The effect of antithyroid drug pretreatment on acute changes in thyroid hormone levels after (131)I ablation for Graves' disease.

Acute changes in thyroid hormone levels before and after radioiodine therapy for Graves' disease were compared in 42 patients randomized to receive either antithyroid drug pretreatment or no pretreatment. Five patients (11.9%), including 3 in the pretreatment arm and 2 in the no pretreatment arm experienced a late exacerbation of thyrotoxicosis after radioiodine therapy. The majority (19 of 21, 90.5%) of pretreated patients experienced a transient increase in free T(4) and free T(3) after discontinuation of antithyroid drugs, with little further elevation after radioiodine therapy. After stopping antithyroid drugs and before radioiodine administration, mean serum free T(4) values rose from 14.7 +/- 6.9 to 21.6 +/- 12.1 pmol/L, representing a 46.9% increase, whereas serum free T(3) levels rose from 4.9 +/- 1.7 to 8.1 +/- 6.3 pmol/L, representing a 65.3% increase. The average pretreated patient experienced a 52.4% increase [95% confidence interval (CI), +26.4% to +78.5%] in free T(4) and a 61.8% increase (95% CI, +23.5% to +100.0%) in free T(3). Conversely, the majority (19 of 21, 90.5%) of nonpretreated patients experienced a rapid decline in thyroid hormone levels after radioiodine treatment. Over the 14 days after radioiodine therapy mean free T(4) values in nonpretreated patients fell from 85.8 +/- 60.4 to 58.0 +/- 76.5 pmol/L, representing a 32.4% decrease, whereas mean free T(3) levels fell from 16.1 +/- 8.0 to 10.8 +/- 11.1 pmol/L, representing a 32.9% decrease. The average nonpretreated patient experienced a 20.6% decrease (95% CI, -47.3% to +7.0%) in free T(4) and a 24.3% decrease (95% CI, -1.2% to -47.4%) in free T(3) during this time period. Excluding 2 patients with a late exacerbation after radioiodine, 19 nonpretreated patients experienced a decrease in mean free T(4) values from 76.8 +/- 46.6 to 36.6 +/- 19.8 pmol/L, representing a 52.3% decrease, whereas mean free T(3) levels fell from 15.5 +/- 7.7 to 7.8 +/- 3.6 pmol/L, representing a 49.7% decrease. The average decrease in free T(4) levels among this subgroup of patients was 30.1% (95% CI, -4.6% to -55.6%), whereas the average decrease in free T(3) was 34.4% (95% CI, -13.7% to -55.1%). High levels of TSH receptor autoantibodies at diagnosis were associated with an acute worsening of thyrotoxicosis after stopping antithyroid drug pretreatment. We conclude that pretreatment with antithyroid drugs does not protect against worsening thyrotoxicosis after radioiodine, but may allow such patients to start from a lower baseline level should an aggravation in thyrotoxicosis occur. The findings support the recommendation that most patients with Graves' disease do not require antithyroid drug pretreatment before receiving radioiodine.

Soluble interleukin-2 receptor is a thyroid hormone-dependent early-response marker in the treatment of thyrotoxicosis.

Thyrotoxic patients exhibit increased levels of immune activation molecules (soluble interleukin-2 receptor [sIL-2R], intercellular adhesion molecule-1 [ICAM-1], and endothelial-leukocyte adhesion molecule-1 [ELAM-1]) in serum, although the clinical significance of these measurements remains unclear. In a randomized 4-week study, we have recently shown that in the treatment of hyperthyroidism, the combination of cholestyramine and methimazole (MMI) resulted in faster lowering of serum thyroid-hormone levels than did MMI alone. Stored serial serum samples from patients participating in this randomized treatment trial were analyzed for sIL-2R, soluble ICAM-1 (sICAM-1), and soluble ELAM-1 (sELAM-1). The levels of all three molecules were elevated in patients with hyperthyroidism. Although the levels of sICAM-1 and sELAM-1 remained elevated through the 4-week follow-up period in both groups of patients, the sIL-2R levels (normal levels, 1.0 to 4.2 ng/ml) decreased significantly in the 10 patients who received cholestyramine in addition to MMI (week 0, 14.2 +/- 1.5 ng/ml; week 2, 10.8 +/- 1.2 ng/ml; week 4, 8.9 +/- 1.5 ng/ml). In eight patients who received MMI alone, sIL-2R decreased less rapidly (week 0, 12.3 +/- 1.4 ng/ml; week 2, 12.3 +/- 1.3 ng/ml; week 4, 10.9 +/- 1.3 ng/ml). sICAM-1 and sELAM-1 were elevated at baseline but did not decrease during therapy. In the former group, free thyroxine and free triiodothyronine decreased faster. These data show that levels of sIL-2R in serum, but not those of sICAM-1 and sELAM-1, may be of clinical use in the early follow-up evaluation of medically treated patients.

Current trends in the management of well differentiated papillary thyroid carcinoma.

Clinical members of the American Thyroid Association were surveyed in regard to their diagnostic assessment, treatment, and long term assessment of differentiated papillary thyroid carcinoma. For a 39-yr-old female with a 2-cm solitary nodule and no history of radiation (index patient), respondents were asked to provide their preferences for diagnostic evaluation, treatment assuming a papillary carcinoma was focal, and follow-up. Of 408 surveys mailed, 233 (57.1%) were analyzed. Diagnostic studies included thyroid scan (56%), fine needle aspiration (96%), total serum T4 (49%), and third generation TSH (56%). Treatment included surgery (99%), with 86% preferring near-total/total thyroidectomy. After surgery, 61% recommended 131I ablation; long term therapy using L-T4 alone was recommended by 97%, with most preferring suppression to a target TSH level of less than 0.01 microIU/mL (22%), 0.01-0.05 (38%), or 0.06-0.50 (32%). For variations from the index patient, respondents' treatment were not different for a history of radiation, age of either 16 or 60 yr, nodule size of 1.5 cm, male sex, the presence of less than 1-cm multiple foci in the contralateral lobe, or capsular invasion of the nodule. Treatment and follow-up did change if there was blood vessel invasion or distant metastasis. In summary, our survey indicated consensus on diagnostic assessment of the index patient by fine needle aspiration and management by surgery and 131I therapy. However, management varied widely for the ablative dose of 131I, the target TSH level after ablation, and the frequency and type of follow up.

Discontinuing antithyroid drug therapy before ablation with radioiodine in Graves disease.

OBJECTIVE: To determine the relative effects on thyroid hormone levels of discontinuing antithyroid drug therapy and subsequent ablation with radioiodine in patients with hyperthyroid Graves disease. DESIGN: A clinical trial with a prospective analysis of the relative change in thyroid hormone levels over time in response to therapy in two study groups. SETTING: An outpatient endocrine clinic at a tertiary care hospital. PATIENTS: 21 patients with a clinical diagnosis of hyperthyroid Graves disease scheduled to receive ablation therapy with radioiodine (131I): 17 patients were pretreated with antithyroid drugs, and 4 were not. METHODS: Antithyroid drugs were stopped 6 days before radioiodine therapy. Patients were monitored clinically and biochemically with measurement of free and total levels of thyroxine (T4) and triiodothyronine (T3) on days -6, -3, -1; the day of radioiodine therapy; and days 1, 2, 3, 4, 5, 7, and 14. RESULTS: Before radioiodine treatment and compared with baseline measurement, the mean increase in free T4 levels after discontinuation of antithyroid therapy was 86% (95% CI, 16.1% to 156%), with a concurrent mean increase in free T3 levels of 71.6% (CI, 31% to 112%). Radioiodine therapy resulted in a mean decrease in free T3 levels of 28.7% (CI, -44.1% to -13.2%), a mean decrease in total T3 levels of 22.9% (CI, -39.4% to -6.4%), and stability in free and total T4 levels rather than aggravation of thyrotoxicosis. A smaller group of patients not receiving antithyroid drugs experienced a course qualitatively similar to that of pretreated patients after 131I treatment, with a mean reduction in free T4 levels of 39.8% (CI, -69.9% to -9.7%) and a mean decrease in free T3 levels of 49.4% (CI, -93.7% to -5.1%). CONCLUSION: Short-term increases in thyroid hormone levels in patients with Graves disease receiving radioiodine ablation occur primarily as a result of discontinuing antithyroid therapy rather than as a result of treatment with 131I. Stability or decrease in thyroid hormone levels, rather than further elevation, occurs during the 2-week interval after ablation therapy with 131I. Antithyroid drug therapy before radioiodine ablation may have little effect on the short-term biochemical course after 131I therapy for Graves disease. The homogeneity of our sample regarding age, diagnosis, and general health may prevent application of these findings to other populations without further study.

Psychologic symptoms before and after parathyroid surgery.

PURPOSE: To identify in an outpatient setting the type and number of psychologic symptoms of patients with primary hyperparathyroidism before and after surgery. PATIENTS AND METHODS: A convenience sample of 18 patients with primary hyperparathyroidism and a comparison sample of 20 patients with benign thyroid disease were scheduled by their primary care physician to have surgery. Assessments of psychologic symptoms, using the Symptom Checklist-90-Revised, and measurements of serum total calcium, ionized calcium, parathyroid hormone, albumin, alkaline phosphatase, urea nitrogen, creatinine, protein, and phosphate were obtained preoperatively. and at 1, 3, and 6 months postoperatively. RESULTS: The hyperparathyroid group had significantly higher (p < 0.01) levels of total and ionized serum calcium and parathyroid hormone preoperatively, with biochemical normalization 1 month postoperatively. These patients showed multidimensional psychologic symptom distress preoperatively in the areas of obsession-compulsion, interpersonal sensitivity, depression, anxiety, hostility, and psychoticism; they also had a greater number and intensity of distressful symptoms. Paranoid ideation was significantly higher in the hyperparathyroid group than in the comparison group, but it did not quite reach the clinical range. The greatest improvement in symptoms occurred by 1 month after surgery, with the hyperparathyroid group approaching the normative mean. There were no group differences before or after surgery for the areas of somatization and phobic anxiety. CONCLUSIONS: The Symptom Checklist-90-Revised is a simple, quick, and cost-effective way to quantitatively assess the psychologic symptoms of patients with primary hyperparathyroidism. We found that psychologic symptom distress is multidimensional, that symptoms had profoundly improved by 1 month after parathyroidectomy, and that somatization and anxiety did not differ between our groups.

Usefulness of antimicrosomal antibody titers in the diagnosis and treatment of postpartum thyroiditis.

BACKGROUND: Postpartum thyroiditis is a common but frequently unrecognized disorder, affecting approximately 5% of women during the first 12 months after delivery. We investigated whether the antimicrosomal antibody titer could be used to determine which women with positive titers postpartum (1) might develop symptomatic or biochemical abnormalities within the first postpartum year (early disease), (2) might require therapy with thyroid hormone, and (3) might have persistent abnormalities (late disease). METHODS: Women (n = 55) who had positive antimicrosomal antibody titers at delivery were prospectively followed for 11 to 45 months. Titers were evaluated again at 6 to 10 weeks postpartum and approximately every 8 weeks for the first year. RESULTS: Early disease occurred in 40 of 55 (73%) women, late disease occurred in 29 of 55 (53%) women, and treatment was required by 21 of 55 (38%) women. The occurrence of early disease was associated with the occurrence of late disease (P < .05). The chances of developing early disease were 6 to 1 (P = .01) when serum titers of antimicrosomal antibodies were > or = 400 at delivery, and 5 to 1 (P = .02) when titers were > or = 1600 at 6 to 10 weeks postpartum. The chances of being given thyroid hormone therapy were 23 to 1 (P = .006) when titers at delivery were > or = 6400, and 6 to 1 when titers at 6 to 10 weeks postpartum were > or = 6400 (P = .004). Titers were not useful in estimating who would have late disease. CONCLUSIONS: Screening for postpartum thyroid dysfunction after delivery using antimicrosomal antibody titers is highly useful. The titer value can help guide the physician in the care of patients with postpartum thyroiditis whose disease may not be self-limiting and who will probably require thyroid hormone therapy.

Prevalence of fractures in postmenopausal women with thyroid disease.

We interviewed 300 white postmenopausal women (160 with thyroid disease, 140 without thyroid disease) to investigate whether having thyroid disease or taking thyroid hormone increased the prevalence of having a hip, vertebral, or forearm fracture. Thirty-seven (23%) women with thyroid disease and 45 (32%) women without thyroid disease had had a fracture, and there were no significant differences between these groups in the number or type of fractures. Dose of thyroid hormone and duration of therapy or disease did not affect fracture occurrence in women with thyroid disease. Women with a history of hyperthyroidism (9 of 32) or thyroid cancer (2 of 11) appeared to have their first fracture earlier (p < 0.01) than women without thyroid disease. In summary, women taking thyroid hormone for a variety of thyroid disorders do not appear to have an enhanced prevalence of a hip, vertebral, or forearm fractures, but women with a history of hyperthyroidism may have a propensity for their fractures to occur earlier in life.

Adjunctive cholestyramine therapy for thyrotoxicosis.

OBJECTIVE: Initial therapy of thyrotoxicosis usually includes beta-blockade for symptom relief and thionamides to block new thyroid hormone synthesis. In view of the increased enterohepatic circulation of thyroxine (T4) and triiodothyronine (T3) in thyrotoxicosis, we proposed that cholestyramine, an anion exchange resin which binds iodothyronines, when used adjunctively with thionamides and a beta-blocker, would lower serum iodothyronine levels faster than would standard therapy alone. DESIGN: A double blind placebo-controlled cross-over design was used with patients randomly assigned to either the treatment or control groups. They received their initial treatment for two weeks (Phase 1) followed by a one-week washout period, and then crossed to the opposite treatment for two weeks (Phase 2). Standard therapy included atenolol 50 mg daily, individualized dosages of methimazole and either 4 g of cholestyramine or 4 g of placebo powder four times per day. PATIENTS: Fifteen patients with thyrotoxicosis (14 Graves' disease, 1 toxic adenoma) participated in this study. MEASUREMENTS: Total and free thyroxine and triiodothyronine, as well as thyroid-stimulating immunoglobulin and thyrotrophin-binding inhibitory immunoglobulin, were measured weekly. RESULTS: Seven patients received cholestyramine and eight patients received placebo during Phase 1. A more rapid decline in all thyroid hormone levels was seen in the cholestyramine-treated group (F = 4-7, P < 0.01) than in the placebo group (F = 2-3.1, P = 0.05). In Phase 2, the eight patients who received cholestyramine showed an additional decline in free thyroxine from weeks one to two, but the overall rate of decline in hormone levels was not different between the groups. Immunoglobulin levels remained unaffected regardless of group, treatment, or time. CONCLUSIONS: We conclude that cholestyramine is a safe and effective adjunctive agent in the treatment of thyrotoxicosis and that its greatest efficacy may be during the first few weeks of treatment.

Remission rates with antithyroid drug therapy: continuing influence of iodine intake?

We retrospectively reviewed the therapeutic efficacy of antithyroid drugs for Graves disease. Sixty-nine patients were divided into three categories according to their response: 28 (40.6%) were unable to achieve a remission; 6 (8.7%) achieved a remission and subsequently had a relapse; and 35 (50.7%) were able to sustain a remission. The mean duration for sustained remissions was 33 months. Our earlier review of outcome of antithyroid therapy showed markedly reduced remission rates, which appeared to be related to increases in dietary iodine intake. Although the greater percentage of patients entering remission today is in marked contrast to the 1973 report, average dietary iodine content has been decreasing. A continuing role for antithyroid drugs should be maintained as an option in the management of Graves disease. Daily dietary iodine intake may influence the anticipated remission rate after antithyroid drug therapy.

An attempt to determine the intellectual strengths and weaknesses of EMR children.

The performance of 101 educable mentally retarded (EMR) children on four annual administrations of the Stanford-Binet Intelligence Scale was analyzed using Sattler's standard deviation method and his Binetgram. Few of the children showed strengths and weaknesses until the original criteria were relaxed, and even then there was little stability over time. The findings suggest that this approach holds little promise for interpreting the Stanford-Binet performance of EMR children.