Miscellaneous
	Singh et al., Los Angeles, California, USA, previously published that chronic administration of calcium carbonate reduces T4 absorption and increases serum TSH levels (JAMA 283:2822-2825,2000). They now report the acute effect of administration of 2.0 g of calcium carbonate on the absorption of 1 mg LT4 in seven normal volunteers. They found a mean reduction in T4 absorption from 83.7% (without calcium carbonate) to 57.9% (with calcium carbonate), 120 minutes after administration. Wilcox et al., San Juan Capistrano, California, USA, tested the hypothesis that automated, hormone analog free T4 methods measure concentrations of protein bound T4 rather than free T4. The assays studied were Access® (Beckman), ACS 180 (Bayer), AxSym (Abbott) and Immno 1 (Bayer). They found reproducible results in three experiments for each kit and the results showed that in no assay free T4 was measured but rather protein bound T4 concentrations irrespective if they used albumin, transthyretin or TBG as the T4 binding-protein. The results also showed that these kits were not able to measure free T4 accurately, when all T4 was in the free moiety. (For further reading of work of this group on this subject, see JCEM:79,76-79,1994, and JCEM 79,1373-1375,1994.) Fatourechi et al., Rochester, Minnesota, USA, retrospectively studied if corticosteroid therapy modified the long-term outcome of subacute thyroiditis. They analyzed 97 patients fulfilling their criteria as having subacute thyroiditis who were diagnosed between 1970 and 1997. Thirty-four/ninety-seven patients were treated with a median dose of 40 mg prednisone/day, range 15-120 mg, duration range 6 days to 6 months. In 40/97 of patients NSAIDs were administered and in 23/97 no NSAIDs or corticosteroids were used. Of the patients treated with corticosteroids 23% developed permanent hypothyroidism, whereas this was only in 8% of the non-corticosteroid group. The authors conclude that administration of the corticosteroids does not prevent development of hypothyroidism. (Comment: As this is a retrospective analysis, these data should be interpreted with care in the sense that patients treated with corticosteroids might have been suffering from more severe thyroiditis than the non-corticosteroid group. In other words, although the conclusion of the authors per se is correct, it is certainly not ruled out that administration of corticosteroids can prevent development of permanent hypothyroidism in a subset of patients.) Sellin et al., Houston, Texas, USA, report the effect of T3 supplementation in 4 patients previously treated (surgery and/or irradiation) for suprasellar lesions and subsequently developing hypothalamic/pituitary dysfunction. It is known that this type of patients develops "hypothalamic" obesity resistant to almost all forms of therapy. After T3 supplementation resulting in supraphysiological serum T3 concentrations without symptoms or signs of thyrotoxicosis, all 4 patients lost weight (range 4.5-10 kg between 6 weeks and 15 months). (Comment: Of course it should be documented if in the long run weight reduction persists and if side effects of T3 administration (e.g. on heart and bone) may still become evident.) Woeber, San Francisco, California, USA, determined serum T4, T3, and the T4-T3 ratio in 20 normal individuals (group A), 18 subjects with chronic autoimmune thyroiditis but normal TSH (group B), and 35 patients who became hypothyroid due to autoimmune thyroiditis and were on T4 substitution with normal serum TSH (group C). They found that in groups A and B serum free T4 and free T3 were similar but free T4 was significantly higher in group C, while the mean free T3 was lower in group C as compared to groups A and B. Consequently, the molar ratio between free T4 and free T3 was higher in group C than in group A and B. The author concludes that in patients with primary hypothyroidism T4 administration to normalize TSH may not be sufficient to normalize T3 as well. (Comment: This finding has been reported earlier several times. It is about time that thyroid hormone preparations are being tested that are a combination of T4 and T3 in slow released form and in a ratio such that beside a normal serum TSH also normal free T4 and free T3 levels are reached.) Knudsen et al., Copenhagen, Denmark, analyzed thyroid volume in 3,712 randomly selected women and found that in users of oral contraceptives (OC) the mean thyroid volume was 11.1 ml vs 12.1 ml (p <0.001) in non-users as determined by ultrasound. Use of OC was thus associated with a decrease in thyroid volume (odds ratio 0.53, 95% confidence interval 0.37-0.74) and of palpable and visible goiter odds ratio 0.24 (0.07-0.81). Serum TSH in users was 1.35 vs 1.24 mU/l, in non-users (p = 0.02), and correspondingly serum Tg was higher among users than in non-users. The authors speculate that the lower thyroid volumes and goiter rate in OC could be due to suppression of a specific endogenous estrogen metabolite(s) or due to suppression of LH and FSH that have been demonstrated to possess stimulatory effects on the TSH receptor. (Comment: No explanation is provided for the statistically increased mean serum TSH in OC users and its apparent lack of effect on thyroid volume.) Kokandi et al., Cardiff, Wales, UK, attempted to define the immunological events that lead to postpartum thyroid dysfunction in 50% of women who were found to be thyroid peroxidase antibody positive. Their analysis concentrated on the Th2 to Th1 immune switch thought to occur peripartum. When measured at 36 weeks antenatally, they found IL-4 expression by CD3+ and CD4+ lymphocytes to be significantly higher in the group that developed postpartum thyroid dysfunction as compared to those who remained euthyroid. Similarly IFN-gamma expression at this time point was higher in the thyroid dysfunction group. The results suggest a difference in Th2/Th2 balance prepartum in women destined to develop postpartum thyroid disease. Two groups, Kon et al., Chicago, Illinois, USA, and Gourgiotis et al., Bethesda, Maryland, USA, report in total 9 patients who suffered from painful Hashimoto's thyroiditis that did not respond to anti-inflammatory agents. The patients underwent near-total or total thyroidectomy and prompt relieve of symptoms occurred in most patients. (Comment: This therapy is effective for this small subgroup of patients. It is however necessary to have the operation done by a very experienced thyroid surgeon, as thyroid fibrosis may be extensive in these cases.) Pearce et al., Boston, Massachusetts, Washington, DC, and Atlanta, Georgia, USA, analyzed the effects on the thyroid of chronic iodine excess in peace corps volunteers between 1995 and 1998 when exposed to ingestion of severe iodine excess of 50-90 mg/day. Results were compared on an average of 30 weeks following correction of iodine intake. During iodine excess the mean serum iodine concentration was 30.6 µg I/dl and decreased to 8.4 µg I/dl after correction of iodine intake. In 47/101 subjects (46.5%) goiter was present during iodine excess but decreased to 30% when iodine intake was corrected. Serum TSH was suppressed in 5/100 and elevated in 22/100 subjects. These figures were during normal iodine intake 14/91 and 2/91 respectively. The mean TPO antibody titers were higher during iodine excess than afterwards. (Comment: Although abnormalities diminish on the average, 30 weeks following correction of iodine intake, substantial thyroid dysfunction was still present. I hope that we will hear the further follow-up of these abnormalities.) Silva et al., Sao Paulo, Brazil, compared the efficacy of RAI treatment in multinodular goiter in 10 patients pretreated with rhTSH and compared the results in 8 patients treated with radioiodine only. The rhTSH patients had a significant higher mean Tg peak after RAI and a significant longer biological half-life of RAI. In both groups thyroid volume decreased by 68% to 86% after 6 and 12 months. The authors conclude that rhTSH stimulated RAI treatment may be useful as it results in more radiation delivered to the thyroid tissue as reflected by the longer biological half-life of RAI and the higher Tg peak after RAI administration. (Comment: The authors suggest that hypothyroidism however may be more frequent in the rhTSH group and my query is if due to stimulation of I-131 uptake in the thyroid, circulating protein-bound RAI may be higher in these patients, leading to a higher dose of whole body irradiation.) Bennedbaek et al., Odense and Roskilde, Denmark, tested feasibility and efficacy of US-guided interstitial laser photocoagulation (ILP) in 16 euthyroid patients with benign thyroid nodules. The mean thyroid nodule volume decreased from 10 ml to 5.4 ml after 6 months. Thyroid function remained unchanged. The treatment was well tolerated except for a transient mild local pain. The authors conclude that these preliminary results are promising as an alternative non-surgical therapy for benign solitary solid cold nodules. Schwartz et al., Rochester, Minnesota, USA, analyzed the efficacy of local corticosteroid therapy for thyroid dermopathy in 178 patients. In this retrospective study from the period of January 1969 to November 1995 the average age at diagnosis was 53.1 years and the average follow-up 7.9 years. Topical corticosteroids were used in 53.9% of cases, especially the more severe ones. Dermopathy was pretibially localized in 99.4% of patients. Thirty-four percent of patients not treated with corticosteroids experienced a complete remission versus 18.7% who did receive local corticosteroid application. However, when complete and partial remission rates were taken together, no significant differences were present between the two groups. The conclusion of the authors is that local application of corticosteroids is questionable. (Comment: I am not sure that this conclusion is correct as the treatment group had significantly more severe dermopathy. As long as this matter has not been settled in a double blind controlled randomized study, I am inclined to still apply corticosteroids locally in patients with severe dermopathy.) Yokozawa et al., Kobe, Japan, report the results in 22 (18 females) patients treated with percutaneous ethanol injection (PEI) for Graves' disease in 1979 and followed until 2001. In 8/22 patients euthyroidism was achieved during a mean follow-up period of 35 months, 12/22 patients were on antithyroid drugs during follow-up, and 2/22 were treated with I-131. (Comment: In this preliminary study 14/22 patients were not rendered euthyroid by PEI. I consider this therapy as experimental for the moment. Further results are awaited to ascertain whether PEI is a suitable therapy for Graves' disease.)