triiodothyronine--reverse and Euthyroid-Sick-Syndromes

Reverse T3 (3,3',5'-triiodothyronine or rT3) is the third most abundant iodothyronine circulating in human blood and is produced by the inner ring deiodination of the pro-hormone thyroxine (T4). Unlike the more abundant and active metabolite T3, the measurement of serum rT3 is yet to find a routine clinical application. As rT3 binds weakly to the T3 thyroid nuclear hormone receptors, it is thought to represent an inactive end-product of thyroid hormone metabolism, diverting T4 away from T3 production. The analysis of serum rT3 has, up until recently, been measured by competitive radioimmunoassay, but these methods have been superseded by mass-spectrometric methods which are less susceptible to interference from other more abundant iodothyronines. Serum rT3 concentration is increased as part of the non-thyroidal illness syndrome, and by administration of common medications such as amiodarone which inhibit the metabolism of rT3. Serum rT3 concentration is also affected by genetic conditions that affect the iodothyronine deiodinases, as well as thyroid transporters and transport proteins. Analysis of rT3 can provide a useful diagnostic fingerprint for these conditions. rT3 has been shown to bind extra-nuclear iodothyronine receptors with a potential role in cell proliferation; however, the clinical relevance of these findings awaits further study.

Topics: Amiodarone; Euthyroid Sick Syndromes; Humans; Iodide Peroxidase; Thyroid Gland; Thyroxine; Triiodothyronine, Reverse

In critically ill patients, pronounced alterations in the hypothalamic-pituitary-thyroid axis occur without any evidence for thyroid disease. T3 decreases and rT3 increases within a few hours of the onset of disease. Severity and duration of disease are related to the magnitude of these changes. This manuscript discusses whether these changes in thyroid hormone levels during critical illness should be treated, and was in part published elsewhere.

Topics: Critical Care; Euthyroid Sick Syndromes; Hormone Replacement Therapy; Humans; Thyroid Hormones; Triiodothyronine; Triiodothyronine, Reverse

Topics: Animals; Cytokines; Enzyme Inhibitors; Euthyroid Sick Syndromes; Humans; Hypothalamus; Iodide Peroxidase; Pituitary Gland; Thyroid Gland; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The inflammatory response of critical illness is accompanied by nonthyroidal illness syndrome (NTIS). Feeding has been shown to attenuate this process, but this has not been explored prospectively over time in critically ill patients.. To explore the impact of calorie exposure on NTIS over time in critically ill patients.. Mechanically ventilated patients with systemic inflammatory response syndrome (SIRS) were randomized to receive either 100% or 40% of their estimated caloric needs (ECN). Thyroid hormones were measured daily for 7 days or until intensive care unit discharge or death. Mixed level regression modeling was used to explore the effect of randomization group on plasma triiodothyronine (T3), reverse triiodothyronine (rT3), thyroxine (T4), and thyroid stimulating hormone (TSH), as well as the T3/rT3 ratio.. Thirty-five participants (n=19 in 100% ECN; n=16 in 40% ECN) were recruited. Adjusting for group differences in baseline T3/rT3 ratio, the parameters defining the fitted curves (intercept, linear effect of study day, and quadratic effect of study day) differed by randomization group (P = 0.001, P = 0.01, and P = 0.02 respectively). Plots of the fitted curves revealed that participants in the 100% ECN group had a 54% higher T3/rT3 ratio on postintervention day 1 compared with the 40% ECN group, a difference which attenuated over time. This was driven by a 23% higher plasma T3 and 10% lower plasma rT3 levels on postintervention 1.. Higher caloric exposure in NTIS patients transiently attenuates the drop of the plasma T3/rT3 ratio, an effect that is minimized and finally lost over the following 3 days of continued higher caloric exposure.

Topics: Critical Illness; Energy Intake; Enteral Nutrition; Euthyroid Sick Syndromes; Female; Humans; Male; Middle Aged; Regression Analysis; Respiration, Artificial; Thyrotropin; Thyroxine; Treatment Outcome; Triiodothyronine; Triiodothyronine, Reverse

Prolonged critically ill patients have low circulating thyroid hormone (TH) levels without a rise in TSH, a condition labeled 'the low tri-iodothyronine (T(3)) syndrome'. Currently, it is not clear whether this represents an adaptive response. We examined the role of TH transporters monocarboxylate transporter 8 (MCT8, also known as SLC16A2) and MCT10 in the pathogenesis of the low T(3) syndrome in prolonged critical illness.. A clinical observational study in critically ill patients and an intervention study in an in vivo animal model of critical illness. Gene expression levels of MCT8 and MCT10 were measured by real-time PCR.. In prolonged critically ill patients, we measured increased MCT8 but not MCT10 gene expression levels in liver and skeletal muscle as compared with patients undergoing acute surgical stress. In a rabbit model of prolonged critical illness, gene expression levels of MCT8 in liver and of MCT10 in skeletal muscle were increased as compared with healthy controls. Treatment of prolonged critically ill rabbits with TH (thyroxine+T(3)) resulted in a downregulation of gene expression levels of MCT8 in liver and of MCT10 in muscle. Transporter expression levels correlated inversely with circulating TH parameters.. These data suggest that alterations in the expression of TH transporters do not play a major role in the pathogenesis of the 'low T(3) syndrome' but rather reflect a compensatory effort in response to hypothyroidism.

Topics: Aged; Amino Acid Transport Systems, Neutral; Animals; Base Sequence; Critical Illness; Disease Models, Animal; Euthyroid Sick Syndromes; Female; Humans; Liver; Male; Molecular Sequence Data; Monocarboxylic Acid Transporters; Muscle, Skeletal; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Symporters; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

To investigate whether early selenium (Se) supplementation can modify the post-traumatic alterations of thyroid hormone metabolism, since the first week after trauma is characterised by low plasma Se and negative Se balances.. Prospective, placebo-controlled randomised supplementation trial.. Surgical ICU in a tertiary university hospital.. Thirty-one critically ill trauma patients aged 42 +/- 16 years (mean +/- SD), with severe multiple injury (Injury Severity Score 30 +/- 7).. Supplementation during the first 5 days after injury with either Se or placebo. The selenium group was further randomised to receive daily 500 microg Se, with or without 150 mg alpha-tocopherol (AT) and 13 mg zinc supplements. The placebo group received the vehicle. Circulating Se, AT, zinc, and thyroid hormones were determined on D0 (= day 0, admission), D1, D2, D5, D10, and D20.. Plasma Se, low on D0, normalised from D1 in the selenium group; total T4 and T3 increased more and faster after D2 (P = 0.04 and 0.08), reverse T3 rising less between D0 and D2 (P = 0.05).. Selenium supplements increased the circulating Se levels. Supplementation was associated with modest changes in thyroid hormones, with an earlier normalisation of T4 and reverse T3 plasma levels. The addition of AT and zinc did not produce any additional change.

Topics: Adult; Analysis of Variance; Antioxidants; Drug Therapy, Combination; Euthyroid Sick Syndromes; Humans; Prospective Studies; Selenium; Thyroxine; Triiodothyronine, Reverse; Vitamin E; Wounds and Injuries; Zinc

The etiology of the prompt decline in serum T(3) in patients with nonthyroidal illness syndrome has not been adequately explained. It has been attributed to various parameters, including test artifacts, inhibitors of T(4) and T(3) binding to proteins, decreased 5'-deiodinase activity, and circulating cytokines. Currently, much attention is centered on the role of IL-6 and TNFalpha in developing the nonthyroidal illness syndrome through an effect on the hypothalamus, pituitary, and possibly 5'-deiodinase activity. We therefore studied the relation of the endogenous serum IL-6 and TNFalpha rise early in the course of nonthyroidal illness syndrome to the early decline in serum T(3) in 19 apparently healthy individuals, aged 43 +/- 16 yr, who underwent elective abdominal surgery for cholelithiasis or gastroplasty. Serum T(3), free T(3), T(4), free T(4), rT(3), TSH, IL-6, and TNFalpha were measured before and at various time intervals up to 42 h after skin incision. We observed a prompt decline in serum T(3) 30 min before skin incision, which continued to decline throughout the observational period. The magnitude of the decline reached 20% from the baseline value at 2 h. The early decline of T(3) was attenuated and lasted from the 2-8 h, probably due to the sharp increase in serum TSH that started immediately after the entrance to the operating room and lasted for 2 h. In contrast, serum T(4) and free T(4) concentrations were increased soon after skin incision and remained elevated during the first postoperative day. Serum rT(3) increased approximately 6 h after the initiation of surgery and remained elevated thereafter. Serum IL-6 remained essentially undetectable for 2 h after skin incision, whereas serum T(3) was low. Two hours after skin incision, serum IL-6 increased sharply and remained elevated throughout the observational period. Serum TNFalpha remained essentially undetectable throughout the postoperative period. Serum cortisol increased rapidly upon entrance to the operating room and remained elevated throughout the postoperative period. We conclude that the decline in serum T(3) early in the course of nonthyroidal illness syndrome is not due to increased serum IL-6 or TNFalpha levels. The brisk TSH secretion soon after the onset of the syndrome attenuates the decline in serum T(3) due to T(3) secretion from the thyroid. The early and brisk cortisol response to surgery may at least in part explain the early decrease in serum T(3) in nonthyroidal illn

Topics: Abdomen; Adult; Euthyroid Sick Syndromes; Female; Humans; Hydrocortisone; Interleukin-6; Male; Middle Aged; Postoperative Complications; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Tumor Necrosis Factor-alpha

To determine the role of tumor necrosis factor (TNF) in endotoxin-induced changes in plasma thyroid hormone and thyroid-stimulating hormone (TSH) concentrations, 24 healthy postabsorptive humans were studied on a control study day (n = 6), after infusion of a recombinant TNF receptor IgG fusion protein (TNFR:Fc; 6 mg/m2; n = 6) after intravenous injection of endotoxin (2 ng/kg; n = 6), or after administration of endotoxin with TNFR:Fc (n = 6). Administration of TNFR:Fc alone did not affect thyroid hormone or TSH levels when compared with the control day. Endotoxin induced a transient rise in plasma TNF activity (1.5 h: 219 +/- 42 pg/ml), which was completely prevented by TNFR:Fc (P < 0.05). After endotoxin administration, plasma L-thyroxine (T4), free T4, 3,5, 3'-triiodothyronine (T3), and TSH were lower and 3,3', 5'-triiodothyronine was higher than on the control day (all P < 0. 05). Coinfusion of TNFR:Fc with endotoxin did not influence these endotoxin-induced changes. Our results suggest that endogenous TNF does not play an important role in the alterations in plasma thyroid hormone and TSH concentrations induced by mild endotoxemia in healthy humans.

Topics: Adult; Endotoxins; Euthyroid Sick Syndromes; Humans; Immunoglobulin Fc Fragments; Immunoglobulin G; Injections, Intravenous; Lipopolysaccharides; Male; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Tumor Necrosis Factor-alpha

To assess the efficacy of reverse T3 in differentiating between the hypothyroid and euthyroid state in the setting of illness, all reverse T3 determinations obtained over a 4-year period in a University teaching hospital were analyzed in the context of concurrent thyroid function tests, bilirubin, albumin, creatinine, subsequent treatment, and follow-up. Based on T4 (or free T4 index) and TSH, the thyroidal state of the patient and the appropriateness of the reverse T3 determination were assigned. A total of 262 reverse T3 determinations were made in 246 patients. There is an inverse linear relationship between the log TSH and the reverse T3. Patients with hypothyroidism plus illness may have a normal reverse T3 and patients with euthyroidism may have a low reverse T3. Reverse T3 is linearly related to bilirubin up to a bilirubin of approximately 171 microM (10 mg/dL). Sixty percent of the reverse T3 determinations were obtained for seemingly inappropriate indications. In association with a low free T4 index/T4, an unmeasurable reverse T3 did not lead to institution of thyroid hormone treatment in over 52% of cases. Although reverse T3 may be elevated in the setting of nonthyroidal illness, it is not reliable in distinguishing between the hypothyroid sick patient and the euthyroid sick patient. This is probably because of drug and disease effects on thyroid hormone metabolism as well as the presence of sufficient T4 substrate for conversion to reverse T3 in many hypothyroid sick patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bilirubin; Diagnosis, Differential; Euthyroid Sick Syndromes; Female; Humans; Hypothyroidism; Iodine Radioisotopes; Male; Middle Aged; Thyroid Function Tests; Thyroxine; Triiodothyronine, Reverse

The sick euthyroid syndrome is a poorly understood hallmark of critical illness. Dopamine is a natural catecholamine with hypophysiotrophic properties, that is used as an inotropic agent of first choice in intensive care medicine. We explored the effect of dopamine infusion (5 micrograms/kg/min) on the sick euthyroid syndrome of critically ill patients.. In a prospective, randomized, controlled and open-labelled study of critically ill, adult polytrauma patients (n = 12), we evaluated the effect of prolonged (83-296 hours) dopamine infusion (5 micrograms/kg/min i.v.) on the thyroid axis. The effect of brief (15-21 hours) dopamine administration was documented in an additional randomized, controlled, cross-over study involving 10 patients. The median age of the studied patients was 29 (16-83) years.. Serum TSH concentrations were measured by IRMA. The TSH profiles were obtained by blood sampling every 20 minutes for 9 hours during two consecutive nights. Serum T4, T3 and reverse T3 concentrations were measured by RIA once per study night.. Withdrawal of prolonged dopamine infusion was found to elicit a tenfold increase of serum thyrotrophin concentrations, a 57 and 82% rise of T4 and T3 respectively, and an increase of the T3/rT3 ratio, resulting in virtual normalization of the thyroid axis within 24 hours. The brief dopamine infusion was documented to have a suppressive effect on the thyroid axis within 24 hours.. Dopamine infusion appears to induce or aggravate the sick euthyroid syndrome in critical illness. As a consequence, the sick euthyroid syndrome of severely ill patients receiving dopamine may be not an adaptive mechanism, but a condition of iatrogenic hypothyroidism.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Critical Illness; Depression, Chemical; Dopamine; Euthyroid Sick Syndromes; Humans; Middle Aged; Prospective Studies; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Topics: Euthyroid Sick Syndromes; Humans; Infant, Newborn; Thyroid Diseases; Triiodothyronine; Triiodothyronine, Reverse

Increased reverse tritiodothyronine (T(3)) used to be described as a part of euthyroid sick syndrome (ESS). It was demonstrated to be associated with increased mortality in acutely ill patients. It can also be found with low or normal T(3) in non-severely ill subjects but its significance remains unclear.. The Alsanut study included a representative sample of 440 independently-living subjects aged 65 or over constituted between January 1988 and September 1989. Past and current medical history and nutritional data were collected at inclusion. Baseline thyroid hormone (TSH, FT(4), FT(3) and rT(3)) serum levels were measured. Life status was determined on 1 December 2005.. Of the 374 elderly subjects included in the final analysis, 52 had abnormal TSH (43 with hyperthyroidism, nine with hypothyroidism) and 80.7% had died by 1 December 2005. There was no statistical difference in survival between subjects according to thyroid function (P=0.54). Of the 322 elderly subjects with normal TSH, mortality rate was 81.1%. ESS was found in 3.4%, whereas 8.1% of the participants displayed elevated rT(3) with normal FT(3). Time to death was strongly related to rT(3) (P<0.0001) and FT(3) (P<0.0001) in a univariate analysis. After adjusting for other confounding variables, rT(3) was the only thyroid hormone associated with shorter survival (P=0.014).. RT(3) was the only thyroid hormone associated with shorter survival in a representative population of independently-living elderly. In these subjects, isolated elevated rT(3) might be an equivalent of ESS, reflecting declining health.

Topics: Activities of Daily Living; Acute Disease; Aged; Aged, 80 and over; Chronic Disease; Euthyroid Sick Syndromes; Female; France; Humans; Kaplan-Meier Estimate; Male; Pregnanediones; Prevalence; Proportional Hazards Models; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Heart failure (HF) is frequently associated with euthyroid "sick" syndrome (low T3 and elevated rT3). We investigated if altered thyroid hormone in HF could affect expression of the TH receptor (TRalpha1), and alpha and beta myosin heavy chains (alpha-MHC, beta-MHC). HF was provoked in rats by aortic stenosis. We showed that rT3 generated from liver and kidney deiodination significantly increased and T3 decreased in HF; there was significantly higher TRalpha1 expression, no alpha-MHC expression, but beta-MHC expression. Changes in TRalpha could be compensating for low T3 from HF.

Topics: Animals; Euthyroid Sick Syndromes; Gene Expression Regulation; Heart Failure; Heart Ventricles; Male; Myosin Heavy Chains; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Statistics, Nonparametric; Thyroid Hormone Receptors alpha; Transforming Growth Factor beta; Triiodothyronine; Triiodothyronine, Reverse

Cardiopulmonary bypass (CPB) is an established cause of nonthyroidal illness syndrome (NTIS). Off-pump coronary artery bypass (OPCAB) has been reported to be less invasive than coronary artery bypass grafting (CABG) with CPB. We prospectively evaluated thyroid metabolism in OPCAB patients.. We analyzed free thyroid hormones (FT3 and FT4), thyroid-stimulating hormone (TSH), and reverse T3 (rT3) in 20 consecutive patients undergoing CABG surgery. Nine patients underwent CABG with CPB, and 11 underwent OPCAB. Blood samples were taken on admission, on the day of surgery (7:30 AM), after sternotomy, at the end of the operation, and at 2, 6, 12, 24, 36, 48, 72, 96, 120, and 144 hours postoperatively. The concentrations of FT3, FT4, and TSH were determined on each sample. Reverse T3 concentration was measured in 10 patients up to 48 hours and at 144 hours postoperatively.. Baseline, operative, and postoperative variables were similar in the two groups. FT3 concentration dropped significantly (p < 0.0001), reaching its lowest value 12 hours postoperatively. There were no significant differences between CPB and OPCAB patients. FT4 varied significantly in both groups (p < 0.0001), but remained in the normal range. TSH variation was not significant. rT3 concentration rose significantly (p = 0.0002) in both groups, peaking 24 hours after surgery. CONCLUSIONS. OPCAB induces a NTIS similar to that observed after CPB, probably due to the inhibition of T4 conversion to T3. This finding suggests that NTIS is a nonspecific response to stress. CPB should not be considered as the sole trigger of NTIS in cardiac surgical patients.

Topics: Aged; Coronary Artery Bypass; Euthyroid Sick Syndromes; Female; Humans; Male; Middle Aged; Postoperative Period; Prospective Studies; Thyrotropin; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Emergency operation in the elderly carries a high risk of death. We investigated the incidence of euthyroid sick syndrome (ESS) and associated nutritional and endocrine abnormalities and their relationship to postoperative outcome in this population.. Sixty-six patients older than 70 years of age requiring emergency operations were assessed before any therapeutic intervention. Values for thyroid hormones, catecholamines, cortisol, interleukin-6, interleukin-1, C-reactive protein, and the Acute Physiology and Chronic Health Evaluation II score were determined. Nutritional assessment was carried out. Mortality rates and duration of hospital stay were related to ESS and albumin concentrations.. ESS was diagnosed in 34 patients (51.50%) and was associated with worse Acute Physiology and Chronic Health Evaluation II scores (10.9 vs 8.6; p = 0.004), hypoalbuminemia (34.7 vs 40.8 gm/L; p = 0.0001), lower triceps skinfold (11.8 vs 14.6 mm; p = 0.03), and higher cortisol and norepinephrine levels (937 vs 741 nmol/L [p = 0.04] and 358 vs 250 pg/ml [p = 0.02], respectively), interleukin-6 plasma concentrations (347 vs 113 pg/ml; p = 0.01), death rate (20% vs 0%; p = 0.02), and length of hospital stay (17.2 vs 11.8 days; p = 0.03). A serum albumin level less than 35 gm/L was virtually always associated with ESS.. ESS is highly prevalent in the elderly with acute surgical problems and is associated with poor nutrition, higher sympathetic response, and worse postoperative outcome. The serum albumin level at admission is a specific marker of ESS.

Topics: Aged; Aged, 80 and over; APACHE; C-Reactive Protein; Communicable Diseases; Emergencies; Euthyroid Sick Syndromes; Fractures, Bone; Hand Strength; Hormones; Humans; Incidence; Infarction; Intestinal Obstruction; Intestines; Ischemia; Leg; Norepinephrine; Nutrition Assessment; Peritonitis; Postoperative Complications; Prevalence; Prospective Studies; Regression Analysis; Risk Factors; Serum Albumin; Skinfold Thickness; Treatment Outcome; Triiodothyronine; Triiodothyronine, Reverse

This study examined salsalate ingestion as a model of the sequelae of acute inhibition of thyroid hormone binding to serum protein. One dose of salsalate (60-65 mg/kg) was administered to healthy volunteers. Serum salsalate concentrations peaked at 2 h (82 micrograms/mL), then declined at 8 h to 1.2 micrograms/mL. Serum total T4 (TT4) and total T3 (TT3) concentrations declined for 4 h, then recovered by 96 h, while T4 binding protein concentrations remained unchanged. TT3 was reduced to a greater extent than TT4 between 2 h and 72 h, and serum total reverse(r)T3 (TrT3) was transiently increased at 8 h. TSH concentrations fell while TT4 and TT3 fell, then recovered while TT4, TT3, and free T3, but not free T4, were still reduced. Subsequently, TSH overshot basal levels and continued to rise after 96 h while TT4, TT3, free T4, free T3, and TrT3 were all at basal levels. We postulate that an acute release of T4 and T3 from circulating transport proteins, induced by an inhibitor of binding, can result in large and rapid redistribution of T4 and T3 into tissue compartments associated with transiently reduced peripheral tissue 5'-monodeiodination and deranged TSH regulation.

Topics: Adult; Blood Proteins; Euthyroid Sick Syndromes; Female; Humans; Kinetics; Male; Models, Biological; Protein Binding; Salicylates; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

To determine if temperature during cardiopulmonary bypass (CPB) has an effect on perioperative and postoperative thyroid function.. Prospective study comparing thyroid function during and after hypothermic and normothermic CPB.. Cardiac surgical unit at a university-affiliated hospital.. Twelve patients scheduled to undergo cardiac operations with normothermic (n = 6) or hypothermic (n = 6) CPB.. Blood was analyzed for serum concentration of total thyroxine (TT4), total triiodothyronine (TT3), free T3 (fT3), reverse T3 (rT3), and thyroid stimulating hormone (TSH) preoperatively, 60 min after CPB was initiated, 30 min after discontinuing CPB, and on postoperative days (POD) 1, 3, and 5.. Patients who underwent either cold (26 degrees +/- 5 degrees C) or warm (35 degrees +/- 1 degree C) CPB were comparable with regard to age, body weight, duration of CPB, cross-clamp time, use of inotropes, total heparin dose, and length of hospital stay. Incidence of postoperative myocardial infarction, congestive heart failure, and death were similar. In both groups, TT4 and TT3 were reduced below baseline values beginning with CPB and persisting for up to 5 days after CPB (p < 0.05), free T3 was reduced for up to 3 days after CPB (p < 0.05), mean serum rT3 was elevated on POD 1 and POD 3 (p < 0.05), and TSH remained unchanged.. The results of this study suggest that normothermic CPB does not prevent the development of the "euthyroid sick syndrome" during and after CPB. Despite these changes in thyroid function, most patients in both groups had a normal postoperative recovery.

Topics: Body Temperature; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Euthyroid Sick Syndromes; Humans; Middle Aged; Postoperative Complications; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

We studied the incidence of thyroid function abnormalities observed soon after allogeneic bone marrow transplantations (BMT) and their predictive value on the overall prognosis. Free serum thyroxine, free serum triiodothyronine, total serum reverse triiodothyronine and serum thyrotropin levels were systematically measured in 78 patients before and 3 months after BMT. 41 (52%) had normal hormone levels and 37 (48%) had abnormal ones, among whom four (5%) had peripheral compensated hypothyroidism and 33 (43%) were described as having 'euthyroid sick syndrome' (low thyroxine state, or low T3 syndrome). Two factors strongly influenced the appearance of thyroid abnormalities: steroid dose at the time of thyroid function testing, and age (< or = 16 years/ > 16 years). Among the younger patients, 21 had no thyroid abnormalities, while five did. Among the older patients, 20 had no thyroid abnormalities, while 32 did (P < 0.001). The occurrence of thyroid abnormalities seemed to influence survival strongly, since the 30-month projected survival time was 83% for patients without abnormalities whereas it was 49% for patients with an abnormal profile (P < 0.001). In conclusion, evidence obtained among our population reveals that euthyroid sick syndrome indicates a poor prognosis and that it is very important to monitor thyroid hormone levels (particularly free hormones) soon after allogeneic BMT and regularly thereafter.

Topics: Adolescent; Adult; Age Factors; Bone Marrow Transplantation; Child; Child, Preschool; Euthyroid Sick Syndromes; Female; Graft vs Host Disease; Humans; Incidence; Leukemia; Male; Middle Aged; Prognosis; Prospective Studies; Risk Factors; Survival Analysis; Thyrotropin; Triiodothyronine, Reverse

The present prospective study was conducted in order to investigate the effect of an acute decrease in serum T3 levels on ANP, aldosterone, angiotensin II, renin and ADH. All patients showed a pathologic TRH stimulation test prior to organ harvesting. Our patients developed secondary T3 hypothyroidism of different severity dependent on intensive care unit (ICU) stay. T3 values in group 1 (ICU stay > or = 77 h) were smaller than 70 ng/dl, those of group 2 (ICU stay < or = 53 h) were greater than 70 ng/dl. In both groups a severe elevation of plasma renin activity was measured, with almost high-normal values for ANP in group 1 and slightly elevated values in group 2 [not significant (n.s.)]. Results demonstrate that, contrary to patients who are not critically ill, brain-dead patients develop a dissociation of the renin-angiotensin-aldosterone mechanism. No statistical significant difference was found between the groups in serum levels of ADH and aldosterone. This endocrine dissociation, however, seems to have no clinical significance with regard to organ function after transplantation in kidney recipients.

Topics: Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Euthyroid Sick Syndromes; Hemodynamics; Humans; Kidney Transplantation; Renin; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Tissue Donors; Triiodothyronine; Triiodothyronine, Reverse

The levels of thyroid hormones were determined by RIA in 65 cases in with stroke, in which 42 cases showed low T3 levels (64.6%). The rates of abnormal T3 and rT3 were much higher in hemorrhage group (72.5%) than those in infarction group (52%). T3 and rT3 abnormalities were apparent in the acute stage compared to those in the chronic stage (P less than 0.01), and closely correlated with size of lesions, that is, size of lesions had negative correlation with T3 and T3/rT3 but positive correlation with rT3 when the volume of hemorrhage was more than 30 ml or the area of infarction more than 20 cm2. Determination of T3 and rT3 levels in patients with stroke may be helpful in assessing the severity and prognosing.

Topics: Adolescent; Adult; Aged; Brain; Cerebrovascular Disorders; Euthyroid Sick Syndromes; Female; Humans; Male; Middle Aged; Prognosis; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Tumor necrosis factor-alpha (TNF) is believed to be an important mediator in many diseases that are associated with the sick euthyroid syndrome. To investigate the effect of TNF on thyroid hormone metabolism, we performed a controlled study in six healthy postabsorptive males, in whom plasma thyroid hormones and TSH were sequentially measured after iv bolus injections of recombinant human TNF (50 micrograms/m2) and isotonic saline. During the 10.5-h study TNF produced the characteristic changes in circulating thyroid hormones and TSH observed in the sick euthyroid syndrome. Compared with the control experiment, TNF induced significant decreases in T3 (-36 +/- 2%; saline, -20 +/- 3%; P less than 0.05) and TSH levels (-68 +/- 3%; saline, -44 +/- 8%; P less than 0.05) and a significant increase in rT3 values (+48 +/- 11%; saline, -12 +/- 7%; P less than 0.05). T4 and free T4 index were not affected by TNF. Free T4 showed a mean transient increase of 18% in five subjects (nonsignificant), which occurred synchronically with a transient 3.5-fold rise in circulating FFA levels. Our results suggest that TNF is involved, either directly or indirectly, in the pathogenesis of the sick euthyroid syndrome.

Topics: Adult; Euthyroid Sick Syndromes; Fatty Acids, Nonesterified; Humans; Kinetics; Male; Recombinant Proteins; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Tumor Necrosis Factor-alpha

The euthyroid sick ("low T3") syndrome occurs in circulatory collapse and could influence survival. To evaluate the role of T3 and rT3 in shock, 36 mongrel dogs were subjected to hemorrhagic shock. In 13 dogs 15 micrograms/kg of T3 was given after 60 min of hypotension and 15 micrograms/kg of rT3 was administered IV 30 min before hemorrhage in 10 dogs. An equal volume of saline was injected in 13 dogs for control study. These dogs were bled rapidly into a reservoir to a mean arterial pressure (MAP) of 40 mmHg. After 60 min of hypotension the reservoir line was clamped for 30 min. The shed blood was then reinfused over 30 min. T3 administration caused significant increases during the clamped period in cardiac output, stroke volume, MAP, right and left ventricular stroke work and systemic vascular resistance, with a decrease in pulmonary vascular resistance (PVR). In the group receiving rT3 the only significant hemodynamic-metabolic differences were PVR and mean arterial pH. In the control group, 6 of 13 dogs died, whereas 9 of 10 dogs given rT3 died (p less than 0.03) and only one of 13 T3 dogs died (p less than 0.05). This study strongly suggests that T3 improves survival by acting on cardiovascular receptors or via the hypothalamic-pituitary-thyroid axis and that exogeneous rT3 is detrimental during the stress of shock and may play a biologically causative role in the sick euthyroid syndrome.

Topics: Animals; Dogs; Euthyroid Sick Syndromes; Hemodynamics; Shock, Hemorrhagic; Triiodothyronine; Triiodothyronine, Reverse

In patients with severely acute diseases, a special relationship of thyroidal hormones with decreased T3 and increased rT3 levels is known, the so-called low T3 syndrome. The aim of this study was to elucidate the involvement of the hypothalamo-pituitary thyroid axis, the pituitary-gonadal axis, the altered hepatic function, the plasma proteins in the low T3 syndrome, and the evaluation of these parameters for prognosis in patients with acute myocardial infarction. Thirty-one patients (29 male, 2 female) with AMI entered the study for the determination of hypothalamo-pituitary thyroid axis and the plasma proteins. Besides routine laboratory determinations, TRH, TSH, T4, T3, rT3, CHE, albumin, total protein, TBG, and estradiol concentrations in plasma were measured daily for 5 days after AMI using immunological and other methods. Twelve male patients with AMI entered the study for the determination of pituitary-gonadal axis; the T3, rT3, estradiol, testosterone, FSH, and LH concentrations in serum were determined using immunological methods. We found that T3 and T4 decreased significantly to a minimum on the first and the second day, respectively, after admission and increased in the course of the observation period. In contrast, rT3 was elevated significantly within the first 2 days and decreased later. TSH and TRH decreased in the first 2 days and increased in the following days. CHE, albumin, and total protein levels significantly showed a minimum on day 4 and TBG significantly showed a minimum on the second day after AMI and increased to day 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Proteins; Estradiol; Euthyroid Sick Syndromes; Female; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Luteinizing Hormone; Male; Middle Aged; Myocardial Infarction; Testosterone; Thyroid Hormones; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse