Demetrios A. Koutras

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 lodides In hyperthyroldlsm, and to Investigate whether Iodides have an additional perlpheral effect on the metabollsm of thyrold hormones, as has been reported for some organic IodIne compounds.

Hypothyroidism and glaucoma. a study of 100 hypothyroid patients

PURPOSE To determine whether glaucoma is associated with hypothyroidism, as has previously been suggested. METHODS This is a cross-sectional study and a noncomparative interventional case series. One hundred consecutive patients with newly diagnosed hypothyroidism were referred for complete ophthalmologic examination, including automated perimetry and examination of the optic disks, to identify the presence of glaucoma. After correction of the hypothyroidism, reexamination was performed. RESULTS No patient had glaucoma and no correlation was found between intraocular pressure and either thyroid stimulating hormone or free tri-iodothyronine. No statistically significant difference was found between intraocular pressure levels before and after treatment of the hypothyroidism. CONCLUSION This study does not demonstrate an association between hypothyroidism and glaucoma.

Free-thyroxine index in mania and depression

Abstract Although free-thyroxine index is commonly used as a reliable method of thyroid function investigation,1,2 only Rybakowski and Sowinski3 have used this method for the assessment of thyroid function in mania. In depression, determination of free-thyroxine index by four research groups3,6 revealed contradictory results. For these reasons, it was thought that further research in this area would be justified.

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 μg T4 or 25 μg 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.

Iodine Nutrition and Iodine Deficiency Disorders in Greece: Signs of Improvement

Endemic goiter is present in Greece and has been studied extensively. Iodine deficiency is the main cause. However, with the increasing use of iodized salt, with better communications and a higher standard of living, the situation has now considerably improved.

The plasma inorganic iodine and the pituitary-thyroid axis in pregnancy

The plasma inorganic iodine (PII), the serum T4, the resin T3 in vitro uptake (RT3U), the free — thyroxine index (FTI) and the serum TSH level before and 30 min after the iv injection of 200 μg TRH were measured serially for several months in 9 pregnant women, whereas in 12 others the TRH test was performed once. The PII was low (<0.08 μg/100 ml) in 6 of the 9 cases, normal in two and greatly increased (probably because of iodine contamination) in one. Excluding this latter case, the PII was significantly lower than the control value for nonpregnant women in Athens (mean ± SE: 0.08 ± 0.01 compared to 0.12 ± 0.01, p<0.02). In spite of this low PII, there was no increased TSH, either before or after the administration of TRH. On the contrary, the TRH response was blunted in 3 of 21 cases. It is concluded that in pregnancy there is a lower PII, because of the increased renal iodide clearance rate, and so iodine supplementation is recommended in countries with a marginal iodine intake, as in Europe. In spite of this low PII, indicating a state of relatively acute iodine deficiency, the thyroid may adapt without an increased serum TSH level. Hence the fact that the serum TSH is normal in endemic goitre with mild iodine deficiency is best explained not by the chronicity of the condition and the establishment of a new steady-state, but by other mechanisms including probably thyroid autoregulation.

Relative ineffectiveness of exogenous triiodothyronine as a thyroid suppressive agent

In 16 patients with nontoxic goiter T3 was given orally, 20 μg daily for the first month, 40 μg for the second and 60 μg for the third. Before and at the end of each month the basal serum TSH levels and the 30 min response to 200 μg TRH iv were measured. The difference was calculated as δ TSH. Serum T4, T3 resin uptake, and T3 were measured at the beginning and at the end of treatment. The results were compared to those obtained in 2 groups of 18 and 54 patients, respectively, treated with increasing doses of oral T4. In the patients treated with exogenous T3 there was a rise of serum T3 from 2.02 ± 0.06 to 3.48 ± 0.08 nmol/l, and whileon 60 μg/day all had serum T3 levels well within the hyperthyroid range. However, the TRH test became negative in only 62.5% of them. On the contrary, in the groups treated with T4 the TRH test was promptly suppressed completely, and ATSH became 0 with 100 μg of T4 daily in virtually all cases. It is concluded that although 60 μg of T3 are more than the daily maintainance dose and result in hyperthyroid serum T3 levels, the pituitary-thyroid axis is not completely suppressed, probably because pituitary TSH secretion is regulated by the intrapituitary conversion of T4 to T3 and not by serum T3 levels. Hence, if one wants to suppress the pituitary TSH release, as in the treatment of nontoxic goiter, T4 and not T3 is the drug of choice: it is selectively converted to T3 in the pituitary, where it produces higher T3 levels and so more complete suppression of the TSH release, without unduly high serum T3 levels and thyrotoxic manifestations from the peripheral tissues.

The correlation of serum amiodarone levels with abnormalities in the metabolism of thyroxine

Amiodarone, a widely used iodine-containing antiarrhythmic drug, has been shown to divert the peripheral metabolism of T4 towards rT3 than T3. In this prospective study we correlated the concentration of the peripheral thyroid hormones in serum with that of amiodarone. Fifteen euthyroid volunteers were studied, 5 men and 10 women, with a mean age of 64.2 yr, who suffered from various cardiac arrhythmias (atrial fibrillation or multiple ventricular extrasystoles). Serum amiodarone, T4, T3, rT3 and TSH were determined before and 3, 7, and 14 days after the administration of 400–600 mg amiodarone/day. There was a small increase in serum T4 and a suggestive decrease in serum T3. The increase in serum rT3 was significant, with p < 0.05 for 3 days, p < 0.01 for 7 days and p < 0.005 for 14 days. There was a significant correlation between the level of serum amiodarone and the rise in serum rT3 (r = 0.385, p < 0.05). The rise in rT3 is the main thyroid abnormality after amiodarone administration and may be used as a rough index of the serum concentration of this drug.

Further Data on Iodine-Induced Autoimmunity

In a previous study we found that 29 out of 58 goitrous patients (50 %) injected with 1 ml iodized oil im developed 3 to 6 months later thyroid autoantibodies against thyroglobulin (TG) and/or the microsomal antigen (MS)1. In the present study we extend previous reports 2,3,4 that such autoantibodies develop also after small ‘physiological’ doses of iodine, and the results are compared with those obtained with iodized oil 1.

The effect of benziodarone on the thyroid hormone levels and the pituitary-thyroid axis

The effect of benziodarone on the levels of thyroid hormones in the serum has not attracted interest, in spite of the prolific literature on the related drug amiodarone. It is shown here that benziodarone administration has several effects, mainly similar to amiodarone, but some possibly opposite and inappropriate. Nine normal volunteers received benziodarone, 100 mg three times daily for 14 days. Before and 1, 3, 7 and 14 days after continuous administration the following estimates were obtained: serum T4, T3, rT3 and TSH, both basal (TSH0) and 30 min after iv administration of TRH (TSH30), the difference being calculated as ΔTSH. Serum T4 remained relatively constant. Serum T3 decreased significantly from the 1 st to the 14th day (eg. before 2.15 ± 0.12 nmol/l, at 3 days 1.45 ± 0.07). Serum rT3 increased significantly from the 1 st to the 14th day (eg. before 0.71 ± 0.16 nmol/l, at 7 days 2.61 ± 0.19). Serum TSH0 and TSH30 decreased significantly on the 1st and 3rd day. Later they increased, and TSH0 at 14 days was significantly higher than the pre-treatment value. Our results suggest that benziodarone has an amiodaronelike action in diverting the peripheral metabolism of T4 towards rT3 rather than T3. However, the effects on the pituitary-thyroid axis are not similar to those previously reported by others and ourselves about amiodarone, and these merit further research.