Serum Total T4 Research Articles

SAT-724 Endocrine Disruption by Phthalate Exposure in the Pediatric Intensive Care Unit

Aim: Pediatric intensive care relies on plastic indwelling medical devices softened by phthalates. Phthalates leach into the circulation and concerns about toxicity were raised. Exceeding a certain threshold of di(2-ethylhexyl)phthalate (DEHP) exposure in the pediatric intensive care unit (PICU) has been associated with an attention deficit 4 years later (1). Moreover, DEHP and its metabolites have endocrine disrupting properties. Critically ill children reveal the non-thyroidal illness syndrome (2) and unexplained relatively low cortisol (3). Whether DEHP exposure in PICU has endocrine disruptive effects is unknown. We investigated whether DEHP exposure in the PICU, exceeding the previously identified “toxic” threshold for attention, is independently associated with thyroid- and HPA-axis alterations upon PICU discharge. Methods: In this preplanned secondary analysis of the PEPaNIC RCT (N=1440) (4), plasma DEHP metabolite concentrations (MEHP, 5OH-MEHP, 5cx-MEPP, 5oxo-MEHP) were quantified for all patients with a last PICU day sample (N=920). Minimal DEHP exposure was defined as the product of the total DEHP metabolite concentrations on the last PICU day and duration of PICU stay, with 0.551 µmol/L.days identified as “toxic” threshold (1). Serum TSH, total T4, total T3 and rT3 concentrations were quantified for patients with an available last day sample (N=913). For patients with a last day plasma sample and who did not receive corticosteroids (N=391), plasma ACTH, total cortisol, albumin and CBG concentrations were quantified and free cortisol calculated. Multivariable linear regression analyses, adjusted for baseline risk factors and for duration of PICU stay, assessed whether exceeding the previously determined threshold of toxic DEHP exposure was independently associated with the hormone levels on the last PICU day. Main results: Median total DEHP metabolite concentration was 0.101 (IQR 0.049 - 0.279) µmol/L on the last PICU day. Minimal DEHP exposure was 0.337 (IQR 0.161 - 0.880) µmol/l.days, and 328 patients (35.7%) exceeded the toxic threshold. Exceeding this threshold was independently associated with lower total T4 (P=0.002), total T3 (P=0.02) and total cortisol (P=0.001), and higher rT3 (P=0.01) concentrations on the last PICU day, but not with TSH, ACTH or free cortisol. Conclusion: Critically ill children had DHEP metabolites in plasma upon PICU discharge and more than a third were exposed to toxic levels. Toxic DEHP exposure was an independent contributor to the severity of the non-thyroidal illness phenotype and to lower cortisol upon PICU discharge. Future research should assess whether such endocrine-disruptive impact of DHEP exposure in the PICU plays a role in the long-term developmental legacy of critical illness in children. 1 Verstraete et al Intensive Care Med 2016 2 Jacobs et al Thyroid 2019 3 Jacobs et al Intensive Care Med 2019 4 Fivez et al N Engl J Med 2016

A study of lipid profile in subclinical hypothyroidism in tertiary care hospital, Kolkata, India

Background: Objective was to study lipid profile in patients of subclinical hypothyroidism in tertiary centre in Kolkata, West Bengal and compare the same with matched controls.Methods: This observational study (single exposure) was conducted May 2019 to Nov 2019 at Department of Medicine, KPC Medical College, Jadavpur, Kolkata in subjects diagnosed with Sub Clinical Hypothyroidism [defined as normal T3 or FT3, normal T4 or FT4, and with increased TSH. Sixty patients with subclinical hypothyroidism were selected after careful exclusion; lipid profile was compared with matched controls.Results: Between the two groups (group I - controls vs. group II - cases), the values were as follows: Mean serum total T3 value was 114.03±29.22 ng/dl vs. 106.15±36.24 ng/dl (p = 0.3476); mean total T4 was 7.07±1.69 μg/dl vs. 6.86±1.31 μg/dl (p = 0.535); mean TSH was 3.17±1.28 μIU/ml vs. 9.77±4.19 μIU/ml (p <0.0001). Lipid profile pattern (group I vs. group II) was as follows: Mean total cholesterol (TC) 125.50±9.18 mg/dl vs. 162.07±42.32 mg/dl (p <0.0001), mean triglycerides (TG) is 136.65±14.82 mg/dl vs. 148.90±65.27 mg/dl (p = 0.3236), low-density lipoprotein (LDL)-cholesterol is 62.17±7.40 mg/dl vs. 98.81±33.26 mg/dl (p <0.0001), high-density lipoprotein (HDL)-cholesterol 39.17±6.62 mg/dl vs. 34.27±9.63 mg/dl (p = 0.0702), very low-density lipoprotein (VLDL) levels are 34.54±15.38 mg/dl vs. 32.08±13.21 mg/dl (p = 0.5245)..Conclusions: Subclinical hypothyroidism is associated with increased serum total cholesterol and LDL-Cholesterol levels. Therefore, there is a potential association between Subclinical hypothyroidism and atherosclerosis.

Thyroid function in children with nephrotic syndrome: A prospective hospital-based study

AbstractBackground. Nephrotic syndrome is a common kidney disease among children which is characterized by proteinuria, hypercholesterolemia, hypoproteinemia, and edema. The urinary losses of proteins including albumin and thyroid-binding globulin might affect the thyroid hormone levels in those children. Objective. To assess the thyroid function in children with nephrotic syndrome during the nephrotic attack and after remission.Methods. This was a prospective study conducted at the Pediatrics department, Sohag University Hospital, Sohag, Egypt over a one-year period (from January to December 2017). Data were collected from 51 children with nephrotic syndrome aged between 1 and 12 years old. The study participants were subjected to investigations including thyroid-stimulating hormone (TSH), thyroxin (T4), triiodothyronine (T3), serum urea, creatinine, cholesterol, triglycerides, albumin, total proteins, urinary albumin-to-creatinine ratio and 24 hours urinary proteins during the nephrotic attack and after remission.Results. The mean age for the study participants was 6.1 ± 2.9 years. Thirty-one participants were males (60.8%). The study found that serum TSH levels were elevated while serum Total T3 and Total T4 were reduced during the nephrotic attack. As regards the thyroid hormone status, we found true hypothyroidism in 12 patients (23.52%) and subclinical hypothyroidism in 24 patients (47.06%) during the nephrotic attack. However, only one patient (1.96%) had true hypothyroidism and 14 patients (27.45%) had subclinical hypothyroidism after remission. Conclusion. A large proportion of children with nephrotic syndrome had thyroid dysfunction in the form of either true (overt) or subclinical hypothyroidism. Therefore, monitoring the thyroid function in those children is important.

Aberrant Cardiac Long Noncoding RNA Expression Following Alterations in Thyroid Hormones

BackgroundHeart failure (HF) mortality is on the rise and altered thyroid hormone (TH) function is a major risk factor. HF can be a result of either decreased (hypothyroidism; HypoTH) or increased (hyperthyroidism; HyperTH) serum TH levels. THs regulate cardiac physiology including contractility and relaxation. We recently showed safe, cardioprotective effects with oral treatment of active form of THs in several rodent models of cardiovascular disorders. Moving forward, novel heart‐specific targets in TH pathway are warranted. About 98% of the genome is non‐protein‐coding and over 90% is transcribable. Long noncoding RNA (lncRNA; transcripts >200 nucleotides) genes outnumber protein‐coding genes by several fold. Deiodinase‐3 converts active forms of THs into inactive metabolites, and its chromosomal domain also encode maternally expressed lncRNAs. However, role of lncRNAs in TH‐mediated cardiac effects is unknown. We hypothesize that alterations in TH levels will impair cardiac lncRNA expression.MethodsHypoTH was induced by feeding adult C57BL/6 mice with 0.15% propylthiouracil with 0.1% methimazole for 5 weeks. HyperTH was established by injecting TH (T4; 1 μg/g i.p.) every 48 hours. Females were used because they maintain a more stable body mass over time than males. Furthermore, women have higher incidence of thyroid anomalies. Echocardiography and heart gravimetry were performed and results analyzed by analysis of variance with Tukey's multiple comparisons test (n=3–5/group). We also performed quantitative real‐time PCR using lncRNA‐specific array of 86 different targets following pre‐amplification. Array reproducibility, reverse transcription efficiency, absence of genomic DNA contamination and normalization were ensured.ResultsSerum total T4 levels were decreased in HypoTH (p<0.05) and increased in HyperTH (p<0.01) [Control: 2.17±0.4; HypoTH: 0.8±0.2; HyperTH: 12.8±2.4; ug/dl]. While HypoTH hearts were atrophic (p<0.05), HyperTH hearts showed significant hypertrophy (p<0.0001). Heart weight to body weight ratio was 4.38±0.2 in controls, 3.8±0.1 in HypoTH and 5.9±0.1 in HyperTH. Left and right ventricular ratios also followed similar patterns (p<0.05). Following HypoTH, echocardiographic left ventricular end‐systolic dimension significantly increased (p<0.05) while fractional shortening decreased (p<0.01). Heart rate decreased with HypoTH and increased with HyperTH (p<0.01). We began investigating involvement of lncRNAs related to inflammatory and immune mechanisms that can be relevant in both TH abnormalities and HF. Quantitative real‐time PCR showed that several of these cardiac lncRNAs were differentially expressed following alterations in TH levels (p<0.05). Importantly, two lncRNAs were significantly downregulated (2.9‐ and 1.73‐fold) in HypoTH, but upregulated (3.4‐ and 1.67‐fold) in HyperTH ventricles. Another lncRNA was significantly increased in HypoTH (2.1‐fold), but decreased with HyperTH (7.63‐fold).ConclusionsThis is the first report to present aberrations in cardiac lncRNAs following altered TH levels. Taken together, this demonstrates potential TH‐dependent regulation of lncRNAs in mammalian hearts that may offer clinical significance.Support or Funding InformationNYITCOM

Thyroid status among critically ill patients admitted in the intensive care unit of the government tertiary care hospital in Mandya: a retrospective study

Background: The nonthyroidal illness syndrome, also known as the low T3 syndrome or euthyroid sick syndrome. Any acute severe illness can cause abnormalities of circulating Thyroid Stimulating Hormone (TSH) or Thyroid Hormone (TH) levels in the absence of underlying thyroid disease. The laboratory parameters of this syndrome include low serum levels of T3 and high levels of reverse T3, with normal or low levels of thyroxine (T4) and normal or low levels of TSH. This condition may affect 60-70% of critically ill patients. The severity of illness correlates well with the reduction in total serum T3 level. Objectives of the study was to assess the thyroid status of critically ill patients admitted in intensive care unit of a tertiary care hospital.Methods: This is a retrospective observational study done at Department of General Medicine, MIMS, Mandya among patients admitted with critical illness to ICU. 100 patients admitted with critical illness to ICU are included in this study. Thyroid function reports obtained from case sheets, data entered into MS Excel sheet and analysed.Results: Out of 100 patients studied 34 patients had sepsis, 26 patients had respiratory failure, 20 patients had Congestive cardiac failure, 12 patients had acute renal failure and 8 patients had Diabetic ketoacidosis. Among 100 patients 63% had abnormal thyroid function test, 56% had low T3, 12% had low T4, 2% had high T4 and 3% had low TSH.Conclusions: Thyroid function abnormality suggesting Non thyroid illness or euthyroid sick syndrome is common among critically ill patients.

Morphological and functional changes in neonatally X-irradiated thyroid gland in rats.

Exposure to ionized radiation in childhood has been recognized as a risk factor for the development of thyroid cancer and possibly for other thyroid disorders. However, the effects of neonatal radiation exposure on thyroid morphology and functions have never been explored despite its potential importance. One-week-old male Wistar rats were subjected to cervical X-irradiation at 6 and 12 Gy. Animals were examined at the ages of 2, 8 and 18 weeks old. For comparison, 8-week-old rats were cervically X-irradiated at the same doses. Thyroid histology was examined by computer-assisted microscopy to measure areas of colloid and epithelium of thyroid follicles as well as epithelial heights. In rats that received cervical X-irradiation at 1 week old, the colloid size of thyroid follicles decreased at the age of 8 weeks old in a radiation-dose dependent manner. This morphological change was persistently found at 18 weeks old. There were no significant differences in serum total T3 or T4 levels among the groups. Serum TSH levels increased significantly in 8-week-old rats neonatally X-irradiated. Thyroglobulin (Tg) mRNA and protein expressions were significantly decreased in the neonatally-irradiated group while thyroid peroxidase mRNA express increased at 18 weeks old. None of these changes were observed in the rats X-irradiated at 8 weeks old. In conclusion, our results clearly demonstrated that neonatal rat thyroid was sensitive to ionized radiation, developing specific morphological changes characterized by smaller thyroid follicles along with changes in serum TSH levels and Tg expressions in the thyroid tissue.

Hypo- versus hyper-thyroidism in 2 cats: the culprit for miliary dermatitis/hypersensitivity versus growth retardation

In the present case series 2 different cats with diagnosis of hypo- versus hyper-thyroidism with distinct clinical signs were reported. The first case was a 3-month-old male domestic short-hair kitten was presented with a disproportionate dwarfism. Radiographic examination of the long bones revealed epiphyseal dysgenesis and delayed epiphyseal ossification. Congenital primary hypothyroidism was established by low serum total thyroxine. Initial treatment composed of levothyroxine. The second case was referred to the clinic with unresolved dermatological problems. On referral alopecia, extensive crusting and matting of the haircoat were evident. Hyperthyroidism and related military dermatitis was detected based on elevated serum total thyroxine and free T4 levels along with skin punch biopsy results. Therapeutical armamentarium composed of methimazole and hyperimmune milk factor. Early recognition, diagnosis and treatment intervention all resulted in clinical remission and relief of clinical signs accompanied by normal thyroidal function and laboratory results in both cats.

Short Call Abstracts

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Urinary bisphenol A and thyroid function by BMI in the Korean National Environmental Health Survey (KoNEHS) 2012–2014

Bisphenol A (BPA) is one of the largest amounts of chemicals in daily life and source of polycarbonate plastics, epoxy resins, medical equipment, plastic consumer products. Recent studies reported that the effects of BPA on human health in the thyroid hormone. Therefore, this study aimed to indicate the association between urinary BPA concentration and thyroid function in total triiodothyronine (T3), thyroxine (T4), thyroidal stimulating hormone (TSH) and stratified the population by body mass index (BMI). This study was performed on 6478 adults aged 19 years and older based on the Second Korean National Environmental Health Survey (KoNEHS, 2012–2014). We measured BPA in urine and total T3, T4 and TSH in serum from the 2nd KoNEHS study. The multiple regression analysis was performed to assess the association of urinary BPA concentrations with thyroid hormone after BMI stratification. Urinary BPA associated with thyroid hormone. Especially, BPA is related to T3 (−0.627) in all group, and T4 (−0.060, −0.098) in all group and the group of BMI 25.0kg/m2 or more negatively. When stratified by BPA, T3 and T4 were significantly decreased with the high BPA exposure compared with the low BPA exposure for BMI more than 25.0kg/m2 (adjusted β = −3.402, 95% CI: 4.942, −1.862, adjusted β = −0.209, 95% CI: 0.328, −0.090). However, no obvious associations were found between BPA concentration and TSH. The results of urinary BPA decrease with T3 and T4 levels increase in the higher BMI group is a new finding which does not exist in recent studies of Korea.

Kanechlor 500‐mediated changes in serum and hepatic thyroxine levels primarily occur in a transthyretin‐unrelated manner

The effects of Kanechlor-500 (KC500) on the levels of serum total thyroxine (T4 ) and hepatic T4 in wild-type C57BL/6 (WT) and its transthyretin (TTR)-deficient (TTR-null) mice were comparatively examined. Four days after a single intraperitoneal injection with KC500 (100mg/kg body weight), serum total T4 levels were significantly decreased in both WT and TTR-null mice. The KC500 pretreatment also promoted serum [125 I]T4 clearance in both strains of mice administrated with [125 I]T4 , and the promotion of serum [125 I]T4 clearance in WT mice occurred without inhibition of the [125 I]T4 -TTR complex formation. Furthermore, the KC500 pretreatment led to significant increases in liver weight, steady-state distribution volume of [125 I]T4 , hepatic accumulation level of [125 I]T4 , and concentration ratio of the liver to serum in both strains of mice. The present findings indicate that the KC500-mediated decrease in serum T4 level occurs in a TTR-unrelated manner and further suggest that KC500-promoted T4 accumulation in the liver occurs through the development of liver hypertrophy and the promotion of T4 transportation from serum to liver.

Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial

Deficiency of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) causes severe intellectual and motor disability and high serum tri-iodothyronine (T3) concentrations (Allan-Herndon-Dudley syndrome). This chronic thyrotoxicosis leads to progressive deterioration in bodyweight, tachycardia, and muscle wasting, predisposing affected individuals to substantial morbidity and mortality. Treatment that safely alleviates peripheral thyrotoxicosis and reverses cerebral hypothyroidism is not yet available. We aimed to investigate the effects of treatment with the T3 analogue Triac (3,3',5-tri-iodothyroacetic acid, or tiratricol), in patients with MCT8 deficiency. In this investigator-initiated, multicentre, open-label, single-arm, phase 2, pragmatic trial, we investigated the effectiveness and safety of oral Triac in male paediatric and adult patients with MCT8 deficiency in eight countries in Europe and one site in South Africa. Triac was administered in a predefined escalating dose schedule-after the initial dose of once-daily 350 μg Triac, the daily dose was increased progressively in 350 μg increments, with the goal of attaining serum total T3 concentrations within the target range of 1·4-2·5 nmol/L. We assessed changes in several clinical and biochemical signs of hyperthyroidism between baseline and 12 months of treatment. The prespecified primary endpoint was the change in serum T3 concentrations from baseline to month 12. The co-primary endpoints were changes in concentrations of serum thyroid-stimulating hormone (TSH), free and total thyroxine (T4), and total reverse T3 from baseline to month 12. These analyses were done in patients who received at least one dose of Triac and had at least one post-baseline evaluation of serum throid function. This trial is registered with ClinicalTrials.gov, number NCT02060474. Between Oct 15, 2014, and June 1, 2017, we screened 50 patients, all of whom were eligible. Of these patients, four (8%) patients decided not to participate because of travel commitments. 46 (92%) patients were therefore enrolled in the trial to receive Triac (median age 7·1 years [range 0·8-66·8]). 45 (98%) participants received Triac and had at least one follow-up measurement of thyroid function and thus were included in the analyses of the primary endpoints. Of these 45 patients, five did not complete the trial (two patients withdrew [travel burden, severe pre-existing comorbidity], one was lost to follow-up, one developed of Graves disease, and one died of sepsis). Patients required a mean dose of 38.3 μg/kg of bodyweight (range 6·4-84·3) to attain T3 concentrations within the target range. Serum T3 concentration decreased from 4·97 nmol/L (SD 1·55) at baseline to 1·82 nmol/L (0·69) at month 12 (mean decrease 3·15 nmol/L, 95% CI 2·68-3·62; p<0·0001), while serum TSH concentrations decreased from 2·91 mU/L (SD 1·68) to 1·02 mU/L (1·14; mean decrease 1·89 mU/L, 1·39-2·39; p<0·0001) and serum free T4 concentrations decreased from 9·5 pmol/L (SD 2·5) to 3·4 (1·6; mean decrease 6·1 pmol/L (5·4-6·8; p<0·0001). Additionally, serum total T4 concentrations decreased by 31·6 nmol/L (28·0-35·2; p<0·0001) and reverse T3 by 0·08 nmol/L (0·05-0·10; p<0·0001). Seven treatment-related adverse events (transiently increased perspiration or irritability) occurred in six (13%) patients. 26 serious adverse events that were considered unrelated to treatment occurred in 18 (39%) patients (mostly hospital admissions because of infections). One patient died from pulmonary sepsis leading to multi-organ failure, which was unrelated to Triac treatment. Key features of peripheral thyrotoxicosis were alleviated in paediatric and adult patients with MCT8 deficiency who were treated with Triac. Triac seems a reasonable treatment strategy to ameliorate the consequences of untreated peripheral thyrotoxicosis in patients with MCT8 deficiency. Dutch Scientific Organization, Sherman Foundation, NeMO Foundation, Wellcome Trust, UK National Institute for Health Research Cambridge Biomedical Centre, Toulouse University Hospital, and Una Vita Rara ONLUS.

Silicone Pet Tags Associate Tris(1,3-dichloro-2-isopropyl) Phosphate Exposures with Feline Hyperthyroidism.

Feline hyperthyroidism is the most commonly diagnosed endocrine-related disease among senior and geriatric housecats, but the causes remain unknown. Exposure to endocrine-disrupting compounds with thyroid targets, such as flame retardants (FRs), may contribute to disease development. Silicone passive sampling devices, or pet tags, quantitatively assessed the bioavailable FR exposures of 78 cats (≥7 y) in New York and Oregon using gas chromatography-mass spectrometry. Pet tags were analyzed for 36 polybrominated diphenyl ethers, six organophosphate esters (OPEs), and two alternative brominated FRs. In nonhyperthyroid cats, serum free thyroxine (fT4), total T4 (TT4), total triiodothyronine, and thyroid-stimulating hormone concentrations were compared with FR concentrations. Tris(1,3-dichloro-2-isopropyl) phosphate (TDCIPP) concentrations were higher in hyperthyroid pet tags in comparison to nonhyperthyroid pet tags (adjusted odds ratio, p < 0.07; Mantel-Cox, p < 0.02). Higher TDCIPP concentrations were associated with air freshener use in comparison to no use (p < 0.01), residences built since 2005 compared to those pre-1989 (p < 0.002), and cats preferring to spend time on upholstered furniture in comparison to no preference (p < 0.05). Higher TDCIPP concentrations were associated with higher fT4 and TT4 concentrations (p < 0.05). This study provides proof-of-concept data for the use of silicone pet tags with companion animals and further indicates that bioavailable TDCIPP exposures are associated with feline hyperthyroidism.

An experimental study on the induction of Graves′ hyperthyroidism with Graves′ ophthalmopathy in BALB/c mice by TSHR gene immunization

Objective To construct a model of Graves′ disease(GD) with (or) Graves′ ophthalmopathy(GO) in BALB/c mice by immunization with pcDNA3.1/TSHR289. Methods pcDNA3.1/TSHR289 was injected into the bilateral gastrocnemius muscle of 35 model mice and electroporation was immediately performed. 10 control mice were injected with sterile saline and electroporated, while 5 blank mice were injected with sterile saline only. Each group of mice was immunized at 1, 4, 7, and 10 weeks, respectively. Serum total T4, TSH, TSAb, and TSBAb were measured before immunization, 2 weeks after each immunization, as well as 5 and 8 weeks after the last immunization. CT scan was used to evaluate the morphological changes of the eyes of the mice.99mTcO4- imaging was used to measure the thyroid uptake function, and the pathological changes of the thyroid and orbital tissues were evaluated by HE staining. Results After the 2nd time immunization, the serum concentrations of TT4, TSAb and TSBAb in GD mice were significantly higher than those of control and blank groups(F=13.781, 31.435, 36.112, P<0.01, respectively). The TSH continued to be significantly lower than that of control and blank groups(F=13.966, P<0.01). After the 4th time immunizations, the ability of uptaking99mTcO4- in GD mice thyroid was significantly enhanced compared with the control group. The thyroid goiter with a large amount of lymphocyte infiltration, and the thyroid follicle was thin. CT scan of GO mice showed thickening and swelling of the extraocular muscles, and no abnormalities in tendon and muscle attachment points. HE staining showed thickening of extraocular muscle fibers, lymphocyte infiltration of extraocular muscles and orbital tissue, increased hyaluronic acid, and infiltration of fat cells. Conclusion GD or GO model can be successfully induced by multiple intramuscular injection of pcDNA3.1/TSHR289 in BALB/c mice. Key words: Graves′ disease; Graves ophthalmopathy; TSHR; Mice models; Electroporation

Validation of plasma thyroxine and triiodothyronine methods on the ADVIA Centaur® XP

Standardization programs for thyroid hormones have revealed bias between immunochemical methods and the reference method ED-ID-LC/MS. Lack of standardization between methods, suboptimal reference intervals and replacement of serum with plasma may compromise the capability of the immunochemical thyroid methods to diagnose thyroid disease. To accommodate the demand for faster turn-around times for laboratory replies, we replaced serum with plasma on some serum CE marked thyroid methods. This forced us to do on-board analytical correction for the plasma total T4 (TT4) method on ADVIA Centaur® XP. We, next, validated the capability of the ADVIA Centaur® XP thyroid methods on plasma by (1) first carrying out a prospective method comparison with the ED-ID-LC/MS reference method using collected plasma samples, (2) we verified the clinical reference intervals by analyzing collected plasma samples from healthy individuals, and (3) retrospectively compared laboratory results from two different time periods using serum TT4 and serum total triiodothyronine (TT3) versus plasma free thyroxine (FT4) and plasma TT3, respectively, to diagnose thyroid disease. The plasma FT4 method displayed a negative concentration-dependent bias against the reference method. This bias was apparently counteracted by a fitted reference interval for the plasma FT4 method. Indeed, overt hyperthyroid disease was found in 1.0% and 1.1% of the cases using serum and plasma and overt hypothyroid condition were in 1.3% and 0.6% of the cases using serum and plasma, respectively. In conclusion, the ADVIA Centaur® XP FT4 method displayed a negative bias at high plasma FT4 concentrations against the reference method, but the diagnostic performance was not compromised due to a fitted reference interval.

Evaluation and management of the child with hypothyroidism.

Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is, therefore, of utmost importance to optimize physical and neurodevelopmental outcomes. A PubMed search was completed in Clinical Queries using the key terms "hypothyroidism". Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first 2weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH < 5mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism.

Clinical significance of thyroid incidentalomas detected on fluorodeoxyglucose positron emission tomography scan (PETomas): An Indian experience.

Thyroid incidentalomas (TIs) are being frequently detected on positron emission tomography (PET) scan. The risk of malignancy in these focal hot spots is substantially high as compared to incidentalomas detected on ultrasonography (USG)/magnetic resonance imaging/computed tomography (CT). Majority of the studies on the prevalence of TIs in PET and the risk of malignancy in them are retrospective and have had varied results. Very few prospective studies are available and very few Indian studies have been done on the subject. Hence, this study was undertaken to evaluate the clinical significance of TIs detected on fluorodeoxyglucose (FDG)-PET scan. The study included all patients undergoing FDG-PET scan for nonthyroid illness from October 2015 to October 2016. Twenty-three consecutive patients detected to have focal TI (FTI) were prospectively evaluated with detailed history and clinical examination, serum thyroid-stimulating hormone, total T4 and total T3 levels, USG neck, fine-needle aspiration cytology (FNAC), and surgery when indicated. The prevalence of FTI was 2.26%. Out of the 23 FTI cases, 19 patients agreed to undergo further evaluation and malignancy was detected in 5 patients (all papillary carcinomas) making a risk of malignancy of 26.3%. There was no significant correlation between CT attenuation characteristics and size of benign and malignant PETomas or between the maximum standardized uptake value (SUVmax) of benign and malignant PETomas. Hence, the risk of malignancy in thyroid PETomas is substantially high and warrants USG-guided FNAC and further work-up. Their SUVmaxvalues, size, and CT attenuation characteristics do not contribute in differentiating benign from malignant lesions.

Thyroid Dysfunction In Patient With Nephrotic Syndrome

A large amount of protein is lost in urine along with thyroid hormones and hormone binding proteins in nephrotic syndrome (NS). This hormone loss may lead to low T4, T3 and sometimes high TSH level and often to be associated with subclinical or overt hypothyroidism. This study was done to assess thyroid dysfunction in patients with NS and to correlate thyroid hormones with albumin level of those subjects. Forty diagnosed patients of idiopathic NS and same number of age matched healthy control were selected in this study. Thyroid status was evaluated in all the subjects. In patients with NS mean (± SD) of T4, T3 and TSH were 39.34 (±29.49), 1.05 (±0.83) and 11.34 (±18.15) respectively. Mean (±SD) of T4, T3 and TSH in healthy control were 83.34 (±27.23), 2.04 (±0.70) and 2.73 (±1.79) respectively. Mean serum total T4 and T3 of patients with NS were found to be significantly lower (t= -6.935, df= 78, p&lt;0.001 and t = -5.750, df = 78, p&lt;0.001 respectively) and mean TSH was found to be significantly higher (t= 2.984, df = 78, p&lt;0.01) in patients with NS as compared to healthy control. Sub clinical hypothyroidism was observed in 20 (50%) and overt hypothyroidism in 4 (10%) of patients. Significant positive correlation was found between serum albumin and serum total T4 (r = 0.818, p &lt;0.001) and also with total T3 level (r = 0.903, p &lt;0.001). But no correlation was found between serum albumin and serum TSH (r = - 0. 292, p&gt;0.05) in patients with NS. So, nephrotic range proteinuria may be associated with loss of thyroid hormone in urine and can lead to subclinical or even overt hypothyroidism.TAJ 2015; 28(1): 40-44

Serum leptin in male hypothyroid prediabetic patients: Association with cardiovascular risk.

Hyperliptenemia is a risk factor for coronary heart disease (CHD). Hypothyroidism and prediabetes confer an increased cardiovascular risk. Few studies have addressed the role of leptin in hypothyroid prediabetic patients and its effect on CHD risk factors. The aim of this study was to detect serum levels of leptin in hypothyroid prediabetic patients and their relationship with risk factors for CHD. The study included three groups; group A included 120 hypothyroid male patients with normal glucose tolerance, group B included 120 hypothyroid male patients with prediabetes, and group C included 120 healthy individuals matched for age and sex as a control group. All groups were subjected to assessment of history, clinical examination, and laboratory investigations including fasting and 2 h postprandial blood glucose, serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), free T3, free T4, thyroid-stimulating hormone, and fasting serum leptin. Serum leptin was significantly higher in groups A and B compared with group C (P=0.0001), whereas there was no significant difference in serum leptin between groups A and B. In comparison with group A, the patients in group B had significantly higher serum TC (P=0.02), LDL (P=0.04), and lower serum HDL (P=0.02). In group B, serum leptin correlated positively with serum TC (P=0.0001), TG (P=0.041), and LDL (P=0.036), and negatively with serum HDL (P=0.039). Hypothyroidism is associated with high serum leptin independent of prediabetic state. Serum leptin in hypothyroid prediabetic patients showed a direct relationship with some primary markers of metabolic syndrome; thus, leptin may predict the development of CHD in those patients.

Canine visceral leishmaniosis: the relationship of blood serum thyroid hormones, lipids, and lipoproteins with clinical status.

The objective of the present study was to investigate the role of thyroid hormones and lipid profile in development and outcome of canine visceral leishmaniosis (CVL). We therefore studied the relationships between blood serum thyroid hormones [total T4, free T4, total T3, and free T3], lipids, and lipoproteins [total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] and clinical status in dogs naturally infected with Leishmania infantum. Two groups of Leishmania-infected dogs [with no clinical signs (NCS; n = 15), and with clinical signs (CS; n = 16)] were assessed and compared with a group of healthy control dogs (n = 15). A significant decrease in serum total T4 (p < 0.05) concentration in the CS group was observed when compared to the NCS and control groups. The dogs in CS group revealed a significant decrease (p < 0.05) in free T4 concentration in comparison to the control group. The CS group presented a significant decrease in HDL-C (p < 0.01) concentrations, when compared to NCS and control groups. The observed findings in the present study suggested that thyroid hormone and lipoprotein alterations may have a role in susceptibility of dogs with Leishmania infection.

Thyroid hormones and breast cancer association according to menopausal status and body mass index

BackgroundThyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women.MethodsTo assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models.ResultsHigher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR) per standard deviation = 5.98, 95% CI 3.01–11.90) and postmenopausal women (OR per standard deviation = 2.81, 95% CI 2.17–3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while the opposite was observed in postmenopausal women. The significance of the effect modification was marginal (p = 0.059) in postmenopausal women and was not significant in premenopausal women (p = 0.22). Lower TT3 concentrations were associated with BC in both premenopausal and postmenopausal women and no effect modification was observed.ConclusionsThere is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.