Serum T4 Concentrations Research Articles

The effects of maternal supplementation of selenium and iodine via slow-release blouses in late pregnancy on milk production of goats and performance of their kids

Forty pregnant dairy goats were used in a 2 × 2 factorial arrangement of treatments to evaluate the effects of prepartum supplementation of selenium (Se) and iodine (I) as slow-release boluses. The boluses were administered four weeks prior to the expected kidding time to supply daily amounts of (1) 0 mg Se and 0 mg I, (2) 0 mg Se and 0.40 mg I, (3) 0.25 mg Se and 0 mg I and (4) 0.25 mg Se and 0.4 mg I. Milk production, milk fat percentage, daily production of milk components, milk selenium and iodine concentrations were greater in goats received 0.25 mg Se/day than no supplemental Se (p < .05). Milk production, daily production of milk compounds, milk iodine concentration, serum T3 and T4 concentrations in goats received 0.40 mg I/day were greater than goats received no supplemental I (p < .05). Bodyweight at weaning and average daily gain in kids whose mothers were received 0.25 mg Se/day were greater than zero Se (p < .05). Bodyweight at weaning and average daily gain in kids whose mothers were given 0.40 mg I/day were greater than zero I (p < .05). Serum Se and T3 concentration and whole blood glutathione peroxidase activity were significantly greater in goats and their kids received 0.25 mg Se/day than goats received no supplemental Se (p < .05). There was no Se level × I level interaction for all assessed parameters. Results showed that maternal supplementation of Se and I as a slow-release ruminal bolus in late pregnancy improved milk production of grazing goats and the performance of their kids. Highlights Intra-ruminal administration of slow-release boluses containing selenium and iodine improved milk production of grazing goats. Kids from goats receiving supplemental selenium and iodine via intra-ruminal boluses perform better. Intra-ruminal administration of slow-release boluses containing selenium in late pregnancy improved the antioxidant status of grazing goats and their kids.

OR01-05 Long-Term Efficacy of T3 Analogue Triac in MCT8 Deficiency

Background: MCT8 deficiency is a severe disorder caused by mutations in the thyroid hormone transporter MCT8. MCT8 deficiency is characterized by severe intellectual and motor disability and high serum T3 concentrations that result in thyrotoxic symptoms in peripheral tissues. This predisposes to substantial morbidity and mortality. Preclinical studies showed that the T3 analogue Triac can bypass defective MCT8 at the cellular level. Recently, we reported the results of an international multicenter trial, in which biochemical and clinical outcomes improved in patients with MCT8 deficiency who were treated with Triac for 12 months (1). However, long-term follow-up data of patients with MCT8 deficiency treated with Triac are lacking, particularly in young children. Therefore, we aimed to investigate the long-term efficacy of Triac therapy in a worldwide cohort of patients with MCT8 deficiency. Methods: We investigated the efficacy of oral Triac treatment in pediatric (n=78) and adult (n=5) patients with MCT8 deficiency in 20 countries. Triac dose was titrated according a predefined dose-escalation scheme aiming to normalize serum T3 concentrations (target 1.4-2.5 nmol/L). Thyroid function tests and biochemical markers of thyroid hormone action in peripheral tissues (SHBG, creatine kinase, creatinine) were measured at baseline and during control visits. Findings: In total, 83 patients with a median baseline age of 5 years (range 6 months – 66 years) were treated, including 24 patients aged 0-2.5 years and 17 patients aged 2.5-5 years. They were treated with Triac during 144 patient years, of whom the follow-up time was >5 years in 9 patients and 2-5 years in 22 patients. Mean dose was 45 µg/kg/day (range 11-107 µg/kg/day). Once a stable dose was achieved, no further dose adjustments were needed.Mean serum T3 concentrations decreased from 5.02 to 1.94 nmol/L (normal 1.4 – 2.5 nmol/L). SHBG concentrations improved from 238 to 204 nmol/L (normal 40-140 nmol/L). Mean creatine kinase and creatinine concentrations improved from 113 to 140 U/L (normal <230 U/L) and from 32 to 38 µmol/L (normal 31-68 μmol/L), respectively. No drug-related severe adverse events were reported. Interpretation: Triac is a safe treatment that results in sustainable improvements of the severe thyrotoxic state in pediatric and adult patients with MCT8 deficiency.

SAT-LB86 Improvement In Metabolic Indices Including Thyroid HormonesVia Enhanced Absorption Of Nutrients By Teduglutide In Short Bowel Syndrome

Background: Short bowel syndrome is characterized by maldigestion and malabsrption resulting in deficiencies of multiple nutrients including vitamins and minerals. Most subjects required parental elimination for survival. GLP 2 RA Teduglutide was recently approved for treatment of short-bowel syndrome especially for those requiring parenteral support. Objective: To demonstrate the utility of GLP2 Receptor Agonist Teduglutide in improvising multiple metabolic indices In presence of short bowel syndrome. Case presentation: 66-year-old Caucasian female presented with a history of short bowel syndrome and associated vitamin deficiencies, hypothyroidism requiring large dose of levothyroxine, diarrhea, and liver cirrhosis. Upon starting teduglutide the subject saw improvement in her symptoms. Moreover, daily dose of levothyroxine required reductions from 300 mcg to 150 mcg to maintain desirable serum concentrations of free T4, free T3 and TSH. Finally, serum levels of several vitamins attained greater than therapeutic concentrations requiring dosage reductions. Also notable was the improvement in her liver function tests, remission from ascites and regeneration of liver nodules. Conclusion: Herein, we report an adult subject with short bowel syndrome with concurrent hypothyroidism and multiple vitamin deficiencies who following administration of GLP2 RA therapy demonstrated a marked improvement in her metabolic parameters with some requiring reduction in daily dose along with improvement in manifestations of liver cirrhosis.

MON-081 Mathematical Modeling of Residual Endogenous FT4 Synthesis and Exogenous L-Thyroxine Administration over the First 2 Years of Life in Infants with Congenital Hypothyroidism

L-Thyroxine (L-T4) is the treatment of choice of congenital hypothyroidism (CH). Longitudinal measurements of free T4 (FT4) serum concentrations were collected over the first two years of life with oral L-T4 treatment in infants with CH. Purpose of this study was to develop an integrated mathematical model to characterize the kinetics of exogenous L-Thyroxine (L-T4) after multiple dosing in infants with CH, and the dynamics of residual endogenous FT4 synthesis under treatment in the context of severe, moderate and mild disease.A total of 200 FT4 concentrations from 30 patients were available for analysis. At start of treatment, mean (standard deviation [SD]) postnatal age and weight of the population were 11 (8) days and 3.9 (1.3) kg. Mean (SD) pretreatment FT4 concentration was 11.3 (7.4) pmol/L. Measured FT4 concentrations were modelled as sum of residual endogenous FT4 and exogenously administered FT4 (L-T4). The integrated mathematical model consists of an absorption compartment for the exogenous FT4 administration, and a central compartment for measured FT4 with linear elimination. Hence, for residual endogenous and exogenous FT4 the same elimination rate constant was assumed. For the residual endogenous synthesis, different approaches were tested: a constant production and typical time-dependent production functions. FT4 data were analyzed using nonlinear mixed-effects modeling.The integrated mathematical model with a time-dependent non-linear Emax function describing a decreasing residual endogenous FT4 synthesis for increasing time provided the best data fit in terms of Akaike value and various goodness-of-fit plots. This is in line with the expected progressive suppression of the thyroid stimulating hormone by the exogenous FT4, and the subsequent decrease of residual FT4 endogenous synthesis. The developed mathematical model allows simulation of FT4 pharmacokinetic profiles for different disease severities and different dosing regimens.

Abdominal Obesity Phenotypes and Incidence of Thyroid Autoimmunity: A 9-Year Follow-up

ABSTRACT Purpose The association between obesity and autoimmune diseases has been suggested by several previous studies. The objective of our study was to assess the association of abdominal obesity phenotypes with thyroid autoimmunity. Materials and methods This study was conducted within the framework of a population-based cohort study, Tehran Thyroid Study (TTS) on 4708 subjects without thyroid autoimmunity at baseline. Participants were categorized into four abdominal obesity phenotypes according to waist circumference (WC) and other metabolic syndrome components. Serum concentrations of thyroid peroxidase antibody (TPOAb), free T4 (FT4), thyrotropin (TSH), glucose, and lipid profiles were measured after 3, 6 and 9 years of follow-up. Cox proportional hazard models were used to evaluate associations of different phenotypes with the incidence of thyroid autoimmunity, adjusted for age, sex, FT4, and TSH. Results Highest and lowest incidence rates of TPOAb positivity were observed among metabolically unhealthy, non-abdominally obese (MUNAO) [8.78 (7.31–10.55) per 1000 person-years of follow-up] and metabolically unhealthy abdominally obese (MUAO) [4.98 (3.88–6.41) per 1000 person-years of follow-up] phenotypes. Considering the metabolically healthy non-abdominal obese (MHNAO) individuals as reference, none of metabolically healthy abdominally obese (MHAO), MUNAO, and MUAO phenotypes were associated with increased risk of developing TPOAb positivity. Compared to individuals with high WC, the incidence rate (95%CI) of TPOAb positivity was higher among those with normal WC: 8.44 (7.13–10.0) vs 5.11 (4.01–6.51) per 1000 person-years, respectively. Higher WC was not associated with incident TPOAb positivity. Conclusion There was no significant association between baseline abdominal obesity phenotype status and development of TPOAb positivity over 9 years of follow-up.

LT4 and Slow Release T3 Combination: Optimum Therapy for Hypothyroidism?

ContextLevothyroxine (LT4) is recommended as replacement therapy for thyroid hormone deficiency. However, some hypothyroid patients receiving LT4 therapy do not feel as well as healthy subjects. This article aimed to review current knowledge regarding LT4 monotherapy versus LT4+LT3 combination therapy and propose future directions regarding LT4+slow release T3 combination treatment for hypothyroidism.Evidence AcquisitionWe searched PubMed and Scopus using related keywords.ResultsThe LT4 monotherapy causes higher serum free T4 (fT4), subnormal serum free T3 (fT3), and fT3/fT4 ratio in one-fourth of patients. The LT4+LT3 combination therapy increases serum T3 and fT3 concentrations and may normalize the fT3/fT4 ratio. However, the primary outcomes, including thyroid hormone deficiency, anxiety, depression, and quality of life, may not be better in LT4+LT3 combination therapy than in LT4 monotherapy. Recent surveys show that combination therapy is on the rise, in particular, due to patient demand. The LT4 plus slow-release LT3 preparation has shown promising results in improving serum thyroid hormone concentrations.ConclusionsThe beneficial effect of LT4+LT3 combination therapy is not clear, and the safety of long-term therapy is yet under question. More scientific well-designed research projects are required in this field.

Effect of cyclic heat stress on thyroidal hormones, thyroid histology, and performance of two broiler strains.

This study determined thyroid hormone (T3 and T4) serum levels and investigated thyroid gland histology, as well as two broiler strains performance kept at different periods of heat stress. Broilers (560 Cobb Slow™ and 560 Hubbard Flex™) were distributed in control environment (0) reared following the thermal recommendations, and environments 1, 2, and 3 exposed to high temperatures for 1h, 2h, and 3h a day, respectively, from 14 to 42days old. At 21, 28, 35, and 42days old, blood samples were collected to determine T3 and T4 serum levels. At 42days old, thyroid glands were removed for histological analyses. The performance was calculated weekly. T3 levels decreased with age advance, while T4 serum concentration was higher at 42days old (23.27nmolL-1) and lower at 28days old (15.69nmolL-1). The histological sections revealed that thyroid morphology was well preserved. Live weight was higher in Cobb Slow™ (2.97kg) than Hubbard Flex™ (2.93kg) broilers at 42days old. It is possible to conclude that cyclic heat stress exposure for a 3-h period from 14 to 42days old did not affect performance, thyroid histology, or T3 and T4 serum levels. Cobb Slow™ broilers had the best live weight values at slaughtering. With increasing age, T3 levels decreased and T4 levels increased for both strains.

Differential effects of leptin administration on feeding and HPT axis function in early-life overfed adult rats

Early-life overfeeding (OF) disrupts neuroendocrine systems, energy homeostasis and food intake regulation inducing overeating and overweight in adults. Adult rats raised in small litters during lactation, display hyperphagia and overweight since weaning and exhibit a decrease in thyrotropin-releasing hormone (TRH) mRNA expression in hypothalamic paraventricular nucleus (PVN). This is counterintuitive because TRH expression should increase to activate the hypothalamic-pituitary-thyroid (HPT) axis and promote energy expenditure, thus, HPT axis seems inhibited in OF rats. Leptin, an adipocyte-synthesized hormone that stimulates hypothalamic TRH expression, enhances both TRH anorectic effects and HPT axis-induced metabolic rate. To evaluate hypothalamic resistance to the anorectic and HPT axis stimulatory actions of leptin, we injected leptin i.p. to ad libitum fed and to 48-h fasted adult control (reared in normal litters) and to small-litter reared (OF) male Wistar rats. Findings showed that HPT axis was still responsive to leptin, since PVN TRH mRNA levels, median eminence TRH release and T4 serum concentration increased in both, ad libitum and fasted OF rats after leptin administrations. Leptin was ineffective to reduce feeding of OF animals. By comparing leptin receptor (ObRb) expression changes between arcuate and PVN nuclei, we observed that arcuate ObRb was not modified in response to leptin administrations in OF rats, likely accounting for the differential effects in feeding and HPT axis function. Nevertheless, ObRb expression was modified by leptin in the PVN of OF rats to the same extent as controls; this supports the hormone’s role as a therapeutic agent for early onset obesity in adults.

Progressive hearing loss in the α-galactosidase A deficient rat model of Fabry disease

Early-life overfeeding (OF) disrupts neuroendocrine systems, energy homeostasis and food intake regulation inducing overeating and overweight in adults. Adult rats raised in small litters during lactation, display hyperphagia and overweight since weaning and exhibit a decrease in thyrotropin-releasing hormone (TRH) mRNA expression in hypothalamic paraventricular nucleus (PVN). This is counterintuitive because TRH expression should increase to activate the hypothalamic-pituitary-thyroid (HPT) axis and promote energy expenditure, thus, HPT axis seems inhibited in OF rats. Leptin, an adipocyte-synthesized hormone that stimulates hypothalamic TRH expression, enhances both TRH anorectic effects and HPT axis-induced metabolic rate. To evaluate hypothalamic resistance to the anorectic and HPT axis stimulatory actions of leptin, we injected leptin i.p. to ad libitum fed and to 48-h fasted adult control (reared in normal litters) and to small-litter reared (OF) male Wistar rats. Findings showed that HPT axis was still responsive to leptin, since PVN TRH mRNA levels, median eminence TRH release and T4 serum concentration increased in both, ad libitum and fasted OF rats after leptin administrations. Leptin was ineffective to reduce feeding of OF animals. By comparing leptin receptor (ObRb) expression changes between arcuate and PVN nuclei, we observed that arcuate ObRb was not modified in response to leptin administrations in OF rats, likely accounting for the differential effects in feeding and HPT axis function. Nevertheless, ObRb expression was modified by leptin in the PVN of OF rats to the same extent as controls; this supports the hormone’s role as a therapeutic agent for early onset obesity in adults.

Lack of the Thyroid Hormone Transporter Mct8 in Osteoblast and Osteoclast Progenitors Increases Trabecular Bone in Male Mice

Background: Bone is an important target of thyroid hormones (THs), which require transport into target cells to exert their actions. Recently, the TH-specific monocarboxylate transporter 8 (Mct8) was reported as a regulator of bone mass in male mice. However, its global deletion leads to high 3,3',5-L-triiodothyronine (T3) serum concentrations that may mask direct effects of Mct8-deficiency on bone. In this study, we assessed the bone cell intrinsic function of Mct8 ex vivo and in vivo using conditional Mct8-knockout lines specifically targeting osteoclast and osteoblast progenitors, as well as mature osteoblasts and osteocytes. Materials and Methods: Twelve-week-old male mice with a global Mct8-deficiency or a conditional Mct8-knockout in osteoclast precursors, osteoprogenitors, or mature osteoblasts/osteocytes were analyzed regarding their bone microarchitecture, turnover, and strength. Furthermore, ex vivo studies were conducted to investigate the role of Mct8 in bone cell differentiation and functionality, as well as TH uptake. Results: Global Mct8-knockout mice demonstrated 1.7-fold higher T3 serum concentrations and trabecular bone loss (-28%) likely due to an increased bone turnover as shown by increased osteoblast (+45%) and osteoclast numbers (+41%). However, cortical bone mineral density was increased. Ex vivo cultures of bone marrow-derived osteoblasts and osteoclasts revealed highest expression of Mct8 in mature bone cells. In addition, Mct8-deficiency resulted in a lower mRNA expression of osteoblast and osteoclast differentiation markers, as well as a reduced mineralization capacity and osteoclast numbers, respectively, indicating a bone cell intrinsic role of Mct8. In fact, conditional Mct8-knockout and inhibition of Mct8 in osteoblasts led to an attenuated T3 uptake ex vivo. In vivo, osteoprogenitor-specific Mct8-knockout enhanced trabecular bone volume (+16%) with osteoblast numbers being increased 3.7 fold. Interestingly, Mct8-deficiency in osteoprogenitors and late osteoblasts/osteocytes both resulted in cortical bone loss. Finally, Mct8-deletion in osteoclast progenitors increased trabecular bone volume (+20%) due to reduced osteoclast numbers (-32%), whereas osteoblast numbers were enhanced (+25%). Conclusions: This study confirms that high systemic T3 in global Mct8-knockout mice masks the direct effect of Mct8. Moreover, it identifies Mct8 as a critical regulator of trabecular vs. cortical bone by regulating T3 uptake and highlights its cell intrinsic role in osteoclast and osteoblast progenitors.

Surgical removal of a thyroglossal duct cyst in a geriatric dog

A 12-year-old, body condition score (BCS) 9, female, Poodle mix dog was presented for coughing, gasping sounds and exercise intolerance. The symptoms started 2 months prior to the presentation. Clinical...

Sexually dimorphic dynamics of thyroid axis activity during fasting in rats.

Starvation induces tertiary hypothyroidism in adult rodents. Response of the hypothalamus-pituitary-thyroid (HPT) axis to starvation is stronger in adult males than in females. To improve the description of this sexual dimorphism, we analyzed the dynamics of HPT axis response to fasting at multiple levels. In adult rats of the same cohort, 24 and 48 h of starvation inhibited paraventricular nucleus Trh expression and serum concentrations of TSH and T4 earlier in males than in females, with lower intensity in females than in males. In adult females fasted for 36-72 h, serum TSH concentration decreased after 36 h, when the activity of thyrotropin-releasing hormone (TRH)-degrading ectoenzyme was increased in the median eminence. The kinetics of these events were distinct from those previously observed in male rats. We suggest that the sex difference in TSH secretion kinetics is driven not only at the level of paraventricular nucleus TRH neurons, but also by differences in post-secretory catabolism of TRH, with enhancement of TRH-degrading activity more sustained in male than female animals.

Demonstration of reciprocal diurnal variation in human serum T3 and rT3 concentration demonstrated by mass spectrometric analysis and establishment of thyroid hormone reference intervals.

Background:There has been a wide range of reference intervals proposed in previous literature for thyroid hormones due to large between-assay variability of immunoassays, as well as lack of correction for collection time. We provided the diurnal reference intervals for five thyroid hormones, namely total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), and reverse T3 (rT3), measured in serum samples of healthy participants using a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method.Methods:Couplet serum samples (a.m. and p.m.) were collected from 110 healthy females and 49 healthy males. Healthy volunteers were recruited from four participating centers between 2016 and 2018. Measurements of thyroid hormones were obtained by LC-MS/MS analysis.Results:Our study revealed significant uptrend in AM to PM FT4 (p < 0.0001) samples, downtrend in AM to PM TT3 (p = 0.0004) and FT3 samples (p < 0.0001), and AM to PM uptrend in rT3 samples (p < 0.0001). No difference was observed for TT4 between AM and PM. No significant sex differences were seen for any of the five thyroid hormones.Conclusion:When diagnosing thyroid disorders, it is important to have accurate measurement of thyroid hormones, and to acknowledge the diurnal fluctuation found, especially for FT3. Our study highlights the importance of standardization of collection times and implementation of LC-MS/MS in thyroid hormone measurement.

SERUM CONCENTRATION OF THYROID HORMONES AND THYROID STIMULATING HORMONE IN ALLOXAN-INDUCED TYPE 1 DIABETIC WISTAR ALBINO RATS

Background: Literature has reported thyroid functional abnormalities in diabetes mellitus. The objectives of this study were to determine and compare the serum concentrations of T3, T4 and TSH in alloxan-induced type 1 diabetic and control Wistar albino rats. Materials &amp; Methods: It was an experimental animal study on 20 Wistar albino rats, extending over a period of eight weeks. Alloxan, a diabetogenic agent, was used to produce animal models of type 1 diabetes. Animals were divided equally into two groups: control and diabetic. The animals in the diabetic group were injected intraperitoneally with 150 mg/kg body weight of 10% alloxan to induce diabetes. After 72 hours, diabetes was confirmed with glucometer (glucose &gt;350mg/dl). During the course of experiment, one rat in control group and 2 rats in diabetic group died. Blood was collected for estimation of serum concentrations of thyroid hormones, thyroid stimulating hormone at the end of experimental period. Serum T3, T4, and TSH were measured using ELISA kits. Results: At the end of eight weeks, the mean concentration of serum T3 was 0.69 ±0.29 ng/ml and 0.44±0.02 ng/ml in control and diabetic groups, respectively. The mean concentration of T4 was 3.78±1.16 μg/dl and 2.24±0.86 μg/dl in control and diabetic groups respectively. The mean concentration of TSH was 0.77±0.20 μU/ml and 1.41±0.23 μU/ml in control and diabetic groups respectively. The mean serum concentrations of T3 (p=.0025) and T4 (p=&lt;.00001) were significantly lower in diabetic and that of TSH (p=&lt;.00001) were significantly higher in diabetic than control group. Conclusion: This study concludes that the serum concentrations of both T3 and T4 are significantly lower and that of TSH is significantly higher in alloxan-induced type 1 diabetic as compared to control group in Wistar albino rats.

Effects of dietary supplementation of chitosan on immune function in growing Huoyan geese

This present experiment was performed to investigate the effects of dietary supplementation of chitosan (CS) on immune function in growing Huoyan geese. A total of 320 28-day-old healthy growing Huoyan geese (sex balance) with similar body weight were randomly allotted into control, CS100, CS200, and CS400 groups. Each group includes 4 replicates with 20 geese per replicate, and the feeding trial lasted for 4 wk. The 4 diets contained 0, 100, 200, and 400 mg CS per kg feed, respectively. The results showed that compared with the control group, the relative weight of thymus, serum concentrations of IGF-I, INS, GH, T3, T4, IgM, IgG, IgA, complement C3, and IL-2 in CS200 group were significantly higher at both 42 and 56 D of age, respectively (P < 0.05). In addition, relative weight of bursa of fabricius (BF), spleen, serum complement C4, and TNF-a concentrations in CS200 group were higher at 56 D of age (P < 0.05), no differences were observed at 42 D of age (P > 0.05). These results indicated that addition of 200 mg/kg CS enhanced immune organs weight, serum concentrations of immunoglobulins, complements, hormone, as well as cytokines, and improved immune function of growing Huoyan geese.

Reducing Inappropriate Serum T3 Laboratory Test Ordering in Patients with Treated Hypothyroidism

Objective: Choosing Wisely is a campaign of the American Board of Internal Medicine that aims to promote evidence-based practices to reduce unnecessary ordering of tests or procedures. As part of this campaign, the Endocrine Society advises against ordering a serum total or free triiodothyronine (T3) level when assessing levothyroxine dosing in hypothyroid patients. This study was performed to assess and reduce inappropriate laboratory ordering practices among providers who manage patients with hypothyroidism within a large U.S. academic health system. Methods: A best practice alert (BPA) in the health record was developed and implemented following the collection of baseline data. This alert consisted of a popup window that was triggered when a serum T3 laboratory test was ordered for patients prescribed levothyroxine. The alert required user acknowledgement before the serum T3 laboratory test could be ordered. Results: During the 6-week period prior to launching the BPA, serum T3 tests were ordered a mean of 162.3 ± 15.4 (standard deviation) occurrences per 10,000 patients per week. Over a 15-week period following implementation of the BPA, the frequency of serum T3 orders steadily decreased and resulted in >44% fewer inappropriate tests being ordered. Conclusion: Although national societal guidelines recommend against ordering serum T3 concentrations while monitoring patients with hypothyroidism managed with levothyroxine, these laboratory tests are frequently ordered. Development of a triggered alert in the health record may reduce inappropriate monitoring practices, decrease costs, and improve utilization of limited health-care resources for this common clinical condition. Abbreviations: ATA = American Thyroid Association; BPA = best practice alert; T3 = triiodothyronine; TSH = thyroid-stimulating hormone.

Physician Perception and Patient Input Are Important Influences in the Treatment of Hypothyroidism

Physician Perception and Patient Input Are Important Influences in the Treatment of Hypothyroidism

Treatment of Hypothyroid Patients With L-Thyroxine (L-T4) Plus Triiodothyronine Sulfate (T3S). A Phase II, Open-Label, Single Center, Parallel Groups Study on Therapeutic Efficacy and Tolerability.

Sodium salt of levothyroxine (L-T4) is the treatment of choice of hypothyroidism. Yet, L-T4 monotherapy produces supoptimal 3,5,3′-triiodothyronine (T3)/T4 ratio in serum, as compared to normal subjects, and a minority of hypothyroid individuals on L-T4 complain for an incomplete well-being. Orally administered 3,5,3′-triiodothyronine sulfate (T3S) can be converted to T3 in humans, resulting in steady-state serum T3 concentrations for up to 48 h. In this study (EudraCT number 2010-018663-42), 36 thyroidectomized hypothyroid patients receiving 100 (group A), 125 (group B), or 150 μg (group C) L-T4 were enrolled in a 75 days study in which 25 μg L-T4 were replaced by 40 μg of T3S. A significant, progressive reduction in mean FT4 values was observed, being the largest in the group A and the smallest in group C, while no relevant variations in FT3 and total T3 serum values were observed in the three groups. TSH serum levels increased in all groups, the highest value being observed in group A. Lipid parameters did not show clinically significant changes in all groups. No T3S-related changes in the safety laboratory tests were recorded. No adverse event was judged as related to experimental treatment, and no patient discontinued the treatment. Twelve patients judged the L-T4+T3S treatment better than L-T4 alone, while no patient reported a preference for L-T4 over the combined treatment.In conclusion, the results of this study indicate that a combination of L-T4+T3S in hypothyroid subjects may allow mainteinance of normal levels of serum T3, with restoration of a physiological FT4/FT3 ratio and no appearance of adverse events. Further studies are required to verify whether the LT4+T3S chronic combined treatment of hypothyroidism is able to produce additional benefits over L-T4 monotherapy.

Levothyroxine supplementation in hypothyroid bitches during pregnancy

Hypothyroidism is the most common endocrine disease in dogs and has been shown to have a hereditary nature in many breeds. Previous studies have documented decreased fertility in bitches with experimentally-induced hypothyroidism, decreased viability at birth, increased periparturient mortality, and reduced birth weight in pups born to hypothyroid dogs. Hypothyroid women have an increased demand for exogenous thyroxine throughout gestation in order to maintain normal plasma concentrations of thyroid hormones and produce neuropsychologically normal children. This study was performed to determine if pregnancy causes a similar need for increased levothyroxine dosages in dogs to maintain a euthyroid state. Serum was harvested from blood collected from six bitches with experimentally-induced hypothyroidism that were receiving standard thyroid hormone replacement therapy and from four euthyroid control bitches. Thyroid function tests performed on these samples included total thyroxine (T4), free T4 (fT4), thyroid stimulating hormone (TSH), and 3,5,3′-triiodothyronine (T3). Thyroid function tests were measured from ovulation through the end of pregnancy. All bitches whelped normal litters. Euthyroid bitches had no significant alterations in their hormone concentrations throughout pregnancy. None of the supplemented hypothyroid bitches had clinical signs of hypothyroidism throughout the study. Serum concentrations of T4 and fT4 were elevated compared to ovulation at multiple sample points during gestation in supplemented dogs. The results from this study indicate that standard levothyroxine supplementation is adequate to maintain a euthyroid state during pregnancy in experimentally-induced hypothyroid dogs. In addition, there is no evidence that canine thyroid profiles in euthyroid dogs are altered during gestation.

Pharmacokinetics of L-Triiodothyronine in Patients Undergoing Thyroid Hormone Therapy Withdrawal

Background: L-triiodothyronine (LT3) is a substitute for levothyroxine (LT4) for thyroid cancer (TC) patients during the preparation for nuclear medicine procedures, and it is used in combination with LT4 in patients who do not respond to the standard treatment for hypothyroidism. This therapy is commonly done by using fixed doses, potentially resulting in supraphysiologic levels of triiodothyronine (T3). A good understanding of the LT3 pharmacokinetics (PK) is necessary to design combination treatment schemes that are able to maintain serum T3 levels within the reference range, but data on the PK of LT3 are conflicting. Here, we present a study designed to characterize the PK of LT3 in patients devoid of endogenous thyroid hormone production, and not receiving LT4 therapy. Methods: We performed an open-label, PK study in patients undergoing thyroid hormone withdrawal in preparation for nuclear medicine procedures for the evaluation and treatment of follicular-derived TC. LT3 was substituted for LT4 at a 1:3 mcg/mcg dosage ratio thrice daily for at least 30 days. PK of the last LT3 dose while at steady state and terminal elimination was assessed over 11 days. Thereafter, a PK study was performed following the nuclear medicine procedure in patients who volunteered for a second study. Results: Fourteen patients age 48.5 ± 16.0 years completed the last dose study and five completed the second PK study. PK analysis indicates a time to maximum serum concentration of 1.8 ± 0.32 hours and two distinct phases of linear elimination, with a fast distribution phase and slow elimination phases with half-lives of 2.3 ± 0.11 hours and 22.9 ± 7.7 hours, supporting a two-compartment model. PK modeling predicts that a twice-daily administration of low-dose LT3 (0.07 mcg/kg twice daily) in combination with LT4 can predictably increase the serum T3 concentration without significant peaks above the reference range. Conclusions: The PK of LT3 is well described by a two-compartment model that assumes elimination only from the sampling compartment, with a rapid distribution phase and a slow elimination phase. This information will contribute to design therapeutic strategies for LT3/LT4 combination therapies directed to maintain stable T3 serum levels.