Increase In FT4 Research Articles

Perfluoroalkyl substances and thyroid function in older adults

Current understanding of the thyroid disruptive properties of perfluoroalkyl substances (PFASs), particularly in aging populations, is limited. The objectives of this study were to (i) assess associations between thyroid function, as measured by serum thyrotropin (thyroid stimulating hormone, TSH), free thyroxine (fT4), total thyroxine (T4), and total triiodothyronine (T3), and serum perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in an aging population and (ii) determine if other persistent organic pollutants with thyroid disruptive properties including polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) modify such associations. We conducted a cross-sectional study of 87 men and women 55 to 74years of age, without clinically-diagnosed thyroid disease, who resided in upper Hudson River communities in New York. Geometric means (standard deviations) of serum PFOS and PFOA were 31.6 (1.7) ng/mL and 9.17 (1.72) ng/mL, respectively. Multivariable linear regression analyses indicated that one interquartile range difference in PFOS corresponded to 4% and 9% increases in fT4 and T4 respectively. We detected statistical interactions between PFOA and age for effects on fT4 and T4; joint increases in PFOA and age were associated with increases in fT4 and T4, of 3% and 7%, respectively. We also detected statistical interactions between PFOS and total PCBs for the effect on T3 and between PFOA and total PBDEs for the effect on TSH. Our results suggest that PFASs are associated with subtle alterations in thyroid hormone levels in this population, and that these associations are likely to vary by age, and levels of PCBs and PBDEs.

Toxic Metal Exposure and Associations with Thyroid and Reproductive Hormone Levels in Pregnant Women Living in Northern Puerto Rico: the PROTECT Study

Toxic metals have been found to be reproductive toxicants as well as suspected endocrine disruptors. Effects on the endocrine and reproductive systems of metals in pregnant women have not yet been thoroughly evaluated. The present exploratory study evaluates the possible relationship between metal exposure and thyroid (thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4)), and sexual hormones (estradiol (E2), progesterone (PROG), sex hormone binding-globulin (SHBG)), among pregnant women participating in a birth cohort study examining the role of environmental toxicants and preterm birth in northern Puerto Rico. Biological samples were collected during two time points in pregnancy (N=133 samples from 84 women). Maternal whole blood samples were analyzed for concentrations of toxic metals (arsenic (As), cadmium (Cd), chromium (Cr), lead (Pb), mercury (Hg), and manganese (Mn) using an inductively coupled plasma-high resolution mass spectrometer. Hormone levels were measured in serum using LC-MS/MS (FT3, FT4) or immunoassay (all others). Linear mixed models were used in preliminary analyses to estimate the association between metals and hormones. After adjusting for maternal age, income, and marital status, Hg concentrations showed statistically significant inverse associations with SHBG (p=0.02). Increases in FT4 and TSH were associated with As exposure (p<0.10); Cd exposure was also associated with increased FT4 (p=0.05). Cr exposure was suggestively associated with decreases in E2, PROG, and SHBG (p<0.10) and As suggested inverse associations with E2 and PROG (p<0.10) but only in unadjusted models. These results may indicate that toxic metals could contribute to endocrine disruption in pregnant women. Given the potential threat of metal exposure from Superfund contaminated sites, associations reported here could indicate a contribution to endocrine-related effects from metals which could lead to adverse reproductive outcomes.

Short call abstracts.

Short call abstracts.

The Relationships between Thyroid Hormones and Thyroid-stimulating Hormone with Lipid Profile in Euthyroid Men

Background and Aim: Alteration in lipid profile is a common observation in patients with thyroid dysfunction, but the current knowledge on the relationship between lipids and thyroid hormone levels in euthyroid state is insufficient. The current study aimed to determine the association between thyroid hormones and thyroid-stimulating hormone (TSH) with lipid profile in a euthyroid male population.Methods: A total of 708 Chinese and Malay men aged 20 years and above were recruited in this cross-sectional study. Their blood was collected for the determination of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), free thyroxine (FT4), free triiodothyronine (FT3) and TSH levels. The association was analyzed using multiple regression and logistic regression models with adjustment for age, ethnicity, body mass index and FT4/FT3/TSH levels.Results: In multiple regression models, TSH was positively and significantly associated with TG (p<0.05). Free T4 was positively and significantly associated with TC, LDL-C and HDL-C (p<0.05). Free T3 was negatively and significantly associated with HDL-C (p<0.05). In binary logistic models, an increase in TSH was significantly associated with higher prevalence of elevated TG in the subjects (p<0.05), while an increase in FT4 was significantly associated with higher prevalence of elevated TC but a lower prevalence of subnormal HDL in the subjects (p<0.05). Free T3 was not associated with any lipid variables in the logistic regression (p>0.05).Conclusions: In euthyroid Malaysian men, there are positive and significant relationships between TSH level and TG level, and between FT4 level and cholesterol levels.

Effects of thyroxin therapy on different analytes related to obesity and inflammation in dogs with hypothyroidism

Hypothyroidism in dogs is accompanied by changes in intermediary metabolism including alterations in bodyweight (BW), insulin resistance, and lipid profile. In this study, changes in selected adipokines (adiponectin, leptin), butyrylcholinesterase (BChE), and acute phase proteins, including C-reactive protein, haptoglobin (Hp) and serum amyloid A (SAA), were studied in dogs with hypothyroidism under thyroxin therapy. Blood samples were collected when hypothyroidism was diagnosed (before treatment) and after treatment with thyroxin. Twenty-eight of 39 dogs exhibited a good therapeutic response (group A), whereas the remainder were considered to have been insufficiently treated (group B). Following treatment, group A dogs demonstrated a statistically significant decrease in canine thyroid stimulating hormone (c-TSH) (P<0.001) and an increase in free thyroxine (fT4) (P<0.001) concentrations, associated with a significant decrease in BW (P<0.05), leptin (P<0.01), and adiponectin, (P<0.001) and an increase in BChE (P<0.01) and Hp (P<0.05). Group B dogs showed no statistically significant changes in c-TSH, but had a significant increase in fT4 (P<0.001) accompanied by a significant decrease in adiponectin (P<0.05) of lower magnitude than group A. No significant changes in the mean circulating levels of APPs were observed in both groups, with the exception of an increase in Hp (P<0.05) in group A. In summary, the successful treatment of hypothyroidism reduces circulating levels of adiponectin and leptin, while increasing BChE activity in dogs. The mean increase in Hp values and decrease in SAA for some of the dogs after treatment warrants further investigation.

Longitudinal Changes in Thyroid Function in the Oldest Old and Survival: The Cardiovascular Health Study All-Stars Study

Data on thyroid function in the oldest old are sparse, and existing studies show conflicting evidence on the relationship between thyroid function and mortality in this age group. We describe longitudinal changes in thyroid function in a cohort of elderly individuals and determine the relationship between thyroid function and mortality. Eight hundred forty-three participants in the Cardiovascular Health Study All Stars Study who were not taking thyroid medications and had thyroid function testing in 2005-2006 (mean age 85 yr). Thyroid-stimulating hormone (TSH), free T(4) (FT4), total T(3), and thyroid peroxidase antibody status were measured in 1992-1993 and 2005-2006. Deaths were ascertained through February 2011. There was a statistically significant 13% increase in TSH, 1.7% increase in FT4, and 13% decrease in total T(3) over the 13-yr period. Two hundred eighty-seven deaths occurred over a median follow-up of 5.1 yr. There was no association between subclinical hypothyroidism[hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.66-1.43], TSH level (HR per milliunits per liter 0.94, 95% CI 0.88-1.01), or persistent thyroid peroxidase antibody positivity (HR 1.09, 95% CI 0.62-1.92), and death. However, FT4 was positively associated with death (HR per nanograms per deciliter 2.57, 95% CI 1.32-5.02). TSH increased over time in these older individuals. This elevation was not associated with increased or decreased mortality, although higher FT4 levels were associated with death. These findings raise concern for treatment of mild elevations of TSH in advanced age. Further studies are needed to determine the potential benefit of treating age-related changes in thyroid function.

Treating primary hypothyroidism with weekly doses of levothyroxine: a randomized, single-blind, crossover study

Compliance to levothyroxine treatment in hypothyroidism is compromised by daily schedule, and a weekly dose may be an alternative. This was a randomized, crossover study. Fourteen females were assigned to daily or weekly doses of LT4. After six weeks, they switched regimens. Thyroid parameters were measured at baseline, and after 42 and 84 days. Echocardiogram and hyperthyroidism symptoms were evaluated before and four hours after LT4 intake. In the weekly dose treatment, fT4 levels were higher after taking LT4, and lower seven days after the last dose; by the 6(th) week there was a small decrease in T3 levels. TSH remained unchanged and there were no hyperthyroidism symptoms or echocardiographic manifestations. Weekly dose leads to transient increases in fT4, without hyperthyroidism or cardiac symptoms. That approach seems to be a safe alternative for the treatment of hypothyroidism.

Evaluation of Thyroid Disorders During Head-and-Neck Radiotherapy by Using Functional Analysis and Ultrasonography

To evaluate thyroid function and vascular changes during radiotherapy for patients with head and neck cancer. Fifty patients treated with primary or postoperative radiotherapy for various cancers in the head and neck region were prospectively evaluated. The serum samples (triiodothyronine [T3], thyroxine [T4], thyroid-stimulating hormone [TSH], free triiodothyronine [FT3], and free thyroxine [FT4]), the echo level of the thyroid gland, and color Doppler ultrasonography (CDU) parameters of the right inferior thyroid artery (RITA) of the patients were measured before and at regular intervals during radiotherapy. The thyroid gland dose-volume histograms of the patients were derived from their computed tomography-based treatment plans. There was a significant fall in TSH level (p < 0.0001) but an increase in FT4 (p < 0.0001) and T4 (p < 0.022) levels during the radiotherapy course. The threshold dose required to produce significant changes was 12 Gy (Biologically Effective Dose in 2-Gy fractions, BED(2)). There were significant rises in the patients' pulsatility index, resistive index, peak systolic velocity, blood volume flow levels, and RITA diameter (p < 0.0001), as detected by CDU during radiotherapy, compared to those parameters measured before the treatment. Hypoechogenicity and irregular echo patterns (p < 0.0001) were seen during radiotherapy compared to those before treatment. There was significant Pearson's correlation between the CDU parameters and T4, FT4, and TSH levels. Radiation-induced thyroiditis is regarded as primary damage to the thyroid gland. Thyroiditis can subsequently result in hypothyroidism or hyperthyroidism. Our results demonstrated that changes in thyroid vessels occur during radiotherapy delivered to patients. Vessel changes also can be attributed to the late effect of radiation on the thyroid gland. The hypoechogenicity and irregular echo patterns observed in patients may result from the increase in intrathyroidal flow.

Effects of fence height on total and free iodothyronine changes in horses after experimental show jumping sessions

Involvement of thyroid function on performance warrants further investigation as limited data exists on the effects of showjumping on the dynamics of total and free iodothyronines. To investigate the response of circulating total and free iodothyronines in horses to experimental showjumping sessions and compare with the effects normally induced by competition and determine if fence height has any effect. Using a randomised crossover study design 6 trained horses were studied during experimental showjumping sessions over 10 fences of different height: 1.00 m (Session 1), 1.10 m (Session 2), 1.20 m (Session 3). Hormone levels were recorded before, after warm-up, 5 and 30 min post exercise. T(3), T(4), fT(3), fT(4) concentrations were analysed by ELISA/competition using streptavidin technology. RM-ANOVA was applied to test for any differences in basal and warm-up values of different sessions. Two way RM-ANOVA was applied to test for any effects of interaction between fence height and time. The differences between individual means over time were assessed using a post hoc multiple comparison test (Bonferroni). Basal T(4) changes over the sessions (P < 0.05) were recorded. After warm-up, T(4) concentration results were lower than basal in Session 1 (P < 0.05). Higher than basal values were recorded 30 min post exercise for T(3) (P < 0.001), T(4) and fT(4) (P < 0.01) in Session 2 and for T(4) (P < 0.05) and fT(4) (P < 0.01) in Session 3. The interaction fence height/time results were significant on T(3) (P < 0.03) and fT(4) (P < 0.03); sampling time on T(3) (P < 0.0007), T(4) (P < 0.001) and fT(4) (P < 0.002) post exercise changes. Showjumping over the highest fences induced a release of T(3) from skeletal muscle, probably due to 5'-desiodase activity and increase of fT(4), due to thyroid stimulation and/or changes in capacity to bind iodothyronines.

Ghrelin affects the hypothalamus–pituitary–thyroid axis in humans by increasing free thyroxine and decreasing TSH in plasma

Ghrelin promotes a positive energy balance, e.g. by increasing food intake. Stimulation of the activity of the hypothalamus-pituitary-thyroid (HPT) axis promotes a negative energy balance, e.g. by increasing energy expenditure. We therefore hypothesized that ghrelin suppresses the HPT axis in humans, counteracting its energy-saving effect. In this single-blind, randomized, cross-over study, we determined secretion patterns of free triiodothyronine (fT(3)), free thyroxine (fT(4)), TSH, and thyroid-binding globulin (TBG) between 2000 and 0700 h in 20 healthy adults (10 males and 10 females, 25.3+/-2.7 years) receiving 50 microg ghrelin or placebo at 2200, 2300, 0000, and 0100 h. FT(4) plasma levels were significantly higher after ghrelin administration than after placebo administration from 0000 h until 0620 h except for the time points at 0100, 0520, and 0600 h. TSH plasma levels were significantly lower from 0200 until the end of the study at 0700 h except for the time points at 0540, 0600, and 0620 h. The relative increase of fT(4) (area under the curve (AUC) 0130-0700 h (ng/dl x min): placebo: 1.31+/-0.03; ghrelin: 1.39+/-0.03; P=0.001) was much weaker than the relative decrease of TSH (AUC 0130-0700 h (mIU/ml x min): placebo: 1.74+/-0.12; ghrelin: 1.32+/-0.12; P=0.007). FT(3) and TBG were not affected. This is the first study to report that ghrelin affects the HPT axis in humans. The early fT(4) increase was possibly induced by direct ghrelin action on the thyroid where ghrelin receptors have been identified. The TSH decrease might have been caused by ghrelin-mediated inhibition at hypothalamic level by feedback inhibition through fT(4), or both.

Dose‐dependent acute effects of recombinant human TSH (rhTSH) on thyroid size and function: comparison of 0·1, 0·3 and 0·9 mg of rhTSH

Recombinant human TSH (rhTSH) is used to augment the effect of radioiodine therapy for nontoxic multinodular goitre. Reports of acute thyroid swelling and hyperthyroidism warrant safety studies evaluating whether these side-effects are dose dependent. To determine the effects on thyroid size and function of various doses of rhTSH. In nine healthy male volunteers, the effect of placebo, 0.1, 0.3 and 0.9 mg of rhTSH was examined in a paired design including four consecutive study rounds. Main outcome measures were evaluated at baseline, 24 h, 48 h, 96 h, 7 days and 28 days after rhTSH and included: Thyroid volume (TV) estimation by planimetric ultrasound, and thyroid function by serum TSH, free T3, free T4 and Tg levels. Following placebo or 0.1 mg rhTSH, the TV did not change significantly from baseline at any time. At 24 and 48 h after administration of 0.3 mg rhTSH, the TV increased by 37.4 +/- 12.3% (SEM) (P = 0.03) and 45.3 +/- 16.1% (P = 0.05) respectively. After 0.9 mg rhTSH, the TV increased by 23.3 +/- 5.8% (P = 0.008) and 35.5 +/- 18.4% (P = 0.02) respectively. The increase in serum FT3, FT4 and thyroglobulin (Tg) was greater when administering 0.3 mg compared with 0.1 mg (P = 0.02) and when administering 0.9 mg compared with 0.3 mg (P = 0.02). After 0.1 mg rhTSH, the increase in FT3 and Tg was not significantly different from placebo whereas the FT4 increase was significantly higher (P = 0.02 compared with placebo). In healthy individuals, rhTSH-induced thyroid swelling and hyperthyroidism is rapid and dose dependent. If valid for patients with goitre, our results suggest that these adverse effects are unlikely to be of clinical significance, following doses of rhTSH of 0.1 mg or less.

High Prevalence of Side Effects After Recombinant Human Thyrotropin–Stimulated Radioiodine Treatment with 30 mCi in Patients with Multinodular Goiter and Subclinical/Clinical Hyperthyroidism

Treatment of multinodular goiters (MNGs) is highly controversial. Radioiodine (RAI) therapy is a nonsurgical alternative for the elderly who decline surgery. Recently, recombinant human thyrotropin (rhTSH) has been used to augment RAI uptake and distribution. In this study, we determined the outcome of 30 mCi RAI preceded by rhTSH (0.1 mg) in euthyroid (EU) and hyperthyroid (subclinical/clinical) patients with large MNGs. This was a prospective cohort study. Forty-two patients (age, 43-80 years) with MNGs were treated with 30 mCi RAI after stimulation with 0.1 mg of rhTSH. Patients were divided into three groups, according to thyroid function: EU (n = 18), subclinically hyperthyroid (SC-H, n = 18), and clinically hyperthyroid (C-H, n = 6). All patients underwent a 90-day low-iodine diet before treatment, and those with clinical hyperthyroidism received methimazole 10 mg daily for 30 days. Serum TSH, free thyroxine (FT4), total triiodothyronine (TT3), and thyroglobulin were measured at baseline and at 24, 48, 72, 168 hours, and 1, 3, 6, 9, 12, 18, 24, and 36 months after therapy. Thyroid volume was assessed by computed tomography at baseline and every 6 months. Patients had high iodine urinary excretion (308 +/- 108 microg I/L) at baseline. TSH levels at baseline were within the normal range (1.5 +/- 0.7 microU/mL) in the EU group and suppressed (<0.3 microU/mL) in the SC-H and C-H groups. After rhTSH, serum TSH peaked at 24 hours reaching 12.4 +/- 5.85 microU/mL. After RAI administration, patients in both hyperthyroid groups had a higher increase in FT4 and TT3 compared with those in the EU group (p < 0.001). Thyroglobulin levels increased equally in all three groups until day 7. Thyroid volume decreased significantly in all patients. Side effects were more common in the SC-H and C-H groups (31.4% and 60.4%, respectively) compared with EU patients (17.8%). Permanent hypothyroidism was more prevalent in the EU group (50%) compared with the SC-H (11%) and C-H (16.6%) groups. Patients with MNG may have subclinical and clinical nonautoimmune iodine-induced hyperthyroidism. Despite a low-iodine diet and therapy with methimazole, hyperthyroid patients have a significantly higher increase in FT4 and TT3 levels after RAI ablation. This can lead to important side effects related mostly to the cardiac system. We strongly advise that patients with SC-H and C-H be adequately treated with methimazole and low-iodine diet aiming to normalize their hyperthyroid condition before rhTSH-stimulated treatment with RAI.

Euthyroid Patient with Elevated Serum Free Thyroxine

A 32-year-old female patient presented complaining of increased flushing, perspiration and heat intolerance of 3 months’ duration. Medical history included idiopathic thrombocytopenic purpura of 4 years’ duration, which had been treated by splenectomy after failed immunosuppression with prednisone and azathioprine and was currently in remission. On examination, she was found to be clinically euthyroid without a goiter. She had also developed a diffuse erythematous papular rash on the face and back, with bullous lesions on the chest. Immunofluorescent antibody studies performed on a punch biopsy of skin were positive for several autoantibodies, leading to a diagnosis of subacute cutaneous lupus erythematosus. This diagnosis was further characterized by positive titers of nuclear and double-stranded DNA autoantibodies in the serum. Thyroid function testing on an Advia Centaur® Immunoassay System (Siemens Medical Solutions Diagnostics) revealed an increased concentration of serum free thyroxine (FT4)1 of 90.1 pmol/L (6.97 ng/dL) (reference range 11.5–22.7 pmol/L), a nonsuppressed thyroid-stimulating hormone (TSH) concentration of 1.8 mIU/L (1.8 μIU/mL) (reference range 0.35–5.5 mIU/L), and normal free triiodothyronine (FT3) concentration of 4.2 pmol/L (0.33 ng/dL) (reference range 3.5–6.5 pmol/L). Repeat investigation 1 and 2 months later revealed a progressive increase in FT4 to 125.3 pmol/L (9.7 ng/dL) and ≥155 pmol/L (≥12.0 ng/dL), respectively. TSH and FT3 remained within reference intervals, as did total T4 by RIA, at 155 nmol/L (12 μg/dL) (reference range 58–161 nmol/L). Furthermore, she tested positive for antithyroperoxidase antibodies at 110 IU/L (reference range <37 IU/L) and antithyroglobulin antibodies at 149 IU/L (reference range <98.1 IU/L). An investigation of her disconcordant thyroid function tests was initiated. Increased serum FT4 concentrations, with a nonsuppressed TSH, are most often seen with erratic thyroxine replacement therapy. Other less common causes include antibody interference in the FT4 assay causing falsely increased …

Exploring the use of recombinant human TSH in the diagnosis of central hypothyroidism

The diagnosis of central hypothyroidism (CH) is often difficult to establish as serum TSH levels may be low, normal, or slightly increased. To explore the use of recombinant human TSH (rhTSH) in the diagnosis of CH. Randomized single-blind clinical trial. Outpatient clinic of a tertiary care referral center. A single intramuscular injection of 0.1 and 0.9 mg rhTSH in random order with 1-week interval. Eighteen adult patients with pituitary insufficiency and six healthy age-, sex-, and body mass index-matched controls. Six patients had untreated CH (newCH), six had treated CH (CH), and six patients were TSH sufficient (nonCH). Five weeks before TSH stimulation, levothyroxine was replaced with tri-iodothyronine (T(3)) for 4 weeks. One week before stimulation, treatment was withdrawn. Thyroid hormones and thyroglobulin (Tg) before and 2, 3(1/2), 7, 24, 48, and 72 h after each injection. In the newCH group, basal free thyroxine (FT(4)) levels were lower than in controls (P<0.05). After 0.9 mg rhTSH, the increases in FT(4) and reverse T(3) (rT(3)) were less marked in the newCH group than in controls (FT(4)+/-s.e.m. 9.2+/-0.5 to 19.7+/-1.2 vs 11.3+/-0.5 to 27.8.2+/-2.4 pmol/l, P<0.05). The CH group exhibited reduced basal and stimulated FT(4) compared with the TSH-sufficient groups. Tg increased similarly among all study groups after rhTSH injection. In this pilot study, patients with untreated CH had lower response to 0.9 mg rhTSH in FT(4) and rT(3) than controls. An rhTSH test may be useful in the diagnosis of CH, but further studies are required.

Thyroid hormone status and pituitary function in adult rats given oral doses of perfluorooctanesulfonate (PFOS)

Introduction Perfluorooctanesulfonate (PFOS) is widely distributed and persistent in humans and wildlife. Prior toxicological studies have reported decreased total and free thyroid hormones in serum without a major compensatory rise in thyrotropin (TSH) or altered thyroid gland histology. Although these animals (rats, mice and monkeys) might have maintained an euthyroid state, the basis for hypothyroxinemia remained unclear. We undertook this study to investigate the causes for the PFOS-induced reduction of serum total thyroxine (TT4) in rats. Hypotheses We hypothesized that exposure to PFOS may increase free thyroxine (FT4) in the rat serum due to the ability of PFOS to compete with thyroxine for binding proteins. The increase in FT4 would increase the availability of the thyroid hormone to peripheral tissues for utilization, metabolic conversation, and excretion. We also hypothesized that PFOS does not directly interfere with the regulatory functions of the hypothalamic–pituitary–thyroid (HPT) axis in rats. Experiments Three experimental designs were employed to test these hypotheses. (1) Female Sprague–Dawley (SD) rats were given a single oral dose of 15 mg potassium PFOS/kg body weight. At intervals of 2, 6, and 24 h thereafter, measurements were made for serum FT4, TT4, triiodothyronine (TT3), reverse triiodothyronine (rT3), thryrotropin (TSH), and PFOS concentrations, as well as liver PFOS concentrations, UDP-glucuronosyltransferase 1A (UGT1A) family mRNA transcripts, and malic enzyme (ME) mRNA transcripts and activity. (2) To provide evidence for increased uptake and metabolism of thyroxine (T4), 125I-T4 was given to male and female SD rats by intravenous injection, followed in 2 h by a single oral dose of 15 mg potassium PFOS/kg body weight. 125I radioactivity was determined in urine and feces collected over a 24-h period and in serum and liver collected at 24 h. (3) To assess the potentials effect of PFOS on the hypothalamic–pituitary–thyroid axis, over an 8-day period, groups of male SD rats were given PFOS (3 mg/kg-d), propyl thiouracil (PTU, 10 μg/mL in water), or PTU and PFOS in combination, with controls receiving 0.5% Tween ® 20 vehicle. On days 1, 3, 7, and 8, TT4, TT3, and TSH were monitored. On day 8, pituitaries were removed and placed in static culture for assessment of thyrotropin releasing hormone (TRH)-mediated release of TSH. Results (1) PFOS transiently increased FT4 and decreased TSH within 6 h, with values returning to control levels by 24 h. TT4 was decreased by 55% over a 24-h period. TT3 and rT3 were decreased at 24 h to a lesser extent than TT4. ME mRNA transcripts were increased at 2 h and activity was increased at 24 h. UGT1A mRNA transcripts were increased at 2 and 6 h. (2) 125I decreased in serum and liver relative to controls and consistent with a reduction in serum TT4. Concomitantly, 125I activity was increased in urine and feces collected from PFOS-treated rats. (3) During the 8 days of dosing with PFOS, TSH was not elevated in male rats, while TT4 and TT3 were decreased. Pituitary response to TRH-mediated TSH release was not diminished after 8-daily oral doses of PFOS. Conclusions These findings suggest that oral dosing in rats with PFOS results in transiently increased tissue availability of the thyroid hormones and turnover of T4 with a resulting reduction in serum TT4. PFOS does not induce a classical hypothyroid state under dosing conditions employed nor does it alter HPT activities.

Percutaneous Laser Ablation in the Treatment of Toxic and Pretoxic Nodular Goiter

To report data regarding treatment with use of percutaneous laser ablation (PLA) in autonomously functioning thyroid nodules (AFTN). We treated 18 patients (10 women and 8 men, 31 to 80 years old) who presented with a single hyperfunctioning thyroid nodule (8 patients) or a multi-nodular goiter (10 patients) with clearly hyperfunctioning areas on a thyroid scintiscan. In 5 cases, free thyroxine (FT4) and free triiodothyronine (FT3) levels were high, and in these patients and a further 9 patients with cardiovascular symptoms, methimazole therapy was initiated to restore euthyroidism. The total number of PLA sessions ranged from 1 to 5 (median, 3). Thyroid-stimulating hormone, FT4, FT3, thyroglobulin, and antithyroglobulin and anti-thyroid peroxidase antibodies were measured by a commercial kit the day after PLA treatment, then weekly during the first month, and monthly thereafter. The Student t test was used for statistical analyses, and data are reported as mean values +/- SE. After each PLA session, there was a transient and mild increase in FT4 and FT3-5.2% to 18.1% (mean, 11.1 +/- 0.69%) (P<0.001) in patients not treated with methimazole and 4.0% to 8.3% (mean, 5.9 +/- 0.31%) (P<0.001) in patients treated with methimazole-relative to values before treatment; however, these values never reached the range of hyperthyroidism. In addition, thyroglobulin showed a remarkable increase after 24 hours- 115% to 390% (mean, 266.0 +/- 12.7%) (P<0.001). Thyroid-stimulating hormone increased in all cases and reached normal values in all patients with single AFTN and in 5 patients (50%) with multinodular goiter within 3 months after PLA. At 1-year follow-up, the decrease in nodular volume was 24% to 72% (mean, 59.3 +/- 8.2%; P<0.001). Our data show that PLA can be a useful treatment in AFTN and particularly in single toxic nodules. Possible elective indications are patients who refuse surgical or radioiodine treatment and patients with cardiovascular comorbidity who need rapid restoration of the euthyroid state and who cannot tolerate the discontinuation of antithyroid drugs for radioiodine treatment.

Transient stimulatory effects on pituitary-thyroid axis in patients treated with interleukin-2.

It has been shown that various cytokine therapies may influence thyroid hormone parameters that may lead to serious side effects including nonthyroidal illness. Interleukin-2 is effective in increasing CD4-T cell numbers in human immunodeficiency virus (HIV)-infected patients and it is used in the treatment of various malignant tumours. However, the association of interleukin-2 (IL-2) therapy and thyroid function is not clearly established as serial systematic measurements of thyroid parameters have not been performed with interleukin-2 as the sole therapeutic agent. Therefore, it was the aim of this study to examine prospectively the impact of a 5-day interleukin-2 therapy on thyroid parameters in asymptomatic HIV-infected patients. Twenty male euthyroid patients (mean age, 42.6 +/- 3.2 years; body weight, 73.4 +/- 3.0 kg) received 9,000,000 IU/d interleukin-2. Thyroid function was evaluated by measurements of serum thyrotropin (TSH), triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), reverse T3 (rT3), thyroglobulin (Tg), thyroxine-binding globulin (TBG), and anti-thyroid-peroxidase (TPO)-antibodies from day 1-4 and on days 7, 14, 20, 40, 60, 80, and 100. All results are given as mean +/- SD. On day 4, we observed a significant increase that was still within normal range of T4 and T3 (p < 0.05). TSH increased from 1.33 +/- 0.57 to 4.53 +/- 1.39 mU/l (p = 0.0001) and FT4 from 18.1 +/- 4.2 to 48.9 +/- 10.9 pmol/L (p = 0.0001) on day 4 with a gradual decrease thereafter. Normalization to baseline levels for TSH (1.45 +/- 0.75 mU/L) and FT4 (18.1 +/- 3.0 pmol/L) was achieved only on day 14. The increase of FT4 was more pronounced (well in the hyperthyroid range) than the increase in total T4 in the presence of normal TBG and albumin concentrations whereas TBG was not affected. We did not observe changes in anti-TPO-antibody levels up to day 100. Our data clearly demonstrate that the administration of interleukin-2 has a stimulatory effect on the pituitary-thyroid axis. The increase of TSH suggests a central stimulation directed by the action of IL-2 as the major mechanism.

Behavioural and physiolgical thermoregulation in groups of pregnant sows housed in a kennel system at low temperatures

The behavioural and physiological responses of pregnant sows to cold exposure in a kennel system were investigated. Ten groups, each of six pregnant sows, were housed over winter in a non-insulated building containing kennels. Lying posture, social thermoregulation, time spent inside the kennels and general activity were recorded in three 48-h periods with different diurnal room temperatures: cold (−9 to −1 °C), medium (0 to +3 °C) and warm (+4 to +9 °C). Blood samples were collected from two of the groups, and the concentrations of glucose, free fatty acids, total thyroxine (TT4) and free thyroxine (FT4) in the plasma were determined.The air temperature difference in between the surrounding room and the kennels increased with decreasing room temperature with a maximum of 12 °C at a room temperature of −10 °C. Activity level did not differ significantly between temperature periods (30.6 ± 1.1%). At all temperature periods, the sows spent between 80 and 90% of their time inside the kennels. The sows spent significantly more time eating/manipulating straw in the cold than in the medium and warm period (P = 0.038). Time spent lying on the belly in body contact with other sows inside the kennel increased significantly from 15.6% in the warm period to 20.3% in the medium period and 44.9 % in the cold period (P = 0.001). The two highest ranked individuals (rank 1 and 2) tended to spend more time inside the kennel than sows with rank order 4 to 6 (P = 0.059). At a diurnal room temperature of −8° C, the sows had a significantly higher level of (FT4) in the plasma than at higher temperatures (P &lt; 0.001). The relationship between the other blood parameters and diurnal room temperature was difficult to interpret.This study suggests that kennels with straw give the sows good protection from climatic conditions, and that social thermoregulation in a micro environment is an important strategy to cope with low temperatures. At a diurnal room temperature of –8°C, however, the increase of FT4 in the plasma may indicate an increased metabolism and thus an increased energy requirement. Since low-ranking individuals spent less time inside the kennels than high-ranking sows, they probably had a greater heat loss. For practical application of the system, the kennel should thus be designed in a way that allows all individuals to get inside. Key words: Pregnant sows, thermoregulation, physiology, kennel, social rank order

Induction of low-T3 syndrome in exercising women occurs at a threshold of energy availability

To investigate the relationship between energy availability (dietary energy intake minus energy expended during exercise) and thyroid metabolism, we studied 27 untrained, regularly menstruating women who performed approximately 30 kcal.kg lean body mass (LBM)-1.day-1 of supervised ergometer exercise at 70% of aerobic capacity for 4 days in the early follicular phase. A clinical dietary product was used to set energy availability in four groups (10.8, 19.0, 25.0, 40.4 kcal.kg LBM-1.day-1). For 9 days beginning 3 days before treatments, blood was sampled once daily at 8 A.M. Initially, thyroxine (T4) and free T4 (fT4), 3,5,3'-triiodothyronine (T3) and free T3 (fT3), and reverse T3 (rT3) were in the normal range for all subjects. Repeated-measures one-way analysis of variance followed by one-sided, two-sample post hoc Fischer's least significant difference tests of changes by treatment day 4 revealed that reductions in T3 (16%, P < 0.00001) and fT3 (9%, P < 0.01) occurred abruptly between 19.0 and 25.0 kcal.kg LBM-1.day-1 and that increases in fT4 (11%, P < 0.05) and rT3 (22%, P < 0.01) occurred abruptly between 10.8 and 19.0 kcal.kg LBM-1.day-1. Changes in T4 could not be distinguished. If energy deficiency suppresses reproductive as well as thyroid function, athletic amenorrhea might be prevented or reversed by increasing energy availability through dietary reform to 25 kcal.kg LBM-1.day-1, without moderating the exercise regimen.

Free T3 levels to monitor 1T4 therapy in congenital hypothyroid (CH) children during the first two years of life

An elevated threshold for TSH suppression has been previously described in children during the first months of replacement therapy. We studied 15 children, diagnosed by neonatal CH screening during the first two years of life. All of them were clinically euthyroid in our multidisciplinary follow-up program(normal growth rate, absence of hypo/hyperthyroidism symptoms, normal neuropsychological development). Clinical evaluation and hormonal profiles (fT3,fT4,T3,T4,TSH) were assessed every three months. We found a significant correlation between total hormones, fT4,lT4 dosage and TSH levels. TSH levels were well above the normal range during the first year of life,varying widely between and within patients;fT3 concentrations were not correlated with TSH levels and were well in the normal range during the study. The correlation between lT4-TSH, fT4-TSH and lT4-fT4 shows that increasing the dose of lT4 decreases TSH levels according to an elevated threshold for TSH inhibition by an increase in fT4 levels but TSH does not fall in the normal range at the recommended therapeutic dose. This increase in fT4 and decrease in TSH does not seem to affect the thyroid status, since fT3 does not change for individual compensatory mechanism in fT4/fT3 conversion in the usual therapeutic range; increase of lT4 to completely inhibit TSH probably renders patients hyperthyroid.FT3 seems to be the best index for therapy.