Changes In T3 Levels Research Articles

Sustained Pituitary T3 Production Explains the T4-mediated TSH Feedback Mechanism.

The regulation of thyroid activity and thyroid hormone (TH) secretion is based on feedback mechanisms that involve the anterior pituitary TSH and medial basal hypothalamus TSH-releasing hormone. Plasma T3 levels can be "sensed" directly by the anterior pituitary and medial basal hypothalamus; plasma T4 levels require local conversion of T4 to T3, which is mediated by the type 2 deiodinase (D2). To study D2-mediated T4 to T3 conversion and T3 production in the anterior pituitary gland, we used mouse pituitary explants incubated with 125I-T4 for 48 hours to measure T3 production at different concentrations of free T4. The results were compared with cultures of D1- or D2-expressing cells, as well as freshly isolated mouse tissue. These studies revealed a unique regulation of the D2 pathway in the anterior pituitary gland, distinct from that observed in nonpituitary tissues. In the anterior pituitary, increasing T4 levels reduced D2 activity slightly but caused a direct increase in T3 production. However, the same changes in T4 levels decreased T3 production in human HSkM cells and murine C2C12 cells (both skeletal muscle) and mouse bone marrow tissue, which reached zero at 50 pM free T4. In contrast, the increase in T4 levels caused the pig kidney LLC-PK1 cells and kidney fragments to proportionally increase T3 production. These findings have important implications for both physiology and clinical practice because they clarify the mechanism by which fluctuations in plasma T4 levels are transduced in the anterior pituitary gland to mediate the TSH feedback mechanism.

Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T3) supplementation.

Diurnal (i.e., 24 hr) physiological rhythms depend on transcriptional programs controlled by a set of circadian clock genes/proteins. Systemic factors like humoral and neuronal signals, oscillations in body temperature, and food intake align physiological circadian rhythms with external time. Thyroid hormones (THs) are major regulators of circadian clock target processes such as energy metabolism, but little is known about how fluctuations in TH levels affect the circadian coordination of tissue physiology. In this study, a high triiodothyronine (T3) state was induced in mice by supplementing T3 in the drinking water, which affected body temperature, and oxygen consumption in a time-of-day-dependent manner. A 24-hr transcriptome profiling of liver tissue identified 37 robustly and time independently T3-associated transcripts as potential TH state markers in the liver. Such genes participated in xenobiotic transport, lipid and xenobiotic metabolism. We also identified 10-15% of the liver transcriptome as rhythmic in control and T3 groups, but only 4% of the liver transcriptome (1033 genes) were rhythmic across both conditions - amongst these, several core clock genes. In-depth rhythm analyses showed that most changes in transcript rhythms were related to mesor (50%), followed by amplitude (10%), and phase (10%). Gene set enrichment analysis revealed TH state-dependent reorganization of metabolic processes such as lipid and glucose metabolism. At high T3 levels, we observed weakening or loss of rhythmicity for transcripts associated with glucose and fatty acid metabolism, suggesting increased hepatic energy turnover. In summary, we provide evidence that tonic changes in T3 levels restructure the diurnal liver metabolic transcriptome independent of local molecular circadian clocks.

THE IMPORTANCE OF THYROID HORMONE LEVELS AFTER HEART SURGERY – PRELIMINARY STUDY

Introduction Thyroid hormone level suppression after serious operations as coronary artery bypass graft (CABG) surgery, and aortic valve replacement (AVR) is a quite common phenomenon. It is called the nonthyroidal illness syndrome. This appears with a decrease in triiodothyronine (T3) and tetra iodothyronine (T4) serum levels with no thyroid disorders in the medical history. Our aim was to investigate the relationship among thyroid hormone levels and postoperative complications after CABG and AVR. Methods This single center retrospective, observational study approved by the IRB (65/2017). 49 patients, who underwent CABG or AVR, were enrolled in our study between the 1st of January 2019 and the 16th of February 2021. Demographic parameters, Euroscore, thyroid disorders, T3, T4 levels in the first postoperative week, the perioperative thyroxine supplementation and the vasopressor- inotropic needs were summarized in our database. Our primary outcome was 1-year mortality, secondary outcome was the length of stay in the intensive care unit (ICU). Spearman's correlation and Cox-regression analysis were used for the statistical analysis. Results Final analysis included 49 patients, 9 (18.4%) were female. The median survival time was 584 days (IQR25-75: 571-614). Five of the 49 patients (10.2%) died until the 16th of February 2021. Seven patients (14.3%) stayed in ICU for more than 72 hours. Four patients (8.2%) were treated with thyroxine in the postoperative period whom did not have preoperative thyroid dysfunction. None of the patients had hypothyroidism nor hyperthyroidism in their medical history. 17 patients (34.7%) had low T3 levels while, none of the patients had low T4 levels on the 1st or 2nd postoperative day. Association was found between the lengths of stay in the ICU and low T4 levels (p=0.048) using nonparametric test. The actual change in T4 levels between the first and the second sample during first postoperative week showed a significant association with 1-year mortality (OR: 1.17; 95%CI: 1.04-1.31; p=0.007). Discussion Our results highlight the role of thyroid function in the postoperative period. The decrease of T4 levels have independent relationship with adverse outcomes as 1-year mortality and the lengths of ICU stay. Thyroid function monitoring could be a beneficial after CABG and AVR operations.

A Comparison Between The Effect Of Shisha And Cigarette Smoking On Thyroid Function Of Males

Studies show, that smoke may effect physiological of the thyroid gland functions, this study aim was to decide the effects of cigarette smoke or hookah smoke on thyroid function in males. Thyroid is a consider endocrine gland located under the larynx, thyroid hormones of the major are thyroxinT4, Tri-iodothyroxine T3 , and thyroid inspiring hormone TSH,. Male divided into cigarette smokeG1, hookah smoking G2,and control group G3, The results indicated that serum TSH levels were significant change low a in the G1 group than with the control group(G3), and we found the levels of TSH hormone were significant change lower P˂0.05 in the cigarette smokers compared with the control group, TSH levels were no significant P≥0.05 between the hookah smokingG2 3.6±0.004 and control group, and highly significant mean differences among two groups in the TSH levels between the G1 and G2, Our findings also indicated a significant increase in T3 or T4 serum levels in smoking, also the levels of triiodothyronine hormone (T3) were P˂0.05 (significantly higher) in the cigarette smokers 3.50±1.1 nmol/l compare with the control group G3, 0.98±0.002nmol/l,, We found also the levels of thyroxine T4 significant higher p˂0.05 than control G3 and cigarette smokers. Also the significant differences in T3 levels P˂0.05 betweenG24.01±`0.4 than G3 0.98±0.002,also we found significant differences in the T4 levels P˂0.05 between G2 140±30 compared G3 120±22, . Also we found no significant change in T3 levels P>0.05 between G1 3.50±`1.1than G2 4.01±`0.4, also we found no significant changes in T4 levels P>0.05 in G1 135±24compared G2

Activation of GLP-1 and Glucagon Receptors Regulates Bile Homeostasis Independent of Thyroid Hormone.

Balanced coagonists of glucagon-like peptide-1 (GLP-1) and glucagon receptors are emerging therapies for the treatment of obesity and diabetes. Such coagonists also regulate lipid metabolism, independent of their body weight lowering effects. Many actions of the coagonists are partly mediated by fibroblast growth factor 21 (FGF21) signaling, with the major exception of bile homeostasis. Since thyroid hormone is an important regulator of bile homeostasis, we studied the involvement of thyroid hormone in coagonist-induced changes in lipid and bile metabolism. We evaluated the effect of a single dose of coagonist Aib2 C24 chimera2 at 150 to 10000 µg/kg on tetraiodothyronine (T4) and triiodothyronine (T3) in high-fat diet-induced obese (DIO) mice and chow-fed mice. Repeated dose treatment of coagonist (150 µg/kg, subcutaneously) was assessed in four mice models namely, on lipid and bile homeostasis in DIO mice, propylthiouracil (PTU)-treated DIO mice, methimazole (MTM)-treated DIO mice and choline-deficient, L-amino acid-defined, highfat diet (CDAHFD)-induced nonalcoholic steatohepatitis (NASH). Single dose treatment of coagonist did not alter serum T3 and T4 in chow-fed mice and DIO mice. Coagonist treatment improved lipid metabolism and biliary cholesterol excretion. Chronic treatment of GLP-1 and glucagon coagonist did not alter serum T3 in hypothyroid DIO mice and CDAHFDinduced NASH. Coagonist increased serum T4 in DIO mice after 4 and 40 weeks of treatment, though no change in T4 levels was observed in hypothyroid mice or mice with NASH. Our data demonstrate that coagonist of GLP-1 and glucagon receptors does not modulate bile homeostasis via thyroid signaling.

A Global Loss of Dio2 Leads to Unexpected Changes in Function and Fiber Types of Slow Skeletal Muscle in Male Mice.

The type 2 iodothyronine-deiodinase (D2) enzyme converts T4 to T3, and mice deficient in this enzyme [D2 knockout (D2KO) mice] have decreased T3 derived from T4 in skeletal muscle despite normal circulating T3 levels. Because slow skeletal muscle is particularly susceptible to changes in T3 levels, we expected D2 inactivation to result in more pronounced slow-muscle characteristics in the soleus muscle, mirroring hypothyroidism. However, ex vivo studies of D2KO soleus revealed higher rates of twitch contraction and relaxation and reduced resistance to fatigue. Immunostaining of D2KO soleus showed that these properties were associated with changes in muscle fiber type composition, including a marked increase in the number of fast, glycolytic type IIB fibers. D2KO soleus muscle fibers had a larger cross-sectional area, and this correlated with increased myonuclear accretion in myotubes formed from D2KO skeletal muscle precursor cells differentiated in vitro. Consistent with our functional findings, D2KO soleus gene expression was markedly different from that in hypothyroid wild-type (WT) mice. Comparison of gene expression between euthyroid WT and D2KO mice indicated that PGC-1α, a T3-dependent regulator of slow muscle fiber type, was decreased by ∼50% in D2KO soleus. Disruption of Dio2 in the C2C12 myoblast cell line led to a significant decrease in PGC-1α expression and a faster muscle phenotype upon differentiation. These results indicate that D2 loss leads to significant changes in soleus contractile function and fiber type composition that are inconsistent with local hypothyroidism and suggest that reduced levels of PCG-1α may contribute to the observed phenotypical changes.

Тиреотропні ефекти води Нафтуся, їх вегетативний прояв і можливість прогнозування

Clinical physiological monitoring of 32 men aged 25-60 years with chronic stoneless cholecystitis in the phase of remission found that in 14 patients 75-85 minutes after drinking the bioactive water Naftussya (3 ml/kg, t(0) 18-20 degrees C) the plasma level of total triiodothyronine (T3) was not significantly changed, while in 9 patients it was reduced to 0.26 +/- 0.10 nM/1 (by 11%). In the other 9 patients the level increased to 0.29 +/- 0,04 nM/1 (by 17%). The changes in T3 level correlated negatively with the changes in absolute (r = -0.55) and relative (r = -0.47) power spectral density (PSD) of ultra very low-frequency components of heart rate variability (HRV). These changes correlated positively (r = 0.46) with the changes in relative PSD of low-frequency components of HRV. Subject to a weak correlation with HRV parameter pNN50 (r = -0.21) canonical correlation coefficient (R) between changes in HRV parameters and T3 reaches 0.68 (p = 0.002). On the other hand, the changes in T3 correlated with its initial level (r = -0.46), as well as initial levels of moda (r = -0.40), its amplitude (r = 0.30) and absolute PSD of low-frequency components HRV (r = -0.33), i.e. thyrotropic effects conditionized these parameters by 30% (R = 0.55; p = 0.038). The method ofdiscriminant analysis has identified 14 primary parameters that allowed predicting the thyrotropic effect of Naftussya water with 100% accuracy.

Thyroid Function and Clinical Outcomes in Kidney Failure

Thyroid hormone synthesis is finely tuned to respond to the variable energy needs of the human body ([1][1]). This process is controlled by two fundamental mechanisms. The first, based on the thyroid-stimulating hormone (TSH)–thyroxine (T4) and triiodothyronine (T3) feed-back loop, constitutes a

Seasonal changes in body mass, energy intake and thermogenesis in Maximowiczi’s voles (Microtus maximowiczii) from the Inner Mongolian grassland

Small mammals inhabiting temperate and arctic regions exhibit annual adaptive adjustments in physiology, anatomy, and behavior. No data on the physiology of Maximowicz's voles (Microtus maximowiczii) are available at present. Here we examined the seasonal changes in body mass, food intake, thermogenic capacity, serum leptin and thyroid hormone levels in wild-captured individuals from Inner Mongolian grassland, China. We further examined the effects of photoperiod on these parameters. Energy intake, resting metabolic rate, nonshivering thermogenesis (NST), and serum tri-iodothyronine (T3) levels increased while serum leptin and body mass decreased in the cold seasons. Serum T3 levels were positively correlated with NST and uncoupling protein 1 (UCP1) contents in brown adipose tissue, and leptin levels were negatively correlated with energy intake and resting metabolic rate. Furthermore, laboratory data showed these changes could be induced by short photoperiod alone. Taken together, our results indicate that Maximowicz's voles can increase thermogenic capacity and energy intake to cope with cold stress. Serum leptin seems to be involved in the regulation of energy intake and changes in T3 level may be important for the variations in NST and/or UCP1. Short photoperiod can serve as a seasonal cue for the winter acclimatization of energy balance in free-living Maximowicz's voles.

Effect of triiodothyronine on gene transcription during cardiopulmonary bypass in infants with ventricular septal defect

We tested the hypothesis that triiodothyronine (T3) supplementation alters gene transcription in the left ventricular myocardium of infants undergoing cardiopulmonary bypass for ventricular septal defect repair. To our knowledge, a novel heteronuclear assay demonstrated for the first time in human heart that rapid change in T3 levels altered the adenine nucleotide translocase-1 transcription rate during cardiopulmonary bypass.

Leptin and thyroxine during sexual development in male monkeys: effect of neonatal gonadotropin-releasing hormone antagonist treatment and delayed puberty on the developmental pattern of leptin and thyroxine secretion

Neonatal treatment of male monkeys with a gonadotropin-releasing hormone antagonist (Ant) increased the incidence of delayed puberty. Using blood samples that had been collected from monkeys with normal or delayed puberty, we assessed the potential involvement of leptin and thyroxine (T4) in sexual development. Monkeys were treated from birth until 4 months of age with vehicle, Ant or Ant/androgen and blood samples were drawn from 10 to 62 months of age. Serum leptin and total T4 concentrations declined in parallel throughout adolescence in all treatment groups. There was no transient rise in leptin before or in association with the onset of puberty. Also, leptin did not differ during the peripubertal period between animals experiencing puberty at that time versus those in which puberty was being delayed. Neonates treated with Ant either alone or with androgen replacement had higher leptin levels than controls throughout development. While leptin exhibited no significant changes during the peripubertal period, T4 values increased and declined in parallel with the peripubertal changes in hypothalamic-pituitary-testicular activity. These data do not support the concept that a transient rise in leptin triggers the onset of puberty in male monkeys. However, the disruption of neonatal activity of the pituitary-testicular axis alters the developmental pattern of leptin. The changes in T4 levels during the peripubertal period suggest that thyroid status may be a significant contributor to the process of sexual development in the male monkey and that peripubertal changes in secretion of this hormone may serve as an effective physiological response during a critical period of elevated energy expenditure.

Transthyretin regulates thyroid hormone levels in the choroid plexus, but not in the brain parenchyma: study in a transthyretin-null mouse model.

Transthyretin (TTR) is the major T4-binding protein in rodents. Using a TTR-null mouse model we asked the following questions. 1) Do other T4 binding moieties replace TTR in the cerebrospinal fluid (CSF)? 2) Are the low whole brain total T4 levels found in this mouse model associated with hypothyroidism, e.g. increased 5'-deiodinase type 2 (D2) activity and RC3-neurogranin messenger RNA levels? 3) Which brain regions account for the decreased total whole brain T4 levels? 4) Are there changes in T3 levels in the brain? Our results show the following. 1) No other T4-binding protein replaces TTR in the CSF of the TTR-null mice. 2) D2 activity is normal in the cortex, cerebellum, and hippocampus, and total brain RC3-neurogranin messenger RNA levels are not altered. 3) T4 levels measured in the cortex, cerebellum, and hippocampus are normal. However T4 and T3 levels in the choroid plexus are only 14% and 48% of the normal values, respectively. 4) T3 levels are normal in the brain parenchyma. The data presented here suggest that TTR influences thyroid hormone levels in the choroid plexus, but not in the brain. Interference with the blood-choroid-plexus-CSF-TTR-mediated route of T4 entry into the brain caused by the absence of TTR does not produce measurable features of hypothyroidism. It thus appears that TTR is not required for T4 entry or for maintenance of the euthyroid state in the mouse brain.

Serum Growth-Hormone-Binding Protein and Growth during Treatment of Children with Hyperthyroidism and Hypotyroidism

Thyroid hormone greatly influences postnatal growth in children and secretion of growth hormone (GH). To study the relation between serum GH-binding protein (GHBP), which is expressed as tissue GH-receptor concentrations and influenced by the nutritional state, thyroid hormone and growth development, we measured serum GHBP in six children with hyperthyoidism and six children with hypothyroidism using samples taken before and during treatment. Mean treatment periods of these diseases are 13 and 10 months, respectively. Mean height velocity standard deviation (SD) score decreased from 2.51 to -0.62, but was not significantly related to the treatment, in hyperthyroidism, and significantly increased from -3.02 to 5.27 due to the treatment in hypothyroidism. There was no significant difference of GHBP levels before the treatment between hyper- and hypothyroidism (mean 9.59 vs. 8.53ng/mL). In hyperthyroidism, GHBP levels decreased significantly during the treatment. In hypothyroidism, insulin-like growth factor I (IGF-I) and IGF binding protein-3 (IGFBP-3) increased, but percent overweight decreased significantly, and GHBP levels did not significantly change during the treatment.ΔGHBP was defined as the change in GHBP during treatment to examine whether or not the change in GHBP was parallel to the change in thyroid hormone. ΔGHBP showed no correlation with Δ height velocity SD score. ΔGHBP showed a significant positive correlation with ΔT4 level and negative correlation with Δpercent overweight. However, only ΔT4 was identified as an influencing factor on ΔGHBP by stepwise multiple regression analysis.The data demonstrate that the changes in serum GHBP level were influenced by the changes in T4 levels during the treatment of abnormal thyroid function. The data also show that GHBP was unrelated to height gain associated with treatment in hyperthyroidism and hypothroidism.

Thyroid function in the cat: assessment by the TRH response test and the thyrotrophin stimulation test

ABSTRACTChanges in total thyroxine (T4), free T4 and total tri‐iodothyronine (T3) were measured in 13 cats after the intravenous injection of varying doses of thyrotrophin stimulating hormone (TSH) (0–5 U/cat n = 6; 1 U/cat n = 8; 1 U/kg bodyweight, n = 7) or thyrotrophin releasing hormone (TRH) (100 ug/cat, n = 10). All three doses of TSH resulted in a significant (P < 0–05) rise in T4, free T4 and T3 levels, with the mean peak in hormone concentrations occurring six to eight hours after injection. The three doses of TSH all appeared to produce maximal stimulation of thyroid hormone secretion. The mean percentage increase in hormone concentrations at seven hours following the three doses of TSH ranged from 167 to 198 per cent for T4, 240 to 365 per cent for free T4, and 73 to 116 per cent for T3. Following administration of TRH there was also a significant (P < 0–05) rise in T4, and free T4. The mean peak in T4 and free T4 levels occurred at four hours, and mean increases in hormone levels at this time were 92 per cent for T4, and 198 per cent for free T4. The administration of TRH produced little change in T3 levels. TSH administration resulted in a significantly higher (P < 0–05) percentage peak increase in T4, free T4 and T3 levels at all three dosages than did TRH.

Seasonal changes in weight gain, growth hormone, and thyroid hormones in male red deer (Cervus elaphus atlanticus)

To elucidate possible endocrine mechanisms in the control of the weight cycle of red deer, we recorded seasonal changes in the concentrations of growth hormone (GH), thyroxine (T4), and triiodothyronine (T3) in serum. T3 and T4 were analyzed with specific radioimmunoassays, GH was analyzed with a hetereologous radioimmunoassay. Changes in the levels of these hormones were compared with changes in weight gain. T3 levels were high in summer and low in winter, corresponding to changes in weight gain. Peak values (1.75–4.82 nmol/L) were found in May or June, nadirs occurred in April (0.22–1.78 nmol/L) or October–November (0–1.19 nmol/L). GH levels increased to peak values, 20–53 ng/mL, in April to June, but were low during most of the period of fast weight gain. There were no consistent changes in T4 levels corresponding to the weight cycle. We conclude that the GH peaks following the casting of old antlers may be related to the onset of antler growth. Seasonal changes in T3 levels may be secondary to changes in food intake.

Changes in Blood Levels of Thyroid Hormones in Two Species of Passerine Birds

Annual changes in plasma levels of thyroxine (T4) and triiodothyronine (T3) were compared in White-crowned Sparrows (Zonotrichia leucophrys gambelii) and House Sparrows (Passer domesticus) using serial blood samples from birds maintained in outdoor aviaries and from feral birds. Gonadal size was monitored by monthly laparotomy, and plumage was examined for molt at frequent intervals. Hormone levels were examined in relation to cycles of reproduction and molt, and to changes in ambient temperature. Thyroxine levels increased during postnuptial molt in both species, although in White-crowned Sparrows the increase was similar to that noted in late April and early May, which may have been associated with premigratory activity. However, in House Sparrows, thyroxine levels were highest throughout the three-month period of molt (mid-August to mid-November). They did not increase immediately after gonadal regression, giving no support for the hypothesis of a thyroid-gonad antagonism. Cold winter temperatures and changes in day length appeared to have little effect on T3 and T4 levels. In both species T3 levels showed little seasonal variation, and changes in T4 levels were independent of those in T3. Beginning more than half a century ago, with the experiments in which thyroid tissue was fed to birds (Carlson et al. 1912), a voluminous literature has accumulated that implicates thyroid hormones as the cause for molt (for reviews see Assenmacher 1958, Voitkevich 1966, Payne 1972). Although thyroidectomy appears to inhibit molt and thyroid-inhibiting drugs often alter feather morphology (Voitkevich 1966), histological studies in several species, using epithelial cell height as a measure of thyroid activity, do not support the hypothesis that an increase in thyroid gland function is the primary mechanism responsible for molt and feather replacement (reviews by Wilson and Farner 1960, Payne 1972). Progesterone and prolactin also induce molt, but in experiments with such hormones feathers are usually dropped in an abnormal sequence (Assenmacher 1958, Tanabe and Katsuragi 1962). Using radioimmunoassay, I measured changes in plasma levels of thyroid hormones in order to determine if there were increases in thyroid activity associated with molt or with seasonal cycles in ambient temperature, and if there was a hormonal basis for the temporal separation of reproduction and molt. I compared the White-crowned Sparrow (Zonotrichia leucophrys gambelii), a migratory species having two molts per year, with the House Sparrow (Passer domesticus), a sedentary species which has a single extended molt

The effect of hGH on hypothalamic-pituitary-thyroid function in patients with pituitary dwarfism.

Abstract. The effect of growth hormone (hGH) on the hypothalamic-pituitary-thyroid function was studied in patients with pituitary dwarfism. Twenty-six patients were given KABI hGH, 0.5 U/kg/week, for a period of 4—18 months. Three groups of patients were identified according to their T4 levels before and during the treatment. Group 1: T4 levels were initially normal and stayed in the normal range throughout a course of treatment. Group 2: T4 levels were initially normal but dropped to the subnormal range after hGH. Group 3: T4 levels were initially subnormal and decreased further after hGH. Changes in T4 levels after hGH in groups 2 and 3 were accompanied by a decrease in plasma T3RSU without concomitant decrease in plasma T3. Clinically, most of them lacked symptoms and signs of hypothyroidism and exhibited a good growth response to hGH. Plasma TSH response to TRH in these patients revealed a sustained delayed pattern, which was suggestive of hypothalamic hypothyroidism. This pattern of TSH response to TRH became further exaggerated after hGH therapy. In contrast, TSH response to TRH among patients in group 1 was normal and was not influenced by hGH. Administration of 4.0 U of KABI hGH daily for 21 consecutive days to 3 patients resulted in a shortened half-life of T4 and inversely prolonged that of T3. These results suggest that various degrees of TRH deficiency exist among patients with idiopathic pituitary dwarfism. Therapy with hGH discloses a mild TRH deficiency by accelerating the half-life of T4. This also causes a further drop in the T4 levels in those with marked TRH deficiency. The development of clinical hypothyroidism is not so obvious in these patients because of inverse delay in half-life of T3 by hGH.

Thyroid Hormones in Alcoholic Liver Disease

The relationship between alcoholic liver disease and circulating thyroid hormones was investigated in 124 hospitalized patients treated with placebo or propylthiouracil (PTU) for a maximum of 46 days in a double-blind study. Serum triiodothyronine (T3) levels on admission were significantly (P less than 10(-6) and inversely correlated with the severity of alcoholic liver disease. After hospitalization, changes in T3-levels in patients with low admission T3 significantly correlated (P less than 0.001) with the degree of spontaneous improvement of liver function (placebo group). Treatment with 300 mg of PTU daily (Orrego et al. Gastroenterology 76:105--115, 1979) markedly increased the rate of improvement in severely ill patients with low T3 on admission. In this group, serum T3-levels were also increased after PTU, but this increase did not correlate with the change in the patient's condition. It is suggested that the known inhibitory effect of PTU on peripheral deiodination of T4 to T3 is marked by a more marked improvement in liver function in this group. PTU treatment in this group reduced the free T4-index and increased TSH levels markedly (16%; P less than 0.02) toward levels found in hypothyroidism. PTU did not improve the condition of mildly ill patients with normal admission T3-levels, nor did it alter free T4-index or serum TSH levels in these patients. Serum T3-levels provide a sensitive indicator of the severity of alcoholic liver disease and of its response to conventional treatment. Serum T3-levels also distinguish between a group of patients, in whom low-dose PTU administration results in a beneficial effect, and another group, in whom no therapeutic effect of PTU is observed.

Thyroid Hormone and Thyrotropin Levels in Patients Placed on Colestipol Hydrochloride*

Bile acid sequestrant resins can bind T4 in vitro and in the gut. Therefore, the effect of colestipol HCl on thyroid function was studied prospectively in 17 subjects with type II hyperlipoproteinemia. Serum T4, T3, T3 resin uptake, and TSH levels were measured before and during therapy. No change in T4 levels and only small transient, but significant, decreases in T3 were noted in a minority of patients; TSH levels did not change. Small increases in T3 resin uptake were noted. We conclude that no major alterations in thyroid function occurred with colestipol therapy.

Effects of Triiodothyronine Administration in Patients with Chronic Renal Failure

Clinically euthyroid patients with severe, chronic, non-thyroidal illnesses usually have decreased serum total and absolute free T3 concentrations. Since T3 is the metabolically more active of the two thyroid hormones, it has been suggested that these patients may be hypothyroid and thus may benefit from T3 therapy. To test this hypothesis, five patients with chronic renal failure requiring maintenance haemodialysis were treated with 5 microgram T3 eight hourly, increasing at three weekly intervals to 10 microgram eight hourly, 20 microgram eight hourly and finally 30 microgram eight hourly. The mean +/- SD serum T3 level did not change over the 12 week period (1.42 +/- 0.17 vs. 1.41 +/- 0.26 nmoll-1 whilst the mean serum T4 and TSH levels fell from 87.0 +/- 15.2 to 47.5 +/- 18.8 nmoll-1 and 1.9 +/- 0.9 to 1.3 +/- 1.6 mUl-1 respectively. Only the change in T4 levels was significant (P less than 0.005). A significant decrease in mean serum T4 levels was apparent even after the treatment period with 5 microgram T3 eight hourly (87.0 +/- 15.2 vs. 51.2 +/- 15.7; P less than 0.005). The mean fasting serum triglyceride level fell from 1.16 +/- 0.74 to 0.94 +/- 0.74 mmoll-1 (P less than 0.05) and the mean fasting serum cholesterol level fell from 6.06 +/- 1.13 to 4.69 +/- 1.10 mmoll-1 (P less than 0.05). There were no subjective improvements in any of the patients. From the marked changes in serum T4 levels during the administration of T3, it is concluded that, prior to treatment, the patients were biochemically euthyroid and not hypothyroid and thus did not require T3 therapy.