triiodothyronine--reverse and Acute-Disease

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

We wanted to evaluate changes in the natural course of serum thyroxine (T4), tri-iodothyronine (T3), reverse tri-iodothyronine (rT3), and thyroid stimulating hormone (TSH) concentrations during hospitalization for an acute illness, in subjects rendered euthyroid with Levothyroxine (LT4) replacement therapy.. Six male subjects ranging in age 30 - 65 years with a history of primary hypothyroidism were included. They were euthyroid prior to hospitalization. LT4 continued to be administered orally in the same pre-admission daily dose. Serum, T4, T3, rT3, and TSH concentrations were determined on day of admission to the intensive care unit (ICU) for an acute illness. These were repeated during the first week on alternate days and again during a follow-up visit 1 week after discharge. Student's t-test, analysis of variance, and linear regression were used to analyze the data.. Serum T4, T3 declined to a nadir and serum rT3 rose to its peak by day 3 of hospitalization before returning to pre admission euthyroid levels. Serum TSH declined initially but rose to supernormal levels on day 7 before normalization. Significant correlations were noted between TSH on one hand and T3/T4 (r = 0.76, p < 0.001) and rT3/T4 (r= - 0.64, p < 0.001) ratios.. Alterations ensuing during a short stay in the hospital due to an acute illness in subjects with primary hypothyroidism rendered euthyroid with appropriate replacement therapy with Levothyroxine (LT4) are almost identical to those in normal subjects. These changes are probably secondary to altered thyroid hormone metabolism. The altered levels of thyroid hormones and TSH noted in these subjects are transient and therefore providers should refrain from initiating frequent changes in daily LT4 replacement dose during the acute illness in these subjects.

Topics: Acute Disease; Aged; Critical Care; Hospitalization; Humans; Hypothyroidism; Male; Middle Aged; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

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.

Topics: Acute Disease; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prealbumin; Thyroid Hormones; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Time Factors; Triiodothyronine; Triiodothyronine, Reverse

Alterations in circulating thyroid hormone concentrations occur in a variety of nonthyroidal disease states. In the present study, thyroid hormone levels were measured every 8 to 12 hours in 19 otherwise healthy individuals suffering acute severe trauma necessitating admission to the Maryland Institute for Emergency Medical Services Systems. Four fatalities occurred within 48 hours of admission. The mean total T3 level fell rapidly after the onset of trauma and remained low throughout the observation period. Reverse T3 rose concurrent with the fall in T3 but gradually returned to normal in the survivors. Total and free T4 levels remained normal in the survivors but fell below normal in the fatalities on the samples obtained preceding death. Changes in free T4 were consistent in three separate radioimmunoassay systems. Pharmacologic doses of glucocorticoids administered to seven of the 15 survivors and to the four fatalities did not result in an acute depression in total and free T4 levels in the survivors. Post-mortem examination of three fatalities did not reveal evidence of significant thyroid or pituitary disease. These results suggest that in acutely traumatized patients: 1) T3 declines rapidly and remains depressed throughout the illness; 2) continued fall of T4 to subnormal levels is associated with a poor prognosis; and 3) steroid therapy alone cannot explain the acute changes observed in hormone levels.

Topics: Acute Disease; Adolescent; Adult; Aged; Female; Glucocorticoids; Humans; Male; Middle Aged; Prognosis; Thyroxine; Time Factors; Triiodothyronine; Triiodothyronine, Reverse; Wounds and Injuries

Although thyroid medications are commonly prescribed, there are only nine case reports describing the consequences of acute excessive ingestion of thyroid hormones. Two additional cases are presented and the prior nine cases are reviewed. The potential for toxicity is discussed in relationship to the cellular mechanisms of action of thyroid hormones. Although the potential for toxicity is low, the following therapy is recommended to decrease further the toxic potential: (1) lavage and activated charcoal to decrease absorption, (2) cholestyramine to decrease enterohepatic circulation (3) prednisone and/or propylthiouracil to decrease conversion of thyroxine to triiodothyronine, and (4) propranolol to block metabolic effects. If symptoms of toxicity develop, then attempts to remove thyroid hormones should be undertaken using exchange transfusion.

Topics: Acute Disease; Adult; Child, Preschool; Female; Hemoperfusion; Humans; Infant; Male; Middle Aged; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

The low thyroxine (T(4)) state of acute critical nonthyroidal illnesses is characterized by marked decreases in serum total T(4) and triiodothyronine (T(3)) with elevated reverse T(3) (rT(3)) values. To better define the mechanisms responsible for these alterations, serum kinetic disappearance studies of labeled T(4), T(3), or rT(3) were determined in 16 patients with the low T(4) state and compared with 27 euthyroid controls and a single subject with near absence of thyroxine-binding globulin. Marked increases in the serum free fractions of T(4) (0.070+/-0.007%, normal [nl] 0.0315+/-0.0014, P < 0.001), T(3) (0.696+/-0.065%, nl 0.310+/-0.034, P < 0.001), and rT(3) (0.404+/-0.051%, nl 0.133+/-0.007, P < 0.001) by equilibrium dialysis were observed indicating impaired serum binding. Noncompartmental analysis of the kinetic data revealed an increased metabolic clearance rate (MCR) of T(4) (1.69+/-0.22 liter/d per m(2), nl 0.73+/-0.05, P < 0.001) and fractional catabolic rate (FCR) (32.8+/-2.6%, nl 12.0+/-0.8, P < 0.001), analogous to the euthyroid subject with low thyroxine-binding globulin. However, the reduced rate of T(4) exit from the serum (Kii) (15.2+/-4.6 d(-1), nl 28.4+/-3.9, P < 0.001) indicated an impairment of extravascular T(4) binding that exceeded the serum binding defect. This defect did not apparently reduce the availability of T(4) to sites of disposal as reflected by the increased fractional disposal rate of T(4) (0.101+/-0.018 d(-1), nl 0.021+/-0.003, P < 0.001). The decreased serum T(3) binding was associated with the expected increases in MCR (18.80+/-2.22 liter/d per m(2), nl 13.74+/-1.30, P < 0.05) and total volume of distribution (26.55+/-4.80 liter/m(2), nl 13.10+/-2.54, P < 0.01). However, the unaltered Kii suggested an extravascular binding impairment comparable to that found in serum. The decreased T(3) production rate (6.34+/-0.53 mug/d per m(2), nl 23.47+/-2.12, P < 0.005) appeared to result from reduced peripheral T(4) to T(3) conversion because of decreased 5'-deiodination rather than from a decreased T(4) availability. This view was supported by the normality of the rT(3) production rate. The normal Kii values for rT(3) indicated a comparable defect in serum and extravascular rT(3) binding. The reduced MCR (25.05+/-6.03 liter/d per m(2), nl 59.96+/-8.56, P < 0.005) and FCR (191.0+/-41.19%, nl 628.0+/-199.0, P < 0.02) for rT(3) are compatible with an impairment of the rT(3) deiodination rate. These alterations in thyroid hormo

Topics: Acute Disease; Adult; Aged; Binding Sites; Female; Humans; Infections; Kinetics; Liver Diseases; Male; Metabolic Clearance Rate; Middle Aged; Respiratory Insufficiency; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Serum thyroid hormones and thyroid hormone binding were sequentially measured in 20 patients with acute hepatitis B infection. Criteria to select patients consisted of a positive test for hepatitis B surface antigen, aspartate aminotransferase (AsAT) concentration greater than 400 U/L during the acute illness, and available serum specimens after recovery. The mean serum thyroxine (T4) concentration (+/- SE) was 12.5 +/- 0.6 microgram/dL during acute infection and 7.4 +/- 0.3 microgram/dL after recovery (p less than 0.001), whereas mean free T4 index values did not significantly differ. The mean serum thyroxine-binding globulin (TBG) concentration was significantly increased (p less than 0.001) during acute illness and accounted for the reversible of serum and the increased serum T4 concentrations. The rise in serum TBG correlated with the rise in AsAT during the acute illness (p less than 0.04) suggesting nonspecific release of these proteins from injured hepatocytes. The mean free triiodothyronine (T3) index was decreased during acute hepatitis (p less than 0.001) and returned to normal after recovery, indicating that acute hepatitis B infection, like other nonthyroidal illnesses, is associated with decreased T4 to T3 conversion in peripheral tissues.

Topics: Acute Disease; Adolescent; Adult; Female; Hepatitis B; Humans; Male; Middle Aged; Thyroid Function Tests; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse

Thyroid function tests were obtained from 335 consecutive patients admitted to an intensive care unit. Twenty patients suffering from severe non-endocrine diseases (septicaemia, fulminant hepatic and renal failure, acute pancreatitis, polytrauma, cerebral haemorrhage) were found to have serum thyroxine levels in the hypothyroid range (less than 4 micrograms/dl). Serum concentrations of total thyroxine (2.3 +/- 0.2 micrograms/dl), triiodothyronine (0.23 +/- 0.03 ng/ml), and thyroxine binding globulin (15.1 +/- 1.3 micrograms/ml) were reduced, but were above normal for reverse triiodothyronine (0.43 +/- 0.06 ng/ml). Response of TSH secretion to iv TRH was found to be either normal, lowered or absent. Primary hypothyroidism was excluded, as no enhanced TSH response was observed in any case. Although decreased thyroxine levels may be due to increased thyroid hormone degradation it appears that associated impaired TSH responsiveness to TRH may result from illness-related inhibition of pituitary TSH release. Although the finding of decreased thyroid hormone levels is not rare in care patients, it represents an index of poor prognosis. Differentiation between this "low-T4 syndrome" and true hypothyroidism depends essentially on clinical symptoms and course of disease.

Topics: Acute Disease; Acute Kidney Injury; Adolescent; Adult; Aged; Critical Care; Female; Hepatic Encephalopathy; Humans; Hypothyroidism; Male; Middle Aged; Pancreatitis; Pituitary Gland; Sepsis; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse; Wounds and Injuries

Topics: Acute Disease; Adult; Aged; Alpha-Globulins; Female; Humans; Male; Middle Aged; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse; Ultrafiltration

Thyroid hormones were serially measured over a 2-week period in thirty-four consecutive patients with acute myocardial infarction (AMI). A transient increase in plasma rT3 and a decrease in plasma T3 was found, with the maximum changes occurring on the third day after the onset of AMI. The changes in plasma rT3 and T3 were greater in the seventeen patients with a complicated AMI (mean peak SGOT 145 mu/l) than in the seventeen patients with an uncomplicated AMI (mean peak SGOT 79 mu/l). A correlation was found between infarct size (as estimated by the peak SGOT value) and the following indices: delta r T3, delta T3, highest rT3/t3 and highest rT3/T4 ratios. A transient increase in plasma TSH (peak on days 4 and 5) and in plasma T4 and FT4 index (peak on days 6 and 7) was also observed, whereas T3 resin uptake (T3U) decreased. These findings suggest that the following sequence of events occurs in thyroid hormone metabolism during AMI: (1) inhibition of the 5'-deiodination of T4, resulting in increased plasma rT3 and decreased plasma T3 values, and in a lower metabolic clearance of T4. (2) Increased secretion of TSH (provoked by the lower T3 levels) resulting in increased thyroidal secretion of T4 and T3, which is then switched off by the negative feedback of thyroid hormones on the pituitary.

Topics: Acute Disease; Aged; Aspartate Aminotransferases; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Serum was obtained from 11 patients with nonthyroidal illness (NTI) and from 9 control subjects. Patients with NTI demonstrated decreased total T4 and T3 levels; increased rT3, T3 resin uptake, and percent free (dialyzable) T4 levels; and normal TSH and free T4 concentrations in vitro. In addition, the effects of control and patient sera on the first pass extraction of labeled T4 and T3 by rat liver was measured with a tissue sampling-single injection technique. The percent of total serum T4 and T3 that was transported into liver on one pass was 17 +/- 2% and 77 +/- 5%, respectively, in the case of NTI, and these values were no different from control estimates. The concentrations of total serum T4 and T3 available for transport into liver in vivo were 0.69 +/- 0.13 micrograms/100 ml and 21 +/- 2 ng/100 ml, respectively, in NTI, and these values were 46% and 18% of control values, respectively. Therefore, in contrast to in vitro estimates of free T4, in vivo measurements indicate the amount of circulating T4 or T3 that is available for transport into liver cells in NTI is reduced in proportion to the decrease in total plasma hormone.

Topics: Acute Disease; Adult; Aged; Animals; Biological Assay; Biological Availability; Biological Transport; Female; Humans; Liver; Male; Middle Aged; Rats; Rats, Inbred Strains; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Thyrotoxicosis with a normal serum triiodothyronine (T3) concentration has been described with a variety of acute and chronic illnesses occurring in association with thyrotoxicosis. We describe the first case to our knowledge of thyroxine (T4) toxicosis in a 16-year-old boy with diabetic ketoacidosis. Although the clinical manifestations of hyperthyroidism were mild, thyromegaly and persistent tachycardia suggested thyrotoxicosis. Serum T4 levels were elevated; however, the serum T3 level was normal. Measurement of reverse T3 (rT3) initially revealed an elevated level that decreased over several days of T3 levels increased into the toxic range. Peripheral conversion of T4 to T3 was apparently inhibited by diabetic ketoacidosis and there was a concomitant increase in rT3 levels, suggesting that conversion of T4 to rT3 was increased during acute ketoacidosis. Assessment of thyroid function based on serum T3 levels in diabetics may be misleading during ketoacidosis or uncontrolled diabetes.

Topics: Acute Disease; Adolescent; Aged; Diabetic Ketoacidosis; Female; Humans; Hyperthyroidism; Male; Middle Aged; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Concentrations of thyroid hormones and thyrotropin (TSH) were measured in sera of clinically euthyroid patients with various liver diseases and compared with normal controls. The mean serum concentration of 3,3',5'-triiodothyronine (reverse T3, rT3) was significantly increased in patients with decompensated liver cirrhosis (p less than 0.01). This increase seemed to be dependent upon the hepatic damage, although it was not significant in patients with acute hepatitis, chronic hepatitis and compensated liver cirrhosis. The mean serum concentration of 3,3',5-triiodothyronine (T3) was significantly decreased in patients with decompensated liver cirrhosis (p less than 0.05). However, in patients with acute hepatitis, chronic hepatitis and compensated liver cirrhosis, the mean concentration of T3 was above the normal. The mean value of rT3/T3 ratios in patients with acute hepatitis, chronic hepatitis and compensated liver cirrhosis were similar to that of normal controls, but in patients with decompensated liver cirrhosis, the mean value of rT3/T3 ratios was markedly higher than that of normal controls. The rT3/T3 ratios have little or no correlation with some standard liver function tests. These results suggest that marked alterations of peripheral conversion of thyroxine (T4) to rT3 or T3 may be found only in a state of decompensated liver cirrhosis among the various liver diseases.

Topics: Acute Disease; Adolescent; Adult; Aged; Chronic Disease; Hepatitis; Humans; Liver Cirrhosis; Liver Function Tests; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

A 48-h dopamine (DA) infusion (5-7.5 microgram/kg . min) given to six healthy euthyroid males resulted in a suppression of thyroidal iodine release and serum TSH by 44 +/- 3% (P less than 0.01), serum T3 by 9 +/- 2% (P less than 0.01), and serum T4 by 5 +/- 1% (P less than 0.05) below baseline levels, without a significant change in serum rT3 levels. In critically ill patients receiving DA (2-21 microgram/kg . min) for treatment of shock, serum TSH values and T4 production rates were decreased 60% and 56%, respectively, below the respective levels observed in non-DA-treated patients (P less than 0.01). Serial serum samples collected before and during DA therapy revealed a decrease of 52% in TSH (P less than 0.005) and 30% in T4 (P less than 0.05). The finding of a normal serum TSH value during DA theray in a critically ill patient with primary hypothyroidism emphasized the inhibitory potential of DA on TSH secretion. These findings indicate that the prolonged administration of pharmcological doses of DA significantly reduced serum TSH levels and thyroid hormone secretion in normal and critically ill patients, most likely by a direct inhibition of pituitary TSH with a secondary effect on thyroid gland secretion. Therefore, DA therapy probably prolongs and aggravates the low T4 state in critical illness.

Topics: Acute Disease; Adult; Dopamine; Humans; Kinetics; Male; Middle Aged; Reference Values; Thyroid Gland; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Depressed triiodothyronine and elevated reverse triiodothyronine levels are commonly seen in patients with acute and chronic illness and in patients receiving markedly hypocaloric diets. To investigate the role of nutritional adequacy in causing the altered thyroid hormone levels found in severe illness, we studied patients with bacterial sepsis who were receiving a variety of nutritional regimens. Thirteen patients received only 5% dextrose in water (600-1000 kcal/day), 7 of whom were in shock. Seven patients received total parenteral nutrition (2500-3500 kcal/day). Analysis of thyroid hormone levels in these groups and in controls shows that a large component of the alteration in thyroid hormone levels found in patients with severe illness is due to the caloric deprivation associated with such severe illness.

Topics: Acute Disease; Adult; Aged; Bacteria; Chronic Disease; Female; Humans; Male; Middle Aged; Nutritional Physiological Phenomena; Sepsis; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

A study was performed to elucidate whether endogenous cortisol, as previously suggested, could be responsible for the decreased T3 levels seen in euthyroid patients with acute myocardial infarction. Levels of these hormones as well as levels of T4 and reverse-T3 were monitored in 31 consecutive patients admitted to the Coronary Care Unit with symptoms of precordial pain or with acute arrhythmias. Sixteen of the patients had proven myocardial infarction, the remaining 15 were used as a control group. The results demonstrated that a reduction of T3 levels was seen in the infarction group without evidence of a statistically significant difference between the daily mean cortisol levels. No significant difference could be observed in T4 or reverse-T3 levels in the two groups or in T3 levels in the control group. It is concluded that the decrease in T3 levels is not a consequence of the increased levels of endogenous cortisol.

Topics: Acute Disease; Adult; Aged; Female; Humans; Hydrocortisone; Male; Middle Aged; Myocardial Infarction; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse

Aim of this report was to define the correlation between hepatic acute damage and thyroxine metabolism. We have studied plasma levels of T4, T3, rT3 and TSH in 18 adult male subjects with acute viral hepatitis. No significant variation of T4, T3 and TSH plasma levels was found in different phases of disease. However, plasma rT3 levels were clearly elevated in 72% of patients in the first 7 days (mean 440 pg/ml vs 198 pg/ml of normal controls) and in 17% of cases in the second 10 days of disease (mean 269 pg/ml). Plasma rT3 concentration was always normal in the subsequent phases of disease. Our results indicate a diversion of peripheral thyroxine metabolism in the early stages of acute hepatitis.

Topics: Acute Disease; Adolescent; Adult; Hepatitis, Viral, Human; Humans; Male; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse