Serum Thyroid Hormone Profile Research Articles

Glycerol Phenylbutyrate treatment of two patients with Monocarboxylate Transporter 8 deficiency.

Monocarboxylate transporter 8 (MCT8) deficiency is a rare genetic disease that leads to severe global developmental delay. MCT8 facilitates thyroid hormone (TH) transport across the cell membrane, and the serum TH profile is characterized by high T3 and low T4 levels. Recent studies have shown that the chemical chaperone sodium phenylbutyrate (NaPB) restored mutant MCT8 function and increased TH content in patient-derived induced pluripotent stem cells, making it a potential treatment for MCT8 deficiency. We aimed to assess the efficacy and safety of glycerol phenylbutyrate (GPB) in MCT8 deficiency. We treated two monozygotic twins aged 14.5 years with MCT8 deficiency due to P321L mutation with escalating doses of GPB over 13 months. We recorded TH, Vital signs, anthropometric measurements and neurocognitive functions. Resting metabolic rate (RMR) was measured by indirect calorimetry. Serum metabolites of GPB were monitored as a safety measure. In-vitro effects of NaPB were evaluated in MDCK1 cells stably expressing the MCT8P321L mutation. The effects of GPB were compared to the effects of DITPA and TRIAC, thyromimetic medications that the patients received in the past. NaPB restored mutant MCT8 expression in MDCK1 cells and increased T3 transport into cells carrying the P321L mutation. GPB treatment reduced high T3 and increased low T4 levels. The patients showed a significant weight gain simultaneously with a reduction in RMR. Only minor neuro-cognitive improvement was observed, in hyperreflexia score and in cognitive functions. Serum metabolites did not exceed the toxic range but elevated liver transaminases were observed. In the first report of GPB treatment in MCT8 deficiency we found an improvement in TH profile and body-mass index, with minor neuro-developmental changes.

EFFECTS OF ORAL SELENIUM REPLACEMENT ON TSH IN PATIENTS WITH SUBCLINIC HIPOTIROIDISM WITH LOW SERUM SELENIUM LEVELS

AMAÇ: Selenyum insan vücudunun önemli metabolik yolaklarının vazgeçilmez bir bileşenidir. Aktif bölgesine selenosistein şeklinde selenyum katılmış proteinler, selenoproteinler olarak tanımlanmaktadır ve bu proteinlerin fonksiyonlarını yerine getirmeleri için selenyuma gereksinimleri vardır. Selenyum elementi, Glutatyonperoksidaz (GPXs), Tioredoksinredüktaz (TRs) ve iyodotironindeiyodinaz (İD) gibi selenoproteinlerin yapısında bulunmaktadır. Selenoproteinler, tiroid hormon biyosentezine ve metabolizmasına, antioksidan savunma sisteminin kontrolüne katkı sağlamaktadır. Çalışmamızda subklinik hipotiroidisi olan otoimmün tiroidit hastalarına selenyum düşüklüğünün ne sıklıkla eşlik ettiğini ve selenyumu düşük olan hastalarda oral selenyum replasmanının tiroit stimülan hormon (TSH) üzerine etkilerini ortaya koymayı hedefledik.GEREÇ VE YÖNTEM: Çalışmamızda Aralık 2019 ile Temmuz 2020 aralığında 18 yaşından büyük olup polikliniğimize başvurmuş olan, asemptomatik subklinik hipotiroidisi olan 69 hastayı değerlendirdik. Serum selenyum düzeyi 80 μg/L’den düşük olan hastalara 3 ay süre ile yumuşak bir jel kapsül içinde oral yolla günde 83 mcg selenometiyonin verildi. Başka bir tedavi uygulanmadı. Üçüncü ayın sonunda tüm hastalarda serum tiroid hormon profiline ve selenyum seviyelerine bakıldı. Subklinik hipotiroidisi olan otoimmün tiroiditli hastaların, yüzdelik dilimler kullanılarak, oral selenyum replasmanı sonrası TSH seviyelerindeki değişiklikler gözlemlendi.BULGULAR: Çalışmamızda Aralık 2019 ile Temmuz 2020 arasında polikliniğimizde tespit edilen 69 asemptomatik subklinik hipotiroidisi olan hasta değerlendirildi. Çalışma kriterlerine uyumlu 43 hastanın 12 tanesinde (%28) serum selenyum düzeyi normal, 31 (%72) tanesinde serum selenyum düzeyi düşük (<80 μg/L) olarak tespit edildi. Üç ay boyunca günlük 83 mcg selenometiyonin oral selenyum replasman tedavisi verilen hastaların 19 (%61)’unda TSH değerinin normal sınırlar içerisine gerilediği görüldü (0,5mIU/L10.00 mIU/L) tespit edilirken, 9 (%29) hastada ise TSH değerinin halen 4.26 mIU/L- 10.00 mIU/L aralığında olduğu görülerek bu hastlara levotiroksin tedavisi başlandı.SONUÇ: Çalışmamızda selenyum eksikliği bulunan asemptomatik otoimmün subklinik hipotiroidi hastalarına oral selenyum replasmanı yaparak, serum TSH değerleri üzerindeki kısa dönem etkilerini değerlendirdik ve hastaların %61 inin 3 ay içerisinde ötiroid olduğunu gözlemledik. Selenyum eksikliğinin replase edilmesinin, teorik anlamda otoimmün tiroidit başta olmak üzere tüm otoimmün hastalıkların inflamatuar ve oksidatif hasar sürecine olan olumlu etkileri mevcuttur. Ancak bu konuda deneysel ve klinik prospektif planlanmış ve alt grupların detaylandırıldığı kapsamlı çalışmaların yapılması gerektiğini düşünüyoruz.

Evaluation of serum thyroid hormone profile and its correlation with the clinical outcome in critically ill children

Critical illness is often accompanied by sick euthyroid syndrome, an endocrine anomaly with characteristically low triiodothyronine (T3), low thyroxine (T4), and altered thyroid-stimulating hormone (TSH) levels in the serum. This warrants exploration of the relationship between thyroid hormone levels and clinical outcome of critical illness. To evaluate the thyroid hormone profile in critically ill children and assess its correlation with disease severity and outcome. Fifty critically ill children, aged 1 month-15 years, admitted to the pediatric intensive care unit with organ dysfunction and requiring pharmacological/mechanical support to maintain vital function, were recruited into this observational study. Risk of Mortality (PRISM) scores were evaluated for all patients as an indicator of disease severity and their thyroid profile investigated for serum T3, T4, and TSH levels. These were correlated with each other and with the disease outcome using statistical software R version 3.6.3. At the end of hospital stay, mean T3, T4, and TSH levels were significantly increased in discharged patients (p<0.001) but reduced in expired patients (p=0.01) compared to their values at admission. Mean T4 levels at discharge/death showed a significant negative correlation with the mean PRISM score recorded 24 h after admission.

The Serum Thyroid Hormone Profile in Mechanically Ventilated Children: Does Euthyroid Sick Syndrome Exist?

The Serum Thyroid Hormone Profile in Mechanically Ventilated Children: Does Euthyroid Sick Syndrome Exist?

Tissue-Specific Alterations in Thyroid Hormone Homeostasis in Combined Mct10 and Mct8 Deficiency

The monocarboxylate transporter Mct10 (Slc16a10; T-type amino acid transporter) facilitates the cellular transport of thyroid hormone (TH) and shows an overlapping expression with the well-established TH transporter Mct8. Because Mct8 deficiency is associated with distinct tissue-specific alterations in TH transport and metabolism, we speculated that Mct10 inactivation may compromise the tissue-specific TH homeostasis as well. However, analysis of Mct10 knockout (ko) mice revealed normal serum TH levels and tissue TH content in contrast to Mct8 ko mice that are characterized by high serum T3, low serum T4, decreased brain TH content, and increased tissue TH concentrations in the liver, kidneys, and thyroid gland. Surprisingly, mice deficient in both TH transporters (Mct10/Mct8 double knockout [dko] mice) showed normal serum T4 levels in the presence of elevated serum T3, indicating that the additional inactivation of Mct10 partially rescues the phenotype of Mct8 ko mice. As a consequence of the normal serum T4, brain T4 content and hypothalamic TRH expression were found to be normalized in the Mct10/Mct8 dko mice. In contrast, the hyperthyroid situation in liver, kidneys, and thyroid gland of Mct8 ko mice was even more severe in Mct10/Mct8 dko animals, suggesting that in these organs, both transporters contribute to the TH efflux. In summary, our data indicate that Mct10 indeed participates in tissue-specific TH transport and also contributes to the generation of the unusual serum TH profile characteristic for Mct8 deficiency.

Serum thyroid hormone profile and trace elements in children receiving valproic acid therapy: A longitudinal and controlled study

Valproic acid (VPA) may affect thyroid hormone profile, causing alteration in serum trace elements concentrations. The aim of this study was to prospectively investigate this relationship in children receiving VPA monotherapy for a period up to 6 months. Serum thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), thyroxine (T4), triiodothyronine (T3), thyroglobuline (TG), selenium (Se), zinc (Zn), and copper (Cu) levels were evaluated at baseline and at the 6th month in all the patients and in the control group. The mean Cu concentration in the 6th months of VPA therapy was significantly lower than that of the control group. TSH level was significantly increased in the patient group whereas FT4 was significantly decreased. The mean TSH level in the 6th month of VPA therapy was significantly higher than that of the control group, whereas mean T4 level was significantly lower. The Cu level in the 6th months of VPA therapy was positively correlated with T4 level. ΔlogCu and ΔTSH were negatively correlated. This study suggests that the alteration in the serum thyroid hormone profile during VPA therapy may result from the reduction in serum Cu levels.

Cardiopulmonary Bypass and Serum Thyroid Hormone Profile in Pediatric Patients with Congenital Heart Disease

To study the effect of cardiopulmonary bypass (CPB) on serum thyroid hormone profile in children undergoing open-heart surgery. Prospective cross-sectional study. Multispecialty tertiary level referral center. One hundred consecutive patients (age 15.9 ± 14.6 months, weight 6.7 ± 2.5 kg) undergoing open-heart surgery under CPB. None. Levels and trends of serum total thyroxine (TT4), free thyroxine (FT4), total tri-iodothyronine (TT3), free tri-iodothyronine (FT3) and thyroid stimulating hormone (TSH), survival, inotropic score, duration of mechanical ventilation, postoperative complications. TT4 levels were 9.08 ± 3.6, 6.4 ± 2.5, 6.24 ± 2.1, 6.43 ± 2.4, 7.20 ± 3.0 µg/dL at baseline and at 1, 24, 48 and 72 hours; FT4 levels were 1.82 ± 0.5, 1.49 ± 0.3, 1.29 ± 0.3, 1.32 ± 0.4, and 1.43 ± 0.5 ng/dL; TT3 levels were 1.81 ± 0.4, 1.31 ± 0.3, 0.99 ± 0.2, 1.0 ± 0.37, and 1.17 ± 0.48 ng/ml; FT3 levels were 4.09 ± 1.0, 3.02 ± 0.8, 2.21 ± 0.6, 2.22 ± 0.7, and 2.66 ± 1.05 pg/ml; TSH levels were 5.40 ± 3.8, 2.0 ± 3.1, 1.24 ± 1.1, 2.90 ± 3.3, and 4.03 ± 3.4 mIU/L. There was significant fall (29.1% for FT4, 32.1% for TT4, 77% for TSH, 46% for FT3 and 45% for TT3, p < 0.0001). When area under curve (AUC) TT4 was compared between survivors (n = 87) and nonsurvivors (n = 12), significantly larger AUC was seen in survivors (492.81 ± 158.6) than nonsurvivors (360.75 ± 179.6 p = 0.0125). In survivors >72 hours, AUC TT4 was larger in patients with uneventful postoperative course versus those with postoperative complications (516.48 ± 18.6 vs. 394.78 ± 29.9, p = 0.001). AUC TT4 showed significant inverse correlation with inotropic score and borderline inverse correlation with duration of mechanical ventilation. Children undergoing surgery under CPB showed significant fall in thyroid hormones. Because TT4 level is modifiable, prophylactic administration of TT4 for improving outcomes needs to be studied further.

Serum thyroid hormone profile in critically III children

To study thyroid hormone profile in critically ill children and its correlation to disease severity and clinical outcome. Total serum triiodothyronine (T3), thyroxine (T4) and TSH were estimated at admission and discharge from PICU/ just before death. Mean T3 levels in cases were significantly lower than controls and lower in patients who expired, both at admission and just prior to death. Mean T4 levels were lower in cases, and just prior to death. Mean TSH levels were not different in cases and controls; or in survived and expired cases. When both T3 and T4 are low, mortality risk increases 30 times. Serum T3, T4 and TSH values improved in patients who survived unlike in those who expired. Age, sex, duration of hospital stay, ventilation, inotropic support, and PICU stay did not show any correlation with patient outcome or thyroid hormone profile. PRISM score at 24 hours and T4 levels in the second sample were significant predictors of survival. T3 levels reflect the patient's clinical status, T4 levels can predict survival.

The feline iodine requirement is lower than the 2006 NRC recommended allowance

The purpose of this study was to determine the iodine (I) requirement in adult cats. Forty-two healthy euthyroid cats (1.6-13.6 years old) were utilized in a randomized complete block design. Cats were fed a dry basal diet (0.23 mg/kg I) for a minimum of 1 month (pre-test) then switched to a different basal diet supplemented with seven levels of KI for 1 year (experimental period). Analysed I concentrations were 0.17, 0.23, 0.47, 1.1, 3.1, 6.9 and 8.8 mg I/kg diet [dry matter (DM) basis] and used to construct a response curve. Response variables included I concentrations in serum, urine and faeces, urinary I:creatinine ratio, I balance, technetium(99m) pertechnetate (Tc(99m)) thyroid:salivary ratio, complete blood count and serum chemistries as well as serum thyroid hormone profiles. No significant changes in food intake, weight gain or clinical signs were noted. Serum I, daily urinary I, daily faecal I and urinary I:creatinine ratio were linear functions of iodine intake. An estimate of the I requirement (i.e. breakpoint) was determined from regression of Tc(99m) thyroid:salivary ratio (scintigraphy) on I intake at 12 months [0.46 mg I/kg diet (DM basis) as well as 9 months I balance (0.44 mg I/kg diet (DM)]. The I requirement estimate determined in our study at 12 months for adult cats (0.46 mg I/kg) was higher than current Association of American Feed Control Officials (AAFCO) recommendations (e.g. 0.35 mg I/kg), but was lower than the 2006 National Research Council (NRC) I recommended allowance (e.g. 1.4 mg I/kg).

Effects of evening vs morning thyroxine ingestion on serum thyroid hormone profiles in hypothyroid patients

Standard drug information resources recommend that l-thyroxine be taken half an hour before breakfast on an empty stomach, to prevent interference of its intestinal uptake by food or medication. We observed cases in which TSH levels improved markedly after changing the administration time of l-thyroxine to the late evening. We therefore conducted a pilot-study to investigate whether l-thyroxine administration at bedtime improves TSH and thyroid hormones, and whether the circadian rhythm of TSH remains intact. DESIGN Patients were studied on two occasions: on a stable regimen of morning thyroxine administration and two months after switching to night-time thyroxine using the same dose. On each occasion patients were admitted for 24 h and serial blood samples were obtained. We investigated 12 women treated with l-thyroxine because of primary hypothyroidism, who used no medication known to interfere with l-thyroxine uptake. Patients were admitted to hospital and blood samples were obtained at hourly intervals for 24 h via an indwelling catheter. Following this first hospital admission, all women were asked to switch the administration time from morning to bedtime or vice versa. After 2 months they were readmitted for a 24-h period of hourly blood sampling. Blood samples were analysed for serum TSH (immunometric assay), FT4 and T3 (competitive immunoassay), T4 and rT3 (radioimmunoassay), serum TBG (immunometric assay) and total protein and albumin (colourimetric methods). A significant difference in TSH and thyroid hormones was found after switching to bedtime administration of l-thyroxine. Twenty-four-hour average serum values amounted to (mean +/- SD, morning vs bedtime ingestion): TSH, 5.1 +/- 0.9 vs 1.2 +/- 0.3 mU/l (P < 0.01); FT4, 16.7 +/- 1.0 vs 19.3 +/- 0.7 pmol/l (P < 0.01); T3, 1.5 +/- 0.05 vs 1.6 +/- 0.1 nmol/l (P < 0.01). There was no significant change in T4, rT3, albumin and TBG serum levels, nor in the T3/rT3 ratio. The relative amplitude and time of the nocturnal TSH surge remained intact. l-thyroxine taken at bedtime by patients with primary hypothyroidism is associated with higher thyroid hormone concentrations and lower TSH concentrations compared to the same l-thyroxine dose taken in the morning. At the same time, the circadian TSH rhythm stays intact. Our findings are best explained by a better gastrointestinal uptake of l-thyroxine during the night.

Starvation induced hypothyroidism involves perturbations in thyroid superoxide‐sod system in pigeons

This study investigated the influence of starvation over seven days on avian thyroidal superoxide radical levels and superoxide dismutase activity profiles in the Indian rock pigeon Columba livia intermeida, in relation with iodine metabolism. The serum thyroid hormone profile was assayed to correlate the thyroidal redox status with the circulating thyroid hormone levels. The spin-trapping results suggest a role for thyroidal superoxide anion (O2.-) in causing a hypothyroid state in pigeons during long term energy withdrawal. Pigeons starved for 1 day generated superoxide and iodide free radicals in their thyroids, with a significant decrease in SOD activity. Regain of SOD activity in 2nd- and 3rd-day starved birds is marked by complete scavenging of radicals in the thyroid, suggesting the significance of SOD in thyroid glands as a potential antioxidant sink against reactive oxygen species, O2.- Resurgence of O2.- radicals with a parallel decrease in SOD activity in the thyroid gland on 5th- and 7th-day of starvation provides evidence of disruption of homeostasis between pro-oxidant and antioxidant states, leading to oxidative stress in avian thyroid during long-term calorie crisis. Following starvation both thyroid hormones thyroxine (T4) and triiodothyronine (T3) decreased, putting pigeons in a hypothyroid state. We argue that oxidative inactivation of thyroid peroxidase and other thyroid proteins by radical attack during starvation invoked oxidative stress, which could be one of the factors responsible for the hypothyroid state in pigeons.

Clinical Approach to Infertility in Bitches with Primary Anestrus

In conclusion, a complete workup of the bitch that has not shown a puberal estrus by 24 months of age should include a general screen with hemogram, chemistries profile and urinalysis, karyotype, serum thyroid hormone profile, serum progesterone concentration, and serum luteinizing hormone concentration, if available. If the results of these tests are normal, an exclusion diagnosis of immune-mediated oophoritis, which can be confirmed by ovarian biopsy, should be considered. Bitches with primary anestrus secondary to thyroid insufficiency or chronic debilitating disease may show normal reproductive cycling and performance after successful treatment of these disorders; in other patients, prognosis for future reproduction is poor.

Thyroid function in fed and fasted white-tailed deer fawns

Serum thyroid hormone concentrations and thyroxine (T4) kinetics were determined in three fed and two fasted white-tailed deer fawns (Odocoileus virginianus borealis). Fasting for 16 days resulted in a drastic decline in total triiodothyronine (T3) (3.22 to 0.49 ng/mL), T4 (241.6 to 68.3 ng/mL) and, to a lesser extent, free T4 (FT4) (2.59 to 1.37 ng/dL). Reverse T3 (rT3) did not change significantly. Although T4 secretion rate (TSR) was greatly reduced (P &lt; 0.05) in the fasted fawns (2.5 (fasted) versus 10.5 (fed) μg T4 per body weight 0.75 (in kilograms) after 20 days of fasting), fractional turnover rate (k/day), total distribution volume (TDV), and metabolic clearance rate (MCR) of injected [131I]T4 did not differ significantly from values in fed fawns. Serum thyroid hormone profiles of the fasted fawns were similar to those reported previously in wild deer collected in Michigan during late winter. In contrast, however, there was no indication of thyroid enlargement.

RAISED TOTAL THYROXINE AND FREE THYROXINE INDEX BUT NORMAL FREE THYROXINE: A Serum Abnormality due to Inherited Increased Affinity of Iodothyronines for Serum Binding Protein

2 people from different families had high levels of serum-thyroxine (T4) and a high free T4 (FT4) index but a normal serum triiodothyronine (T3) and serum-reverse-T3 (rT3). The abnormal serum thyroid hormone profile appeared to be inherited in an autosomal dominant manner. Serum-FT4 in affected relatives was normal. The increases in serum-T4 and FT4 index are explained on the basis of an observed increase in affinity of T4 for thyroxine-binding globulin, thyroxine-binding prealbumin, and albumin. The FT4 index did not reflect the true concentration of circulating free T4 in these cases. Thyroid function in the propositi was normal and the results of T4, T3, and rT3 kinetic studies accorded with increased binding of T4 by serum proteins and normal binding of the other iodo-thyronines. This "euthyroid high total T4, normal T3 syndrome" should be kept in mind during diagnostic evaluation of thyroid function.