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Biomedical subjects

T Friis

Publications and source records attributed to T Friis.

At least 37 records · Page 2Linked to original sources
PubMed1986

Changes in blood pressure, heart rate and thyroid hormones after sudden withdrawal of pindolol and atenolol in hypertensive patients.

In a double-blind study 19 patients with mild and uncomplicated arterial hypertension were randomized to treatment with either pindolol 10 mg or atenolol 100 mg once daily for 4 weeks. After abrupt withdrawal a minor overshoot of free-T3 was seen in both groups. This was, however, statistically significant in the pindolol group only. The only overall haemodynamic changes which was observed after the withdrawal was an overshoot in heart rate in the standing position in the atenolol group. Great inter-individual differences in the haemodynamic parameters were found, however, and changes suggestive for withdrawal syndrome were found in 14 patients (pindolol = 7). The time for this overshoot varied considerably from 48-132 h post-drug in both groups. No correlation between the alterations in free-T3 and the cardiovascular parameters was found.

Adult↗
PubMed1985

Urinary excretion of unconjugated and conjugated 3,5-diiodothyronine.

A radioimmunoassay for the estimation of 3,5-diiodothyronine (3,5-T2) in human urine has been established. The urinary excretion of both glucuronide and sulfate conjugates of 3,5-T2 were estimated after enzymatic deconjugation. In 19 healthy controls the median excretion of unconjugated 3,5-T2 was 276 pmol/d, whereas the median excretion of glucuronidated and sulfated 3,5-T2 in 7 healthy subjects was 448 and 451 pmol/d, respectively. The median excretion of 154 pmol/d in 9 hypothyroid patients did not differ from that found in controls. In contrast 12 patients with hyperthyroidism had an enhanced excretion, 1312 pmol/d (P less than 0.01). Compared with previous data on the daily degradation of 3,5-T2, it is concluded that approximately one-sixth of degradated 3,5-T2 is excreted in the urine.

Adult↗
PubMed1985

The effects of phenytoin (diphenylhydantoin) on the extrathyroidal turnover of thyroxine, 3,5,3'-triiodothyronine, 3,3',5'-triiodothyronine, and 3',5'-diiodothyronine in man.

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)

Aged↗
PubMed1985

The bioavailability of thyroxine and 3,5,3'-triiodothyronine in normal subjects and in hyper- and hypothyroid patients.

A new method for the estimation of the bioavailability of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) is described based on gel separation followed by antibody extraction of labelled T4 and T3 from serum, and using the area under the curve of disappearance of the tracer (AUC) for the calculations. The peak serum concentrations of radioactive labelled T4 and T3 were reached approximately 90 min after oral administration of both tracers. The relative difference of duplicate estimations was below 10% (n = 3). The bioavailability of T4 in 6 euthyroid controls was in median 65% (range 64-75%), and it was significantly increased both in hyperthyroidism (88% (75-99%), n = 6, P less than 0.01) and hypothyroidism (84% (67-100%), n = 6, P less than 0.02). The bioavailability of T3 in 6 euthyroid controls was in median 78% (69-99%) and significantly greater than that of T4 (P less than 0.02). The bioavailability was unaffected by hyperthyroidism (79% (61-98%), n = 9) and hypothyroidism (77% (66-97%), n = 7). No significant difference between T4 and T3 bioavailabilities was found in hyper- or hypothyroidism. The clinical implication of the present study is that the bioavailability of T4 and T3 is almost identical and approximately 80% in patients with severe hypothyroidism.

Adult↗
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

The prognostic value of parallel measurements of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb) in Graves' disease after longterm antithyroid treatment.

Thyroid stimulating immunoglobulins were measured in 43 patients with Graves' disease both before and at the end of longterm antithyroid treatment. Parallel determinations were performed of thyrotropin binding inhibiting immunoglobulins (TBII) and thyroid adenylate cyclase stimulating antibodies (TSAb). Before treatment 33 patients were TBII positive and 32 TSAb positive, and at the end of treatment 19 remained TBII positive and 14 TSAb positive. The frequency of relapse was about 70% in the positive patients and about 40% in the patients, who became negative in either test for thyroid stimulating immunoglobulins. By combination of the two assays 23 patients were positive in both before treatment. In these patients 5 relapsed of the 6 who remained positive for both, while none relapsed of the 5 patients, who became negative during treatment. In the remaining 12 patients either TBII or TSAb became negative during treatment and 7 of these relapsed. It is concluded, that the combined measurement of TBII and TSAb in this study seemed superior to the separate determinations of either activity in predicting relapse after medical treatment of Graves' disease, though this evaluation was only possible in part of the patients.

Adenylyl Cyclases↗
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

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

Thyroid-stimulating immunoglobulins in Hashimoto's thyroiditis measured by radioreceptor assay and adenylate cyclase stimulation and their relationship to HLA-D alleles.

The relationship between thyroid-stimulating immunoglobulins, measured by both radioreceptor assay and adenylate cyclase stimulation, and the HLA alleles was studied in 41 patients with Hashimoto's thyroiditis. TSH binding-inhibiting immunoglobulins (TBII) were detected in 9 (22%) patients, and human thyroid adenylate cyclase-stimulating immunoglobulins (HTACS) were found in 21 (51%) patients. Only 2 patients were positive in both assays, and an inverse relationship was observed between TBII and HTACS. In the 21 HTACS-positive patients, HLA-Dw5 was only found in 1 subject, compared to 8 of the 20 HTACs-negative patients (P less than 0.01), while 4 of the 9 TBII-positive patients had HLA-Dw5 compared to 5 of the 32 TBII-negative subjects (P = -0.09). No significant relations were observed between the presence of HTACS or TBII and HLA-Dw3 or HLA-B8. It is concluded, that TBII and HTACS are produced independently in Hashimoto's thyroiditis, and that the production of these autoantibodies seems to be related to the HLA-D region in this disease.

Adenylyl Cyclases↗
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

131I treatment of diffuse and nodular toxic goitre with or without antithyroid agents.

The results of 131I treatment in combination with pre- and post-treatment with carbimazole (n = 122) were compared to the results of 131I used as the only antithyroid treatment (n = 203). The two groups of patients were fully comparable in regard to age, size of goitre and time of observation, and the same diagnostic criteria and dosage regimen of 131I were used. The incidence of early myxoedema in patients with diffuse goitre was significantly reduced after combination therapy, 5 per cent, compared to 16 per cent after 131I as the only antithyroid therapy (P less than 0.05). The incidence of late myxoedema was 6 per cent in both groups 3 years after the last treatment, and fully compensated myxoedema was found in 13 and 22 per cent (n.s.). No severe acute side effects were observed after 131I therapy in any of the two groups. It is concluded that--in diffuse toxic goitre--a lower early incidence of myxoedema was obtained on the combined regimen because of either a possibly lower absorbed radiation dose or a more fractionate therapy. A major advantage of the combination therapy is also, that the patients are rendered euthyroid shortly after the diagnosis and remain so during the prolonged period of treatment. 131I treatment in combination with carbimazole is advocated in all patients with diffuse and nodular toxic goitre if the patient is above fertile age and thyroidectomy is not indicated.

Adenoma↗