Barbara L. Solomon

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.

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.

Discontinuing Antithyroid Drug Therapy before Ablation with Radioiodine in Graves Disease

Table. SI Units and Abbreviations Radioactive iodine has been used to treat hyperthyroidism associated with Graves disease for nearly 50 years [1]. The efficacy, safety, and low cost of this therapy have made it the preferred definitive treatment in most patients with this disorder [2]. Radioiodine (Iodine-131) produces an intense radiation thyroiditis followed by progressive interstitial fibrosis and glandular atrophy, resulting in the destruction of the synthetic capacity of the gland [3]. Thyroiditis after Iodine-131 therapy is believed to peak between 10 and 14 days after ablation and may be associated with an exacerbation of hyperthyroidism as early as 1 to 7 days after therapy [4-6]. This exacerbation has been presumed to be caused by the release of hormones from the damaged thyroid and may occasionally be of sufficient severity to precipitate a life-threatening thyroid crisis or storm [6, 7]. Concern over the rapid release of glandular hormone stores after Iodine-131 ablation represents a rationale for adjunctive therapy with antithyroid drugs before or after ablation, a practice adhered to by 20% to 40% of thyroidologists according to a recent international survey [2]. However, because these agents inhibit the organification of iodine within the thyroid, they may limit the effectiveness of radioiodine therapy and therefore are generally stopped 4 to 7 days before treatment with Iodine-131 [8]. The discontinuation of antithyroid therapy might be expected to be associated with a rebound in thyroid hormone synthesis, such as to exacerbate thyrotoxicosis; in fact, discontinuation of antithyroid therapy is a frequently cited but probably rare precipitant of thyroid storm [7, 9, 10]. To the best of our knowledge, a systematic study of short-term changes in thyroid hormones after discontinuation of antithyroid therapy has not been previously published. Little information exists regarding short-term changes in thyroid hormones after administration of Iodine-131. Further, the existing literature in this area provides conflicting information: Some studies show short-term elevation in thyroid hormones after Iodine-131 therapy [11-13], others show no consistent short-term changes in hormone levels [14, 15], and still others show short-term decreases in these levels after radioiodine therapy [16]. None of the above studies compared the relative effects of discontinuing antithyroid therapy and administration of Iodine-131, and no study has measured changes in free thyroid hormone levels, which, as opposed to total thyroid hormone levels, may have predictive value for the development of thyroid storm [17]. We sought to determine prospectively the relative effects of stopping antithyroid therapy and subsequent radioiodine administration on free and total thyroid hormone levels in patients with Graves disease who have received thyroid ablation therapy. We also studied a subgroup of patients not receiving antithyroid therapy to evaluate short-term changes in thyroid hormone levels that occurred in the absence of pretreatment. Finally, we did an analysis of patient characteristics associated with the biochemical and clinical course after antithyroid therapy was discontinued and radioiodine was administered. Methods Patient Selection Patients were diagnosed as having hyperthyroidism caused by Graves disease on the basis of elevated thyroid hormone levels and suppressed thyroid-stimulating hormone levels by sensitive assay in the setting of diffuse goiter, elevated 24-hour radioiodine uptake, and in most cases, detectable levels of antibodies against the thyroid-stimulating hormone receptor. Patients with other causes of hyperthyroidism or cold nodules on pertechnetate scanning were excluded from the study. Unless contraindicated, patients had been treated with the antithyroid medications methimazole or propylthiouracil until they showed biochemical improvement or returned to a euthyroid state before referral for radioiodine ablation. Baseline Assessment At baseline, the presence and duration of antithyroid drug therapy were noted, a smoking history was obtained, and thyroid size was assessed by a single examiner. Levels of thyroid-stimulating immunoglobulins and thyroid-stimulating hormone-binding inhibiting immunoglobulins and basal levels of free and total thyroxine (T4) and triiodothyronine (T3) were measured. Treatment Protocol and Serial Evaluation Six days before patients were given Iodine-131, antithyroid therapy was discontinued in patients who received these agents. Serial clinical and laboratory assessment was done on days 6, 3, and 1 before therapy; the day of treatment; and days 1, 2, 3, 4, 5, 7, and 14 after treatment. In patients not receiving antithyroid drugs, assessment was initiated from the day before therapy with Iodine-131. On each morning listed, free and total levels of T4 and T3 were measured, as were pulse and estimated thyroid size by palpation. Patients graded their symptoms of heat intolerance, nervousness, confusion, insomnia, dyspnea, palpitations, and hyperdefecation on a scale ranging from 0 to 3 as follows: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. On the day of treatment, radioiodine uptake was measured to allow calculation of the dose of Iodine-131 according to the following formula: 200 to 250 microcuries/g of estimated thyroid weight/radioiodine uptake. Unless contraindicated, -adrenergic blocking agents (atenolol or metoprolol) were given to all patients throughout the study. No patient received antithyroid drug therapy during the 14 days after Iodine-131 treatment. Laboratory Testing Thyroid hormone assays were done at Hazelton Laboratories (Vienna, Virginia) on batched serum samples that had been stored at 20C pending study completion. Total T4 and T3 levels were measured using radioimmunoassay, and free T4 and T3 levels were measured using Coat-a-Count assay kits (Diagnostic Products, Los Angeles, California). Interassay coefficients of variation for values in the euthyroid range are as follows: total T4, 8.1%; free T4, 7.4%; total T3, 6.3%; and free T3,3.9%. For values in the hyperthyroid range, interassay coefficients of variation are the following: total T4, 5.9%; free T4, 6.8%; total T3, 5.7%; and free T3, 4.8%. Thyroid-stimulating hormone-receptor antibody assays were done at SmithKline Bio-Science Laboratories (Baltimore, Maryland). We measured thyroid-stimulating immunoglobulin levels using bioassay for production of cyclic adenosine monophosphate by cultured thyrocytes and expressed as thyroid-stimulating hormone equivalents. Thyroid-stimulating hormone-binding inhibiting immunoglobulin was measured with a radioreceptor assay and was expressed as the percentage inhibition of thyroid-stimulating hormone binding. Normal ranges for each of these assays are given in Table 1. Table 1. Characteristics at Study Entry of Patients Receiving or Not Receiving Pretreatment with Antithyroid Drugs* Statistical Analysis We used StatView statistical software (Abacus Concepts, Calabasas, California) for the statistical analyses. Changes in thyroid hormone levels over time were assessed for significance using repeated-measures analysis of variance. Post hoc testing was done using the Fisher protected least significant difference and the Scheffe F-test procedures. Whenever relevant, we calculated confidence intervals to supplement null hypothesis testing. Comparison of the rate of change in thyroid hormone levels after radioiodine therapy in patients who received and those who did not receive pretreatment was done by linear regression analysis of disappearance curves of individual patient hormone, followed by the Mann-Whitney U-test. Correlation between patient clinical measurements (duration of antithyroid drug therapy, current smoking status, goiter size, radioiodine uptake, dosage of Iodine-131, and basal thyroid hormone and thyroid-stimulating-receptor antibody levels) and change in thyroid hormone levels over time was assessed using Pearsons correlation procedure for continuous variables and analysis of variance for calculations involving discrete dependent variables. Results Patient Characteristics Twenty-one patients (12 women and 9 men) gave informed consent to participate in the study, which was approved by the Walter Reed Army Medical Center Human Use Committee. Patients ranged in age from 19 to 71 years (mean, 38.1 11.2 years). Seventeen patients received pretreatment with antithyroid drugs before receiving radioiodine: Nine patients received methimazole, 5 received propylthiouracil, and 3 received both agents sequentially because of rash or pruritus with the first agent used. Four patients could not receive either preparation because of rash (2 patients), a history of hepatitis (1 patient), and social circumstances (1 patient). Estimated baseline thyroid size ranged from 25 to 80 g, with a mean of 44 11 g. Duration of antithyroid therapy ranged from 4 to 52 weeks, with a mean duration of 14 weeks. Baseline clinical and laboratory characteristics are summarized in Table 1. Treatment doses of Iodine-131 ranged from 9.8 to 22.0 mCi, with a mean dose of 16.6 3.7 mCi. Clinical Course All patients remained clinically stable throughout the study. No consistent change occurred in symptoms during the study period; nearly equal numbers of patients experienced worsened and improved symptoms, either during preparation for Iodine-131 therapy or after therapy. Changes in Thyroid Hormone Levels Figure 1 shows the short-term changes in thyroid hormones after antithyroid therapy was discontinued in the 17 patients receiving this treatment before administration of Iodine-131. Two patients were missing a single time point for which data were derived by regression analysis. Compared with baseline measurements, levels of each of the hormones measured increased significantly during the 5 days after antithyroid therapy was discontinued and before patients received Iodine-131 ablation therapy.

Thyroglobulin messenger ribonucleic acid levels in the peripheral blood of children with benign and malignant thyroid disease

Reverse transcriptase–PCR has identified thyroglobulin mRNA (Tg mRNA) in peripheral blood of normal adults and adults with thyroid cancer. However, no children were studied. The primary objective of this study was to determine whether whole blood Tg mRNA levels differ between benign and malignant thyroid disease in children. The secondary goals were to determine whether whole blood Tg mRNA levels vary with age or pubertal development among children with thyroid disease. Whole blood Tg mRNA levels were determined in 38 children (29 girls, nine boys; median age, 14.5 y; range, 4.8–20.4 y) with benign and malignant thyroid disease and correlated with diagnosis, age, pubertal status, thyroid size, and serum levels of free thyroxine, TSH, and Tg protein. Tg mRNA levels ranged from 3.3 to 104 pg Eq/μg total thyroid RNA (mean, 28 ± 20.2 pg Eq/μg total thyroid RNA) and were similar in benign and malignant disorders (p = 0.67). However, in children with previously treated papillary thyroid cancer, Tg mRNA levels directly correlated with total body 131I uptake (p = 0.026) and serum Tg protein (p = 0.037). There was no difference between boys and girls, and no change with pubertal maturation. In children with benign thyroid disease, Tg mRNA levels correlated with serum TSH (p = 0.031), but not with diagnosis, age, Tanner stage, or thyroid size. We conclude that Tg mRNA levels are similar in children with benign and malignant thyroid disease and unchanged by age or pubertal status, but correlated with tumor burden in previously treated papillary thyroid cancer.