4).

METHODS

TSH, free T3, and free T4 levels at baseline.

RESULTS

Euthyroidism was present in 78.1% of patients; subclinical hyperthyroidism, in 13.7%; and subclinical hypothyroidism, in 1.6%. Euthyroid sick syndrome was exhibited by 5.4% of patients. The adjusted short-term risk of sudden cardiac death was more than doubled (HR, 2.03; 95% CI, 0.94-4.36) in patients with subclinical hyperthyroidism, and similarly for patients with euthyroid sick syndrome (HR, 2.74; 95% CI, 0.94-7.98) compared with patients with euthyroidism. Short-term mortality was increased almost 3-fold for patients with euthyroid sick syndrome (HR, 2.97; 95% CI, 1.66-5.29), but this effect was not seen in the long term. Subclinical hypothyroidism was not associated with CV events or all-cause mortality. Risks of stroke and myocardial infarction were not affected meaningfully by thyroid disorders.

CONCLUSIONS

Observational study design.

CONCLUSIONS

Sudden cardiac death may be influenced by subclinical hyperthyroidism and euthyroid sick syndrome in the short term. Furthermore, euthyroid sick syndrome is associated strongly with mortality in hemodialysis patients. Regular assessment of thyroid status may help estimate the cardiac risk of dialysis patients.

OBJECTIVE

The aim of the study was to evaluate the early changes in pituitary hormone levels after severe traumatic brain injury (sTBI) and compare hormone levels to basic neuro-intensive care data, a systematic scoring of the CT-findings and to evaluate whether hormone changes are related to outcome.

METHODS

Prospective study, including consecutive patients, 15-70 years, with sTBI, Glasgow Coma Scale (GCS) score ≤ 8, initial cerebral perfusion pressure>> 10 mm Hg, and arrival to our level one trauma university hospital within 24 hours after head trauma (n = 48). Serum samples were collected in the morning (08-10 am) day 1 and day 4 after sTBI for analysis of cortisol, growth hormone (GH), prolactin, insulin-like growth factor 1 (IGF-1), thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), follicular stimulating hormone (FSH), luteinizing hormone (LH), testosterone and sex hormone-binding globulin (SHBG) (men). Serum for cortisol and GH was also obtained in the evening (17-19 pm) at day 1 and day 4. The first CT of the brain was classified according to Marshall. Independent staff evaluated outcome at 3 months using GOS-E.

RESULTS

Profound changes were found for most pituitary-dependent hormones in the acute phase after sTBI, i.e. low levels of thyroid hormones, strong suppression of the pituitary-gonadal axis and increased levels of prolactin. The main findings of this study were: 1) A large proportion (54% day 1 and 70% day 4) of the patients showed morning s-cortisol levels below the proposed cut-off levels for critical illness related corticosteroid insufficiency (CIRCI), i.e. <276 nmol/L (=10 ug/dL), 2) Low s-cortisol was not associated with higher mortality or worse outcome at 3 months, 3) There was a significant association between early (day 1) and strong suppression of the pituitary-gonadal axis and improved survival and favorable functional outcome 3 months after sTBI, 4) Significantly lower levels of fT3 and TSH at day 4 in patients with a poor outcome at 3 months. 5) A higher Marshall CT score was associated with higher day 1 LH/FSH- and lower day 4 TSH levels 6) In general no significant correlation between GCS, ICP or CPP and hormone levels were detected. Only ICPmax and LH day 1 in men was significantly correlated.

CONCLUSIONS

Profound dynamic changes in hormone levels are found in the acute phase of sTBI. This is consistent with previous findings in different groups of critically ill patients, most of which are likely to be attributed to physiological adaptation to acute illness. Low cortisol levels were a common finding, and not associated with unfavorable outcome. A retained ability to a dynamic hormonal response, i.e. fast and strong suppression of the pituitary-gonadal axis (day 1) and ability to restore activity in the pituitary-thyroid axis (day 4) was associated with less severe injury according to CT-findings and favorable outcome.

Acute illness is well known to affect thyroid function, but there are few studies correlating the severity of the underlying medical problem with indexes of thyroid function and little is known about its cause. Traumatically brain-injured patients were selected because they were a relatively homogeneous, previously healthy group with a condition whose severity was readily quantifiable. In 66 such patients, the relationships between changes in thyroid function tests (thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, and thyrotropin levels), catecholamine and cortisol concentrations measured on admission and again four days after the accident, and neurologic function assessed by the Glasgow Coma Score (GCS) were studied. Triiodothyronine and thyroxine levels fell significantly within 24 hours of injury. Four days after the accident, patients with the greatest neurologic dysfunction had the lowest triiodothyronine and thyroxine levels; significant correlations were present between the Day 4 GCS and concomitant thyroxine (r = 0.47, p less than 0.0001), free thyroxine (r = 0.32, p less than 0.02), and triiodothyronine (r = 0.50, p less than 0.0001) levels. Reverse triiodothyronine values remained unchanged throughout the study even in the most severely affected patients; the rise in thyrotropin levels was not significant (1.2 +/- 0.2 to 1.7 +/- 0.3 microU/ml, p = NS). Patients who died or remained vegetative had thyroxine and triiodothyronine levels 30 percent to 50 percent lower than those who had a good recovery (p less than 0.05). Highly significant correlations were present between Day 4 thyroxine and triiodothyronine levels and admission and Day 4 norepinephrine and epinephrine concentrations. There was no association between admission or concomitant cortisol levels and thyroid function on Day 4; treatment with high-dose dexamethasone did not influence these indexes. Thus, patients with traumatic brain injury exhibit a gradient of thyroid dysfunction that occurs promptly, is dependent upon the degree of neurologic impairment, and reflects ultimate outcome. The significant association with catecholamine levels suggests a role for sympathetic nervous system activation in its causation, independent of a generalized stress response, since there is no correlation of thyroid test abnormality with the degree of adrenocortical secretion.

The influence of partial sleep deprivation during the second half of the night on the secretion of thyroid stimulating hormone (TSH), thyroxin (T4), free T4 (fT4), triiodothyronine (T3), prolactin (PRL), growth hormone (GH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E2) was investigated in 10 healthy young women. Blood samples were drawn at hourly intervals over a 64-hour period (i.e., 3 consecutive days and nights). During night 2, all subjects were awakened at 1:30 a.m. During partial sleep deprivation, TSH concentrations increased significantly and remained elevated throughout the following day. Levels of T4, fT4, and T3 were enhanced during the partial sleep deprivation hours only, and changes in these hormones seemed to be independent of TSH. PRL levels decreased, LH and E2 concentrations increased, and GH and FSH secretion remained unchanged during partial sleep deprivation. This pattern of change of different endocrine axes during partial sleep deprivation resembles those seen after total sleep deprivation, suggesting that similar neurochemical changes are induced by both forms of antidepressant therapy. The late evening GH peak occurred almost exclusively before the onset of sleep. Partial sleep deprivation did not influence the chronobiological profiles of any of the hormones investigated. The chemical changes underlying these alterations are speculated to involve enhancement of central norepinephrine and dopamine activity with a concomitant increase in the activity of the sympathetic nervous system.

Thyroid disease affects up to 0.5 percent of the population of the United States. Its prevalence is higher in women and the elderly. The management of hypothyroidism focuses on ensuring that patients receive appropriate thyroid hormone replacement therapy and monitoring their response. Hormone replacement should be initiated in a low dosage, especially in the elderly and in patients prone to cardiac problems. The dosage should be increased gradually, and laboratory values should be monitored six to eight weeks after any dosage change. Once a stable dosage is achieved, annual monitoring of the thyroid-stimulating hormone (TSH) level is probably unnecessary, except in older patients. After full replacement of thyroxine (T4) using levothyroxine, the addition of triiodothyronine (T3) in a low dosage may be beneficial in some patients who continue to have mood or memory problems. The management of patients with subclinical hypothyroidism (a high TSH in the presence of normal free T4 and T3 levels) remains controversial. In these patients, physicians should weigh the benefits of replacement (e.g., improved cardiac function) against problems that can accompany the excessive use of levothyroxine (e.g., osteoporosis).

In clinically euthyroid subjects on long-term amiodarone therapy free thyroxine (T4) concentrations were increased and free triiodothyronine (T3) levels reduced. There was also a marked increase in reverse T3 in the treated group. These changes are consistent with inhibition of peripheral deiodination of T4 and reverse T3. Despite the rise in T4 serum thyrotrophin (TSH) levels were increased, suggesting an effect of amiodarone on the anterior pituitary. To investigate the interaction of amiodarone with the cellular actions of thyroid hormones we examined the influence of the drug in vitro on the binding of T3 to isolated nuclei prepared from rat anterior pituitary tissue. Amiodarone inhibited the nuclear binding of T3 in a dose dependent fashion. Addition of amiodarone in vitro also stimulated TSH release from cultured rat anterior pituitary cells, consistent with a T3 antagonistic effect. These studies provide evidence for a direct influence of amiodarone on the thyrotroph, mediated via nuclear T3 receptor binding.