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.

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)

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.

The effects of mild iodine deficiency on neonatal thyroid function.

In order to assess neonatal thyroid function in the endemic goitre areas of Greece, T4 and TSH have been measured. Previous studies had shown that in these endemic areas, adults had low T4 but normal TSH values, probably because of an increase in the serum T3 level. In this study, T4 and TSH were measured in dried blood spots from 259 neonates. The fifty-four full-term neonates from the Greek endemic villages had a lower T4 value (8.8 +/- 0.66 micrograms/dl SE) but a higher TSH (15.37 +/- 1.12 mu/l) than the seventy-three full-term neonates from the non-endemic villages (T4:10.0 +/- 0.33 micrograms/dl, TSH:11.93 +/- 0.59 mu/l) or the ninety-eight from Athens (T4:10.0 +/- 0.33 micrograms/dl, TSH:10.96 +/- 0.64 mu/l). Premature neonates, both from Athens and from the endemic areas, have significantly lower T4 and significantly lower TSH values than the full-term ones from the same areas, probably because of the immaturity of the pituitary-thyroidal axis. It is concluded from these observations that (a) Neonates suffer more from the consequences of iodine deficiency than adults. The biochemical hypothyroidism reported here may be relevant to the delayed skeletal maturation previously reported from children of these same areas. This emphasizes the need for correcting even moderate iodine deficiency. (b) The occurrence of non-toxic goitre with normal TSH levels in adults is best explained by assuming that increased TSH stimulation is necessary for goitre formation during neonatal life, but not for goitre maintainance during adulthood. (c) Newborn screening programmes in these areas should take into account the present findings.

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.

Thyroid scanning with gallium-67 and cesium-131.

The roles of 131Cs and 67Ga in the evaluation of solitary thyroid nodules were investigated. Radionuclide scans were performed with 67Ga and 131I in 27 patients and with 131Cs and 131I in 43 patients. Gallium-67 detected only two of eight malignant nonfunctioning nodules and 131Cs detected one of three such nodules. The contribution of 131Cs and 67Ga to the preoperative identification of malignant thyroid lesions is of doubtful value.

Comparison of various treatment schedules for accelerating the elimination of radioiodine from the thyroid and the human body.

In 68 euthyroid patients undergoing 131I thyroid function tests the thyroidal, urinary and plasma protein-bound radioactivity has been serially measured for 14 days. The patients were subdivided in controls and 9 groups treated with potassium iodide, carbimazole, potassium perchlorate and TSH, singly or in combination. The aim was to devise a treatment scheme for accelerating the release of iodine from the thyroid and the elimination from the body in cases of accidental radioiodine poisoning if the patient is seen after the radioiodine has already been taken up by the gland. All treatment schedules were effective, but TSH injections gave the best results, especially if combined with carbimazole and potassium perchlorate. This combination is the treatment of choice under these circumstances.