OBJECTIVE: To compare the effects of pregnancy on the serum free thyroxine (FT4) levels in two cohorts of primary hypothyroid women treated with different levothyroxine (L-T4) doses before gestation. DESIGN AND METHOD: Twenty-five women with compensated hypothyroidism of different aetiology (thyroidectomized and Hashimoto's thyroiditis) were enrolled in this prospective study. The women were receiving substitutive doses of L-T4 and were anticipating pregnancy. They were assigned to two groups: 14 patients (group I) were switched to partially suppressive treatment while 11 patients (group II) continued the same therapeutic regimen. RESULTS: Pre-conceptional thyroid function evaluation demonstrated significantly higher FT4 and lower TSH in group I (P<0.001, for both hormones) and comparable free 3,5,3'-triiodothyronine (FT3) levels. The first post-conception thyroid function evaluation occurred at a median time of 6 (5-8) and 7 (5-9) weeks of gestation, for groups I and II respectively (P<0.05); all women in group I showed adequate serum FT4 levels while three patients in group II showed low-normal FT4 levels and one case was below normal levels. Statistical analysis demonstrated significantly higher frequencies (0% vs 36.4%; P<0.05) of low-normal FT4 levels in patients receiving substitutive doses of L-T4. None of the Hashimoto's-affected patients showed low or low-normal serum FT4 levels regardless of their therapeutic regimen. CONCLUSION: Our results suggest that in hypothyroid women anticipating pregnancy (with serum TSH in the lower quartile of normal range), the pre-conception adjustment of L-T4 doses may result in adequate maternal thyroid function up to the first post-conception evaluation. The procedure seems safe and inexpensive; it may be a worthwhile treatment, at least in thyroidectomized women, in view of the well-known potential effects of even marginal maternal thyroid hypofunction on the subsequent IQ of the progeny.
M Rotondi, G Mazziotti, F Sorvillo, M Piscopo, M Cioffi, G Amato and C Carella
C Carella, G Mazziotti, F Morisco, M Rotondi, M Cioffi, C Tuccillo, F Sorvillo, N Caporaso and G Amato
OBJECTIVE: The aim of this study was to investigate whether the addition of ribavirin (RIBA) to interferon-alpha (IFN-alpha) therapy increases the risk of developing thyroid autoimmunity and/or dysfunction. DESIGN AND METHODS: The study group (group A) included 72 patients undergoing treatment with IFN-alpha (3-6 million units three times weekly) plus RIBA (1.0-1.2 g/day) for chronic hepatitis C (CHC), as first line therapy (30 cases) or as a second therapeutic attempt after a previous ineffective IFN-alpha treatment (42 cases). The control group (group B) encompassed 75 age- and sex-matched patients affected by CHC, undergoing treatment with IFN-alpha alone as first line therapy (35 cases) or as a second therapeutic attempt (40 cases). Thyroid autoimmunity and function were retrospectively evaluated on frozen aliquots, drawn before, after 6 months, and at the end of the antiviral treatment. In patients receiving two antiviral treatments (42 cases in group A and 40 cases in group B) thyroid parameters were also assayed on serum samples drawn before and at the end of the first IFN-alpha therapy. RESULTS: Thyroid autoimmunity rate (17/72 for group A and 17/75 for group B) as well as anti-thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase antibodies (TPOAb) serum levels were comparable between the two groups. Similarly, in patients undergoing two consecutive antiviral treatments (42 cases in group A and 40 cases in group B) the percentage of positivity for thyroid autoantibodies did not change significantly from the first to the second therapeutic schedules in both groups, with no significant increase of median TgAb and TPOAb levels. By the same token, all but one patient negative for thyroid autoantibodies at the end of the first treatment remained so also during the subsequent treatment. In group A patients, the rate of hypothyroidism (11/72) was significantly higher than that observed in group B (3/75). Similarly, in patients undergoing two consecutive antiviral treatments the percentage of hypothyroidism increased significantly from the first to the second therapeutic schedule in group A (from 4.8% to 19.0%; P<0.05) but not in group B (from 4.7% to 7.1%; not significant). In group A, the occurrence of hypothyroidism during treatment with IFN-alpha+RIBA was significantly correlated with a long-term remission of CHC. CONCLUSIONS: Our study shows that: (i) the addition of ribavirin to IFN-alpha therapy for CHC does not modify the thyroid autoantibody pattern but it is associated with a higher risk of hypothyroidism; (ii) the patients without thyroid autoantibodies at the end of a previous treatment with IFN-alpha alone are protected from the development of thyroid autoimmunity and/or dysfunction in a second course of antiviral treatment with IFN-alpha+RIBA; (iii) the development of hypothyroidism in patients with thyroid autoantibodies undergoing treatment with IFN-alpha+RIBA is significantly associated with the long-term remission of CHC.
V Estienne, C Duthoit, VD Costanzo, PJ Lejeune, M Rotondi, S Kornfeld, R Finke, JH Lazarus, U Feldt-Rasmussen, WG Franke, P Smyth, M D'Herbomez, B Conte-Devolx, L Persani, C Carella, Jourdain JR, M Izembart, ME Toubert, A Pinchera, A Weetman, R Sapin, P Carayon and J Ruf
OBJECTIVE: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. METHODS: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. RESULTS: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n=437 patients), those with Graves' disease, a prevalence of 34.6% (n=645) and those with post-partum thyroiditis, 16.0% (n=243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n=246) to 0% among those with toxic thyroid nodules (n=47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n=78) to 0% in that of premature ovarian failure (n=44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. CONCLUSION: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.