RESUMO
Androgen deprivation therapy (ADT) improves life expectancy in prostate cancer (PCa) patients, but is associated with adverse effects on muscle mass. Here, we investigated the effects of strength training during ADT on muscle fiber cross-sectional area (CSA) and regulators of muscle mass. PCa patients on ADT were randomized to 16 weeks of strength training (STG) (n = 12) or a control group (CG; n = 11). Muscle biopsies were obtained from m. vastus lateralis and analyzed by immunohistochemistry and western blot. Muscle fiber CSA increased with strength training (898 µm(2) , P = 0.04), with the only significant increase observed in type II fibers (1076 µm(2) , P = 0.03). There was a trend toward a difference in mean change between groups myonuclei number (0.33 nuclei/fiber, P = 0.06), with the only significant increase observed in type I fibers, which decreased the myonuclear domain size of type I fibers (P = 0.05). Satellite cell numbers and the content of androgen receptor and myostatin remained unchanged. Sixteen weeks of strength training during ADT increased type II fiber CSA and reduced myonuclear domain in type I fibers in PCa patients. The increased number of satellite cells normally seen following strength training was not observed.
Assuntos
Antagonistas de Androgênios/efeitos adversos , Fibras Musculares de Contração Rápida/patologia , Fibras Musculares de Contração Lenta/patologia , Neoplasias da Próstata/fisiopatologia , Músculo Quadríceps/patologia , Treinamento Resistido , Idoso , Antagonistas de Androgênios/uso terapêutico , Núcleo Celular , Distrofina/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fibras Musculares de Contração Rápida/química , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Lenta/química , Fibras Musculares de Contração Lenta/fisiologia , Força Muscular , Miostatina/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Músculo Quadríceps/fisiopatologia , Receptores Androgênicos/metabolismo , Células Satélites de Músculo Esquelético/patologiaRESUMO
The sequential deiodination of thyroxine (T4) gives rise to several iodothyronine analogs including 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2). In vitro animal studies suggest that the liver and the kidneys are the main sites of both formation and degradation of 3,3'-T2 and 3',5'-T2. To determine the metabolism of 3,3'-T2 and 3',5'-T2 in human liver and kidneys plasma samples were obtained from (a) a brachial artery and a hepatic vein in 20 normal subjects, and from (b) a femoral artery and a renal vein in 11 normal subjects. Further, the hepatic plasma flow (a) and the renal plasma flow (b) were determined. Both plasma 3,3'-T2 and 3',5'-T2 levels were reduced in the hepatic venous blood as compared to arterial values (1.09 +/- 0.40 vs. 1.75 +/- 0.74 ng/dl (P < 0.02)) (mean +/- 1 SD). This resulted in a hepatic extraction of both, 3,3'-T2 and 3',5'-T2, which averaged 8.2 and 5.2 microgram/d, respectively. Plasma 3,3'-T2 as well as 3'5'-T2 levels were higher in the renal vein as compared to arterial values, 1.49 +/- 0.42 vs. 1.39 +/- 0.45 ng/dl (P < 0.05) and 2.35 +/- 0.83 vs. 2.09 +/- 0.81 ng/dl (P < 0.05), respectively. This positive venoarterial difference implies a net production of 3,3'-T2 and 3',5'-T2 in the kidneys of 1.2 and 3.0 microgram/d, respectively. It is concluded that the liver is an important site of 3,3'-T2 and 3',5'-T2 extraction in normal man. In contrast, the renal production of 3,3'-T2 as well as 3'5'-T2 exceeds the degradation and urinary excretion.
Assuntos
Di-Iodotironinas/sangue , Rim/metabolismo , Fígado/metabolismo , Tironinas/sangue , Adolescente , Adulto , Artéria Braquial , Feminino , Artéria Femoral , Artéria Hepática , Veias Hepáticas , Humanos , Masculino , Proteínas de Ligação a Tiroxina/análiseRESUMO
BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with several side effects, including loss of muscle mass. Muscle atrophy is associated with reduced mitochondrial function and increased muscle cellular stress that may be counteracted by strength training. Thus, the aim of this study was to investigate the effect of strength training on mitochondrial proteins and indicators of muscle cellular stress in PCa patients on ADT. METHODS: Men diagnosed with locally advanced PCa receiving ADT were randomised to a strength training group (STG) (n=16) or a control group (CG) (n=15) for 16 weeks. Muscle biopsies were collected pre- and post-intervention from the vastus lateralis muscle, and analysed for mitochondrial proteins (citrate synthase, cytochrome c oxidase subunit IV (COXIV), HSP60) and indicators of muscle cellular stress (heat shock protein (HSP) 70, alpha B-crystallin, HSP27, free ubiquitin, and total ubiquitinated proteins) using Western blot and ELISA. RESULTS: No significant intervention effects were observed in any of the mitochondrial proteins or indicators of muscle cellular stress. However, within-group analysis revealed that the level of HSP70 was reduced in the STG and a tendency towards a reduction in citrate synthase levels was observed in the CG. Levels of total ubiquitinated proteins were unchanged in both groups. CONCLUSION: Although reduced HSP70 levels indicated reduced muscle cellular stress in the STG, the lack of an intervention effect precluded any clear conclusions.
RESUMO
Thyroid levels were estimated in 15 patients with endogenous depressions. Before electroconvulsive treatment (ECT), serum thyroxine (T4) and free T4 index values were elevated (P less than .02). After recovery from depression, the levels were normal. Serum triiodothyronine (T3) and free T3 index were normal both before and after ECT. Serum thyrotropin (TSH) levels were also normal and not substantially altered by the ECT procedure. The mean maximal TSH response to protirelin (thyrotropin-releasing hormone) was diminished in the depressed patients and normal after recovery. In three patients, the increase in TSH response to protirelin after recovery did not occur and they relapsed within six months, while in seven patients with increased TSH response to protirelin after recovery only one relapse occurred. The disturbances in the free T4 index, T4, and the protirelin test may in some depressed patients resemble hyperthyroidism, but this condition can be excluded by means of serum, T3 and free T3 index.
Assuntos
Transtorno Bipolar/fisiopatologia , Glândula Tireoide/fisiopatologia , Hormônio Liberador de Tireotropina , Adulto , Idoso , Transtorno Bipolar/sangue , Transtorno Bipolar/terapia , Eletroconvulsoterapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
The thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH 200 microgram intravenously was studied in 19 patients with unipolar depression, 12 with bipolar depression, 14 with mania, and 5 with mixed manic-depressive illness. The TSH responses were decreased in all of these affective disorders compared to those found in 10 patients with reactive depression, 5 with reactive paranoid psychosis, 14 with neurotic depression, and 60 controls. The decrease of the TSH response in manics could not be accounted for by the effects of neuroleptic drugs. The TSH response in the groups with reactive depression, reactive paranoid psychosis, and neurotic depression, respectively, did not differ significantly from that found in controls. With the exception of a decrease in serum T3 level and free T3 index in the manics, no significant differences in serum T3 level or in free T3 and T4 indexes were found between the groups. Changes found in serum T4 level were due to changes in the thyroxine-binding proteins.
Assuntos
Transtorno Bipolar/sangue , Depressão/sangue , Hormônio Liberador de Tireotropina/farmacologia , Tireotropina/sangue , Transtornos de Adaptação/sangue , Adulto , Fatores Etários , Idoso , Biperideno/farmacologia , Feminino , Haloperidol/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Paranoides/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
RIAs for the estimation of 3',5'-diiodothyronine (3',5'-T2) and 3,3'-diiodothyronine (3,3'-T2) in human urine have been established. The urinary excretion of both glucuronide and sulfate conjugates of T2 and of T4, T3, and rT3 were estimated by means of enzymatic deconjugation. In healthy controls, the mean excretion (picomoles per 24 h) of free T4 was 1820, that of free T3 was 813, that of free rT3 was 77, that of free 3',5'-T2 was 13, and that of free 3,3'-T2 was 674. The total excretion of free and conjugated T4 was 2941, that of T3 was 1283, that of rT3 was 791, that of 3',5'-T2 was 709, and that of 3,3'-T2 was 2688. Significant amounts of sulfated T4 and T3 could not be demonstrated, amounts of sulfated T4 and T3 could not be demonstrated, whereas the excretion of sulfated rT3 was higher than that of glucuronidated rT3 (P less than 0.001). In contrast, glucuronidated and sulfated 3',5'-T2 as well as glucuronidated and sulfated 3,3'-T2 were found in the urine in equal amounts. In hyperthyroidism, the excretions of free and glucuronidated iodothyronines were increased, whereas the increase of the excretions of sulfated iodothyronines were less pronounced, only reaching statistical significance for 3,3'-T2 (P less than 0.02). In hypothyroidism, the excretions of both free, glucuronidated and sulfated iodothyronines were reduced. Significant amounts of sulfated T4 and T3 could not be demonstrated in urine from hyperthyroid or hypothyroid patients. Our data demonstrate that the amounts of free iodothyronines excreted in the urine vary considerably, suggesting active renal handling. The amounts of urinary glucuronidated and sulfated conjugates of the different iodothyronines studied vary considerably and are affected by thyroid function.
Assuntos
Di-Iodotironinas/urina , Tironinas/urina , Reações Cruzadas , Glucuronatos/urina , Humanos , Hipertireoidismo/urina , Hipotireoidismo/urina , Radioimunoensaio/métodos , Ácidos Sulfúricos/urina , Glândula Tireoide/fisiologiaRESUMO
Kinetic studies of T4 and T3 using a noncompartmental approach were performed in seven patients with pretreatment severe hypothyroidism maintained on L-T4 replacement. Each subject received a combined tracer dose of labeled T4 and T3 as an iv bolus before and during peroral treatment with propranolol. Serum T4 was unchanged, while a significant decrease of 13% was found in serum T3. The disposal rates (DR) of T4 and T3 decreased significantly, and the ratio between the DR off T3 and the DR of T4, the conversion rate, was significantly reduced during propranolol treatment. The decrease in the DR of T4 suggests a reduction in the bioavailability of L-T4 during propranolol, possibly due to a decrease in intestinal absorption. The decrease in the conversion rate indicates a reduced extrathyroidal conversion of T4 to T3 during propranolol treatment.
Assuntos
Hipotireoidismo/metabolismo , Propranolol , Tiroxina/metabolismo , Tri-Iodotironina Reversa/metabolismo , Tri-Iodotironina/metabolismo , Adulto , Idoso , Feminino , Humanos , Hipotireoidismo/tratamento farmacológico , Cinética , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Tiroxina/uso terapêuticoRESUMO
The effect of D,L-propranolol (80 mg daily) on the peripheral monodeiodination of rT3, 3',5'-diiodothyronine (3',5'-T2), 3,3'-diiodothyronine (3,3'-T2), and 3'-monoiodothyronine (3'-T1) was studied in seven out-patients with severe pretreatment hypothyroidism. The patients were maintained euthyroid on a constant L-T4 replacement therapy. A bolus injection technique was used; MCR, production rate (PR), and conversion rate were determined using a noncompartmental kinetic model. During D,L-propranolol, serum rT3 and 3',5'-T2 increased (P less than 0.02), and 3,3'-T2 seemed to decrease. The MCRs of rT3, 3',5'-T2, and 3,3'-T2 (P less than 0.02) decreased during drug treatment. The MCR and PR of 3'-T1 were reduced, albeit not significantly (P less than 0.10). The PR of 3,3'-T2 was reduced (P less than 0.02), whereas the PRs of rT3 and 3',5'-T2 were unaltered. The conversion rate of rT3 to 3',5'-T2 was unaltered. No changes were seen in the apparent distribution volumes of the iodothyronines studied. The results are compatible with the assumption that D,L-propranolol, or a metabolite thereof, inhibits the 5'-deiodination of all of the iodothyronines.
Assuntos
Di-Iodotironinas/sangue , Propranolol/farmacologia , Tironinas/sangue , Tri-Iodotironina Reversa/sangue , Tri-Iodotironina/sangue , Idoso , Feminino , Humanos , Hipotireoidismo/sangue , Isomerismo , Cinética , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-IdadeRESUMO
Simultaneous kinetic studies of 3,5-diiodothyronine (3,5-T2) and T3 were performed in 15 healthy controls (8 men and 7 women), 7 hyperthyroid patients (2 men and 5 women), and 6 hypothyroid women using the single injection, noncompartmental approach. The serum concentrations (picomoles per liter), MCRs (liters . day-1 . (70 kg)-1), and production rates (PRs; nmol . day-1 . (70 kg)-1) of 3,5-T2 in healthy men and women were (mean +/- SD): 100 +/- 23 vs. 80 +/- 23 (P = NS), 59 +/- 31 vs. 123 +/- 58 (P less than 0.025), and 5.6 +/- 1.9 vs. 9.1 +/- 2.6 (P less than 0.02). The conversion rate (CR) of T3 to 3,5-T2 was 12.0 +/- 3.8% in men compared to 18.5 +/- 3.7% in women (P less than 0.01). Serum 3,5-T2 levels in five mildly hyperthyroid women were elevated to 123 +/- 33 pmol/liter (P less than 0.05), whereas the MCR and PR were unchanged. However, two hyperthyroid men with more pronounced elevation of serum T3 had enhanced PRs (26.9 and 23.9 nmol . day-1 . (70 kg)-1). The CR in hyperthyroid women was significantly reduced to 5.6 +/- 2.9% (P less than 0.001). The serum levels, MCR, and PR of 3,5-T2 in hypothyroid women were: 58 +/- 25 pmol/liter (P = NS), 71 +/- 52 liters . day-1 . (70 kg)-1 (P = NS), and 3.4 +/- 2.4 nmol . day-1 . (70 kg)-1 (P less than 0.005). The CR was enhanced to 34.8 +/- 15.7% (P less than 0.05). Our data demonstrate that in euthyroid subjects, approximately 15% of T3 is deiodinated to 3,5-T2, and this 5'-deiodination of T3 is influenced by thyroid function.
Assuntos
Di-Iodotironinas/sangue , Hipertireoidismo/sangue , Hipotireoidismo/sangue , Tironinas/sangue , Tri-Iodotironina/sangue , Adulto , Feminino , Humanos , Cinética , Masculino , Taxa de Depuração MetabólicaRESUMO
Simultaneous kinetic studies of 3,5-diiodothyronine (3,5-T2) and T3 were performed in 8 patients with biopsy proven cirrhosis and in 15 healthy subjects using the single injection, noncompartmental approach. The following T3 kinetic data were obtained in patients with cirrhosis and normal subjects (mean +/- SD): serum T3 (nmol/liter) 1.27 +/- 0.30 vs. 1.79 +/- 0.28 (P less than 0.001); MCR [liters X day-1 X (70 kg)-1] 22.9 +/- 5.3 vs. 26.7 +/- 4.4 (P less than 0.10); production rate [nmol X day-1 X (70 kg)-1] 29.0 +/- 9.6 vs. 47.7 +/- 9.0 (P less than 0.001). In patients with cirrhosis serum 3,5-T2 levels were reduced to 58 +/- 38% of those found in normal subjects (P less than 0.02). The MCR was unaffected, 125 +/- 85%, whereas the production rate was reduced to 57 +/- 26% (P less than 0.005). The conversion rate from T3 to 3,5-T2 was unaltered, 96 +/- 34% of that found in normals. It is concluded that reduced serum levels of 3,5-T2 in cirrhosis are due to a diminished amount of substrate, T3, and not to decreased 3'-deiodination of T3 or to an increase clearance of 3,5-T2.
Assuntos
Di-Iodotironinas/sangue , Cirrose Hepática Alcoólica/sangue , Tironinas/sangue , Tri-Iodotironina/sangue , Adulto , Feminino , Humanos , Cinética , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
Turnover studies of T4, T3, rT3, 3',5'-diiodothyronine (3',5'-T2), 3,3'-diiodothyronine (3,3'-T2), and 3'-monoiodothyronine (3'-T1) were performed in 10 patients with alcoholic cirrhosis of the liver and 9 euthyroid, healthy controls using the single injection, noncompartmental approach. The kinetics of all 6 iodothyronines were studied in the same individuals. A newly developed, simple and reproducible gel separation technique, followed by antibody extraction, was used for the quantitation of tracer in serum. Serum T4, T3, and 3,3'-T2 levels were reduced in patients with liver cirrhosis, whereas serum rT3 and 3',5'-T2 levels were increased, Serum 3'-T1 levels were unaltered. A general tendency toward reduced MCRs was observed. The following median MCRs (liters per day per 70 kg BW) were found (cirrhotics vs. controls): T4, 1.13 vs. 1.19 (P = NS); T3, 16 vs. 20 (P less than 0.05); rT3, 81 vs. 147 (P less than 0.01); 3',5'-T2, 131 vs. 279 (P less than 0.01); 3,3'-T2, 533 vs. 1116 (P less than 0.01); and 3'-T1, 375 vs. 539 (P less than 0.05). The production rates (nanomoles per day per 70 kg BW) of T4, rT3, and 3,'5'-T2 were not significantly altered in patients with cirrhosis (cirrhotics vs. controls): 100 vs. 117, 47.5 vs. 52.0, and 14.5 vs. 13.9, respectively. In contrast, the following pronounced reductions in production rates of T3, 3,3'-T2, and 3'-T1 were found: 19.1 vs. 38.8 (P less than 0.01), 13.2 vs. 36.8 (P less than 0.01), and 15.7 vs. 28.6 (P less than 0.05), respectively. Assuming that thyroidal secretion contributes little rT3 and 3',5'-T2, the conversion rates from T4 to rT3 and further to 3',5'-T2 were calculated and found to be unaffected in patients with liver cirrhosis (48% vs. 34% in controls and 34% vs. 26% in controls, respectively). No tendency toward major changes in the activity of the nondeiodinative metabolic pathways was observed. In conclusion, our data show that liver cirrhosis profoundly changes the kinetics of all iodothyronines studied. Further, the 5-deiodination of T4 and rT3 is unaffected in patients with liver cirrhosis. In contrast, a general inhibition of the 5'-deiodinations seems to exist in patients with liver cirrhosis. Thus, our data are compatible with the existence of a common 5-deiodinase and a common 5'-deiodinase for the sequential deiodination of the iodothyronines in man.
Assuntos
Cirrose Hepática Alcoólica/sangue , Hormônios Tireóideos/sangue , Adulto , Idoso , Di-Iodotironinas/sangue , Feminino , Humanos , Cinética , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Tironinas/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Tri-Iodotironina Reversa/sangueRESUMO
The present study evaluates the sequential extra-thyroidal monodeiodination of thyroid hormones through tri-, di-, and monoiodothyronines in chronic renal failure (CRF) in man. Simultaneous turnover studies of T4, T3, rT3, 3,5-diiodothyronine (3,5-T2), 3,3'-T2, 3',5'-T2, 3'5'-T2, and 3'-monoiodothyronine (3--T1) were conducted in six patients with CRF (creatinine clearance, 9-18 ml/min) using the single-injection, noncompartmental approach. Serum levels of T4, T3, and 3,5-T2 were reduced to two thirds of control levels (P less than 0.05), whereas serum rT3 and 3,3'-T2 levels were reduced to a minor degree. Serum 3'-5'-T1 was doubled (p less than 0.05). The MCRs of T4, rT3, and 3',5'-T2 were enhanced to 168%, 127%, and 187% of normal (P less than 0.05), respectively, whereas those of T3, 3,5-T2, 3,3'-T2, and 3'-T1 were unaffected. The mean production rates (PRs) of the iodothyronines in CRF were as follows (CRF vs. control values, expressed as nanomoles per day/70 kg): T4, 119 vs. 125; T3, 26 vs. 44 (P less than 0.01); rT3, 49 vs, 48; 3,5-T2, 3.5 vs. 7.2 (P less than 0.001); 3,3'-T2, 25 vs. 35 (P less than 0.01); 3',5'-T2, 25 vs. 14 (P less than 0.01); and 3'-T1, 39 vs. 30. Previous studies have demonstrated reduced phenolic ring (5'-) deiodination of T4 in CRF, which is supported by the present finding of unaltered PR of T4 and reduced PR of T3. In contrast the 5'-deiodination of T3 leading to the formation of 3,5-T2 was found unaffected by CRF, since the conversion rate (CR) of T3 to 3,5-T2 (PR 3,5-T2/PR T3) was unaltered (16% vs. 15% in controls). The tyrosylic ring (5-) deiodination of T4 to rT3 was unaffected in patients with CRF, the CR being 42% vs. 40% in controls, in contrast to an enhanced CR of rT3 to 3',5'-T2 (53% vs. 29%, P less than 0.01), which also is a 5-deiodination step. In conclusion, our data show that CRF profoundly changes the kinetics of all iodothyronines studied. Furthermore, our data are compatible with the existence of more than one 5'-deiodinase as well as more than one 5-deiodinase in man.
Assuntos
Falência Renal Crônica/sangue , Hormônios Tireóideos/sangue , Adulto , Idoso , Di-Iodotironinas/sangue , Feminino , Humanos , Radioisótopos do Iodo , Cinética , Masculino , Pessoa de Meia-Idade , Albumina Sérica/metabolismo , Tironinas/sangue , Tireotropina/sangue , Hormônio Liberador de Tireotropina , Tiroxina/sangue , Tri-Iodotironina/sangue , Tri-Iodotironina Reversa/sangueRESUMO
Serum TSH, as measured by a sensitive assay, and serum free T4 and T3, as measured by an ultrafiltration technique, were compared in 14 euthyroid patients with multinodular goiter and 14 normal subjects. T4 and T3 turnover studies also were performed, using the single injection, noncompartmental approach. The goitrous patients had serum free T3 levels within the normal range, but their median serum T3 level was increased compared to that in the normal subjects [goitrous patients, 5.48 pmol/L (range, 4.41-9.03); normal subjects, 4.12 pmol/L (range, 2.58-5.78); P less than 0.01]. The T3 production rate (PR) also was elevated in the patients (median, 39.4 nmol/day X 70 kg; range, 28.7-70.5) compared to that in the normal subjects 31.1 nmol/day X 70 kg; range, 24.4-45.2); P less than 0.05). No differences were found between the two groups with regard to serum free T4 levels or T4 PRs. Serum TSH levels in the patients were reduced (median, 0.20 mU/L; range, less than 0.05-1.6) compared to those in normal subjects (1.8 mU/L; range, 0.36-5.1; P less than 0.01). A significant inverse correlation was found between serum TSH levels and free T3 levels (r = 0.70; P less than 0.001), whereas serum TSH did not correlate with serum free T4 or the PR of T4 or T3. Our data suggest that clinically and biochemically euthyroid patients with multinodular goiter have slight T3 hyperproduction, and TSH secretion in the patients studied was more closely related to serum free T3 levels than to serum free T4 levels or the T3 or T4 PR.
Assuntos
Bócio Nodular/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tiroxina/biossíntese , Tri-Iodotironina/biossíntese , UltrafiltraçãoRESUMO
Severe nonthyroidal illness has been claimed to cause secondary hypothyroidism. We reevaluated this concept measuring serum free T4 and free T3 by an ultrafiltration method and serum TSH by an ultrasensitive technique (detection limit, and serum TSH by an ultrasensitive technique (detection limit, 0.05 mU/L). Forty-five critically ill patients suffering from hepatic coma (n = 10), terminal cancer (n = 9), stroke (n = 8), and respiratory insufficiency not treated (n = 7) and treated (n = 11) with dopamine were studied. The mortality rate was 80%. No patients received glucocorticoids, and only patients in the last group received dopamine. Serum total as well as free thyroid hormone index values were grossly reduced in the majority of the patients. The 34 patients not receiving dopamine in general had normal values of serum free T4 (32 of 34) and free T3 (31 of 34), measurable TSH (33 of 34), and detectable TSH responses to iv TRH (33 of 34). In contrast, the dopamine-treated patients had reduced serum free T4 and TSH levels compared to normal subjects (P less than 0.05), as well as reduced TSH responses to TRH (P less than 0.01). Serum free T4 and free T3 were below the normal range in 3 patients and 1 patient, respectively, and serum TSH was below the detection limit in 2 patients. We conclude that critically ill patients with nonthyroidal illness not receiving dopamine have normal pituitary-thyroid function, whereas dopamine induces some degree of secondary hypothyroidism.
Assuntos
Hipotireoidismo/etiologia , Testes de Função Hipofisária , Testes de Função Tireóidea , Adulto , Idoso , Idoso de 80 Anos ou mais , Dopamina/farmacologia , Feminino , Humanos , Hipotireoidismo/sangue , Masculino , Pessoa de Meia-Idade , Gravidez , Doenças da Glândula Tireoide/sangue , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , UltrafiltraçãoRESUMO
The extrathyroidal metabolism of T4, T3, rT3, and 3',5'-diiodothyronine (3',5'-T2) was studied before and after treatment with 350 mg phenytoin (DPH) daily for 14 days in six hypothyroid patients receiving constant L-T4 replacement. The total and free serum concentrations of the four iodothyronines were reduced by approximately 30% during DPH treatment, whereas the free fractions in serum were unaltered. Concomitantly, serum TSH increased 137% (P less than 0.02). The production rate (PR) of T4 decreased 16% (P less than 0.005), indicating decreased intestinal absorption (bioavailability) of oral L-T4 during DPH treatment. The fractional rate of 5'-deiodination of T4 to T3 increased from 27% to 31% (P less than 0.05), whereas the rate of 5-deiodination of T4 to rT3 decreased from 45% to 25% (P less than 0.05). The urinary excretion of free and conjugated T4 was 2.3% of the T4 PR and was unaffected by DPH. Thus, the amount of T4 metabolized through nondeiodinative pathways apart from urinary excretion increased from 25% to 44% (P less than 0.05). The apparent distribution volume (Vd) of T4 increased (P less than 0.05), whereas the pool size was unchanged. The PR of T3 did not change during DPH treatment, nor did the mean transit time or the cellular clearance. The rT3 PR was reduced by 54% (P less than 0.02) during DPH treatment. Concomitantly, the transit time increased 10-fold (P less than 0.05), whereas Vd and pool size increased 5-fold (P less than 0.01 and P less than 0.05, respectively). The turnover of 3',5'-T2, in contrast to that of the other iodothyronines, did not change significantly during DPH treatment. T3 formation from T4 was measured in liver microsomal fractions from rats treated for 8 days with DPH and was almost identical to that in untreated animals. The data demonstrate that DPH in therapeutic concentrations did not affect serum protein binding of the iodothyronines. DPH reduced the intestinal absorption of T4 and increased the nondeiodinative metabolism of T4. The resulting decrease in total and free serum T4 and T3 was associated with an increase in serum TSH, demonstrating reduced negative feedback on the pituitary. Our data do not support the assumption that DPH induces increased hepatic deiodinating enzyme activity.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Di-Iodotironinas/sangue , Hipotireoidismo/sangue , Fenitoína/farmacologia , Tironinas/sangue , Tiroxina/sangue , Tri-Iodotironina Reversa/sangue , Tri-Iodotironina/sangue , Idoso , Animais , Biotransformação , Feminino , Humanos , Hipotireoidismo/tratamento farmacológico , Técnicas In Vitro , Cinética , Masculino , Microssomos Hepáticos/metabolismo , Pessoa de Meia-Idade , Ratos , Ratos Endogâmicos , Tiroxina/uso terapêutico , Tiroxina/urina , Tri-Iodotironina/urinaRESUMO
The increased serum thyroxine (T4) levels in endogenous depression (ED) might be due to an increased production or a reduced degradation of T4. We therefore performed turnover studies of radiolabeled T4 and 3,5,3'-triiodothyronine (T3) in 6 patients with ED and 8 age-matched healthy controls. In ED, the median daily production of T4 was 130 nmol/day/70 kg, (range 100-186 nmol/day/70 kg) and elevated compared to control values which were 99 nmol/day/70 kg (range 85-142 nmol/day/70 kg) (p less than 0.05), whereas that of T3 was similar in the two groups. Serum thyrotropin (TSH) levels (0.90 mU/liter, 0.18-2.15 mU/liter) were elevated in ED compared to a group of 7 L-T4-treated hypothyroid subjects with similar production and serum levels of T4 and T3 (0.11 mU/liter, 0.07-1.10 mU/liter) (p less than 0.02). The data show that increased serum T4 levels in ED are secondary to an increased thyroidal production of T4, which is at least partly due to inappropriately high serum TSH levels.
Assuntos
Transtorno Depressivo/sangue , Tireotropina/sangue , Tiroxina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/psicologia , Feminino , Humanos , Hipotireoidismo/sangue , Masculino , Pessoa de Meia-Idade , Testes de Personalidade , Radioimunoensaio , Tri-Iodotironina/sangueRESUMO
The authors conducted a double-blind prospective study of 39 patients with unipolar endogenous depression who recovered after ECT. Thyrotropin (TSH)-releasing hormone (TRH) tests were performed before and after ECT. Patients were divided into three groups on the basis of their altered TSH response: Persistent remission was predicted for patients in group 1 (N = 15) and relapse was predicted for groups 2A (N = 13) and 2B (N = 11). Patients in groups 1 and 2A received placebo and those in group 2B received amitriptyline for 6 months. Fewer relapses occurred in groups 1 and 2B than in group 2A (p less than .05), showing that relapse can be predicted by the TRH test and prevented by amitriptyline.
Assuntos
Amitriptilina/uso terapêutico , Transtorno Depressivo/terapia , Eletroconvulsoterapia , Hormônio Liberador de Tireotropina , Adulto , Idoso , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/prevenção & controle , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Placebos , Probabilidade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Recidiva , Tireotropina/sangueRESUMO
A retrospective analysis of data from 73 consecutive patients with toxic multinodular goitre treated with iodine-131 (131I) during a 2-year period was performed to investigate if serum TSH at the time of 131I treatment influences the outcome. The dose of 131I was calculated according to a model compensating for thyroid size estimated by palpation and 24-h 131I uptake. Serum TSH was determined by a third-generation assay with a functional sensitivity of 0.03 mU/l. A significantly more pronounced response to 131I treatment was observed in patients with TSH > 0.0 mU/l than in patients with TSH = 0.0 mU/l (P = 0.0006. This difference resulted in a threefold lower frequency of non-responders and a fivefold higher rate of early hypothyroidism in the group with detectable serum TSH. While the high frequency of hypothyroidism among patients with measurable serum TSH can be explained by destruction of normal thyroid tissue, the high frequency of treatment failure in the group with serum TSH = 0.0 mU/l suggests that autonomous thyroid tissue may also be sensitized to a deleterious effect of 131I through stimulation by TSH. We conclude that serum TSH has a significant influence on the outcome of 131I treatment of toxic multinodular goitre. The results of 131I treatment may be improved by adjustment of the dose of 131I according to the serum TSH level, in addition to adjustment for goitre size and 24-h 131I uptake.
Assuntos
Bócio Nodular/radioterapia , Radioisótopos do Iodo/uso terapêutico , Tireotropina/sangue , Feminino , Bócio Nodular/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Concentração Osmolar , Retratamento , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate if serum TSH at the time of 131I therapy influences the outcome. DESIGN: A retrospective analysis of data on 39 consecutive patients with toxic solitary autonomous thyroid nodules treated with 131I during a 4 year period. METHODS: Serum TSH was determined by an ultrasensitive RIA with a functional sensitivity of 0.03 mU/l. The 131I dose was calculated blind to the actual serum TSH according to a model compensating for thyroid size estimated by palpation as well as 24 h 131I uptake. RESULTS: After a mean follow-up period of 30 months, 34 patients (87% of all patients) were euthyroid, three (8%) had responded insufficiently and required further antithyroid therapy, and two (5%) had developed hypothyroidism. No significant difference in the response pattern between patients with suppressed or detectable serum TSH could be demonstrated. The two patients who developed hypothyroidism both had detectable serum TSH at the time of 131I treatment. No other clinical parameter seemed to influence the outcome. CONCLUSION: There is no clinically significant effect of circulating TSH on the response of toxic solitary autonomous thyroid nodules to 131I therapy. However, keeping the patients subclinically hyperthyroid when receiving 131I treatment may possibly result in a reduced frequency of hypothyroidism.
Assuntos
Radioisótopos do Iodo/uso terapêutico , Nódulo da Glândula Tireoide/radioterapia , Tireotropina/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Estudos Retrospectivos , Fatores de Risco , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
The TSH response to TRH (delta max TSH) and the serum concentrations of free thyroxine (FT4), 3,5,3'-, and 3,3',5'-triiodothyronine (FT3 and FrT3) were studied in two groups of patients with endogenous depression before and after clinical recovery following electroconvulsive treatment (ECT). Before ECT, the patients from group 1 (n = 17) had a reduced delta max TSH (p less than 0.01), which after ECT rose to values not different from those found in controls. FT4 levels were elevated before ECT (p less than 0.01), and they decreased after ECT (p less than 0.05) to levels similar to those found in controls. FT3 and FrT3 levels were not different from the control values, but FrT3 decreased during ECT (p less than 0.01). In group 2 (n = 19), delta max TSH was reduced both before (p less than 0.02) and after (p less than 0.01) ECT. FT4 levels were increased both before and after ECT (p less than 0.02). Both parameters were unaffected by ECT. The data are compatible with the assumption that the decreased TSH response to TRH found in patients with endogenous depression is secondary to an increase in circulating FT4.