Evaluation of a New In-vitro Blood Test for Determining Thyroid Status: The Effective Thyroxine Ratio

Estimation of serum thyroxine concentration in test serum was performed in the presence of test serum itself and expressed as a fraction (Effective Thyroxine Ratio, E.T.R.) of serum thyroxine concentration similarly determined in normal serum. From studies of serum obtained from euthyroid, hyperthyroid, and hypothyroid patients and from euthyroid pregnant women and women taking contraceptive (oestrogen) medication, the E.T.R. estimation has been shown to have a diagnostic accuracy (99%) in defining thyroid status comparable to that shown by the free thyroxine index (98%). Because of the ease and rapidity with which the procedure can be completed, estimation of E.T.R. shows promise as a single, accurate measure of thyroid status.     

Effects of Oestrogen on Urinary Thyroxine Excretion

The day to day variation and the effects of oestrogen on the urinary excretion of thyroxine (T-4) were studied in euthyroid women and men. Serial urinary T-4 values over a period of 28 consecutive days were found to lie within relatively narrow limits except for a transient increase during menstruation in women. During oestrogen therapy urinary T-4 was unchanged, but an appreciable rise was seen after stopping oral ovulation inhibitors in women. A similar effect was seen in men after three days'' treatment with 20 μg/day of ethinyloestradiol. The increased urinary T-4 excretion on oestrogen withdrawal reached a maximum in one to three days. This response contrasted with that produced by phenytoin, a drug known to bind to thyroxine binding globulin, and which resulted in increased urinary T-4 excretion during the period that it was being administered.     

Thyroxine replacement dose in patients with Hashimoto disease: a potential role for interleukin-6

OBJECTIVE: To investigate the potential association between serum inflammatory cytokine levels and thyroxine replacement dose in patients with Hashimoto disease. PATIENTS AND METHODS: The study included 40 patients (12 men) with a mean age of 56.52+/-6.12 years who had hypothyroidism due to Hashimoto disease. Serum interleukin-1b (IL-1b), tumour necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels, as well as TSH, T(3) and T(4) were measured (ELISA). RESULTS: Serum IL-6 showed a significant positive correlation both with total thyroxine replacement dose (r=0.551, p=0.001) and with dose per kilogram of body weight (r=0.482, p=0.002). There was also a significant negative linear correlation between serum IL6 and T(3) (r=-0.322, p=0.043), as well as between serum IL6 and T(3)/T(4) ratio (r=-0.332, p=0.036). A further significant (r=0.419, p=0.007) positive association was demonstrated between IL6 and TNF-alpha. However, no association was found between T(3) or T(3)/T(4) ratio and TNF-alpha or IL1b. CONCLUSIONS: In patients with Hashimoto disease serum IL-6 levels are positively associated with thyroxine replacement dose and negatively associated with T(3) and T(3)/T(4) ratio. These results are possibly attributable to the inhibitory effect of IL6 on deiodination of T(3) and imply a role for IL6 in determining thyroxine replacement dose among these patients.     

Concentration of thyroxine-binding globulin: value of direct assay.

The concentration of thyroxine-binding globulin (TBG) in the serum can now be measured by direct assays that are simple and inexpensive. Comparison of a direct measurement of TBG concentration with a widely used indirect method (Thyopac-3) showed that the indirect method was inaccurate when TBG concentrations were high. This will result in an increase in the derived free thyroxine index (FTI), so that euthyroid patients with a raised TBG concentration may be at risk of being labelled thyrotoxic. Correction of serum total thyroxine (T4) concentration according to the actual TBG concentration (T4:TBG ratio) provided a better correlation with thyroid state than FTI.     

Direct Determination of Serum T-4 by Isotopic Exchange: Comparison with T-3 * and PBI in 1700 Cases

We have studied in detail the procedure for the direct determination of serum thyroxine based on the liberation of ¹²⁵I T-4 from a tagged euthyroid serum reagent, the thyroxine being liberated by alcohol denaturation from 0.5 ml. of patient serum.We have established that there is proceeding simultaneously a second mechanism of T-4 liberation which is in no way associated with patient thyroxine. A simple technique for determining the extent of, and correcting for this second reaction is described.The procedure employs the same equipment used for the ¹²⁵I T-3 and involves only one additional step. No calibration curve is required. Results are not influenced by iodine in any form.The T-4 content is best expressed as a ratio to that of a standard mid-euthyroid serum. The ratio values for the hypothyroid, hyperthyroid and euthyroid states are characteristic and free from overlap. Separation between low normals and hypothyroids is very sharp. The relation between the serum T-4 ratio and the assayed thyroxine content has a correlation coefficient of 0.91. The product of the ¹²⁵I T-3 ratio and the T-4 ratio makes the procedure applicable in pregnancy and during steroid use, and provides a good indication of the free thyroxine present.The values of T-4, the ¹²⁵I T-3 and the PBI have been applied to 1084 patient sera and the T-4 and the ¹²⁵I T-3 to an additional 616. In this series of 1700 patients the serum T-4 was found to indicate the most probable clinical classification with a reliability of at least 95%.     

阿立哌唑与利培酮对男性精神分裂症患者性功能、甲状腺素水平及糖脂代谢的影响

目的:探讨阿立哌唑与利培酮对男性精神分裂症患者性功能、甲状腺素水平及糖脂代谢的影响。方法:选取我院于2016年1月至2017年10月期间收治的92例精神分裂症患者。根据数表法将患者随机分为对照组(n=46)与研究组(n=46),对照组给予利培酮治疗,研究组给予阿立哌唑治疗,两组均治疗8周。观察两组患者临床疗效、性功能、糖脂代谢、甲状腺素水平。结果:研究组患者临床总有效率为84.78%(39/46),高于对照组的78.26%(36/46),但差异无统计学意义(P0.05)。研究组治疗前后性欲、性唤起以及性高潮比较差异无统计学意义(P0.05);对照组治疗后上述指标低于治疗前和研究组(P0.05)。研究组治疗前后三碘甲状腺原氨酸(T3)、甲状腺素(T4)、游离三碘甲状腺原氨酸(FT3)比较差异无统计学意义(P0.05),游离甲状腺素(FT4)低于治疗前(P0.05);对照组治疗后T4、FT3以及FT4低于治疗前和研究组(P0.05)。研究组治疗前后总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)以及餐后2 h血糖(2hPG)比较差异无统计学意义(P0.05);对照组治疗后TG、HDL-C、FPG以及2hPG高于治疗前和研究组(P0.05)。结论:阿立哌唑对男性精神分裂症患者的性功能、甲状腺素水平及糖脂代谢影响较小,与利培酮均具有较好的治疗效果,可做进一步推广应用。     

Total Thyroxine and Free Thyroxine Index in Plasma of Dairy Cows in Relation To Strength of Heat

Total thyroxine (TT4) and free thyroxine index (FT4I) were measured in peripheral plasma of cows. The samples were collected at the time of insemination from 66 cows showing pronounced signs of the heat and from 56 cows showing weak or silent heat. Neither TT4 or FT4I in plasma differed significantly between the two categories of oestrous cows.     

Optimal Free Thyroxine Levels for Thyroid Hormone Replacement in Hypothyroidism

ObjectiveTo determine whether a difference exists in the free thyroxine level required to achieve a normal thyrotropin (thyroid-stimulating hormone or TSH) level between patients with primary hypothyroidism and euthyroid control subjects and compare the free thyroxine levels in patients with primary and secondary hypothyroidism receiving thyroid hormone replacement.MethodsWe retrospectively assessed TSH and free thyroxine values in 58 patients with primary hypothyroidism and 78 euthyroid control subjects for whom screening thyroid function tests had been performed. From the medical records, we also obtained free thyroxine values for 23 patients with central hypothyroidism receiving stable levothyroxine replacement therapy.ResultsThe mean free thyroxine level was significantly higher in patients with primary hypothyroidism than in euthyroid control subjects (1.36 ± 0.201 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), whereas the corresponding mean TSH concentrations did not differ significantly (1.60 ± 1.183 mlU/L versus 1.73 ± 0.792 mlU/L, P = .46). The mean free thyroxine value was also significantly higher in the patients with central hypothyroidism in comparison with that in the euthyroid control subjects (1.31 ± 0.278 ng/dL versus 1.10 ± 0.155 ng/dL, respectively, P < .0001), and no significant difference was noted between the patients with primary and central hypothyroidism (1.36 ng/dL versus 1.31 ng/dL, P = .60).ConclusionPatients with hypothyroidism require a higher level of serum free thyroxine to achieve a normal TSH value in comparison with euthyroid control subjects. This finding suggests that patients with central hypothy-roidism should be treated to achieve free thyroxine levels in the upper part of the reference range. (Endocr Pract. 2008;14:550-555)     

Unusual Ratio between Free Thyroxine and Free Triiodothyronine in a Long-Lived Mole-Rat Species with Bimodal Ageing

Ansell''s mole-rats (Fukomys anselli) are subterranean, long-lived rodents, which live in eusocial families, where the maximum lifespan of breeders is twice as long as that of non-breeders. Their metabolic rate is significantly lower than expected based on allometry, and their retinae show a high density of S-cone opsins. Both features may indicate naturally low thyroid hormone levels. In the present study, we sequenced several major components of the thyroid hormone pathways and analyzed free and total thyroxine and triiodothyronine in serum samples of breeding and non-breeding F. anselli to examine whether a) their thyroid hormone system shows any peculiarities on the genetic level, b) these animals have lower hormone levels compared to euthyroid rodents (rats and guinea pigs), and c) reproductive status, lifespan and free hormone levels are correlated. Genetic analyses confirmed that Ansell''s mole-rats have a conserved thyroid hormone system as known from other mammalian species. Interspecific comparisons revealed that free thyroxine levels of F. anselli were about ten times lower than of guinea pigs and rats, whereas the free triiodothyronine levels, the main biologically active form, did not differ significantly amongst species. The resulting fT4:fT3 ratio is unusual for a mammal and potentially represents a case of natural hypothyroxinemia. Comparisons with total thyroxine levels suggest that mole-rats seem to possess two distinct mechanisms that work hand in hand to downregulate fT4 levels reliably. We could not find any correlation between free hormone levels and reproductive status, gender or weight. Free thyroxine may slightly increase with age, based on sub-significant evidence. Hence, thyroid hormones do not seem to explain the different ageing rates of breeders and non-breeders. Further research is required to investigate the regulatory mechanisms responsible for the unusual proportion of free thyroxine and free triiodothyronine.     

131I对男性甲状腺功能亢进症血清性激素及甲状腺球蛋白水平影响研究

目的:探讨~(131)I对男性甲状腺功能亢进症患者血清性激素及甲状腺球蛋白水平的影响。方法:收集我院收治的男性甲状腺功能亢进症患者74例,随机分为对照组和实验组,每组各37例,对照组患者给予他巴唑口服,20-30 mg/次,每日口服1次。实验组患者在对照组基础上给予~(131)I治疗。治疗结束后,检测并比较两组患者血清游离三碘甲状腺素(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、睾酮(T)、雌二醇(E2)、甲状腺球蛋白(TG)水平的变化以及临床疗效。结果:与治疗前相比,两组患者血清FT3、FT4、T、E2、TG水平均显著下降,TSH水平明显升高(P0.05);与对照组相比,实验组患者血清FT3、FT4、T、E2、TG水平较低,TSH水平以及临床治疗有效率较高(P0.05)。结论:~(131)I能够显著降低男性甲状腺功能亢进症血清FT3、FT4、T、E2、TG水平,升高TSH水平,临床效果较好。     

Long-term haemodialysis and thyroid function.

Several indices of thyroid function were assessed in 74 patients with chronic renal failure. Sixty patients had undergone haemodialysis for varying periods. Within the first six months of haemodialysis treatment protein-bound iodine and total thyroxine (T4) levels rose, but after this T4 levels and the free thyroxine index fell progressively. Three out of the 12 patients who had undergone haemodialysis for longer than three years had subnormal T4 and supranormal thyrotrophin concentrations and a subnormal response to thyrotrophin stimulation. Lon-term haemodialysis may be a cause of biochemical hypothyroidism.     

Closer correlation between serum triiodothyronine and basal metabolic rate during antithyroid drug treatment in patients with Graves' disease.

The correlations between serum triidothyronine (T3), thyroxine (T4), 131I-triiodothyronine resin sponge uptake (RT3U) or free thyroxine index (T7) and the basal metabolic rate (BMR) during antithyroid drug treatment in 86 patients with Graves' disease were investigated. Although serum T3, T4, RT3U and T7 during therapy with MMI showed significant positive correlations with BMR, the coefficient of correlation (r = 0.6088, P less than 0.001) between T3 and BMR was the highest of all. While the normal range of BMR in control subjects was between -1.9 and +14.9 (the range of mean +/- SD), the corresponding values of T3, T4, RT3U and T7 calculated from the regression lines, ranged from 94.2 to 184.0 ng/dl, from 5.32 to 8.75 microgram/dl, from 26.5 to 28.9% and from 1.57 to 2.47 respectively. On the other hand, when the corresponding values of BMR to normal values of T3 (100-170 ng/dl), T4 (7.6-12.2 microgram/dl), RT3U (26.7-36.5% and T7 (2.29-3.49) in control subjects were calculated from the regression lines, the range of value obtained from the regression line of T3 coincided better with normal value of BMR in control subjects that those calculated from other regression lines (T4, RT3U and T7). These results suggest that serum T3 level would be a better index of evaluation of the thyroid function that T4 or RT3U in patients with Graves' disease under antithyroid drug treatment.     

Thyroxine induced stress and its possible prevention by catechin

Free radicals are all known to damage cell components. The present study was designed to evaluate the free radical generation in the testis and liver and also to determine the testicular and hepatic antioxidant enzyme activities with and without catechin administration in thyroxine induced male Sprague-Dawley rats. The experimental animals were divided into four groups, six on each division. L-thyroxine (T4) (0.3 mg/kg body weight) was administered to experimental groups for 15 days. Another group (CAT-T4) was administered with L-thyroxine (T4) in the dose as mentioned and catechin (100 mg/kg of body weight/day) simultaneously. Third group was administered only with catechin, and the remaining group was kept as control. Lipid peroxidation level (LPO) increased in L-thyroxine treated rats as compared to control, while LPO level was almost normal in L-thyroxine (T4) and catechin (CAT-T4) treated group. Superoxide dismutase (SOD) and catalase activities were increased in L-thyroxine (T4) treated rats as compared to control, where as there were almost at normal level in L-thyroxine (T4) and catechin (CAT-T4) treated groups. The results show that, thyroxine administration develops oxidative stress; the organism defends it against the effects of oxidative stress by increasing SOD and catalase activities as a protective mechanism and catechin, being an antioxidant, normalizes lipid peroxidation in testis and liver including SOD and catalase activities.     

Chronic exposure to short photoperiod inhibits free thyroxine index and plasma levels of TSH, T4, triiodothyronine (T3) and cholesterol in female Syrian hamsters

1. Chronic exposure of female Syrian hamsters (Mesocricetus auratus) for 9 weeks to a short photoperiod (10L:14D) depressed the pituitary-thyroid axis as indicated by a drop in circulating titers of thyroid stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3) and the free thyroxine index (FT4I) compared to animals maintained under long photoperiodic conditions (14L:10D). 2. Short day treatment also reduced plasma cholesterol levels. 3. Neither plasma triglycerides, glucose nor growth hormone (GH) levels differed between hamsters exposed to short or long daily photoperiods.     

Plasma Thyroxine in the Sow During Pregnancy and Lactation and During Resumption of Ovarian Activity After Weaning

Total thyroxine in plasma was studied during pregnancy, lactation and during the post weaning period. The ovarian activity was monitored by progesterone determinations, and oestrous symptoms were recorded. In the two sows studied during pregnancy there was a distinct decrease in total thyroxine values in the last month of pregnancy, reaching a minimum about the time of farrowing. Total thyroxine values stayed low during lactation, but from about the time of weaning and during the following two weeks the concentrations increased rapidly. There was no difference in the thyroxine pattern in sows resuming ovarian activity within normal time (10 days) after weaning (72 sows) compared with sows with delayed resumption of ovarian activity (19 sows). The thyroxine level after weaning did not differ between sows with “silent 11631” and sows with overt oestrus. Primiparous and pluriparous sows had also similar thyroxine values after weaning. Sows weaned in January—June had a little higher thyroxine concentrations after weaning than sows weaned in July—December. There was a significant negative correlation between number of suckling piglets and thyroxine concentrations before weaning. Free thyroxine index was calculated in some selected samples. The results suggested that the changes observed in total thyroxine reflect changes in the free thyroxine concentrations.     

Effect of intravenous methimazole on serum levels of thyroid hormones in patients with hyperthyroidism resistant to oral thyrostatic drugs

The effectiveness of therapy involving intravenous administration of methimazole applied in patients with hyperthyroidism resistant to oral thyrostatic drugs has been investigated. Methimazole (Favistan, Asta) was administered intravenously to 3 patients (two women and one man, of ages 21, 24 and 67 years, respectively) in whom there was no remission of the disease after oral methimazole therapy lasting at least two months. Blood serum concentrations of thyroxine (T4), triiodothyronine (T3), reverse++ triiodothyronine (rT3) and triiodothyronine binding index (T3I) have been measured and free thyroxine index (FT4I) calculated before the treatment and on the 4-th, 7-th, 11-th, 14-th and 17-th day of the treatment. The mean value of T4 concentration decreased from 17.0 micrograms/dl before the treatment to 9.7 micrograms/dl after the treatment. T3 from 352 to 177 ng/dl, rT3 from 114 to 103ng/dl the value of T3I from 183 to 161%, and that of FT4I from 30 to 17, respectively. A significant fall of T3 level was observed on the 11-th day of the therapy, that of rT3 on the 14-th day, and that of FT4I on the seventh day. It was concluded that the resistance of some patients with hyperthyroidism to the oral thyreostatic therapy may be caused by the defective absorption of these drugs from the intestinal tract.     

Thyroxine levels and antler growth in white-tailed deer

1. Five normal male, 5 female, and 3 castrated fawns and 5 adult male white-tailed deer were housed in individual pens for one year to compare the relationships between thyroxine (T4) and other blood parameters and the antler cycle. 2. Biweekly serum samples were examined for T4 titers and levels of serum calcium (Ca), inorganic phosphorus (P), and alkaline phosphatase activity (AP). 3. Seasonal T4 changes were found in all deer groups, with elevated titers in the fall. Female fawns had overall lowered T4 levels. In male fawns and adult bucks, T4 seemed to play a synergistic role in antler initiation and growth. 4. Serum Ca levels remained constant throughout the year, but with lower levels in the female fawns. 5. Serum P levels were also constant seasonally, but with higher levels in the female fawns. There was no age effect on either Ca or P. 6. An age effect was evident on plasma alkaline phosphatase with lower activity in adult bucks. There was no sex effect on AP activity. 7. T4 might have an indirect association with the enzyme AP in Ca and P transport system in white-tailed deer.     

Thyroid function tests in children with congenital hypothyroidism on L-thyroxine treatment

The plasma levels of thyroxine (T4), triiodothyronine (T3), free T4 (FT4), free T3 (FT3), reverse T3 (rT3) and immunoradiometrically assayed thyrotropin (IRMA TSH) have been measured in 28 L-T4-treated children with congenital hypothyroidism as well as in a control group (group C). The patients were subdivided into 2 groups according to the nonsuppressed (group A) or suppressed (group B) TSH response to TSH-releasing hormone (TRH). Basal IRMA TSH correlated with the TSH increment after TRH and it was significantly lower in group B vs. groups A and C, while no difference was present between groups A and B in regard to T4, FT4 and rT3, all higher than in group C. FT3 levels were similar in the 3 groups. In children, as in adults, basal IRMA TSH seems to be a reliable index in monitoring overtreatment.     

T4 metabolism in age matched heavy and light rats with good and bad feed efficiency following high- or low-in-fat diet

Rats, fed two diets (high or low in fat content), were at the and of the feeding-period separated in light and in heavy animal groups. The leaner rats from the diet group high in fat content show opposite to the heavier animals of this diet group significantly increased T4 distribution spaces, significantly shortened T4 half life time and lower feed efficiency. T4 serum values, absolute T4 degradation per day and body mass and free thyroxine index in these leaner rats also increased significantly. However comparing heavy rats feed a diet low and light rats fed a diet high in rat content the latter show also a decreased feed efficiency, but no differences in T4 serum concentration or T3 binding capacity of serum proteins, free thyroxine index and T4 degradation. The results in T4 metabolism are discussed in relation to feed efficiency of the investigated animal groups.     

The Clinical Utility of Free Thyroxine in Oral Levothyroxine Absorption Testing

ObjectiveOriginal absorption studies for levothyroxine (LT₄) were validated using total thyroxine (TT₄) measurements. Free thyroxine (FT₄) has largely supplanted TT₄ in clinical practice. The objective of our study was to assess the clinical utility of FT₄ in oral LT₄ absorption testing.MethodsIn this retrospective electronic health record analysis, we recorded data of patients who underwent LT₄ oral absorption testing between November 2010 and January 2012 because of persistent hypothyroidism despite a greater than anticipated weight-based dose of LT₄. Patients included had primary hypothyroidism and an absorption test with assessment of both TT₄ and FT₄ measured at times 0, 30, 60, 90, 120, 180, 240, 300, and 360 minutes. The test was conducted with 1 mg (five 200-μg tablets) of Synthroid® after an overnight fast by a standard nonisotopic method.ResultsA total of 10 patients (3 men/7 women) underwent absorption testing. Prior to testing, the median daily LT₄ dose was 250 μg (range, 150 to 350 μg). Three patients were also on liothyronine (10, 20, or 50 μg daily). Based on the calculated amount absorbed, 1 patient demonstrated subnormal absorption, and 9 patients were normal. Median body mass index was 33 kg/m² (range, 21 to 50 kg/m²). Median calculated absorption was 105% (range, 3.7 to 195.6%). The correlation comparing FT₄ and TT₄ was 0.88 (95% confidence interval, 0.56 to 0.97, P < .001), a significant correlation.ConclusionFT₄ and TT₄ correlated highly, even in patients who were severely hypothyroid; FT₄ may be used interchangeably with TT₄ as a qualitative assessment of suspected malabsorption using an oral LT₄ absorption test. (Endocr Pract. 2014;20:925-929)