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D A Koutras

Publications and source records attributed to D A Koutras.

At least 55 records · Page 3Linked to original sources

Human thyroglobulin reference material (CRM 457). 1st Part: Assessment of homogeneity, stability and immunoreactivity.

This paper describes the assessment of the homogeneity and stability of a purified and lyophilized human thyroglobulin (Tg), and characterizes its immunoreactivity. The purified and lyophilized Tg is intended to be used as a primary reference material to establish calibration of working serum based reference material. The programme involved the participation of 15 European laboratories and one laboratory from the United States. The homogeneity of the content of the ampoules was considered acceptable (< 9%). The stability was tested by accelerated temperature degradation showing predicted annual relative losses of 0.01% at -70 degrees C and 1.04% at -20 degrees C. The immunoreactivity of the Tg material as measured in different laboratories varied mostly according to the method used rather than the laboratory. The interlaboratory variability showed that the two commercial methods used in several laboratories (kit 1 and 2) had an interlaboratory variation (CV) of 15.9% (N = 5) and 7.1% (N = 3), respectively, whereas the total interlaboratory CV was 64.3% (N = 18). The immunoreactive Tg had dilution curves parallel with other Tg calibrators (those of the methods). Dilution curves of the Tg material after storage at various temperatures and time were parallel in both RIA and IRMA. In conclusion, we have prepared a Tg reference material which in extensive studies in several participating laboratories has demonstrated a sufficient homogeneity and stability as well as dilution curves parallel to the calibrators of all the immunoassays tested in the study. This reference material is considered the first step towards decreasing the interlaboratory variability between Tg immunoassays.

Drug Stability↗

Human thyroglobulin reference material (CRM 457). 2nd Part: Physicochemical characterization and certification.

This report describes the characterization of a purified human thyroglobulin (Tg) reference material, and details the procedures used in its certification. The purified Tg is intended to be used as a primary reference material to establish calibration of working serum based reference material for immunoassay procedures. The programme involved the participation of 15 European laboratories and one laboratory from the United States. The physicochemical characterization showed by polyacrylamide gel electrophoresis and immunoblotting that the purified Tg had for the major part the expected molecular size of 660 kDa with traces of lower molecular forms. The amino acid composition was close to that demonstrated for the cDNA and the content of iodine was in keeping with a moderately to highly iodinated Tg. The mass concentration in reference material RM 457 is certified to be (0.324 +/- 0.018) g/L on the basis of protein determined by the Lowry method and supported by nitrogen determination, absorbance measurement, and amino acid analysis. This reference material is considered the first step towards decreasing the interlaboratory variability between Tg methods of measurement.

Amino Acids↗

Thyroid autoantibodies in the subsets of lupus erythematosus: correlation with other autoantibodies and thyroid function.

Thirty four sera from: 12 patients with Systemic Lupus Erythematosus (SLE), 9 with Subacute Cutaneous Lupus Erythematosus (SCLE) and 13 with Discoid Lupus Erythematosus (DLE) (disseminatus 3, localised 10) were tested for the presence of: (a) anti-thyroglobulin and anti-microsomal autoantibodies (b) anti-Sm/RNP, anti-doublestranded. DNA (anti-ds. DNA), anti-single-Stranded. DNA (anti-ss. DNA), anti-cardiolipin (anti-Cl), anti-SSA, anti-SSB, Antinuclear Antibodies (ANA). T3, T4, TSH levels were also determined. Five patients with SLE (41.6%), 4 with SCLE (44.4%), and 2 with DLE (15.3%) had thyroid autoantibodies and only three of the 41 controls (7.3%). Five patients (14.7%), especially from SLE and SCLE groups, had biochemical hypothyroidism whereas only one had hyperthyroidism. Statistical evaluation for the possible coexistence of thyroid autoantibodies with a panel of lupus characteristic autoantibodies, revealed highly significant correlations with anti-Sm/RNP, IgG (p = 0.003) and anti-ds. DNA, IgM (p = 0.012). It may be concluded, that not only SLE but also SCLE predisposes to autoimmune thyroid disease and the prevalence of the latter is related to a great extent to the subset of the LE spectrum. From these results and from the inhibition experiments, it seems that some of the specific mono- or polyclonal autoantibodies may be multiple organ reactive.

Adult↗

The medical treatment of non-toxic goiter: several questions remain.

In this review it is concluded that thyroxine (T4), triiodothyronine (T3) and iodine (KI), singly or in combination, are all effective in reducing the goiter size, but there is insufficient evidence to prove which is the best (possibly the combination of T4 + KI?). Higher doses are more effective than smaller, but also lead to more side-effects. Thus, the optimal dose has yet to be found. The suppression of the pituitary thyroid axis plays a major role in the treatment of non-toxic goiter, but it is not definite that this is the only mechanism responsible for the beneficial effect of the agents mentioned. In view of the lack of better evidence, it is simply suggested that non-toxic goiters in young persons should be initially treated aggressively with 200 micrograms of T4/day or more for some months. If the goiter shrinks then the dose should be gradually decreased. If the goiter persists, it is futile to continue with large doses for more than 6-12 months. One may continue with smaller doses, maintaining the serum TSH in the low-normal range. The treatment of benign thyroid nodules with thyroxine is controversial. Probably thyroxine is beneficial in about a third of the cases. For both non-toxic goiters and nodules, autonomy should be excluded before starting thyroxine treatment, and old age, cardiac disease and a poor general condition are contraindications.

Drug Therapy, Combination↗

The effect of iodide on serum thyroid hormone levels in normal persons, in hyperthyroid patients, and in hypothyroid patients on thyroxine replacement.

OBJECTIVE: To clarify the duration and the extent of the antithyroid effect of iodides in hyperthyroidism, and to investigate whether iodides have an additional peripheral effect on the metabolism of thyroid hormones, as has been reported for some organic iodine compounds. DESIGN: The effect on the peripheral thyroid hormone levels of 150 mg of potassium iodide daily (equivalent to 114 mg of iodide) for 3-7 weeks was compared in 21 hyperthyroid patients and 12 healthy controls. A possible effect of iodide on the peripheral metabolism of thyroid hormones was investigated by assessing the serum levels of thyroid hormone in 12 hypothyroid patients on thyroxine replacement for 2 weeks. PATIENTS: There were 21 thyrotoxic patients, 12 healthy hospital controls, and 12 patients with complete or near-complete hypothyroidism, on thyroxine replacement. MEASUREMENTS: The following were measured before and at weekly intervals after iodide administration: (1) pulse rate, (2) serum T4, (3) serum T3, (4) serum TSH, (5) serum thyroxine-binding capacity (TBC), (6) serum rT3, (7) serum thyroxine-binding globulin (TBG), (8) the free-T4 Index, calculated as T4/TBC. RESULTS: In the hyperthyroid patients serum T4, T3 and rT3 decreased, whereas serum thyroxine-binding globulin and thyroxine binding capacity increased. Serum T3, however, did not become completely normal in all cases. After 21 days, serum T4 and T3 started increasing again in some cases, but other patients remained euthyroid even after 6 weeks. In the normal controls there was a small but significant and consistent decrease in serum T4, T3 and rT3 and an increase in serum TSH. Finally, in the T4-treated hypothyroid patients there was no consistent change, except for an increase of serum T4 at 1 and 14 days and a decrease of serum TSH the first day. CONCLUSION: Iodides in hyperthyroidism have a variable and unpredictable intensity and duration of antithyroid effect. Their antithyroid effect is smaller in normal controls. They have no important effect on the peripheral metabolism of thyroid hormones.

Adult↗

Increased mean serum thyrotropin in apparently euthyroid hypercholesterolemic patients: does it mean occult hypothyroidism?

Serum thyroid hormones and antithyroid autoantibodies (AAB) were assayed in 87 randomly selected hypercholesterolemic persons compared to 80 controls with normal serum total cholesterol (TC). Of the 87 hypercholesterolemic persons 22 (25%) had positive AAB compared to 5 (6%) controls. Furthermore, 8 of the hypercholesterolemic patients had a serum TSH level above 5 mU/l, i.e. the had subclinical hypothyroidism, not diagnosed before, whereas thyroid function was normal in all normocholesterolemic persons. The new and unexpected finding was that the hypercholesterolemic persons had on average a significantly higher serum TSH than the controls, and this was true even when persons with positive AAB were excluded. There was a significant correlation between TC and serum TSH. It is concluded that hypothyroidism may not be an all-or-none phenomenon, and that many hypercholesterolemic persons with thyroid tests within the conventional normal range may have a slight impairment of their thyroid function.

Female↗

Treatment of hyperthyroidism with potassium iodide.

Potassium iodide was given to 17 cases of Basedow's disease in comparison to 12 normal controls for 5 weeks. In the thyrotoxic patients, the maximum decrease in serum T3 and T4 levels was observed 2 and 3 weeks, respectively, but in some cases remained normal even at 5 weeks. The euthyroid persons showed a small decrease in T4 and T3 and an increase in serum TSH.

Adult↗

The outcome of benign thyroid nodules correlates with the findings of fine needle biopsy.

204 patients with a single or dominant 'cold' thyroid nodule were treated with l-thyroxine, 150-250 micrograms/d, for 4 to 12 months. The two clinicians who evaluated the evolution of the nodules knew that fine-needle biopsy (FNB) had excluded malignancy, but ignored any other morphologic data of the FNB smears. Good outcome, i.e. disappearance of the nodule or definite decrease in its size, was observed in 66 cases (32%). This good clinical outcome was correlated with various morphologic characteristics of the FNB aspirate. The nodule was more likely to regress if FNB showed much colloid, many degenerative changes and many phagocytes, whereas the presence of extensive hyperplasia, lymphocytes or fibrosis were associated with an unfavourable prognosis. With logistic regression, controlling for the confounding effects of sex, age, clinical and histological picture and thyroxine dose, significant correlations were shown with the presence of colloid, hyperplasia and fibrosis. It is concluded that the morphologic characteristics of the FNB aspirate may, to some extent, predict the outcome of cold thyroid nodules.

Adult↗

Clinical, laboratory and immunologic effects of the treatment of endemic goiter with T4, T3 and KI.

We treated 204 patients with endemic nontoxic goiter with T4, T3 and KI, singly or in combination. Definitely nodular goiters were excluded, since the possibility of autonomy would be increased. Goiter size was evaluated before and 6 months after treatment clinically in a blind way, i.e. the observer (always the same) did not know either the pretreatment goiter size or the treatment the patient had received. At the same time various laboratory parameters were recorded. All the active treatments (but not placebo) resulted in a highly significant decrease in the gland size. The effectiveness decreased in the following order: 1) T3 50 micrograms/d (most effective), 2) (T4 50 micrograms/d + T3 12.5 micrograms) x 2, 3) T4 150 micrograms + iodide 150 micrograms/d, 4) T4 75 micrograms + T3 18.75 micrograms/d, 5) T4 200 micrograms/d, 6) T3 37.5 micrograms/d, 7) Iodide 300 micrograms/d, 8) T4 150 micrograms/d, 9) Iodide 150 micrograms/d (least effective) and 10) Placebo (not effective). The results show that T4 200 micrograms and T3 50 micrograms are roughly equipotent, and slightly more effective than 300 micrograms of Iodide. Taking into consideration the side effects (increase in pulse rate, shortening of the Achilles tendon reflex) did not change the order of effectiveness in an important way. The clinical outcome correlated in general with the suppression of the 131I uptake (r = 0.220, p = 0.03) and the TRH test (r = 0.248, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Glycosaminoglycans in urine, articular and periarticular tissues in streptozotocin diabetes in rats.

Experimental data support the hypothesis that insulin deficiency increases the degradation of glycosaminoglycans (GAGs) and decreases their synthesis. The purpose of this study was to investigate the effect of streptozotocin-induced experimental diabetes on mucopolysaccharide content of the articular and periarticular tissues as well as on the urine GAGs excretion. In two groups (A and B) of ten white Wistar rats, experimental diabetes was induced after administration of streptozotocin in a dose of 65 and 45 mg/kg of body weight, respectively. The animals of group A (short term diabetes) and B (long term diabetes) were sacrificed on the 8th and 87th day of the experimental procedure respectively. GAGs were determined in urine specimens collected before and on the 8th day in group A and before and on 3rd, 8th, 16th, 23rd, 36th, 52nd, 71st and the 87th day in group B. At the end of the experiment articular and periarticular tissue specimens were examined for changes in their mucopolysaccharides content and compared to a group of five animals of the same age and dietary conditions (control group, C). We found a marked increase (P less than 0.001) of urine GAGs excretion during streptozotocin-induced diabetes as compared to the respective values before the experiment in both groups, while in group B a positive relationship (P less than 0.001) between 24 hour urine GASGs excretion, and the duration of diabetes was observed. The histochemistry of the articular and periarticular tissues revealed marked decrease in GAGs content, as well as hardening of the tendons.

Animals↗

Comparison of the effect of amiodarone and benziodarone on thyroxine metabolism and surface ECG.

This study examined whether or not the electrophysiological effect of amiodarone on the heart is mediated through its action on thyroxine metabolism. Serum thyroid hormones and ECG were evaluated before and serially during amiodarone (15 subjects) and benziodarone (15 subjects) administration. Both amiodarone and benziodarone shifted the peripheral conversion of thyroxine (P less than 0.001 for amiodarone and P less than 0.001 for benziodarone) towards reverse triiodothyronine and away from triiodothyronine, whilst TSH levels initially fell and then rose with both drugs. After amiodarone the heart rate decreased (P less than 0.025), whilst the PR (P less than 0.005) and the QT interval (P less than 0.005) corrected for the heart rate increased. By contrast with benziodarone only the PR interval decreased (P less than 0.05). Since both drugs had roughly similar effects on thyroid hormone metabolism but different ones on the ECG, our results provide indirect evidence against the hypothesis that the antiarrhythmic effects of amiodarone are mediated through a decrease in the serum T3 presented to the peripheral tissues.

Adolescent↗

The relation of serum T4 and TSH with the urinary iodine excretion.

The urinary iodine excretion, expressed as the iodine/creatinine (I/Cr) ratio, was correlated with the serum T4 and TSH levels in persons with a relatively constant iodine intake for at least 6 months. It was found that the group with an I/Cr ratio of 151-200 micrograms/g had on average the lowest serum TSH and the highest serum T4 level. The differences in serum TSH from the other groups were statistically significant, whereas the differences in serum T4 were not. It is concluded that an I/Cr ratio of 151-200, corresponding to an iodine intake of about 200 micrograms/day, is associated with the lowest TSH stimulation of the thyroid gland in man and probably represents the optimal conditions for its function.

Adult↗

Thyroid and parathyroid response to subtotal thyroidectomy.

Hypocalcemia occurring a few days after total subtotal thyroidectomy has been attributed either to parathyroid insufficiency or to calcitonin release. To investigate this matter further, we measured serum calcium, phosphate, T3, T4, TSH, parathormone (PTH), calcitonin (CT) and cAMP, in 27 women aged 23 to 63 years, before and also 3 and 7 days after subtotal thyroidectomy for multinodular nontoxic goiter. Ca, T3 and T4 decreased, whereas TSH increased appropriately to the decrease in T4 and T3. There was no increase in PTH appropriate to the Ca decrease. In contrast, PTH, cAMP and CT showed statistically unsignificant tendency to decrease. It was concluded that hypocalcemia after thyroidectomy is not due to CT release, but rather to a relative PTH insufficiency.

Adult↗