PubMed Health⌕ Search

Biomedical subjects

C Kirkegaard

Publications and source records attributed to C Kirkegaard.

At least 55 records · Page 3Linked to original sources
PubMed1984

The effect of D,L-4-hydroxypropranolol on the thyroxine to 3,5,3'-triiodothyronine conversion in rat renal and liver microsomes.

The in vitro effect of D,L-4-hydroxypropranolol, a major pharmacological active metabolite of the beta adrenoceptor blocking drug D,L-propranolol, on the thyroxine (T4) to 3,5,3'-triiodothyronine (T3) conversion has been studied using rat renal and liver microsomal fractions. The results showed, that primarily the metabolite, but also the parent drug inhibits the T3-production in a dose dependent manner. The potency, expressed as the 50% inhibition of the T3-production, was reached using 65 +/- 12 (SD) microM D,L-4-OH-propranolol and 1000 +/- 22 (SD) microM D,L-propranolol, respectively in both tissues. The efficacy of 4-OH-propranolol corresponded to a maximal inhibition of 86 +/- 7% while it for D,L-propranolol corresponded to 58 +/- 6% (P less than 0.001). The beta adrenoceptor agonist isoprenaline itself did not effect the T4 to T3 conversion but considerably opposed the inhibitory effect of D,L-4-OH-propranolol but not of D,L-propranolol. The D-isomer form of propranolol, which is without beta receptor blocking activity inhibited the T3-production in the same degree as D,L-propranolol. Evaluation of the enzyme kinetic data suggested that 4-OH-propranolol caused a competitive inhibition of both T4 and DTT. It is concluded, that the metabolite D,L-4-OH-propranolol is a much more potent and efficacious inhibitor of the T4-5'-deiodination than D,L-propranolol.

Animals↗
PubMed1984

Serum free T4, T3, rT3, 3,3'-diiodothyronine and 3',5'-diiodothyronine measured by ultrafiltration.

A simple and accurate method for estimation of the free fractions (FFT) of T4, T3, rT3, 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) in serum is presented. The method is based on ultrafiltration of serum pre-incubated with tracers of high specific activity, followed by purification of the ultrafiltrate on small Sephadex columns. The addition of tracer only dilutes serum negligible (about 5%) and the ultrafiltration procedure only removes about 7% of the volume of serum, thus probably not disturbing the equilibrium between the free and protein bound fraction of iodothyronine. Progressive reduction of tracer to less than 10% of the amount usually used did not reduce the FFT of any of the iodothyronines. In contrast, addition of T4 to serum led to an increase of all FFTs except that of 3',5'-T2. These data suggest that FFT of T4, T3, rT3 and 3,3'-T2 primarily is determined by the amount of T4 present in serum and that significant amounts of these iodothyronines are bound to TBG, whereas 3',5'-T2 possibly primarily is bound to albumin. The median FFT of T4, T3, rT3, 3,3'-T2 and 3',5'-T2 in serum from euthyroid subjects (n = 38) was: 0.030, 0.29, 0.14, 1.10 and 1.07%, respectively. The corresponding median free concentrations in pmol/l were: 30, 4.79, 0.59, 0.44 and 0.77, respectively. Pregnant women in 3rd trimester had normal levels of free T4, free T3 and free rT3, whereas the median free 3,3'-T2 was reduced in contrast to elevated median free 3',5'-T2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Dexamethasone suppression test and TRH test in endogenous depression.

Dexamethasone suppression test (DST) and thyrotropin releasing hormone (TRH) stimulation test were performed in 34 patients with endogenous depression. Compared with 33 psychiatric controls (limit of discrimination for serum cortisol of 275 nmol/l = 10 micrograms/100 ml) the specificity of the DST was 91% and the sensitivity was 65%. Compared with 24 healthy subjects the sensitivity of the TRH test was 24%, and the combined sensitivity for the DST and the TRH test was 76%. In contrast to the TRH test the DST showed a significant relationship (r = 0.54, P less than 0.01) to the Hamilton Rating Score. Repeating the tests after clinical recovery parallel changes of the two tests were found in 14 of 19 patients with abnormal DST in the depressed phase. In the remaining five patients the DST normalized, while the TRH test remained unchanged. It is suggested that both the apparent higher diagnostic sensitivity and the higher rate of normalization after clinical recovery of the DST is due to the dependency of the severity of depression.

Adolescent↗
PubMed1983

Simultaneous turnover studies of thyroxine, 3,5,3' and 3,3',5'-triiodothyronine, 3,5-, 3,3'-, and 3',5'- diiodothyronine, and 3'-monoiodothyronine in chronic renal failure.

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.

Adult↗
PubMed1983

The extrathyroidal conversion of 3,5,3'-triiodothyronine to 3,5-diiodothyronine in patients with liver cirrhosis.

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.

Adult↗
PubMed1982

Circadian variation of serum thyrotropin in endogenous depression.

The circadian variation of serum thyrotropin (thyroid-stimulating hormone; TSH) was studied in nine patients with endogenous depression before and after recovery. Depressed state did not appear to influence the pattern of TSH. When 2 mg of dexamethasone was administered, serum TSH was significantly reduced for 18 hours, whereafter the effect leveled off. The TSH response to thyrotropin-releasing hormone (TRH) was evaluated 25 hours after the administration of dexamethasone and the response was found to be unchanged.

Aged↗
PubMed1982

The extrathyroidal effect of D,L-propranolol on 3,3',5'-triiodothyronine, 3',5'-diiodothyronine, 3,3'-diiodothyronine, and 3'-monoiodothyronine kinetics.

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.

Aged↗
PubMed1982

Simultaneous measurement of 3,5-diiodothyronine and 3,5,3'-triiodothyronine turnover kinetics in euthyroid hyperthyroid, and hypothyroid subjects.

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.

Adult↗
PubMed1982

Isolation of radioactive iodothyronines for kinetic studies: a comparison of two methods.

A method based on the principle of gel separation followed by antibody extraction (GSAE) has been developed for isolation of radioactive thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3'5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2), 3',5'-diiodothyronine (3',5'-T2) and 3'monoiodothyronine (3'-T1) in serum. This method was used for the estimation of the metabolic clearance rate (MCR( of the iodothyronines using the single injection, non-compartmental approach, and was compared to the conventional trichloroacetic acid precipitation/ethanol extraction (TCA-E) technique. The GSAE method excluded the co-determination of radioactive iodine ad iodoproteins, whereas the co-determination of radiolabelled daughter iodothyronines was found negligible. The relative difference of duplicate estimation of MCR was approximately 10%. Using the TCA-E method for isolation of tracer, the MCR of T4, T3 and rT3 was underestimated to a minor degree (20%), whereas the MCRs of 3,3'-T2, 3'5'-T2 and 3'-T1 were 20-40% of the estimated by the GSAE method. In conclusion the GSAE method was found suitable for kinetic studies of iodothyronines, whereas the TCA-E method cannot be used for turnover studies of 3,3'-T2, 3'5'-T2 or 3'T1.

Adult↗
PubMed1982

The oral TRH stimulation test. A new diagnostic tool in "non-toxic" multinodular goitre.

We have developed a 28-hour TRH stimulation test based on the FT3I response to repeated oral TRH stimulation. The normal FT3I response in 15 controls was greater than or equal to 40 arb.U. Twenty-five euthyroid patients with multinodular goitre were studied. Fourteen had normal FT3I responses and normal basal levels of serum T4, FT4I, serum T3 and FT3I. Eleven patients had FT3I responses below 20 arb.U. Although the patients' individual basal values of serum T4, FT4I, serum T3 and FT3I were within the normal range, the median values of FT4I, serum T3 and FT3I were significantly elevated compared to the controls, suggesting that these patients were in a "pretoxic" condition. This assumption seems to be supported by the fact that 3 of these patients subsequently became frankly hyperthyroid, whereas all patients with normal FT3I response remained euthyroid. A comparison between the TSH response to i.v. TRH and the FT3I response to oral TRH showed concordance in 21 of the 25 patients studied.

Administration, Oral↗
PubMed1981

Serum levels of T4, T3, reverse T3, 3,3'-diiodothyronine and 3',5'-diiodothyronine in obesity, before and after jejuno-ileal bypass.

Serum T4, 3,5,3'triiodothyronine (T3), 3,3',5'-triiodothyronine (reverse T3, rT3), 3,3'-diiodothyronine (3,3'-T2), 3',5'-diiodothyronine (3',5'-T2) and thyrotrophin (TSH) levels were studied in nineteen obese patients before and 6, 12, and 18, months after a jejuno-ileal bypass. Before surgery, the obese patients had increased serum T3 levels compared with a group of lean, matched controls (median: 1.94 nmol/l v. 1.44 nmol/l, P less than 0.01). Serum T3 decreased to normal (1.64 nmol/l) 18 months after surgery. A slight decrease was also observed in serum 3,3'-T2 levels, whereas progressive reductions in serum concentrations of rT3 and 3',5'T2 occurred. Eighteen months postoperatively the serum levels of rT3 and 3',5'-T2 had decreased from 0.676 nmol/l to 0.430 nmol/l (P less than 0.02) and 55.2 pmol/l to 40.0 pmol/l (P less than 0.01), respectively, and the values at 18 months were also reduced compared with the control group [0.722 nmol rT3/1 (P less than 0.01), 51.4 pmol 3',5'-T2/1 (P less than 0.01)]. concomitant with the decrease in serum level of the iodothyronines, serum TSH concentrations increased from 0 Micro U/ml to 0.9 microu/ml (P less than 0.01).

Adult↗
PubMed1981

Urinary excretion of free and conjugated 3',5'-diiodothyronine and 3,3'-diiodothyronine.

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.

Cross Reactions↗
PubMed1981

Kinetic studies of thyroxine, 3,5,3'-triiodothyronine, 3,3,5'-triiodothyronine, 3',5'-diiodothyronine, 3,3'-diiodothyronine, and 3'-monoiodothyronine in patients with liver cirrhosis.

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.

Adult↗
PubMed1981

Altered serum levels of thyroxine, triiodothyronines and diiodothyronines in endogenous depression.

Serum levels of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) were studied in 80 patients with endogenous depression before and after electroconvulsive treatment (ECT). Compared to the values found after recovery, the patients when depressed had significant increased serum levels of T4, rT3, 3,3'-T2 and 3',5'-T2. Serum concentrations of T3 and 3,5-T2 were not significantly altered. Similarly the free T4 index (FT4I) was increased, while the free T3 index (FT3I) was unaffected. Previous studies have shown a reduced TSH response to TRH in patients with endogenous depression and that the long-term outcome after ECT is strongly related to changes in the TSH response. However, patients with increased TSH response to TRH (n = 23) had a pattern of serum iodothyronine concentrations similar to those (n = 57) with an unchanged TSH response. A similar pattern was also found in 7 patients with nonendogenous psychosis, in whom the TSH response to TRH was unchanged after recovery. It is concluded that the alterations of the TSH response to TRH found in endogenous depression cannot be explained by changes of FT4I or FT3I.

Depression↗
PubMed1981

A radioimmunoassay of serum 3,5-diiodothyronine.

A radioimmunoassay (RIA) for serum 3,5-diiodothyronine (3,5-T2) was developed using small Sephadex G 25 (fine) columns. Prior to the RIA an alcohol extraction of 3,5-T2 from serum and an evaporation of the extract was performed. The recovery of 3,5-T2 added to serum was in mean (plus or minus SEM) 101 plus or minus 11%. The lower detection limit was 0.012 pmol/column corresponding to 14 pmol/l using 3 ml serum. Due to a 5% cross-reaction of 3,5-T2 antibody with 3,5,3'-triiodothyronine (T3) individual correction for T3 present in serum was necessary. Serum 3,5-T2 levels in 52 éuthyroid controls were (mean plus or minus SD) 105 plus or minus 51 pmol/l. Serum levels were higher in men (125 plus or minus 56 pmol/l. Serum levels were higher in men (125 plus or minus 56 pmol/l) than in women (84 plus or minus 34 pmol/l, P less than 0.005). In 17 hyperthyroid subjects serum 3,5-T2 levels were elevated (232 plus or minus 187 pmol/l, P less than 0.005). In hypothyroid patients and patients with non-toxic goitre serum 3,5-T2 levels did not differ significantly from control values, whereas 8 patients with liver cirrhosis had severely reduced serum 3,5-T2 concentrations (20 plus or minus 23 pmol/l, P less than 0.001).

Adolescent↗