Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study. [Treatment of Basedow disease with synthetic antithyroid drugs. Evaluation of the dose on the efficacy of the long term treatment]. Low-activity (2.0 GBq; 54 mCi) radioiodine post-surgical remnant ablation in thyroid cancer: comparison between hormone withdrawal and use of rhTSH in low-risk patients. Does treatment with L-thyroxine influence health status in middle-aged and older adults with subclinical hypothyroidism? Thyroid hormone early adjustment in pregnancy (the THERAPY) trial. A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Effects of increased thyroxine dosage pre-conception on thyroid function during early pregnancy. Thyroid functioning during treatment for depression.
After surgery for differentiated thyroid carcinoma, many patients are treated with radioiodine to ablate remnant thyroid tissue. This procedure has been performed with the patient in the hypothyroid state to promote endogenous TSH stimulation and is often associated with hypothyroid symptoms and impaired quality of life. OBJECTIVE AND INTERVENTION: This international, randomized, controlled, multicenter trial aimed to compare the efficacy and safety of recombinant human TSH (rhTSH) to prepare euthyroid patients on L-thyroxine therapy (euthyroid group) to ablate remnant thyroid tissue with 3.7 GBq (100 mCi) 131I, compared with that with conventional remnant ablation performed in the hypothyroid state (hypothyroid group). Quality of life was determined at the time of randomization and ablation. After the administration of the 131-I dose, the rate of radiation clearance from blood, thyroid remnant, and whole body was measured.
                The predefined primary criterion for successful ablation was "no visible uptake in the thyroid bed, or if visible, fractional uptake less than 0.1%" on neck scans performed 8 months after therapy and was satisfied in 100% of patients in both groups. A secondary criterion for ablation, an rhTSH-stimulated serum thyroglobulin concentration less than 2 ng/ml, was fulfilled by 23 of 24 (96%) euthyroid patients and 18 of 21 (86%) hypothyroid patients (P = 0.2341). Quality of life was well preserved in the euthyroid group, compared with the hypothyroid group, as demonstrated by their lower pretreatment scores on the Billewicz scale for hypothyroid signs and symptoms, 27 +/- 7 vs. 18 +/- 4 (P < 0.0001) and their significantly higher Short Form-36 Health Assessment Scale scores in five of eight categories. Euthyroid patients had a statistically significant one third lower radiation dose to the blood, compared with patients in the hypothyroid group.
                This study demonstrates comparable remnant ablation rates in patients prepared for 131I remnant ablation with 3.7 GBq by either administering rhTSH or withholding thyroid hormone. rhTSH-prepared patients maintained a higher quality of life and received less radiation exposure to the blood. A direct immunosuppressive action of antithyroid drugs (ATD) has been suggested by the progressive decrease of thyroid antibodies during treatment. High doses of ATD were then proposed to improve the level of remissions of Graves' disease but the results of such high doses remain a matter of controversies. The french Group of Research on Thyroid (GRT) underwent a multicenter study comparing the efficacy of 60 mg/d of carbimazole with the minimal dose required to obtain euthyroidism in 197 randomly and equally distributed patients. After 18 months of therapy and a 2-year follow-up the remissions are 70.9% with high and 53% with low doses (p = 0.03). After the third year of follow-up, this difference was not significative (p = 0.06). Moreover after a 3-year follow-up the remission rate of high dose (60.3%) is not different from which is obtained with intermediate one (20 to 30 mg/d) associated with a permanent decrease of TSH by thyroid hormone. (a) To compare the efficacy of low-activity (2 GBq; 54 mCi) (131)I ablation using l-thyroxine withdrawal or rhTSH stimulation, and (b) to assess the influence of thyroid remnants volume on the ablation rate.
                Patients underwent neck ultrasound, (131)I neck scintigraphy and radioiodine uptake. Post-therapy whole body scan (WBS) was acquired after 4-6 days. Ablation was assessed after 6-12 months by WBS, Tg and TgAb following l-thyroxine withdrawal.
                Group A: preparation by L-T(4) withdrawal (37 days); 21 patients received (131)I (2.02+/-0.22 GBq; 54.6+/-5.9 mCi) and on the day of treatment, TSH, Tg, TgAb were measured; Group B: stimulation by rhTSH; 21 patients received (131)I (1.97+/-0.18 GBq; 53.2+/-4.9 mCi) 24 h after the second injection of rhTSH (0.9 mg) and TSH, Tg and TgAb were measured after 2 days.
                At follow-up, 90.0% of patients from group A and 85.0% of patients from group B had Tg levels <1 ng/ml; no uptake was observed in 95.2% and in 90.5% of patients from group A or B respectively, with no statistical differences for both ablation criteria. Before (131)I treatment, small thyroid remnants (<1 ml) were detected by US in <25% of all patients.
                The use of rhTSH for the preparation of low-risk patients to ablation therapy with low activities of (131)I (2 GBq; 54 mCi) is safe and effective and avoids hypothyroidism. The presence of thyroid remnants smaller than 1 ml at US evaluation had no effect on the ablation rate. To determine if health-related quality of life (HRQL) in patients of middle age and older with elevated thyroid-stimulating hormone (TSH) and normal total thyroid hormone levels-subclinical hypothyroidism-improves with L-thyroxine replacement therapy.
                Randomized, double-blind, placebo-controlled trial.
                Outpatient clinic.
                Thirty-seven patients with subclinical hypothyroidism, most with symptoms consistent with hypothyroidism, over 55 years of age.
                Placebo or L-thyroxine replacement therapy to achieve normal TSH level.
                Disease-specific and general HRQL, cognitive function, bone mineral density, lipid levels. The mean daily dose of L-thyroxine replacement in the active group was 68 +/- 21 micrograms. TSH decreased by 8.6 mIU/L (95% confidence interval [CI] 4.1 to 13.1) and T4 increased by 27.9 nmol/L (95% CI 14.8 to 41.2). There was a statistically significant improvement in a composite psychometric memory score in treated versus control patients; all other outcomes showed similar findings in the two groups. Although confidence intervals for most measures did not exclude an important improvement in HRQL with thyroid replacement, no measure of symptoms or HRQL either showed clinically important trends in favor of treatment, or approached conventional levels of statistical significance.
                In middle-aged and older patients with elevated TSH and normal T4, it may not be harmful to follow biochemical and clinical status even in the presence of nonspecific symptoms potentially associated with hypothyroidism. Thyroid hormone requirement increases 20-40% during gestation. Women with treated hypothyroidism must increase their l-T(4) in pregnancy to prevent maternal hypothyroidism, although how this should be accomplished is unclear.
                We prospectively enrolled 60 women with treated hypothyroidism seeking pregnancy. Once pregnant, women were randomized to increase l-T(4) by either two tablets/wk (group A) or three tablets/wk (group B). Thyroid function was tested biweekly through midpregnancy and at 30 wk gestation. Levothyroxine was adjusted to maintain goal TSH concentrations. The primary objective was to assess efficacy in preventing maternal hypothyroidism and the safety of this intervention.
                Forty-eight women completed the protocol. Increasing the l-T(4) dose once pregnant (regardless of study arm) prevented TSH elevation over 5.0 mIU/liter throughout the first trimester and replicated physiological changes of pregnancy. The early l-T(4) increase caused TSH suppression below 0.5 mIU/liter in eight of 25 women in group A compared with 15 of 23 women in group B (P < 0.01). This risk was significantly increased in athyreotic patients [odds ratio (OR) = 3.3; 95% confidence interval (CI) = 1.1-11.1], those with prepregnancy TSH less than 1.5 mIU/liter (OR = 4.6; 1.3-16.2), and those receiving prepregnancy l-T(4) doses of 100 microg/d or more (OR = 7.2; 1.7-30.6). However, if a trimester-specific TSH lower reference range of 0.1 mIU/liter was used, only two patients (8%) in group A required dose reduction. TSH testing every 4 wk identifies 92% of abnormal values.
                A two-tablet increase in l-T(4) initiated at confirmation of pregnancy significantly reduces the risk of maternal hypothyroidism during the first trimester and mimics normal physiology. Monitoring TSH every 4 wk through midgestation is recommended. Recently, a multicenter study in differentiated thyroid cancer (DTC) patients showed that 3700 MBq 131-iodine ((131)I) after recombinant human TSH (rhTSH) had a successful thyroid ablation rate similar to that obtained after thyroid hormone withdrawal. We investigated whether 1850 MBq (131)I had a similar successful rate to 3700 MBq in patients prepared with rhTSH.
                A total of 72 patients with DTC were randomly assigned to receive 1850 (group A, n = 36) or 3700 MBq (group B, n = 36) (131)I after rhTSH. One injection of 0.9 mg rhTSH was administered for 2 consecutive days; (131)I therapy was delivered 24 h after the last injection, followed by a posttherapy whole-body scan. Successful ablation was assessed 6-8 months later.
                Successful ablation (no visible uptake in the diagnostic whole-body scan after rhTSH stimulation) was achieved in 88.9% of group A and B patients. Basal and rhTSH-stimulated serum thyroglobulin was undetectable (<1 ng/ml) in 78.9% of group A and 66.6% of group B patients (P = 0.46). Similar rates of ablation were obtained in both groups also in patients with node metastases.
                Therapeutic (131)I activities of 1850 MBq are equally effective as 3700 MBq for thyroid ablation in DTC patients prepared with rhTSH, even in the presence of node metastases. The role of thyroxine replacement in subclinical hypothyroidism remains unclear. We performed a 6-month randomized, double-blind, placebo-controlled trial to evaluate the effects of thyroxine treatment for mild subclinical hypothyroidism, defined as a serum thyroid-stimulating hormone level between 5 to 10 microU/mL with a normal serum free thyroxine level (0.8-16 ng/dL).
                We randomly assigned 40 women with mild subclinical hypothyroidism who had presented to their family practitioners to either thyroxine treatment (n = 23; 50 to 100 microg daily) or placebo (n = 17). Health-related quality of life (Hospital Anxiety and Depression scale, 30-item General Health Questionnaire), fasting lipid profiles, body weight, and resting energy expenditure were measured at baseline and 6 months.
                The most common presenting symptoms were fatigue (n = 33 [83%]) and weight gain (n = 32 [80%]). At presentation, 20 women (50%) had elevated anxiety scores and 22 (56%) had elevated scores on the General Health Questionnaire. Thirty-five women completed the study. There were no significant differences in the changes from baseline to 6 months between women in the thyroxine group and the placebo group for any of the metabolic, lipid, or anthropometric variables measured, expressed as the mean change in the thyroxine group minus the mean change in the placebo group: body mass index, -0.3 kg/m(2) (95% confidence interval [CI]: -0.9 to 0.4 kg/m(2)); resting energy expenditure, -0.2 kcal/kg/24 h (95% CI: -1.3 to 1.0 kcal/kg/24 h); and low-density lipoprotein cholesterol, -4 mg/dL (95% CI: -23 to 15 mg/dL). There was a significant worsening in anxiety scores in the thyroxine group (scores increased in 8 of 20 women and were unchanged in 2 of 20) compared with the placebo group (scores increased in 1 of 14 women and were unchanged in 6 of 14; P = 0.03). CONCLUSIONS; We observed no clinically relevant benefits from 6 months of thyroxine treatment in women with mild subclinical hypothyroidism. 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.
                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.
                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.
                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. Thirty-nine unipolar depressed patients were treated, after a washout period of seven days in a double blind study with either moclobemide, placebo or amitriptyline, for 42 days. The psychopathological assessment and HRSD were done on seven day intervals and thyroid analysis was done on 14 day intervals. At the end of therapy, the levels of T4 and fT4 decreased significantly in the responders if amitriptyline was used, and non-significantly if placebo or moclobemide were used. The T4 and fT4 values of the non-responders increased non-significantly. The weight change was minimal and non-significant.
We found a paucity of large, high quality studies to inform analysis of thyroid hormone interventions for the treatment of people with AKI. Current evidence suggested that thyroid hormone therapy may be associated with worse outcomes for patients with established AKI; therefore, its use for these patients should be avoided. The role of thyroid hormone therapy in preventing AKI has not been adequately investigated and may be considered in future clinical studies.