T4 but not T3 administration is associated with increased recurrence of Graves' disease after successful medical therapy.

TSH has been incriminated in Graves' disease for increasing the production of antibodies against TSH receptor (TRAb). It has been, therefore, suggested that T4 administration after successful antithyroid drug (ATD) treatment may indirectly decrease the production of TRAb and, therefore, the frequency of recurrence of hyperthyroidism. To study the role of T4 and T3 on the recurrence rate of Graves' disease 108 patients with Graves' disease (22 males, age: 49.8 +/- 14.3 yr, mean +/- SD, and 86 females, age: 41.7 +/- 12 yr) were followed-up for 24 months after successful treatment with ATD (carbimazole). During the follow-up period, patients daily received either 100 microg T4 or 25 microg T3 or placebo after random and double-blinded assignment into three groups. They were evaluated trimonthly up to 12 months and at 24 months. Plasma TRAb levels were measured at the beginning and at 12 months. At 12 months of the follow-up period, 14 out of 33 (42.4%), 6 out of 38 (15.8%), and 9 out of 37 (24.3%) patients receiving T4, T3 and placebo, respectively, recurred. Recurrence rate of T4-treated patients was statistically higher than that of the T3-treated patients or controls (p < 0.05). At the beginning of the follow-up period patients who were going to recur had significantly higher TRAb levels and goiter weight than patients who were not (p < 0.05). At 24 months of the follow-up period, from the patients who did not drop out of the study, none out of 11 (0%), 2 out of 19 (10.5%) and 1 out of 12 (8.3%) receiving T4, T3 and placebo, respectively, recurred. We conclude that T4 administration after successful ATD treatment of Graves' disease is associated with increased recurrence of hyperthyroidism as compared to the T3 or placebo administration. High TRAb levels and goiter weight at the end of ATD treatment may hint at recurrence.

The predominant form of non-toxic goiter in Greece is now autoimmune thyroiditis.

Endemic non-toxic goiter (NTG) in Greece has been attributed primarily to iodine deficiency. Thirty years ago about 60% of the prepubertal boys and girls examined in endemic goiter regions presented with NTG and among them thyroid autoimmunity was rarely detected. Although iodine supplementation has corrected this deficiency during the past 30 years, new cases of NTG still appear. To evaluate the prevalence and type of NTG and the effect of iodine supplementation on them in Greece at present, we performed two cross-sectional clinical studies and a retrospective pathology one: (i) thyroid gland volume and urinary iodine excretion (UIE) were assessed in a representative sample of 1213 schoolchildren from previously endemic and non-endemic regions; (ii) serum thyroxine, tri-iodothyronine, TSH, thyroid autoantibodies (AAB) (anti-thyroid peroxidase and anti-thyroglobulin antibodies) and UIE (in 60 patients) were measured in 300 consecutive patients with NTG from Athens and Heraklion; and (iii) we compared the prevalence of autoimmunity among fine needle aspiration smears of benign thyroid pathologies performed by the same pathologist between 1985 and 1986 (975 cases) and between 1994 and 1995 (2702 cases). We found that 12. 5% of the schoolchildren examined in regions with a previous history of endemic goiter had NTG, whereas this percentage was only 1.7% in areas without such a history. In Athens (61.6%) and Heraklion (58. 5%) a substantial number of NTG patients were AAB positive and biochemically hypothyroid. UIE in Athens did not differ between patients with autoimmune goiter (ATG) and simple goiter. The prevalence of autoimmune stigmata in pathology smears has increased from 5.94% (years 1985-1986) to 13.91% (years 1994-1995) (P<0.05). We conclude that: (i) the persistence of endemic goiter in regional foci despite iodine deficiency correction suggests a possible role for a naturally occurring goitrogen; (ii) ATG is the predominant form of NTG in Greece nowadays; and (iii) the five-fold decrease in the prevalence of NTG during the past 30 years followed by the increase of ATG may support the relative character of the latter.

Flow-mediated, endothelium-dependent vasodilation is impaired in subjects with hypothyroidism, borderline hypothyroidism, and high-normal serum thyrotropin (TSH) values.

Patients with hypothyroidism are considered to have an increased risk of developing atherosclerosis; because endothelial dysfunction is an early sign of atherosclerosis, we investigated whether endothelial dysfunction is present in patients with hypothyroidism. Thirty-five subjects with various TSH levels were investigated by high-resolution ultrasound imaging of the brachial artery to assess endothelial and smooth muscle responses. Flow-mediated, endothelium-dependent vasodilatation was significantly higher in subjects with TSH 0.4-2 microIU/mL (11.8 +/- 2.7%), compared with subjects with TSH 2.01-4 microIU/mL (6.8 +/- 2.9%), 4.01-10 microIU/mL (5.2 +/- 6.3%) and >10 microIU/mL (4.0 +/- 4.4%); TSH levels correlated inversely to endothelium-dependent dilatation. Thus, flow-mediated vasodilatation, a marker of endothelial function, is impaired not only in patients with mild hypothyroidism but also in subjects with "high-normal" serum TSH levels (ie, 2.01-4.0 microIU/mL) that may be characterized as possibly abnormal.

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)

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.

A simple and reproducible method for the estimation of triiodothyronine uptake (thyroxine binding index) using a new adsorbent.

A simple, rapid and reproducible method for the determination of triiodothyronine uptake using heat-treated wheat flour (TWF) as adsorbent is described. Three ml of TWF suspension in barbital buffer containing 125I triiodothyronine is added to 0.1 ml of serum sample in a plastic tube. The mixture is shaken for 30 seconds and is left to settle for 12 minutes or alternatively is centrifuged for one minute at 600 X g. The 1.0 ml of supernatant is transferred to another tube for counting. This method is virtually time and temperature independent. The effects of altering the concentration of 125I triiodothyronine and TWF are reported. Within-run precision has been estimated for normal (C.V. 1.2), high (C.V. 1.2) and low (C.V. 1.8) ranges. Estimation of between -run precision gave similar results. Comparison of results obtained by this method and by Thyopac-3 reagent kit (Radiochemical Centre, Amersham, England) shows good correlation for Thyopac-3 values about 105, while for values below 105 the present method gives lower values than Thyopac-3.

Radioassay of serum folate with use of pig plasma folate binders.

Pig plasma has been used as a source of specific folate binders for the development of a rapid radioassay to measure the concentration of folate in serum. The assay uses 3H-pteroylglutamic acid as tracer and N-5-methyltetrahydrofolic acid for the construction of the standard curve. The assay is run in a two-step incubation system of 15 min each at room temperature. Comparison between the results obtained with this method and a microbiological one indicated that for sera with relatively high folate levels there was a good agreement between the two methods, whereas for sera with low folate levels the present method produces lower values than the microbiological one. The diagnostic value of the results obtained by the two methods is discussed on the basis of the availability to the tissues of the folates which are firmly bound to specific folate binders of human serum.

The effect of ionizing irradiation on the oxidation of palmitate-1-14C by thymus and liver.

New Zealand rabbits, fasted for 12 hours, were subjected to 500 rads of whole-body irradiation. K+-palmitate-1-14C oxidation was assayed with the 600 X g supernatant of thymus and liver homogenates, in the presence of ATP, at various time intervals from irradiation. For a period of 24 hours following irradiation, oxidation by liver preparations was not significantly affected. The rate of oxidation by thymus was decreased to less than one-third of the control value within 12 hours from irradiation and, at 24 hours, was almost completely abolished. Increased ATP concentration could increase only to a small extent the oxidation by thymus preparations of irradiated animals. Oxidation by isolated thymus mitochondria was also inhibited by irradiation. Counting of the water-soluble oxidation products of palmitate-1-14C suggests that the inhibition is not due to the impairment of the reactions of the citric acid cycle. The non-esterified fatty acid concentration of thymus was not altered at 12 hours following irradiation. Esterification of K+-palmitate-l-14C into the thymus lipids was not affected 12 hours after irradiation.

The effect of ionizing irradiation on the lipid biosynthesis by thymus and liver.

New Zealand rabbits, fasted for 12 hours, were subjected to 500 rads of whole-body irradiation. Analysis of thymus lipids, at various time intervals following irradiation, showed a threefold increase of triglycerides at 24 hours. Fatty acid composition of the 600 X g supernatant was not affected at 24 hours after irradiation. Lipid biosynthesis from acetate-1-14C by the thymus homogenates was increased to a small extent at 4 hours following irradiation, while the radioactivity distribution into fatty acids was not considerably affected. Contrary to the above findings, fatty acid synthesis from acetate-l-14C by the liver preparations showed a decreased incorporation between the fourth and twelfth hour following irradiation. Counting of the radioactivity of the separated fatty acids suggested that the system for synthesis of short-chain fatty acids was impaired as early as 4 hours following irradiation.