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Article: Roberto Negro, Gianni Formoso, Tiziana Mangieri, Antonio Pezzarossa, Davide Dazzi, and Haslinda Hassan Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications J Clin Endocrinol Metab 2006; 0: jc.2005-1603v1 [Abstract]

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Euthyroid TPOAb positive pregnant women: the importance of having a real normal thyroid function

Roberto Negro   (30 August 2006)

LT4 Treatment in Euthyroid Pregnant Women with Autoimmune Thyroid Disease: which mechanism operates?

Rosa Corcoy   (9 August 2006)

Euthyroid TPOAb positive pregnant women: the importance of having a real normal thyroid function 30 August 2006
Roberto Negro, Endocrinologist Dept. Endocrinology, Send letter to journal: Re: Euthyroid TPOAb positive pregnant women: the importance of having a real normal thyroid function robnegro{at}tiscali.it Roberto Negro	Dr. Corcoy suggests another possible explanation for the beneficial effects of levothyroxine (LT4) on obstetrical complications in pregnant women positive for TPOAb. By suppressing TSH, they suggest that LT4 may reduce thyroid antigen availability and lessen humoral and cellular autoimmunity. Although both studies cited by Dr Corcoy reported reduced thyroid autoantibody levels in the LT4 treated groups with respect to controls (1, 2), the observed reductions of thyroid autoantibodies in our study were similar in both the LT4-treated and untreated pregnant women. Of course, these circulating antibody levels may or may not accurately reflect the activity of cellular autoimmunity actually responsible for thyroid dysfunction in autoimmune thyroiditis. Nonetheless, even if there is LT4-induced amelioration of thyroid autoimmunity, it remains unclear how this could be responsible for altering obstetrical complications. Consequently, we think that it is more plausible that TPOAb-positive pregnant women suffer from subtle thyroid dysfunction during pregnancy, and that the observed higher TSH values are not completely compensatory and reflect subtle thyroid hormone deficiency with consequent adverse obstetrical complications (3). References 1. Aksoy DY, Karimoglu U, Okur H, Canpinar H, Karaagaoglu E, Yetgin S, Kansu E, Gedik O 2005 Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto’s thyroiditis. Endocrine J 52:337-343 2. Padberg S, Heller K, Usadel KH, Schumm-Draeger PM 2001 One-year prophylactic treatment of euthyroid Hashimoto’s thyroiditis patients with levothyroxine: is there a benefit? Thyroid 11:249-255 3. Poppe K, Glinoer D 2003 Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update 9:149-161
LT4 Treatment in Euthyroid Pregnant Women with Autoimmune Thyroid Disease: which mechanism operates? 9 August 2006
Rosa Corcoy, endocrinologist Servei d'Endocrinologia, Hospital de Sant Pau, Barcelona Send letter to journal: Re: LT4 Treatment in Euthyroid Pregnant Women with Autoimmune Thyroid Disease: which mechanism operates? rcorcoy{at}santpau.es Rosa Corcoy	Negro et al. (1) have shown a prospective, randomized, and controlled, although unblinded trial, a reduction in the rate of spontaneous abortions and preterm delivery with levothyroxine treatment of euthyroid pregnant women with positive thyroid peroxidase antibodies (TPOAb). That the intervention has benefit seems clear, but its mechanism remains un-established. The authors ascribe the effect to increased thyroxine availability, which seems plausible with regard to preterm delivery, but not for spontaneous abortion, based on reported serum thyroxine values in the treated group at the relevant gestational age. I suggest that another possible explanation for this salutary effect of thyroxine could be a reduction in underlying autoimmunity despite the fact that the accompanying editorial expresses the view that there is no reason to suppose that (2). Thyroxine treatment of euthyroid subjects has been shown to improve humoral and cellular autoimmunity (3, 4) even though this finding has not been confirmed in all studies (5). The presumed mechanism for this effect would be the reduced antigen availability to the immune system, due to reduced thyroid stimulation by TSH (6). Additional studies confirming the benefit of thyroxine treatment in euthyroid pregnant women with TPOAb will be welcome, and determining the underlying mechanism would be as well. 1. Negro R, Formoso G, Mangieri T, Pezzarosa A, Dazzi D, Hassan H. 2006. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 91: 2587-2591 2. Glinoer D. 2006. Miscarriage in women with positive anti-TPO antibodies: Is thyroxine the answer? J Clin Endocrinol Metab 91: 2500-2502 3. Aksoy DY, Kerimoglu U, Okur H, Canpinar H, Karaagaoglu E, Yetgin S, Kansu E, Gedik O. 2005 Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto's thyroiditis. Endocr J 52:337-343 4. Padberg S, Heller K, Usadel KH, Schumm-Draeger PM 2001 One-year prophylactic treatment of euthyroid Hashimoto's thyroiditis patients with levothyroxine: is there a benefit? Thyroid 11:249-255 5. Chiovato L, Marcocci C, Mariotti S, Mori A, Pinchera A 1986 L-thyroxine therapy induces a fall of thyroid microsomal and thyroglobulin antibodies in idiopathic myxedema and in hypothyroid, but not in euthyroid Hashimoto's thyroiditis. J Endocrinol Invest 9:299-305 6. Rieu M, Richard A, Rosilio M, Laplanche S, Ropion V, Fombeur JP, Berrod JL. 1994 Effects of thyroid status on thyroid autoimmunity expression in euthyroid and hypothyroid patients with Hashimoto's thyroiditis. Clin Endocrinol (Oxf) 40:529-535