Mariacarla Moleti

Iodine Prophylaxis Using Iodized Salt and Risk of Maternal Thyroid Failure in Conditions of Mild Iodine Deficiency

CONTEXT Mild to moderate iodine deficiency during pregnancy can cause transient maternal hypothyroidism and impaired mental development of the progeny. These unfavorable effects are preventable by iodine supplementation. In Europe, however, less than 50% pregnant women receive iodine-containing supplements, thus representing dietary iodized salt the only carrier of iodine for most women in this life stage. OBJECTIVE/DESIGN This longitudinal study is aimed to investigate the effects of long-term iodized salt consumption on maternal thyroid function during gestation. PARTICIPANTS/OUTCOME MEASURES: We prospectively evaluated thyroid function in 100 consecutive thyroperoxidase antibody-negative pregnant women from a mildly iodine-deficient area. Sixty-two women who had regularly used iodized salt for at least 2 yr prior to becoming pregnant and 38 who commenced iodized salt consumption upon becoming pregnant were classified as long-term (LT) and short-term (ST) iodine supplemented, respectively. RESULTS Long-term iodized salt consumption resulted in a very low prevalence of maternal thyroid failure (MTF) in LT women. Conversely, short-term iodine prophylaxis does not seem to protect against the risk of MTF, the prevalence of which was almost 6-fold higher in ST than LT women (36.8% vs. 6.4%; chi(2) 14.7, P < 0.0005; relative risk 5.7, 95% confidence interval 2.03-16.08, P < 0.001). The relative risk reduction amounted to 82.5%, this measure indicating the extent to which long-term iodine prophylaxis using iodized salt would reduce the risk of MTF in ST women. CONCLUSIONS Prolonged iodized salt significantly improves maternal thyroid economy and reduces the risk of maternal thyroid insufficiency during gestation, probably because of a nearly restoring intrathyroidal iodine stores.

Gestational thyroid function abnormalities in conditions of mild iodine deficiency: early screening versus continuous monitoring of maternal thyroid status

OBJECTIVE To longitudinally evaluate the timing of maternal thyroid underfunction occurrence in mildly iodine-deficient (ID) pregnant women, and ultimately assess the benefit of thyroid function testing at early gestation only in identifying maternal thyroid underfunction. PARTICIPANTS/METHODS Serum free-thyroxine and TSH were measured in 220 consecutive women once in early pregnancy (by week 12) and twice per trimester subsequently. Anti-thyroperoxidase and anti-thyroglobulin were also determined at initial and final observation. RESULTS Thyroid autoantibodies were detectable in 8.2% women. Overall, the prevalence of hypothyroidism over the course of gestation was 11.8% (26/220), with a relative risk of hypothyroidism in antibody-positive women of 5.0 (chi(2) 20.02, P<0.0005). Nonetheless, almost 70% hypothyroid women tested negative for thyroid autoantibodies. Fifteen/26 (57.7%) hypothyroid women were identified at presentation, and the remaining 11 at either early (6/11) or late (5/11) phases of the 2nd trimester. Isolated hypothyroxinemia was observed in 56/220 (25.4%) women, mostly from the 2nd trimester onwards. CONCLUSIONS In mildly ID areas thyroid function testing early in gestation seems to be only partly effective in identifying thyroid underfunction in pregnant women. Indeed, in our series more than 40% hypothyroid women would not have been diagnosed had we limited our observation to early thyroid function tests alone. Although thyroid autoimmunity carried a 5-fold increased risk of hypothyroidism, iodine deficiency seems to be a major determinant in the occurrence of thyroid underfunction. Adequate iodine supplementation should be strongly recommended to meet the increased hormone demand over gestation.

Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency: an observational study.

Objective  We examined the effect of different conditions of nutritional iodine intake on maternal thyroid function throughout gestation in a cohort of healthy, anti‐thyroid antibody‐negative women from a mild‐moderately iodine‐deficient (ID) area.

Thyroid Function in Women Found to Have Early Pregnancy Loss

BACKGROUND Pregnancy influences thyroid function and may bring to light mild and latent disorders. Thyroid dysfunction has been related to obstetrical complications such as premature delivery, gestational hypertension, preeclampsia, and placental abruption. The aim of our study was to evaluate whether the occurrence and timing of pregnancy loss could be related to thyroid autoimmunity or subclinical hypothyroidism (SH) per se. METHODS Two hundred sixteen apparently healthy pregnant women with no previous history of thyroid disease and with diagnosis of early miscarriage (before the 12th week of gestation) were enrolled. Miscarriages were classified as very early pregnancy loss (EPL) or embryo loss (crown rump length < or =10 mm) and EPL or fetal loss (crown rump length > 10 mm). Women were subdivided into four groups: euthyroid (ET), SH, overt hypothyroidism, and thyroid autoimmunity group. RESULTS One hundred seventy-six women had a normal thyroid function (84.6%), 24 patients were found to have positive thyroid antibodies (11.5%), 8 women (3.8%) an SH, and 8 cases were excluded. Thyroid-stimulating hormone levels were found to be higher in the very early (1.4 +/- 1.0 mU/L) than in the EPL group (1.1 +/- 0.7 mU/L) (p = 0.04), and in patients affected by SH (3.9 +/- 0.1 mU/L) compared to ET (1.0 +/- 0.5 mU/L) (p < 0.001) and autoimmune women (1.0 +/- 0.4 mU/L) (p < 0.001). Although the multivariate logistic regression analysis revealed that both autoimmunity and SH were independently correlated with the onset of very EPL, abortion was more precocious in the SH group (6.5 +/- 0.9 weeks), followed by the autoimmune (8.2 +/- 2.1 weeks) and ET groups (8.2 +/- 1.6 weeks) (p = 0.02). CONCLUSIONS Both thyroid diseases SH and autoimmune disorder are independently associated with very early embryo loss, but women suffering from SH have a lower gestational age at abortion.

Doubts and Concerns about Isolated Maternal Hypothyroxinemia

There is evidence that isolated maternal hypothyroxinemia may have detrimental effects on both mother and foetus. Nonetheless, this condition is still far from being universally accepted as a separate thyroid disease, and a standard definition of this state of mild thyroid underfunction is still lacking. We will review the biochemical criteria used to define isolated maternal hypothyroxinemia, together with current methodological issues related to FT4 assays. We will also discuss its epidemiological impact in both iodine-deficient and-sufficient areas, and the effectiveness of iodine prophylaxis on maternal thyroid function and neuropsychomotor development in offspring.

Thyroid physiology in pregnancy.

OBJECTIVE Various physiological changes occur in maternal thyroid economy during pregnancy. This review focuses on the events taking place during gestation that together strongly influence maternal thyroid function. METHODS Scientific reports on maternal thyroid physiology in pregnancy. RESULTS During the 1st trimester, human chorionic gonadotropin (hCG) induces a transient increase in free thyroxine (FT4) levels, which is mirrored by a lowering of thyroid-stimulating hormone (TSH) concentrations. Following this period, serum FT4 concentrations decrease of approximately 10 to 15%, and serum TSH values steadily return to normal. Also starting in early gestation, there is a marked increase in serum thyroxine-binding globulin (TBG) concentrations, which peak around midgestation and are maintained thereafter. This event, in turn, is responsible for a significant rise in total T4 and triiodothyronine (T3). Finally, significant modifications in the peripheral metabolism of maternal thyroid hormones occur, due to the expression and activity of placental types 2 and 3 iodothyronine deiodinases (D2 and D3, respectively). CONCLUSION In line with these variations, both free thyroid hormone and TSH reference intervals change throughout pregnancy, and most scientific societies now recommend that method- and gestation-specific reference ranges be used for interpreting results in pregnancy.The maternal iodide pool reduces during pregnancy because of increased renal clearance of iodine and transfer of iodine to the feto-placental unit. This results in an additional requirement of iodine during pregnancy of ~100% as compared to nonpregnant adults. In accordance, the recommended iodine intake in pregnancy is 250 μg/day. A daily iodine intake below this threshold poses risks of various degrees of thyroid insufficiency for both the mother and the fetus.

Changes in both size and cytological features of thyroid nodule after levothyroxine treatment

objective We prospectively evaluated the effects of 12 months thyrotropin suppressive levo‐thyroxine (L‐T4) therapy in terms of changes in both thyroid nodule size and cytological features and considered whether thyroid nodule size changes actually resulted in (or were the result of) cytological changes.

Clinical usefulness of 99mtc-mibi scintigraphy in the postsurgical evaluation of patients with differentiated thyroid cancer

Objective99mTc-methoxyisobutyl isonitrile (MIBI) has been reported to show considerable clinical utility in the study of many neoplastic diseases. The aim of our study was to investigate the possible role of 99mTc-MIBI in the initial follow-up of patients with differentiated thyroid cancer (DTC) for detecting residual thyroid uptake and/or loco-regional/distant metastases. MethodsEighty-two patients with DTC (61 women, 21 men; mean age: 49 years) were studied after total or near-total thyroidectomy (not earlier than 3 months after thyroidectomy but before they underwent radioiodine therapy). About 20 min after the intravenous administration of 370 MBq of 99mTc-MIBI, planar images (and, if necessary, tomographic images, single photon emission tomography) of the cervical and thoracic regions were recorded and compared with posttherapy radioiodine scanning and thyreoglobulin serum levels. ResultsMIBI scans detected thyroid remnants in 53 of 82 patients (65%) and metastatic foci in 10 of 11 (91%) patients, in whom a standard activity of 1110 MBq of 131I administered following MIBI scan had shown the presence of thyroid remnants or metastatic foci, respectively. One metastatic patient was false negative for both MIBI scan and post-131I dose whole body scan. ConclusionOur data indicate that an MIBI scan has a high sensitivity in detecting metastatic lesions from DTC. Therefore, an MIBI scan after thyroidectomy and immediately before radioiodine treatment may be clinically useful for choosing the best therapeutic approach in terms of either ablative or therapeutic 131I activity for both thyroid remnants and/or DTC metastases and for evaluating surgical reappraisal of metastatic lymph nodes.

Thyroid remnant ablation in differentiated thyroid cancer: searching for the most effective radioiodine activity and stimulation strategy in a real-life scenario.

ObjectiveDifferentiated thyroid cancer is rare, but the incidence has been increasing in the last few decades. Early treatment is based on surgery and thyroid remnant ablation (TRA) by means of radioiodine therapy. Despite radioiodine being widely used for decades, the choice of ablative activity is generally empirical and no consensus has been reached to date. The aim of our study was to compare the efficacy and safety of different radioiodine activities. In addition, we compared the ablation rate in patients treated in the hypothyroid state or after recombinant human thyroid-stimulating hormone (rhTSH) administration, retrospectively reviewing the records of 471 patients affected by differentiated thyroid cancer. Patients and methodsPatients were subdivided into three groups on the basis of the different activities of radioiodine administered and taking into account the different approaches used to perform the therapy: thyroid hormonal withdrawal or rhTSH stimulation. ResultsThe success of TRA was evaluated 12 months later. TRA was obtained in 62/79 (78.5%) in group A (1110 MBq in the hypothyroid state), 183/190 (96.3%) in group B [2220 MBq in the hypothyroid state or after rhTSH administration: 87/90 (97%) and 96/100 (96%) patients, respectively], 199/202 (98.5%) in group C [3700 MBq in hypothyroid state or after rhTSH administration: 98/100 (98%) and 101/102 (99%) patients, respectively]. ConclusionOur data demonstrate that 2220 and 3700 MBq radioiodine are more effective compared with 1110 MBq in TRA, without significant differences between 2220 and 3700 MBq or between hypothyroidism and euthyroidism. We suggest rhTSH-aided TRA with 2220 MBq iodine-131, as this approach permits efficacious treatment, thereby reducing side effects, absorbed dose to body and hospital stay.

Female Reproductive Factors and Differentiated Thyroid Cancer

Differentiated thyroid cancer (DTC) is markedly more common in women than men, the highest female-to-male ratio being recorded during the reproductive period. This evidence has led to the suggestion that female hormonal and reproductive factors may account for the observed DTC gender disparity. This review focuses on current evidence on the risk of DTC in conjunction with major female reproductive factors, including the impact of pregnancy on DTC occurrence and progression/recurrence. Overall, studies exploring the link between the risk of DTC and menstrual and menopausal factors, oral contraceptives and/or hormone replacement therapy, showed these associations, if any, to be generally weak. Nonetheless, there is some evidence that higher levels of exposure to estrogens during reproductive years may confer an increased risk of DTC. As far as pregnancy is concerned, it is unclear whether a potential association between parity and risk of DTC actually exists, and whether it is enhanced in the short-term following delivery. A possible role for pregnancy-related factors in DTC progression has been recently suggested by some reports, the results of which are consistent with a worse outcome in the short-term of women diagnosed with DTC during gestation compared to non-pregnant control patients. Also, some progression of disease has been described in women with structural evidence of disease prior to pregnancy. However, there seems to be no impact from pregnancy in DTC-related death or overall survival. Several in vitro and animal studies have evaluated the influence of estrogens (E) and estrogen receptors (ERs) on thyroid cell proliferation. Presently available data are indicative of a role of E and ERs in thyroid cancer growth, although considerable discrepancies in respect to ER expression patterns in thyroid cancer tissues actually exist. Further studies providing more direct evidence on the possible role of E and of placental hormones and growth factors on thyroid growth may expand our knowledge on the mechanisms beyond the gender disparity of proliferative thyroid diseases.