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)

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.

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.

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.

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 delta TSH. Serum T4 remained relatively constant. Serum T3 decreased significantly from the 1st 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 1st 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 amiodarone-like 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.

Treatment of endemic goitre with iodine and thyroid hormones, alone or in combination. (Preliminary report).

108 patients with endemic nontoxic goitre have been treated in the field with thyroxine (T4), triiodothyronine (T3), and potassium iodide (KI), singly or in combination, or with placebo. After 6 months of continuous treatment, goitre size decreased significantly in the 7 actively treated groups, but not in the one treated with placebo. The combination of 150 micrograms T4 + 150 micrograms KI daily seemed the most effective treatment, both clinically and by its suppression of the 131I uptake and the TSH response to TRH, followed by 100 micrograms T4 + 25 micrograms T3 or 200 micrograms T4, but the difference from the other groups was not statistically significant. The increase in the pulse rate (PR) and the shortening of the photomotogram of the Achilles tendon reflex (PMG) were taken as indices of thyrotoxicity and side-effects of the treatment. There was no significant difference in the side-effects between any two of the active groups if effectiveness was also taken into account. The decrease in goitre size was not correlated to either the final serum T3 value achieved at the end of the treatment, or the thyroidal 131I uptake. There was, however, a weak but significant correlation between the decrease in goitre size and the TSH response to TRH. This casts some doubt to the concept that thyroid hormones decrease goitre size solely by suppressing the pituitary TSH release. Of the 30 patients treated with KI singly or in combination and studied in this respect, 8 developed autoantibodies against thyroglobulin and/or the thyroidal microsomal antigen compared to 1 of 22 not receiving KI (P = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

An epidemiologic survey of thyroid enlargement among schoolchildren in a non-endemic area.

In 534 unselected schoolchildren aged 6-14 yr from the greater Athens area the size of the thyroid gland was assessed by palpation, and information was obtained on sex, age, height, weight, skinfold thickness, socioeconomic class, eye colour and urinary iodine excretion. The results were analysed by discriminant analysis. Altogether 14% of these children had a thyroid enlargement (7% had a definite goitre and another 7% a smaller enlargement). The set of variables studied were significantly discriminatory (Wilk's lambda 0.926, p approximately equal to 0.004). Most of the discrimination was accounted for by height (positive association, b coefficient 0.0114, SE 0.0029, t = 3.95) and weight (negative association, b coefficient 0.0107, SE 0.0030, t = 3.61). No other parameter, including iodine excretion, showed a significant difference between goitrous and nongoitrous. It is concluded that the only genuine difference is that goitrous are heavier for a given height or shorter for a given weight, i.e. more obese. The reason for which obesity protects from sporadic nontoxic goitre is not entirely clear, but probably both nutritional and genetic factors are involved.

Metabolic insufficiency as a limiting factor in the dietetic treatment of obesity.

Previous observations that acute total fasting decreases serum T3 and increase rT3 has prompted the following study. 17 obese women were placed on a 1000 kcal/day weight-reducing diet, and body weight (BW), serum T4, RT3U, T3, rT3, TSH and the Achilles tendon reflex (ATR) were estimated before and after each month for 3 consecutive months of the diet. The results showed a consistent decrease in serum T3, and inconsistent increase in rT3, a consistent prolongation of the ATR and a levelling-off of the BW loss after the second month of the diet. At 3 months there was a negative correlation between the decrease in BW and the increase in ATR, i.e. the more abnormal the ATR became, the less weight the patient lost. It is concluded: 1) Even a moderate hypocaloric diet in ambulatory patients induces a disturbance in the peripheral conversion of T4 to T3 and a secondary state of metabolic insufficiency. 2). This insufficiency is probable related to the observed tendency of the BW loss to level off after two months. 3) A controlled trial of physiologic doses of T3, such as 40 mu g/day, seems indicated, as opposed to pharmacologic dosed of T3 used by previous investigators.

Some epidemiologic studies of HBSAg in Greece.

In an epidemiologic study in 17 villages from different areas of Greece, 2898 persons were examined in order to find possible relations between HBSAg prevalence, altitude and endemic goitre morbidity. A lower prevalence with a significant difference was found in areas with a high altitude as compared with those with a low one, in endemic goitre than non-endemic areas, and in low altitude endemic than in low altitude non-endemic areas. Goitrous subjects had a lower HBSAg prevalence than non-goitrous subjects, but the difference was of borderline significance. The results can probably be explained by the presence of an environmental factor associated with altitude acting together with a host factor predisposing to endemic goitre and favouring the immunity to HBV infection.

Iodide organification defect in iodine deficiency endemic goiter.

In 17 goitrous persons in an iodine-deficient area, in 23 nongoitrous inhabitants of the same village, in 10 goitrous persons in Athens, and 8 normal controls the perchlorate discharge test was performed, either in the simple standard form or after pretreatment with either 0.5 or 2.0 mg potassium iodide or 2.5 mg carbimazole. With the simple test or with 0.5 mg potassium iodide, there was no significant discharge in any group studied. With 2.5 mg carbimazole, there was a profound discharge of the trapped iodide in both groups in the iodine-deficient area. With 2.0 mg potassium iodide, however, there was a clear discharge in the two goitrous groups (i.e. the one in the endemic area and the second in Athens), a less pronounced discharge in the controls studied in Athens, and no discharge at all in the nongoitrous inhabitants of the iodine-deficient endemic area. These findings provide evidence for an abnormality present in the patients with endemic goiter, most probably faulty iodine utilization due to impaired organic binding. The nongoitrous persons in the endemic areas, on the other hand, seem to be even more efficient in handling the trapped iodide than the controls studied in Athens. These findings may provide an explanation for previous observations that in endemic areas only part of the population develop a goiter, whereas the others adapt successfully to iodine deficiency without significantly enlarging their glands.

Lack of influence of povidone-iodine on tests of thyroid function.

The external application of povidone-iodine, an antiseptic agent, was tested for its influence on thyroid function. Previous workers have described some in vitro changes in thyroid function tests following its use. In the present study topical application of povidone-iodine did not affect thyroid function as measured some days later using both in vivo and radio-active iodine in vitro test methods, despite the fact that the latter are notorious for being influenced by exogenous iodine.