Urinary total T3 levels as a method to monitor metabolic changes in relation to variation in caloric intake in captive bonobos (Pan paniscus).

Monitoring metabolic activity in wild living animals has become of particular interest in the field of ecological research. Methods for the repeated non-invasive sampling of individuals are needed. Thyroid hormones (TH) are involved in the regulation of metabolic activity, and their measurement can be used as a proxy to monitor metabolic changes. During periods of low energy intake, serum TH levels are reduced, leading to a decrease in metabolic activity. Using urine samples collected during a food restriction experiment in captive bonobos we validated a total triiodthyronin (TT3) enzyme immunoassay (EIA) for the monitoring of metabolic changes. We found that the majority of immune reactivity of the assay in the urine samples could be explained through immunoreactivity to T3. Furthermore, urinary T3 was stable through repeated freeze-thaw cycles but prolonged exposure to room temperature lead to degradation. Most importantly, we found that for all animals urinary total T3 levels were higher when more digestible energy was consumed. We concluded that urinary total T3 measurements are a suitable method for monitoring metabolic changes in bonobos and potentially in a wide range of animal species.

Comprehensive Metabolic Profiling Reveals a Lipid-Rich Fingerprint of Free Thyroxine Far Beyond Classic Parameters.

Objective: Thyroid hormones are ubiquitously involved in human metabolism. However, the precise molecular patterns associated with alterations in thyroid hormones levels remain to be explored in detail. A number of recent studies took great advantage of metabolomics profiling to outline the metabolic actions of thyroid hormones in humans. Methods: Among 952 participants in the Study of Health in Pomerania, data on serum free thyroxine (FT4) and thyrotropin and comprehensive nontargeted metabolomics data from plasma and urine samples were available. Linear regression analyses were performed to assess the association between FT4 or thyrotropin and metabolite levels. Results and Conclusion: After accounting for major confounders, 106 of 613 plasma metabolites were significantly associated with FT4. The associations in urine were minor (12 of 587). Most of the plasma metabolites consisted of lipid species, and subsequent analysis of highly resolved lipoprotein subclasses measured by proton nuclear magnetic resonance spectroscopy revealed a consistent decrease in several of these species (e.g., phospholipids) and large low-density lipoprotein and small high-density lipoprotein particles. The latter was unique to men. Several polyunsaturated and saturated fatty acids displayed an association with FT4 in women only. A random forest-based variable selection approach using phenotypic characteristics revealed higher alcohol intake in men and an adverse thyroid state and menopause in women as the putative mediating factors. In general, our observations have confirmed the lipolytic and lipogenic effect of thyroid hormones even in the physiological range and revealed different phenotypic characteristics (e.g., lifestyle differences) as possible confounders for sex-specific findings.

Triclosan and triclocarban exposure and thyroid function during pregnancy-A randomized intervention.

Triclosan and triclocarban (TCs) are broad-spectrum microbicides found in household and personal wash products. We sought to determine whether TC exposure from wash products or urinary triclosan level modified thyroid function during pregnancy or anthropometric measurements at birth. A randomized intervention of wash products with or without TCs, including toothpaste, enrolled pregnant women from 20 weeks' gestation. Urinary triclosan, TSH, T4 and T3 were assessed at enrollment, 36weeks' gestation and/or post-delivery; anthropometric measures at birth were ascertained from medical records. 78 and 76 mothers were assigned to the TC-containing and no-TC-containing product arms, respectively. No differences were observed in any thyroid function measure at any time point or in any anthropometric measurement at birth between either exposure arms or lowest and highest urinary triclosan quartile groups. TCs from wash products, primarily liquid and bar soaps, did not affect thyroid function measures during pregnancy or babies' anthropometric measures at delivery.

Correlation between urinary cadmium and thyroid hormones in outdoor workers exposed to urban stressors.

OBJECTIVES: The aim of this study is to evaluate whether exposure to low concentrations of cadmium (Cd) can have effects on the thyroid hormone level of outdoor workers exposed to urban pollutants. METHODS: The study was conducted on a final sample of 277 individuals (184 males and 93 females). The environmental monitoring of Cd was evaluated through the use of portable dosimeters, while the biological monitoring was achieved through the assessment of urinary Cd and thyroid hormones. The total sample was divided according to sex and task. The Pearson's correlation coefficient among the variables was calculated after subdivision on the basis of sex and task. The multiple linear regression was performed to take into account the major confounding factors. RESULTS: Statistical tests showed a negative correlation between urinary Cd levels and free triiodothyronine and free thyroxine and a positive correlation between urinary Cd and thyroid-stimulating hormone levels. CONCLUSIONS: Our early results seem to point out that occupational exposure to low concentrations of Cd present in urban air affects the thyroid hormone levels in exposed workers.

Urinary thyroid hormone parameters test for evaluating the thyroid function during pregnancy.

It is necessary to regularly monitor thyroid function status during pregnancy. The repeated tests on serum thyroid hormones are invasive and can be uncomfortable. Sampling urine may provide an effective alternative. The primary aim of this study was to investigate if there is a correlation between the serum and urine levels of thyroid hormones during pregnancy. The secondary aim was to investigate their variation during pregnancy. This study collected the serum specimens of 30 healthy pregnant women at 9-12, 14-17, 23-26, and 37-40 weeks of gestation, respectively, simultaneously along with random urine specimens. This study compared the median levels of free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) in serum and urine among four gestational stages. The differences were statistically significant (p < 0.05). There were positive correlations between serum FT3 (sFT3) and uFT3/uRBP (the ratio of urine FT3(uFT3) and urine retinol binding protein (uRBP)), r = 0.38 (I(2) = 0%, 95% CI: 0.21 ∼ 0.54), serum FT4 (sFT4) and uFT4/uRBP (the ratio of urine FT4 (uFT4) and uRBP), r = 0.29 (I(2) = 68.9%, 95% CI: 0.07 ∼ 0.51), and no correlation between serum TSH (sTSH) and uTSH/uRBP (the ratio of urine TSH (uTSH) and uRBP), r = 0.11 (I(2) = 86.7%, 95% CI: -0.24 ∼ 0.45). In conclusion, the levels of sFT3, sFT4, uFT3/uRBP, and uFT4/uRBP continued to decrease until the 27th week of gestation, when it was almost invariant. The levels of uFT3/uRBP and uFT4/uRBP correlated well with the sFT3 and sFT4 during pregnancy, which may provide a more convenient and secure way to monitor the maternal thyroid function status during pregnancy.

Age-related changes in thyroid hormone levels of bonobos and chimpanzees indicate heterochrony in development.

We present information on age related changes of thyroid hormone levels in bonobos (N = 96) and chimpanzees (N = 100) ranging between one and 56 years of age. Fresh urine samples were used for hormone measurements with a commercial competitive total triiodothyronine (T3) ELISA. In both species, immature individuals had higher TT3 levels than adults and there was a marked decrease in TT3 levels between age classes. The two species differed in terms of the timing of TT3 level changes, with chimpanzees experiencing a significant decline in TT3 levels after 10 years of age and bonobos after 20 years of age. The decline of TT3 in chimpanzees appears to coincide with the time when somatic growth terminates while TT3 values in bonobos decrease much later. This temporal asymmetry in urinary thyroid hormone levels indicates heterochrony in the ontogenetic changes of the two sister species and developmental delay in bonobos. The prolongation of high TT3 levels in bonobos, which is characteristic of immatures of both Pan species may affect the behavior of bonobos; namely, the low intensity of aggression they display. Given that developmental studies are often based on post-mortem analyses of skeletons, measures of urinary thyroid hormones offer a non-invasive tool for exploring ontogenetic changes in living wild and captive hominoids.

Tyrosine kinase inhibitors noncompetitively inhibit MCT8-mediated iodothyronine transport.

CONTEXT: Tyrosine kinase inhibitors (TKI) are used for the treatment of various cancers. Case reports and clinical trials have reported abnormal thyroid function tests (TFT) after treatment with sunitinib, imatinib, sorafenib, dasatinib, and nilotinib. An increased requirement for levothyroxine was reported in thyroidectomized patients during TKI treatment. OBJECTIVE: We hypothesized that abnormal TFT are compatible with inhibition of thyroid hormone (TH) transporters and subsequently reduced pituitary-TH feedback. Monocarboxylate transporter 8 (MCT8) is a TH transmembrane transporter in brain, pituitary, and other organs. MCT8 mutation leads to abnormal TFT in patients and respective mouse models. We tested whether TKI are able to inhibit MCT8-mediated TH uptake into cells. DESIGN: Madin-Darby-canine kidney (MDCK1) cells stably expressing human MCT8 were exposed in vitro to TKI at increasing concentrations, and MCT8-mediated [(125)I]T(3) uptake and efflux were measured. The mode of inhibition was determined. RESULTS: TKI exposure dose-dependently inhibited MCT8-dependent T(3) and T(4) uptake. IC(50) values for sunitinib, imatinib, dasatinib, and bosutinib ranged from 13-38 µm, i.e. similar to the Michaelis-Menten constant K(m) for T(3) and T(4), 4 and 8 µm, respectively. Kinetic experiments revealed a noncompetitive mode of inhibition for all TKI tested. CONCLUSIONS: Partial inhibition by TKI of pituitary or hypothalamic TH feedback may increase TSH or increase the levothyroxine requirement of thyroidectomized patients. It is still possible that other mechanisms contribute to TKI-mediated impairments of TFT, e.g. altered metabolism of TH. Bosutinib was not previously reported to alter TFT.

Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency: an observational study.

OBJECTIVE: We examined the effect of different conditions of nutritional iodine intake on maternal thyroid function throughout gestation in a cohort of healthy, anti-thyroid antibody-negative women from a mild-moderately iodine-deficient (ID) area. DESIGN: Observational cohort study. PATIENTS: The study included 168 women receiving prenatal preparations containing 150 µg of iodine from early pregnancy (150-I group); 105 women who had regularly used (>2 years) iodized salt prior to becoming pregnant (I-salt group); 160 women neither taking iodine supplements nor using iodized salt (no-I group). MEASUREMENTS: Maternal TSH, FT3 and FT4 were determined throughout gestation. RESULTS: Mean TSH concentrations were higher among the 150-I women than in the remaining two groups, and in a high proportion of them, TSH values were found to exceed the upper limit for gestational age. Conversely, the prevalence of low free-thyroxine levels in the 150-I women was similar to that observed in the I-salt women and markedly lower than that recorded for the no-I group. CONCLUSIONS: The regular use of iodine-containing supplements proved effective in reducing the risk of inappropriately low FT4 levels during pregnancy. The observed TSH increase in 150-I women may be because of a transient stunning effect on the thyroid gland, occurring as a result of the abrupt increase in daily iodine intake. Whilst the importance of gestational iodine supplementation is undisputed, we believe that in mild-moderately ID areas, women considering conception should be advised to take iodine supplementation for several months prior to pregnancy.

Lycopus europaeus (Gypsywort): effects on the thyroidal parameters and symptoms associated with thyroid function.

The aim of the prospective two-armed open study was to examine the effect of Lycopi europaei herba on thyroid function and on associated symptoms during a 3-month follow-up phase. The study population consisted of patients with a basal TSH<1.0 mU/l and hyperthyroidism-associated symptoms. For the first time, the T3/T4 excretion in 24h urine was measured as a primary objective parameter. As secondary parameters, further hormones, the general condition and the symptoms associated with hyperthyroidism were registered. The urinary T4 excretion was significantly increased in Lycopus europaeus-treated patients (p=0.032). It is supposed that renal mechanisms cause the increased T4 excretion either by a modification within the glomeruli or by impaired reabsorption. Symptoms being specific to the thyroid gland were diminished, as e.g. the increased heart rate in the morning. The Lycopus europaeus preparation showed a good tolerance. These findings confirm positive effects of Lycopus europaeus in slight forms of hyperthyroidism.

[Determining the thyroid hormones T3 and T4 in the urine: an unreliable test for hypothyroidism]. / Bepaling van schildklierhormoon (T3 en T4) in de urine: een weinig betrouwbare test voor de diagnose 'hypothyreoïdie'.

A 24-year-old woman complained of tiredness, sensitivity to cold, and feelings of depression. A diagnosis of hypothyroidism based on decreased 24 h urinary T3 and T4 excretion was made, and she was treated with levothyroxin. No blood tests were done. She was referred with the question if she had other endocrine disorders. Her periods were regular, and on physical examination no abnormalities except slight acne were found. Similarly, hypothyroidism was diagnosed by decreased thyroid hormone excretion in 24 h urine, again without blood tests, in a 68-year-old woman whose mother had a goitre, and who had already been prescribed liothyronine. She had no complaints, and physical examination was unremarkable. The thyroid gland was not palpable. Thyroid peroxidase antibodies were absent in both patients. After discontinuation of medication with thyroid hormones they both remained euthyroid. It is concluded that thyroid disease did not exist in those 2 patients. Measurement of 24 h urinary T3 and T4 excretion is not an accurate diagnostic test for hypothyroidism.

Effect of radish (Raphanus sativus Linn.) on thyroid status under conditions of varying iodine intake in rats.

Cruciferous plants viz. cabbage, cauliflower, turnip, radish, mustard etc. that contain goitrogenic/antithyroid substances, constitute a portion of regular human diet. The effect of chronic feeding of fresh and cooked radish, R. sativus under varying state of iodine intake on morphological and functional status of thyroid in albino rats was evaluated by thyroid gland morphology and histology, thyroid peroxidase activity, serum triiodothyronine, thyroxine and thyrotropin levels. The consumption pattern of iodine and goitrogens of cyanogenic origin was evaluated by measuring urinary iodine and thiocyanate levels respectively. After chronic radish feeding, increased weight of thyroid gland, decreased thyroid peroxidase activity, reduced thyroid hormone profiles and elevated level of thyrotropin were observed resembling a relative state of hypoactive thyroid gland in comparison to control even after supplementation of adequate iodine.

The pituitary-thyroid axis in healthy men living under subarctic climatological conditions.

In order to evaluate the effects of climatic factors on the secretion of thyroid hormones and TSH in a high latitude population, we have taken serum and urine samples from 20 healthy men from northern Finland (67 degrees -68 degrees N) every 2 months for a period of 14 months. Serum free triiodothyronine (T(3)) levels were lower in February than in August (3.9 vs 4.4 pmol/l, P<0.05) and TSH levels were higher in December than during other months (2.1 vs 1.5-1.7 mU/l, P<0.01). Serum total and free thyroxine (T(4)), total T(3) and reverse T(3) levels and urinary T(4) levels were unchanged. Urinary T(3) levels were significantly higher in winter than in summer. Serum free T(3) correlated highly significantly with the outdoor temperature integrated backwards weekly for 7-56 days (r=0.26 for 1-56 days) from the day when the blood samples were taken. Serum TSH did not show any significant correlation with the thyroid hormones or with the integrated temperature of the previous days, but it did show an inverse and significant correlation (r=-0.31) with the ambient luminosity integrated backwards for 7 days from the day when the blood sample was taken. The gradually increasing correlation between outdoor temperatures and serum free T(3) suggests that the disposal of thyroid hormones is accelerated in winter, leading to low serum free T(3) levels and a high urinary free T(3) excretion. Since there was no correlation between thyroid hormones and serum TSH, the feedback mechanism between TSH and thyroid hormones may not be the only contributing factor, and other factors such as ambient luminosity may at least partly determine serum TSH in these conditions. Also urinary free T(3) appears to be a novel and non-invasive indicator for thyroid physiology.

Changes in renal tri-iodothyronine and thyroxine handling during fasting.

OBJECTIVE: Liver handling of thyroid hormones (TH) has been known to alter significantly during fasting. This study investigates whether renal handling of TH is also changed during fasting. METHODS: We measured urinary excretion rates and clearances of free tri-iodothyronine (T(3)) and free thyroxine (T(4)) in healthy subjects prior to and on the third day of fasting. RESULTS: During fasting, both mean T(3) and T(4) urinary excretion decreased significantly to a mean value of 42% of control. Also, total and free (F) serum T(3) concentrations declined significantly, but serum T(4) did not change. Both FT(3) and FT(4) clearance decreased significantly during fasting (62% and 42% of control). The fasting-induced decrease in uric acid clearance correlated well with the decrease in FT(3) clearance (r=0.94; P<0.001). Serum concentrations of non-esterified fatty acids (NEFA) were significantly elevated during fasting. CONCLUSIONS: The findings cannot be fully explained by the fasting-induced decrease in serum T(3), and are in accordance with inhibition of uptake of T(3) and T(4) at the basolateral membrane of the tubular cell. This inhibition may be caused by a decreased energy state of the tubular cell and by other factors such as ketoacidosis and/or increased NEFA concentrations during fasting.

Fetal-to-maternal transfer of 3,3',5-triiodothyronine sulfate and its metabolite in sheep.

Earlier studies have shown that sulfoconjugation is a major pathway of thyroid hormone metabolism in fetal mammals. To assess the placental transfer of sulfoconjugates in the pregnant sheep model, we measured 3,3',5-triiodothyronine (T(3)) sulfate (T(3)S), 3, 3'-diiodothyronine sulfate (T(2)S), and T(3) concentrations in fetal serum and in maternal serum and urine after T(3)S infusion to the fetus (n = 5) or the ewe (n = 6). Maternal infusion of T(3)S did not increase fetal serum T(2)S, T(3)S, or T(3) concentrations. In contrast, fetal infusion of T(3)S produced significant increases in maternal serum T(2)S and T(3)S but not T(3) concentrations. Fetal T(3)S infusion also increased maternal urine excretion of T(3)S. However, the 4-h cumulative maternal urinary excretion of T(2)S and T(3)S after fetal T(3)S infusion was less than the excretion observed after fetal infusion of equimolar amounts of T(3) in our previous study. It is concluded that fetal serum T(2)S and T(3)S can be transferred to maternal compartments. However, compared with T(3), these sulfoconjugates may be less readily transferred.

Endocrine relationships during human spaceflight.

Human spaceflight is associated with a chronic loss of protein from muscle. The objective of this study was to determine whether changes in urinary hormone excretion could identify a hormonal role for this loss. Urine samples were collected from the crews of two Life Sciences Space Shuttle missions before and during spaceflight. Data are means +/- SE with the number of subjects in parentheses. The first value is the mean preflight measurement, and the second value is the mean inflight measurement. Adrenocorticotropic hormone (ACTH) [27.7 +/- 4.4 (9) vs. 25.1 +/- 3.4 (9) ng/day], growth hormone [724 +/- 251 (9) vs. 710 +/- 206 (9) ng/day], insulin-like growth factor I [6.81 +/- 0.62 vs. 6.04 +/- 0.51 (8) nM/day], and C-peptide [44.9 +/- 8.3 (9) vs. 50.7 +/- 10.3 (9) micrograms/day] were unchanged with spaceflight. In contrast, free 3,5,3'-triiodothyronine [791 +/- 159 (9) vs. 371 +/- 41 (9) pg/day, P < 0.05], prostaglandin E2 (PGE2) [1, 064 +/- 391 (8) vs. 465 +/- 146 (8) ng/day, P < 0.05], and its metabolite PGE-M [1,015 +/- 98 (9) vs. 678 +/- 105 (9) ng/day, P < 0. 05] were decreased inflight. The urinary excretion of most hormones returned to their preflight levels during the postflight period, with the exception of ACTH [47.5 +/- 10.3 (9) ng/day], PGE2 [1,433 +/- 327 (8) ng/day], PGF2alpha, [2,786 +/- 313 (8) ng/day], and its metabolite PGF-M [4,814 +/- 402 (9) ng/day], which were all increased compared with the preflight measurement (P < 0.05). There was a trend for urinary cortisol to be elevated inflight [55.3 +/- 5. 9 (9) vs. 72.5 +/- 11.1 micrograms/day, P = 0.27] and postflight [82.7 +/- 8.6 (8) micrograms/day, P = 0.13]. The inflight human data support ground-based in vitro work showing that prostaglandins have a major role in modulating the changes in muscle protein content in response to tension or the lack thereof.

Iodine status of New Zealand residents as assessed by urinary iodide excretion and thyroid hormones.

The aims of this study were (1) to compare various measures of I status, and (2) to assess urinary I and thyroid hormone status of residents of two areas of New Zealand where, before the iodization of salt, goitre was endemic due to low soil I. A total of 189 subjects (102 males, eighty-seven females) were recruited from the Dunedin Blood Transfusion Centre, and 144 (sixty-seven males, seventy-seven females) from the Waikato Blood Transfusion Centre between November 1993 and June 1994. Blood was taken for thyroid hormone assays, and subjects collected a fasting overnight urine specimen, a double-voided fasting urine sample, and a complete 24 h specimen for iodide and creatinine analyses. Positive correlations (P < 0.0001) between daily iodide excretion and iodide concentrations in fasting and double-voided fasting urines, identical median values for iodide concentrations in the three samples, and similar numbers of subjects classified as at risk from I deficiency disorders according to the International Committee for the Control of Iodine Deficiency Disorders/World Health Organization categories (World Health Organization, 1994) confirmed indications from earlier studies that fasting urine samples were suitable for population studies. However 24 h urinary iodide excretion remains the recommended measure for individual I status. Waikato residents excreted more iodide in urine and all measures were significantly greater than for Otago residents. However median urinary iodide excretions for both areas (60 and 76 microgram/d for Otago and Waikato respectively) were considerably lower than those reported previously for New Zealand. Thyroid hormone concentrations were within normal ranges. Our findings suggest that I status of New Zealanders may no longer be considered adequate and may once again be approaching levels of intake associated with clinical I deficiency.

Thyroid function in children with nephrotic syndrome.

The thyroid function of seven children with untreated nephrotic syndrome who had a normal serum creatinine concentration was compared with that of the same patients in remission and age-matched controls. There was a significant decrease in serum thyroxine (T4), tri-iodothyronine (T3) and thyroid-binding globulin (TBG) concentrations in untreated nephrotic children compared with the same patients in remission and age-matched controls. Most values for serum free T4, free T3 and thyroid-stimulating hormone (TSH) in the patients with nephrosis were within the normal range. However, the mean serum free T4 and free T3 concentrations were significantly (P < 0.05) lower in the untreated patients than in the same patients in remission, and the mean serum TSH concentrations were significantly (P < 0.05) higher in the untreated patients than in the same patients in remission. There were massive urinary losses of T4, T3, TBG, free T4 and free T3 in the untreated nephrotic children compared with the same patients in remission and age-matched controls. The daily urinary protein excretion showed a positive correlation with the urinary T4, T3, free T4, free T3 and TBG excretion. Furthermore, the urinary protein excretion showed a negative correlation with the serum T4, T3, free T4, free T3 and TBG levels. There was a negative correlation between serum albumin and serum TSH. These findings provide evidence of mild hypothyroidism in children with untreated nephrotic syndrome, partly because of losses of T4, T3, free T4, free T3 and TBG into the urine.

Urinary excretion of thyroid hormones in rainbow trout, Oncorhynchus mykiss.

Urinary excretion of the thyroid hormones (TH) L-thyroxine (T4), and 3,5,3'-triiodo-L-thyronine (T3) and their derivatives was studied in urinary-catheterized rainbow trout (mean wt. 227 g) fasted for 2 days under a 12-hr L:12-hr D photocycle in running water (12 degrees). Catheterized trout were intracardiac-injected with [125I]T4 (*T4) or [125I]T3 (*T3) and urine was collected as 2-hr fractions over 48 hr. The 125I corresponding to I-, TH conjugates (sulfates and glucuronides), or TH was separated by LH-20 column chromatography and HPLC. Urine production (daily mean, 72.5 ml/kg/day) was lowest during the scotophase and doubled at the start of photophase, causing acute fluctuations in excretion of 125I-labeled materials, and implying dependence on glomerular filtration rate. During the first 48 hr, 8.2% of *T4 (I-, 3.6%: TH conjugates, 1.7%; TH, 2.9%) and 6.7% of injected *T3 (I-, 1.8%; TH conjugates, 2.5%; TH, 2.4%) was excreted in urine; 32.6% (*T4) and 26.4% (*T3) was in the gall bladder; 45.5% (*T4) and 45.7% (*T3) were in the remaining carcass; and 13.7% (*T4) and 23.7% (*T3) were lost via other routes. We extrapolate that about 15% of *T4-injected and 12% of *T3-injected total radioactivity would be excreted ultimately in urine, with 8.4% (*T4) and 9.0% (*T3) as TH or their conjugates. Neither a T4 nor a T3 challenge (20 ng/g) influenced the amount of radioactive loss in urine over 48 hr. We conclude that the urine is a significant route for excretion of TH and their conjugates, and that urinary TH loss depends to a large extent on the rate of urine production.