Dilantin and salicylate effects on hepatic thyroxine bio-availability and dialyzable thyroxine

Earlier studies have shown that drugs such as dilantin inhibit T4 binding by thyroid hormone binding globulin (TBG) and cause a displacement of T4 from TBG to prealbumin with no change in the albumin-bound T4 fraction. Since recent studies have shown albumin-bound T4 is freely transported into liver, the present studies are designed to investigate drug effects on T4 transport in liver. The effect of salicylate and diphenylhydantoin (Dilantin) on T4 in human serum were examined both in vitro by using equilibrium dialysis and in vivo in the rat liver by using a tissue sampling single injection technique. Serum was obtained from 6 healthy normal volunteers and was made either 0 or 0.5 mM Dilantin and either 0 or 10 mM sodium salicylate. The portal vein injection vehicle contained 125I-T4/3H-water (highly diffusible internal reference) mixed with either a) Ringer's (0.1 g/dl albumin), b) 5% T4 antiserum, or c) 80% human serum. The free dialyzable fraction in vitro was raised by 40 and 125% after the addition of Dilantin and salicylate respectively. However, the percent of total T4 that was transported into liver on one pass, 17 +/- 1%, was not different in the control, the salicylate treated, or the Dilantin-treated sera. Therefore, in contrast to the in vitro dialyzable measurement of free T4, which is elevated by toxic concentrations of Dilantin or salicylate, the bio-available fraction of T4 as determined by the single pass perfusion technique, is unchanged in rat liver in vivo. These drug-induced changes in free T4 in vitro and bio-available T4 in vivo are similar to the ones reported previously in non-thyroidal illness.     

Interaction of thyroxine,energy metabolism and swimming performance of rats

Time required for exhaustive swimming by young-mature rats weighted with lead weights (4% of body weight) was found to decline over a ten week experimental period. While a positive relationship existed between thyroid status and swimming time, a concomitant decrease in swimming time occurred in each of the respective five groups of rats: control (C) rats with intact thyroids, athyroid (A-Tdx), hypothyroid (Hypo-Tdx), euthyroid (Eu-Tdx), and hyperthyroid (Hyper-Tdx) rats between day 70–140. The latter three groups were thyroidectomized (Tdx) and given daily replacement therapy of L-thyroxine (L-T₄) during the experimental period. Epididymal fat pads were found to be almost non-existent in the A-Tdx rats. Serum triglycerides of A-Tdx, Eu-Tdx, and Hypo-Tdx animals were significantly lower than in C. Daily food intakes were also lower in the A-Tdx and Hypo-Tdx groups than in C and Hyper-Tdx groups. Thyroxine insufficiency, the decreasing feed intake, and particularly the ability to carry the increasing absolute weight load during exercise are factors that may be important in explaining the observed decline in work capacity during the ten week experimental period.     

Free thyroxine, cognitive decline and depression in Alzheimer's disease

The role of thyroid function in Alzheimer's disease (AD) has been subject to a number of studies during the last years. We investigated the possible relationship between plasma levels of the biologically active free form of thyroxin (fT4) and cognitive function in 227 outpatients with mild to moderate Alzheimer s disease (AD) in a cross-sectional study design. A significant negative correlation was found between plasma fT4-levels and Mini-Mental state examination (MMSE) score (Spearman Rho = -0.14, p=0.04). When the lowest quartile of fT4-levels (<15.1 pmol/l) was compared to the highest quartile (>19.0 pmol/l), statistically significant lower mean MMSE-scores were seen in the group with the highest fT4-levels (p<0.05, ANOVA). The mean difference between the 1st and the 4th quartile of fT4 was 2.6 MMSE-score points. No correlations were found between plasma total T4-levels, plasma total T3-levels, plasma TSH-levels and the MMSE score (p>0.05). When fT4 quartile groups were compared for depression measured in the Geriatric Depression Score (GDS 15), a slightly higher score was seen in the 1s and 2nd compared to the 3rd and 4th quartile groups without reaching statistical significance (1st quartile of fT4: GDS 5.2 +/- 3.8; 2nd: 5.3 +/- 4.0; 3rd: 4.4 +/- 3.4; 4th: 4.5 +/- 3.8) pointing to a reverse correlation of fT4 levels and depressive mood. This study leads to the conclusion that high levels of plasma fT4 might result in a worsening of cognitive impairment and a positive effect on depressive mood in AD.     

Seasonal levels of cortisol, triiodothyronine and thyroxine in male axis deer

1. Seasonal plasma levels of thyroxine (T4), triiodothyronine (T3) and cortisol were investigated between November and June in seven penned male Axis deer. 2. No distinct seasonal variation of cortisol has been detected. The levels oscillated between 1 and 5 micrograms/dl. 3. The stress of immobilization and sampling had little effect on cortisol levels. Concentrations remained mostly stable in three consecutive samples taken 10 min apart. 4. T3 concentrations were stable between November and March (average values 110-120 ng/dl). After a sharp decline in April (average 70 ng/dl), a strong rebound in May and June was observed. 5. A distinct seasonal peak of T4 (highest individual value, 12.1 micrograms/dl) was detected in March. After a sharp decline in April (lowest individual value, 4.5 micrograms/dl) a strong rebound followed in May.     

Thyroxine-binding globulin, triiodothyronine, thyroxine and thyrotropin in newborn infants and children.

Thyroxine-binding globulin (TBG), triiodothyronine (T3), thyroxine (T4) and thyrotropin (TSH) have been determined by radioimmunoassay in plasma of newborn infants and throughout childhood until puberty. Mean maternal TBG concentration was 1.65 +/- 0.09 mg/100 ml (SEM) and significantly higher (p less than 0.01) than cord blood levels of TBG (1.16 +/- 0.08 mg/100 ml (SEM). Throughout infancy and childhood TBG remained significantly elevated (p less than 0.01) compared to a middle age control group of healthy blood donors. T3, T4 and TSH concentrations behaved postnatally as known from previous studies. The T3 and T4 increase observed immediately after birth was not a secondary phenomenon due to changes in TBG concentration since this globulin did not change significantly during this period.