Fall In T3 Research Articles

Prognostic significance of non-thyroidal illness syndrome in sepsis

Background and objectives. Sepsis is a common diagnosis among ICU patients. Therefore, the present study aimed at assessing the prognostic significance of non-thyroidal illness syndrome (NTIS) in sepsis. Materials and methods. The study was done as a retrospective analysis on adult patients of age greater than 18 years who were admitted with sepsis to an urban tertiary care ICU at Saveetha Medical College and Hospital. Results. The study found that NTIS can manifest as a fall in T3 alone, T4 alone, or both T3 and T4. A combined fall in T3 and T4 strongly correlates with poor primary outcomes (28-day mortality) compared to a fall in either hormone alone. Advancing age in septic patients leads to a greater combined fall in T3 and T4 values and an increased mortality rate, especially among females. The overall mortality rate in this series was 55%, with severe infections and high APACHE II scores contributing to lower hormone levels and higher severity. Conclusion. NTIS should be considered an indicator of poor prognosis in septic patients, necessitating aggressive management. It underscores the importance of assessing TSH alongside T3 and T4 in critically ill patients, although treating NTIS was beyond the scope of this study.

Arecoline inhibits pineal–testis function in experimentally induced hypothyroid rats

Arecoline is known to cause endocrine dysfunction. In the current article role of arecoline on pineal–testis activity was investigated in hypothyroid rats induced by propylthiouracil (PTU). PTU treatment caused thyroid dysfunction ultrastructurally with a fall in T3 and T4 levels followed by a rise of thyroid stimulating hormone (TSH) level. Pineal activity was impaired by PTU treatment, as evident from degenerated synaptic ribbons and mitochondria of the pinealocytes with depletion of pineal and serum N-acetyl serotonin and melatonin levels. Leydig cell function was suppressed, evident from reduced smooth endoplasmic reticulum and depletion of testosterone level. Sex accessories function was impaired by showing scanty rough endoplasmic reticulum with depletion of fructose and sialic acid levels. Arecoline treatment that caused pineal dysfunction and testicular stimulation in control rats, suppressed both pineal and testis functions after PTU treatment. The findings suggest that arecoline inhibits pineal–testis function in experimentally induced hypothyroid rats.

Contribution of Nutritional Deficit to the Pathogenesis of the Nonthyroidal Illness Syndrome in Critical Illness: A Rabbit Model Study

Both starvation and critical illness are hallmarked by changes in circulating thyroid hormone parameters with typically low T(3) concentrations in the absence of elevated TSH. This constellation is labeled nonthyroidal illness (NTI). Because critical illness is often accompanied by anorexia and a failing gastrointestinal tract, the NTI of critical illness may be confounded by nutrient deficiency. In an experimental study performed in a rabbit model, we investigated the impact of nutritional deficit on the NTI of sustained critical illness. Critically ill rabbits were randomly allocated to parenteral nutrition (moderate dose 270 kcal/d) initiated on the day after injury and continued until d 7 of illness or to infusing a similar volume of dextrose 1.4% (14 kcal/d). With early parenteral nutrition during illness, the decrease in serum T(3) observed with fasting was reversed, whereas the fall in T(4) was not significantly affected. The rise in T(3) with parenteral nutrition paralleled an increase of liver and kidney type-1 and a decrease of liver and kidney type-3 deiodinase activity and an increase in circulating and central leptin. Nuclear staining of constitutive androstane receptor and its downstream expression of sulfotransferases were reduced in fasting ill animals. TRH expression in the hypothalamus was not different in fasted and fed ill rabbits, although circulating TSH levels were higher with feeding. In conclusion, in this rabbit model of sustained critical illness, reduced circulating T(3), but not T(4), levels could be prevented by parenteral nutrition, which may be mediated by leptin and its actions on tissue deiodinase activity.

Effects of a low-calorie diet on resting metabolic rate and serum tri-iodothyronine levels in obese children.

The purpose of the study was to examine the effects of weight loss on resting metabolic rate (RMR) and on serum T3 levels in obese children and to investigate whether RMR changes are related to T3 changes. Sixty-four healthy, overweight, children (age: 12.1+/-1.1 years, body mass index 29.3+/-4.3 kg/m2) were studied during a 6-week weight reduction programme. RMR (by indirect calorimetry) total T3, total T4, TSH and fat-free mass (FFM) (by anthropometry) were measured at baseline and after 6 weeks of dietary treatment. Weight loss resulted in a 10.1% decline in RMR (P < 0.01) and a 23.4% decrease in serum T3 levels (P < 0.001). RMR was correlated with FFM before (r = 0.78, P < 0.001) and after weight loss (r = 0.76, P < 0.001). The changes in RMR were positively correlated with the changes in FFM (r = 0.48, P < 0.05) but also with the changes in serum T3 levels (r = 0.47, P < 0.05). The initial T3 levels predicted the subsequent fall in T3 that occurred after 6 weeks of dietary treatment (r = -0.60, P < 0.001). A significant decrease in serum T3 concentrations and resting metabolic rate occurred as a result of a 6-week weight reduction programme in an obese child population. The decline in T3 levels combined with fat-free mass loss could be responsible for the reduction in resting metabolic rate.

Triiodothyronine (T3) reflects renal graft function after renal transplantation.

Abnormalities in thyroid function are observed in patients with end stage renal disease. However, there are no data available evaluating sequential changes of thyroid function after renal transplantation. Therefore, we have studied thyroid hormone function in the immediate post-operative period after renal transplantation in order to determine the relationship between improving renal function and changes in thyroid hormone economy. Thyroid function was evaluated in 22 patients before and on days 1, 3, 7 and 15 after renal transplantation. All patients received prednisone and cyclosporin as immunosuppressive therapy. Twelve patients with normal renal function undergoing comparable surgical procedures served as a control group. Serum creatinine and thyroid hormone parameters (total T4, total T3, free T4, free T3, thyroxin binding globulin (TBG), reverse T3, T3 sulphate and TSH) were measured. According to post-operative kidney function after renal transplantation, patients could be subdivided into three groups: five patients had primary graft function (group I); seven patients had delayed graft function because of acute renal failure (group II); 10 patients had delayed graft function requiring high doses of prednisone and some also of OKT3 because of acute rejection (group III). There was a significant fall in T3 and T4 concentrations with a concomitant rise in reverse T3 in all patients up to 3 days after renal transplantation. However, only patients in group I reached pre-operative values on day 15 after renal transplantation (serum creatinine 167 +/- 52 microM), whereas patients in group II (creatinine 609 +/- 118 microM) and group III (creatinine 839 +/- 71 microM) continued to have T3 concentrations well in the hypothyroid range (group I, 1.68 +/- 0.28 nM) vs 0.87 +/- 0.09 nM in group II and 0.76 +/- 0.10 nM in group III; P < 0.01). Serum T4 concentrations were also low in group III (47.7 nM vs 100.2 nM in group I; P < 0.05) 15 days after renal transplantation. These changes were accompanied by a concomitant fall in T3/TBG ratio and in free T3. Elevated reverse T3 returned to normal values in all groups on the 15th day after renal transplantation. TSH fell significantly on the first post-operative day, but did not return to pre-operative values in renal transplantation patients. In the control group, TSH did not change during the study period. T3 sulphate, known to be elevated in chronic renal failure, remained above normal in all patients irrespective of graft function during this study period. T3 concentrations reflect renal graft function after renal transplantation. T3 is below normal in patients with delayed graft function (acute renal failure or acute rejection). The post-operative period (up to 3 days after renal transplantation) is associated with a low T3 syndrome. TSH does not return to pre-operative values even in patients with primary graft function. This might be due to the administration of prednisone. T3-sulphate is elevated before and after renal transplantation irrespective of graft function.

The "feto-maternal" thyroid function interrelationships in an iodine-deficient region in Africa—the role of T3 in possible fetal defence

The thyroid status was investigated in 26 pregnant African women at term delivery in an iodine-deficient region (Jengere) of Nigeria, West Africa including the measurement of serum T4, T3, TSH, thyroxine binding capacity, TBG, free thyroxine index (FT4I) and the results were matched with those obtained in a corresponding group of 46 women at delivery in Jos, the non-iodine-deficient region which was used as a control. Corresponding cord-blood samples were obtained from all the neonates of the two groups. Twenty-three urinary samples in the former and 14 in the latter group were analysed for iodide levels to ascertain the degree of iodine deficiency. The results demonstrate that compared to the values seen in the Jos group the maternal serum T4, T3 and FT4I levels were significantly reduced in the iodine-deficient group, while TSH, TBG and thyroxine binding capacity were elevated. Cord serum samples showed a corresponding fall in T4 and FT4I levels in the group from the iodine-deficient region, while the T3 levels were significantly elevated with a concurrent significant rise in TSH and TBG levels. Significant correlations were found between the maternal and cord serum T4, TSH, TBG, thyroxine binding capacity and FT4I levels, but not T3. From these findings we suggest that fetal T3 plays an important defensive role against the danger of long-standing environmental iodine deficiency.

Glucagon-induced changes in plasma thyroid hormone concentrations in healthy dogs resemble “euthyroid sick syndrome”

We recently demonstrated that glucagon infusion induced a decline in T3 and a rise in rT3 in anesthetized dogs. These changes in T3 and rT3 may be attributed, at least in part, to anesthesia itself, since general anesthesia is known to cause lowering of T3 and an elevation in rT3 during the perioperative period. Therefore, to eliminate the contribution, if any, of anesthesia to these changes in T3 and rT3, we assessed plasma glucose, T3 resin uptake (T3RU), T4, free T4, T3 and rT3 concentrations following intravenous glucagon (0.5 mg) or normal saline (0.5 ml) administration at frequent intervals for 3 h in 6 conscious dogs fasted for 16 h. No significant alterations were noted in T4, free T4, and T3RU levels during either study. However, glucagon infusion alone induced a significant fall in T3 (0.33 +/- 0.06 in nmol/l vs -0.03 +/- 0.03 nmol/l with normal saline; p less than 0.01) and marked elevations in glucose (3.66 +/- 0.22 mmol/l vs 0.61 +/- 0.11 nmol/l with normal saline, p less than 0.001) and rT3 concentrations (0.11 +/- 0.02 nmol/l vs 0.005 nmol/l; p less than 0.001). Furthermore, the integrated responses of T3 and rT3 as assessed by cumulative changes and areas under the curves were markedly greater during glucagon infusion when compared with saline administration (p less than 0.01 for all comparisons). Since the elevations in levels of stress hormones known to ensue during anesthesia do not occur during a conscious resting state, we believe that hyperglucagonemia may be a major contributor of thyroid hormone alterations observed in several euthyroid sick states, not associated with stress, and may enhance these changes during euthyroid sick syndrome associated with stressful crises. Finally, these changes may be attributed to altered metabolism of iodothyronines in peripheral tissues as reflected by lowered T3/T4 and increased rT3/T4 ratios.

Evaluation of phenotype of mononuclear host cells isolated from primary tumour and peripheral blood of patients with laryngeal carcinoma.

Mononuclear host cells isolated from primary laryngeal carcinoma were assessed by means of indirect immunofluorescence with a panel of monoclonal antibodies against various lymphocyte subsets and macrophages. Tumours of various staging groups were examined in parallel with cells isolated from patient and donor peripheral blood (PBL). It was found that percentage values of cells bearing T3 and T4 phenotype were reduced both in tumour infiltrating cells (TIC) and in PBL population. The fall in T4+ cells in PBL from cancer patients in T3 and T4 staging groups was statistically significant (p less than 0.01) as compared with donor cells. Corresponding values for T8+ cells from TIC were increased in T1 and T2 staging groups of cancer, but showed a gradual fall in advanced stages. The T4+/T8+ cell ratio was decreased in both TIC and PBL cells. The HNK-1+ (NK) cell pattern in TIC was analogous to that for T8+ cells, i.e. the cell percentage decreased with advance in tumour growth. Corresponding values for OKM-1+ were increased in TIC and in patient blood, though in TIC they grew in proportion to tumour growth. Ia+ (HLA-DR+) cells in peripheral blood were significantly increased in patients versus those of donors (p less than 0.01), but only in T3 and T4 staging groups of examined cancer. These results show that subsets of tumour infiltrating cells in laryngeal carcinoma are a complex phenomenon, associated with growth and progression of tumour.

Thyroid status in patients after acute myocardial infarction.

Subjects followed serially after acute myocardial infarction demonstrated a rapid and sustained fall in serum total tri-iodothyronine (T3) concentration and a rise in reverse tri-iodothyronine (rT3) concentration. There was a transient fall in total thyroxine (T4) concentration. Thyroxine binding globulin (TBG) levels were unchanged after acute myocardial infarction but prolonged falls were observed in thyroxine binding prealbumin (TBPA) and albumin concentrations. In contrast to the fall in total T4, both measured and calculated free T4 concentrations were unchanged but measured and calculated free T3 concentrations fell as did total T3. Despite the observed fall in T3, basal thyrotrophin (TSH) concentrations did not rise. The reduction in circulating T3 levels after acute myocardial infarction suggests that a hypothyroid state exists. Until tissue thyroid status can be assessed directly, however, this conclusion must remain in doubt.

Hyperthyroxinemia with bradycardia and normal thyrotropin secretion after chronic amiodarone administration.

Pituitary-thyroid function was tested in 15 euthyroid patients before, during, and after long term oral treatment with amiodarone (2-n-butyl-3,4'-diethylaminoethoxy-3',5'-diiodobenzoylbenzofurane; 600-1200 mg daily), an iodine-containing potent antiarrhythmic drug. The drug caused increases in serum total T4, free T4, and rT3, with a concomitant decrease in T3. Baseline serum TSH was significantly higher after 1 week of drug treatment and returned to normal levels after 12 weeks of treatment. All patients receiving amiodarone had a slowing of their heart rate (P less than 0.01), and heart rate gradually increased 6 weeks after drug withdrawal, concurrent with the slow fall in T4 and rT3 levels. Amiodarone did not cross-react in the iodothyronine RIAs. The results suggest that amiodarone inhibits the peripheral conversion of T4 to T3 and may block the metabolic action of thyroid hormone in man.

A model of sustained activation of the symphatetic nervous system (SNS) using anterior hypothalamic cooling in the baboon

A model has been developed to simulate central activation of the sympathetic nervous system (SNS) in unanesthetized baboons. By continuously cooling the preoptic anterior hypothalamus with an implanted thermode, a chronic heat production response is generated. In the primate, SNS activation is a major feature of the response to cold stress. During central cooling, oxygen consumption and catecholamine excretion doubled. These responses have been sustained for 30 days. Metabolic and endocrine changes accompanying chronic SNS activation include (1) an early period of basal hyperinsulinemia followed by restoration of normal insulin sensitivity, (2) an unexpected maintenance of normal (or even increased) responsiveness to isoproterenol (heart rate, insulin secretion and lipolysis, (3) increased glucagon levels throughout, (4) a persistent and progressive fall in T3 without change in T4 which was not explained by decreased food intake since this did not diminish, and weight was maintained. The model may prove useful in characterizing the adaptations and maladaptations which accompany sustained increases in central SNS activity in primates.

Effects and plasma levels of propranolol and metoprolol in hyperthyroid patients

The effects and plasma concentrations of different doses of propranolol and metoprolol were studied in 34 hyperthyroid patients. The initial daily doses were propranolol 160 mg or metoprolol 200 mg. If the resting heart rate remained above 75 beats per min after treatment for 4-7 days, the dose was increased and the patient re-examined after a further 4-7 days. Propranolol (n = 17) caused a reduced heart rate, a decrease in serum 3,3',5-triiodothyronine (T3) and an increase in serum 3,3',5'-triiodothyronine (reverse T3, rT3). In 10 patients, there was no change in T3 or rT3 until the daily dose of propranolol had been increased to 240 or 320 mg. The plasma level of propranolol was significantly correlated with the decrease in T3 and the increase in rT3. Metoprolol (n = 17) caused a reduction in heart rate similar to that following propranolol. However, serum T3 was only slightly reduced even after an increase in dose to 300 or 400 mg, and serum rT3 was not altered. Metoprolol concentrations were not significantly correlated with the fall in T3. It appears that the influence of beta-blockers on T4 conversion is of little importance for the clinical improvement in hyperthyroid patients, and rather it is a consequence of beta 1-adrenergic blockade interfering with the effect of T3. In addition, the findings support the assumption that therapeutic failure with beta-blockers in hyperthyroidism may be due to suboptimal treatment, and that individualized dosage is necessary.

Effectiveness of insulin-glucose in preventing adrenaline-induced myocardial and systemic disturbances in the dog.

The aim of this study was to investigate whether insulin-glucose (IG) is able to prevent detrimental systemic and myocardial changes induced in healthy dog by adrenaline (AD) infused at a rate which mimics spontaneous secretion after coronary occlusion. Insulin (0.3 u/kg) and glucose (10% ml/kg) mixture was infused intravenously concurrently with AD (1.2 microgram/kg/min) for 4 h and blood values of FFA, triiodothyronine (T3) immunoreactive insulin (IRI) and glucose measured initially, after 2 and 4 h of infusion were compared with the values found in dogs infused with AD alone and with saline. IG suppressed a rise in FFA, attenuated a fall in T3, reversed AD-induced histoenzymatic changes in SDH and ATPase activity and completely prevented the development of mitochondrial alterations shown by electron microscopic study. These data provide evidence for usefulness of IG in preventing the consequences of catecholamine excess in acute stage of MI.

The Effect of Suppressive Therapy of Nontoxic Diffuse Goiter on Serum Levels of Thyroxine, 3,5,3‘‐Triiodothyronine and 3,3’,5‘‐Triiodothyronine

We studied the effect of suppressive therapy with graded doses of thyroxine (T4) on serum levels of T4, 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine [rT3] in patients with diffuse, nontoxic goiter. For comparison and in order to elucidate the degree of suppression of the pituitary thyroid axis by T3 the effect of suppressive therapy with T3 was studied in the same type of patients. We found that T4 in serum rose significantly to a constant level during T4 treatment (0.10, 0.15 and 0.20 mg/day). Dose-related rises in T4 were only seen after 3 months of treatment. T3 and rT3 only changed minimally. The T4/T3 ratio rose to a constant level during the initial 3 months of treatment. T3/rT3 ratio remained unchanged. No dose-related differences in T4/T3 and T3/rT3 ratio were observed. Treatment with T3 in doses of 0.06 mg per day caused a significant but slow fall in T4 and rT3 to hypothroid levels while T3 only rose slightly. The T4/T3 ratio dropped significantly during T3 therapy.

188 THE PRENATAL TRIIODOTHYRONINE (T3) SURGE IN THE FETAL SHEEP

Thomas, et al, reported an increase in fetal T3 concentrations during cortisol induced premature labor in sheep. The present study characterizes changes in Thyroxine (T4), T3, and reverse T3 (rT3) concentrations during the 2 week period prior to spontaneous vaginal delivery (PTD) and during the immediate neonatal period in the sheep. Serial blood samples were collected from 5 chronically catheterized fetal sheep during the 2 weeks PTD. All 5 fetuses were live born. Serum was analyzed for T4, T3, and rT3 by radioimmunoassay. Serum T3 began to increase 4-6 days PTD from a stable geometric mean of 30 ng/dl (upper 95% confidence limit = 39 ng/dl) to a geometric mean of 131 ng/dl (lower 95% confidence limit = 100 ng/dl) on the day of delivery (Day 0). Serum T4 decreased in 4 of the animals and remained unchanged in 1 during this time interval. Serum rT3 decreased from a stable mean of 472 ng/dl to 249 ng/dl on Day 0. The fetal serum T3/T4 ratio increased markedly during the week PTD. Serum T3 levels increased further after delivery; a mean level of 487 ng/dl was measured in 3 lambs at 2-4 hours of age. Conclusions: a) fetal serum T3 levels gradually increase while T4 and rT3 concentrations decrease during the 4-6 days PTD in sheep; b) the increase in serum T3 and fall in T4 and rT3 before birth probably are due to augmented T4 to T3 conversion; c) the perinatal T3 surge has 2 phases: a slow prenatal phase and an abrupt postnatal phase. The prenatal phase may be cortisol induced.

The Acute Thyroidal Response to Iodized Oil in Severe Endemic Goiter

The acute changes in serum thyrotropin (TSH) triiodothyronine (T3) and thyroxine (T4), were measured in 14 subjects, 4 to 10 (mean = 6) days following intramuscular iodized oil injection. In 8 subjects with small or absent goiter there was a significant fall in T3 and a rise in TSH concentrations, suggesting an acute inhibitory effect of the iodine. In 6 subjects with large multinodular goiters there was a marked rise in both T3 and T4, and reduction in the elevated basal TSH. Biochemical hyperthyroidism occurred in 3 of these subjects. The acute thyroid hormone response to iodized oil, whether inhibitory or stimulatory in a particular subject, depends both on goiter size and on the serum concentration of TSH.

Propylthiouracil blocks extrathyroidal conversion of thyroxine to triiodothyronine and augments thyrotropin secretion in man.

Propylthiouracil (PTU) inhibits peripheral deiodination of thyroxine (T4) and triiodothyronine (T3) and decreases the metabolic effectiveness of T4 in animals. To assess the effect of PTU on extrathyroidal conversion of T4 to T3 in man, 15 studies were performed in athyreotic patients treated with 100 or 200 mug of L-T4 daily for 1 mo before the addition of PTU, 250 mg every 6 h for 8 days. serum T3, T4, and thyrotropin (TSH) were measured daily by radioimmunoassay; serum TSH response to 500-mug thyrotropin-releasing hormone (TRH) was measured before and on the last day of giving PTU. On the 100-mug LT4 dose, serum T3 fell from 120 plus or minus 5 (SE) to 83 plus or minus 6 ng/dl (P less than 0.005) with return to 113 plus or minus 5 ng/dl after stopping PTU; serum T4 (4.5 plus or minus 0.3 mug/dl) did not change. Similar results were seen in patients taking 200 mug of L-T4 daily. On the 100-mug dose of L-T4 the fall in T3 was accompanied by a reciprocal rise in serum TSH to 195 plus or minus 33% of initial concentration (P less than 0.01) with return to 104 plus or minus 8% after PTU. The serum TSH response to TRH (DELTAMUU/ml over base line) was greater during PTU therapy than during the control period. On 100-mug L-T4 DELTA TSH rose from 64 plus or minus 19 to 101 plus or minus 23 muU/ml (P less than 0.005). Expressed as percent of base-line TSH concentration, TSH rose from 140 plus or minus 52 to 280 plus or minus 44% (control vs. PTU) at 15 min, 265 plus or minus 72 to 367 plus or minus 63% at 30 min, 223 plus or minus 54 to 313 plus or minus 54% at 45 min, 187 plus or minus 45 to 287 plus or minus 51% at 60 min, and 145 plus or minus 22 to 210 plus or minus 28% at 120 min after TRH. The data suggest that PTU blocks extrathyroidal conversion of T4 to T3, thus increasing pituitary TSH secretion and augmenting the TSH response to TRH.

Effect of iodine deficiency on iodine-containing compounds of rat tissues.

The distribution and quantitation of endogenously labeled iodine-containing compounds in normal and iodine-deficient rats were determined under steady state conditions. An isotope equilibrium method based on chronic feeding of 125I-labeled diet of known specific activity containing 0.06 μg 127I/g (experimental) and 0.22 fig 127I/g (control) was employed. Iodine deficiency was associated with the usually described rise in thyroid weight and MIT/DIT and T3/T4 ratios, even though there was a significant absolute decrease in all iodine compounds. Despite the iodine deficiency state the absolute concentration of T4 exceeded that of T3. Quantities found per g thyroid were 5.3 μg DIT, 5.7 μg MIT, 2.6 μg T4 and 1.7 μg T3. The T3/T4 ratio in plasma and tissues also rose, but for different reasons, as there was an absolute rise in T3 in plasma and most tissues and an absolute fall in T4 in plasma and all tissues. Despite these changes the absolute concentration of T4 still exceeded that of T3 in plasma and most tis...