Miscellaneous
	Polyanskaya et al., Minsk, Belarus, Bethesda, MD, New York, NY, USA, studied the effects of radioactive fallout from the Chernobyl accident in children <18 years at the time of the accident. The methods used were thyroid palpation and ultrasound, serum assays of TSH, TPO and ionised calcium, and backup procedures for serum FT4, anti TG, and PTH. The following groups were studied: All 4800 children in Belarus exposed to a dose of >1 Gy, 3500/11000 (randomly selected) dose 0.3 to <1 Gy, and 3500/19700 (randomly selected) dose <0.3 Gy. The study is not completed yet but 3649 subjects have been screened till March 1999 with the following results: 134/3649 (3.7%) had nodular goitre, of these 80% were solitary; 41/3649 (1.1%) had thyroid carcinoma. All had papillary carcinoma. As compared to unexposed Belarus controls, 687/3357 (20%) had thyroid volumes above normal, 140/3357 (4.2%) >150% of normal, and 28/3357 (0.8%) >200% of normal. Two studies were published with regard to thyroid and the heart. Tielens et al., Rotterdam, The Netherlands, performed radionucleide angiography following 20 min. rest, before and after treatment to euthyroidism in 24 consecutive hyperthyroid patients (21 F, mean age 44). Elevated heart rate, contractility and relaxation of the left ventricle, and pulse rate decreased significantly after treatment, while time characteristics of left ventricular performance significantly lengthened. Statistical correlations before treatment were found between FT4 and these parameters, except for blood pressure and pulse pressure. The authors conclude that in untreated hyperthyroidism, heart rate rather than pulse pressure is a sensitive clinical parameter of severity of thyrotoxicosis and that both systolic and diastolic cardiac performance are augmented before treatment. The same group, Van de Wetering et al., analysed pulse rate and any presence of arrhythmias in a group of 23 consecutive patients with clinically euthyroid multinodular goitre with a low mean TSH (0.7 ± 5 mU/L, normal mean 2.6 + 1.2 mU/L, p=0.001), a normal FT4 (14.2 ± 2.1 pmol/L vs. 13.9 + 2.4, pmol/L, NS), a mean TT3 within normal range but significantly elevated from the normal mean (2.4 ± 0.2 nmol/L vs 1.8 + 0.5 nmol/L, p=0.0009). Results were compared with that of controls. No differences from controls were found with regard to 24h-heart rate, maximal heart rate, and minimal heart rate. Furthermore, arrhythmias did not occur more frequently than in controls. Values of serum lipids were also measured and significantly lower values in the patient groups were found for total cholesterol, LDL cholesterol, and triglycerides. The conclusion of the authors is that despite a significant metabolic effect on serum lipids, suggesting increased thyroid hormone activity at the tissue level, no effects were detected at the cardiac level with regard to heart rate or arrhythmias. (Comment: Significant effects have been reported with regard to heart rate and arrhythmias in patients treated with suppressive doses of L-T4. The explanation for the apparently discrepant results of this study may be that in patients on T4 therapy, FT4 in serum is elevated whereas serum T3 is usually normal. The reverse is true in the patients of the present report. One could speculate therefore that the heart is more sensitive to mild elevations FT4 than of T3.) Faber et al., Glostrup, Denmark, studied central haemodynamics in supine and upright position as well as vasoactive peptides in 16 otherwise healthy females (mean age 59 years) with subclinical hypothyroidism (SH) before and after L-T4 treatment. Cardiac output (CO) increased from 5.9 ± 1.5 to 6.7 ± 2.4 (p = 0.10) in the supine position and from 5.0 ± 1.2 to 5.7 ± 1.4 (p <0.05) in the upright position. Total peripheral resistance (TPR) decreased significantly both in supine and in upright position, and mean arterial blood pressure (MAP) decreased significantly in supine position. Plasma norepinephrine ad plasma epinephrine decreased during L-T4 treatment whereas plasma endothelin and plasma calcitonin gene-related peptide did not change significantly. Apparently, treating subclinical hypothyroidism with T4 improves central haemodynamics and reduces sympathetic tone. The authors conclude that these findings are in favour of treatment of subclinical hypothyroidism with L-T4. (Comment: I agree fully on these and other grounds, showing that SH is a health risk factor). Kalmijn et al., Rotterdam, The Netherlands, investigated prospectively the relationship between thyroid status and the risk of dementia and Alzheimer’s disease among a random sample of 1.843 participants aged > 55 years. Persons with reduced TSH had a more than tripled risk of dementia and of Alzheimer’s disease while T4 levels were positively related to the risk of dementia. All T4 levels however remained within normal range. In addition it was found that subjects with subnormal TSH and positive for TPO-Ab had a further increased risk for dementia. (Comment: These results are interesting and, if confirmed, is (another) reason to treat patients with subclinical hyperthyroidism.) Van Wassenaer et al., Amsterdam, The Netherlands, supplemented 200 infants < 30 weeks of gestation with T4 during the first 6 weeks of life to assess whether this improves neurodevelopmental outcome. T4 supplementation was done 5 years ago and assessment was only recently started. At the moment of this communication only the data of thyroid tests of 144/200, 5-year old children are known. These tests included serum T4, FT4, T3, rT3, TBG, TSH and TG. All values were within normal range. The conclusion is, that 6 weeks of treatment with T4 of very pre-term infants does not alter thyroid function at 5 years of age. (Comment: We are all, of course, waiting for any effects of T4 treatment on neurodevelopment.) Benvenga et al., Messina, Italy, evaluated differences between early morning (7–8.30 am) and late morning (9–11.30 am) basal and TSH-TRH in consecutive adult women who were either TG-Ab and/or TPO-Ab positive. The authors found that both basal TSH and TSH-TRH are significantly higher when serum is taken before 9 am than after. They suggest that for diagnosis of subclinical hypothyroidism estimation of TSH and TSH-TRH from sera taken after 9 am will underestimate the prevalence. (Comment: It would be of interest to compare the results with matched controls without circulating thyroid autoantibodies.) Brix et al., Odense, Denmark, studied the effect of cigarette smoking on the risk of developing clinically overt thyroid disease. They performed a matched case-control study of 132 same sex twin pairs discordant for clinical overt thyroid disease. They found that smoking was associated with an increased risk of developing clinically overt thyroid disease with odds ratio 3.0 and confidence interval 1.4–6.6 (p = 0.003). The effect was true for both monozygotic and dizygotic twins but more pronounced in monozygotic twins. Additionally they found that among twin pairs concorded for smoking the proband with clinically overt autoimmune thyroid disease smoked significantly more than their healthy co-twin (p = 0.026). (Comment: The relationship between smoking and autoimmune thyroid disease is now well-established. It is about time that fundamental studies are being started to elucidate its pathogenesis.) Brabant et al. measured at regular intervals leptin parameters, i.e. total leptin (TL) free leptin (FL), receptor bound leptin (BL) and soluble leptin receptor (LR) in 9 thyrotoxic patients during normalisation of thyroid function and in 9 euthyroid control patients under a comparable dose of antithyroid drugs. Both groups were followed for 1 year. During treatment in thyrotoxic patients, TL increased as did FL that were both paralleled with increase in body fat mass. Serum BL and LR concentrations however significantly decreased and changes in BL were related to thyroid status. In the control group all these parameters remained unchanged during the study period. From these data and other data in a group of healthy controls, that indicated a strong relationship between serum and CSF levels of BL and a weaker one between FL levels in serum and CSF, the authors conclude that FL only reflects body mass but that BL is the active component in the central feedback action of the leptin system. Miyake et al., Kurume, Japan, performed color Doppler ultrasonography (CDU) in 30 patients with untreated Graves’ disease (GD) and 3 patients with subacute thyroiditis (SAT). They found pronounced increased vascularity in untreated Graves’ disease and slightly increased vascularity during the recovery stage of SAT. Blood velocity in the superior thyroid artery was significantly greater in GD than in SAT. The authors comment that CDU is useful in the differential diagnosis between SAT and GD. (Comment: I can imagine that this technique is of some use in the differential diagnosis between painless thyroiditis (although not studied here) and Graves’ disease. The clinical difference between SAT and GD is so great that CDU will probably not have additional value here). Erdogan et al., Ankara, Turkey, studied HLA A, B, C, DR, and DQ antigens in 22 patients with amiodarone induced thyroid disease (AITD), 21 with induced thyrotoxicosis, and 1 patient with induced hypothyroidism, and in 206 controls. They found that HLA B40, C3, and DR 5 carried a relative risk (RR) for AITD of 4.95, 3.46, 6.85 respectively. When HLA B40 and C3 were both present, RR was 7.97. (Comment: Unfortunately it is not known if amiodarone induced thyrotoxicosis was due to increased thyroid hormone synthesis (type I) or thyroid destruction (type II).) Bjøro et al., Aker, Norway, assessed the frequency of thyroid diseases in 35.584 individuals in a county in Mid-Norway. They found a prevalence of elevated TSH (>10 mU/l) of 0.87% in females and 0.37% in males, while only 56% and 41% respectively of these patients had FT4 levels below normal. About 85% of both females and males with TSH elevation also had positive anti-TPO. The prevalence of suppressed TSH (<0.03 mU/l) was 0.45% and 0.20% respectively. Smyth et al., Dublin, Ireland and Sheffield, UK, measured the expression of the sodium iodide symporter (NIS) and tissue iodine content in normal and abnormal breast tissues. Mean tissue iodine concentration was higher in 22 benign tumours as compared to breast carcinoma or in normal tissue taken from the same breast. Iodine content in normal breast tissue (reduction mammoplasty) was also significantly higher than in breast cancer. NIS was expressed in both fibroadenoma’s and breast carcinoma’s but not in control tissue from healthy breasts. Inhibition of iodine uptake in NIS transfected CHO cells was observed when incubated with sera from patients with Graves’ disease, sera from patients with breast carcinoma, and with benign breast disease, significantly more frequently than when incubated with control sera. Inhibition of uptake was associated with the presence of TPO-Ab in sera from breast cancer patients but not from patients with benign breast disease. The authors’ thesis is that there is an as yet undetermined role for iodine in the natural history of breast carcinoma. (Comment: In fact two abnormalities are found in cancerous breast tissue vs tissue from normal breasts i.e. the expression of NIS in cancerous tissue but not in normal tissue and inhibition of NIS activity by sera from breast cancer patients. The end result is that breast cancer tissue contains significantly less iodine than breast cancer tissue. The results are interesting but confusing and the following questions arise: 1) How does iodine enters normal breast cells without the presence of NIS? 2) Apparently not (only) NIS activity is inhibited in breast cancer tissue by an as yet unknown serum component of the patient, but also the putative NIS- independent mechanism. Otherwise, iodine content in breast tissue would not be lower than in tissue of normal breasts.) Two papers were communicated on thyroid status and plasma homocysteine. Barbé et al., Vandoeuvre-lès-Nancy, France, studied prospectively 36 patients on suppressive T4 therapy after treatment for thyroid carcinoma, before and 4 weeks after withdrawal of T4. Plasma homocysteine levels were significantly higher in the hypothyroid state than during T4 suppression [11.7 µmol/l vs 6.5 µmol/l (p<0.01]). Nedrebø et al., Bergen, Norway, measured plasma homocysteine in 40 hyperthyroid patients and 12 hypothyroid patients before and during treatment. The authors found higher than normal levels in hypothyroidism and lower levels in hyperthyroidism which both normalised after reaching euthyroidism. Both research groups speculate that the elevated homocysteine plasma levels in hypothyroidism may contribute to the development of atherosclerosis in addition to changes in serum lipids.