Thyroid hormone and immunological studies in endemic goiter.

Iodized oil (1 ml im) was given to 58 goitrous patients from a mildly iodine-deficient area in Greece. Goiter size, urinary iodine, and serum T4, T3RU, T3, rT3, TSH, thyroxine-binding globulin (TBG), and thyroid autoantibodies were measured before and 1, 3, and 6 months after the injection. Goiter size decreased. Serum T4 remained relatively constant, but TBG decreased and therefore T3RU and FTI increased. Serum T3 and rT3 initially decreased (P less than 0.001) and then increased at the sixth month (P less than 0.001), both showing roughly parallel changes. Serum TSH, initially normal (1.42 +/- 0.11 (SEM) mU/liter), decreased to 0.65 +/- 0.01 and 0.76 +/- 0.05 mU/liter at the third and sixth month (difference from baseline P less than 0.001). Thyroid autoantibodies, both against thyroglobulin and the microsomal antigen, were undetectable before treatment, but became positive in 42.8% of the patients 3 and 6 months later. Three patients developed transient hyperthyroidism. This occurred 3 or 6 months after treatment, and was associated with high titers of thyroid autoantibodies. These results indicate that: 1) transient hyperthyroidism may occur after the administration of iodized oil, possibly because of thyroid tissue necrosis and leakage of hormones, and 2) serum TBG decreases after iodized oil, a finding not previously reported and one whose cause is not known.

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.

Anterior, posterior, or laparoscopic approach for the management of adrenal diseases?

BACKGROUND: At the advent of laparoscopic adrenalectomy it seemed timely to us to assess the advantages and the overall results of the different techniques that are currently used in an approach to adrenalectomy. PATIENTS AND METHODS: Between 1984 and 1995, 165 patients underwent adrenalectomy. Eighty-six patients (37 men and 49 women with a mean age of 46.4 years) underwent adrenalectomy via the anterior approach, 61 patients (18 men and 43 women with a mean age of 43.8 years) underwent posterior extraperitoneal adrenalectomy, and 18 patients (8 men and 10 women with a mean age of 48.7 years) underwent anterior laparoscopic adrenalectomy. For statistical analysis of the different comparisons between the groups we used the t test for independent samples, the Wilcoxon test, chi-square, and one way analysis of variance. RESULTS: There was no operative mortality. The morbidity was 13.9% in the anterior approach, 9.8% in the posterior approach, and 0% in the laparoscopic approach. The mean operating time for unilateral adrenalectomy was 155.3 min (range 75 to 315) for the anterior approach, 108.6 min (range 60 to 195) for the posterior approach and 116.1 min (range 75 to 180) for the laparoscopic approach. For bilateral adrenalectomy the mean operating time was 165 min for the anterior and 178 min for the posterior approach. The average diameter of tumors resected anteriorly was 8.07 cm (range 2.5 to 20), posteriorly was 5.25 cm (range 0.5 to 14), and laparoscopically was 4.03 cm (range 2 to 6.5). The mean length of postoperative hospitalization for patients undergoing unilateral adrenalectomy was 8 days (range 2 to 25) for the anterior approach, 4.5 days (range 1 to 11) for the posterior approach, and 2.2 days (range 1 to 5) for the laparoscopic approach. Patient controlled analgesia lasted 3.4 days for those operated anteriorly, 2.3 days for those operated posteriorly, and 1.08 days for those that underwent laparoscopic adrenalectomy. CONCLUSIONS: The laparoscopic approach to the adrenal promises the safest and least painful operation with shorter in-hospital stay and the best cosmetic and long-term results. The posterior approach is the fastest of all and a better overall operation than the anterior approach that should only be reserved for removing very large adrenal tumors and when concomitant intra-abdominal procedures, that can't be handled laparoscopically, are anticipated.

Pituitary and thyroid insufficiency in thalassaemic haemosiderosis.

Thyroid and pituitary function tests using hypothalamic releasing factors were performed in seven patients with thalassaemia and secondary haemosiderosis and in a control group of seven healthy subjects. The TSH level in the thalassaemic patients (18.07 +/- 1.10 microU/ml) was higher than in the controls (1.01 +/- 0.14 microU/ml, P less than 0.001). After TRH administration the TSH values increased less than in controls. Serum thyroxine and FT41 values were lower in the group of patients with thalassaemia (76.7 +/- 7.8 nmol/l and 19.3 +/- 2.2) compared to the controls (116.1 +/- 6.9 nmol/l, P less than 0.005 and 38.6 +/- 3.6, P less than 0.001). The basal prolactin values did not differ significantly between the two groups, but after TRH administration the increment was significantly lower in thalassaemics than in controls (P less than 0.005). The basal LH values were lower in the thalassaemic patients (1.37 +/- 0.24 ng/ml) than in the controls (3.23 +/- 0.50 ng/ml) and did not increase significantly after LHRH administration. The FSH values were also lower in the thalassaemic group (0.46 +/- 0.15 ng/ml) compared to the controls (2.06 +/- 0.08 ng/ml, P less than 0.001), and increased only slightly after LHRH administration. We conclude that in thalassaemia pituitary deficiency exists, mostly of gonadotrophs, but possibly also for the thyrotrophs and the lactotrophs. Latent primary hypothyroidism has also been found in the thalassaemic group. The functional abnormalities found in both endocrine glands are best explained as a consequence of coexisting haemosiderosis.

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 less than 0.05 for 3 days, p less than 0.01 for 7 days and p less than 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 less than 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.

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 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)