Stephanie L. Lee

Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer

BACKGROUNDnThyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Associations guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines.nnnMETHODSnRelevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force.nnnRESULTSnThe revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, and suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using ultrasound and serum thyroglobulin as well as those related to management of recurrent and metastatic disease.nnnCONCLUSIONSnWe created evidence-based recommendations in response to our appointment as an independent task force by the American Thyroid Association to assist in the clinical management of patients with thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders.

A Comparison of the Frequency of Hepatitis-B Antigen and Antibody in Hospital and Nonhospital Personnel

Abstract The frequency of hepatitis B antigen and antibody among health-care personnel was compared with that among matched controls with no exposure to patients or blood products. The frequency of the antigen in personnel and controls did not differ significantly. However, the causes may have been different, the antigen correlating with past transfusion in the controls but not in personnel. A history of past hepatitis did not correlate with antigenemia in either population, impugning the validity of hepatitis history as a cause for donor exclusion. Antibody was twice as frequent in health personnel, indicating increased exposure to the antigen; antibody correlated with past hepatitis in personnel, but not in controls, suggesting that overt hepatitis B infection is more common among health personnel. The frequency of hepatitis B antigen among health workers is not currently alarming, but the risk that each antigen-positive health worker represents to his patients remains unknown. (N Engl J Med 289:647–651...

Controlled Studies in Clinical Cancer Research

Abstract A review of abstracts and papers reporting clinical trials of new anticancer agents reveals that only a small percentage have been controlled. Arguments against employing randomized controls in such trials are understandable but hardly valid at the present stage in cancer research. Randomization of drugs tested or dosage regimens at the earliest stages of clinical use is needed to evaluate relative therapeutic efficacy and toxicity. Potent ethical arguments also require that when a new drug is tried, patients should be given a 50–50 chance of receiving the conceivably better standard therapy. An important and subtle consideration, that of how long to continue a controlled trial, requires continued development of the study-design process and new uses of peer review.

Comparative Outcomes of T-Cell–Depleted and Non–T-Cell–Depleted Allogeneic Bone Marrow Transplantation for Chronic Myelogenous Leukemia: Impact of Donor Lymphocyte Infusion

PURPOSEnDonor lymphocyte infusion (DLI) can restore complete remission in patients with chronic myelogenous leukemia (CML) who have relapsed after T-cell-depleted (TCD) allogeneic bone marrow transplantation (BMT). The existence of salvage treatment for patients with DLI after TCD allogeneic BMT prompted an evaluation of overall outcome after CD6+ -TCD allogeneic BMT for patients treated during the time when DLI has been available.nnnPATIENTS AND METHODSnWe performed a retrospective analysis of outcomes of 46 patients who underwent TCD allogeneic BMT for stable-phase CML and compared these outcomes with those of 40 patients who underwent non-TCD allogeneic BMT. All subjects were patients at one of two neighboring institutions during a period when DLI was available. All patients received marrow from HLA-identical sibling donors, underwent similar myeloablative regimens, and had similar pretreatment characteristics.nnnRESULTSnAfter BMT, the TCD group had a lower incidence of grade 2 to 4 acute (15% v 37%, P = .026) and chronic graft-versus-host disease (GVHD) (18% v 42%, P = .024) than did the non-TCD group. The 1-year treatment-related mortality rates for the TCD group and the non-TCD group were 13% and 29%, respectively (P = .07). The estimated 3-year probability of relapse (cytogenetic or hematologic) was higher for patients in the TCD group than for patients in the non-TCD group (62% v 24%, P = .0003). Twenty-three patients (20 in the TCD group and three in the non-TCD group) received and were assessable for response to DLI. After DLI, 17 of 20 patients in the TCD group and two of three patients in the non-TCD group achieved complete remission. Donor lymphocyte infusion induced GVHD in nine of 23 patients. Thirty (65%) of 46 patients in the TCD group and 27 (69%) of 39 assessable patients in the non-TCD group remained alive without evidence of disease. The estimated 3-year overall survival rates were similar for the TCD group and the non-TCD group (72% v 68%, respectively; P = .38). At last follow-up, there was no difference in the overall prevalence of GVHD or the proportion of patients requiring immunosuppressive agents between groups.nnnCONCLUSIONnThese results suggest that the combination of T-cell depletion and post-BMT DLI is a viable treatment option for patients undergoing allogeneic BMT for CML and should be prospectively compared with traditional forms of GVHD prophylaxis.

Neonatal Thyroxine, Maternal Thyroid Function, and Child Cognition

CONTEXTnThyroid hormone is essential for normal brain development. Limited data are available regarding whether thyroid function in neonates influences later cognitive development.nnnOBJECTIVEnOur objective was to study associations of newborn T4 levels with maternal thyroid function and childhood cognition.nnnDESIGN AND SETTINGnWe studied participants in Project Viva, a cohort study in Massachusetts.nnnPARTICIPANTSnWe studied a total of 500 children born 1999--2003 at 34 wk or more.nnnMAIN OUTCOME MEASURESnWe determined cognitive test scores at ages 6 months and 3 yr.nnnRESULTSnMean newborn T4 at a mean age of 1.94 d was 17.6 (sd 4.0) microg/dl, and levels were higher in girls [1.07 microg/dl; 95% confidence interval (CI) 0.38, 1.76] and infants born after longer gestation (0.42 microg/dl; 95% CI 0.17, 0.67 per wk). Newborn T4 levels were not associated with maternal T4, TSH, or thyroid peroxidase antibody levels. On multivariable linear regression analysis, adjusting for maternal and child characteristics, higher newborn T4 was unexpectedly associated with poorer scores on the visual recognition memory test among infants at age 6 months (-0.5; 95% CI -0.9, -0.2), but not with scores at age 3 yr on either the Peabody Picture Vocabulary Test (0.2; 95% CI -0.1, 0.5) or the Wide Range Assessment of Visual Motor Abilities (0.1; 95% CI -0.2, 0.3). Maternal thyroid function test results were not associated with child cognitive test scores.nnnCONCLUSIONSnNewborn T4 concentrations within a normal physiological reference range are not associated with maternal thyroid function and do not predict cognitive outcome in a population living in an iodine-sufficient area.

ASSOCIATION OF FIRST-TRIMESTER THYROID FUNCTION TEST VALUES WITH THYROPEROXIDASE ANTIBODY STATUS, SMOKING, AND MULTIVITAMIN USE

OBJECTIVEnTo determine first-trimester thyroid function values and associations with thyroperoxidase antibody (TPO-Ab) status, smoking, emesis, and iodine-containing multivitamin use.nnnMETHODSnWe collected information by interview, questionnaire, and blood draw at the initial obstetric visit in 668 pregnant women without known thyroid disease. We compared thyroid-stimulating hormone (TSH), total thyroxine (T4), and free T4 index (FT4I) values by TPO-Ab status. Multiple regression was used to identify characteristics associated with thyroid function values.nnnRESULTSnThe following median (range containing 95% of the data points) thyroid function test values were obtained in 585 TPO-Ab-negative women: TSH, 1.1 mIU/L (0.04-3.6); FT4I, 2.1 (1.5-2.9); and T4, 9.9 microg/dL (7.0-14.0). The following median (range containing 95% of the data points) thyroid function test values were obtained in 83 TPO-Ab-positive women: TSH, 1.8 mIU/L (0.3-6.4) (P<.001); FT4I, 2.0 (1.4-2.7) (P = .06); and T4, 9.3 microg/dL (6.8-13.0) (P = .03) (P values denote statistically significant differences between TPO-Ab-positive and negative participants). Among TPO-Ab-negative participants, TSH level was not associated with use of iodine-containing multivitamins, smoking, or race. TSH increased 0.03 mIU/L for every year of maternal age (P = .03) and decreased by 0.3 mIU/L for every increase in parity (P<.001). T4 decreased 0.04 microg/dL for every year of maternal age (P = .04). Mean FT4I was 2.05 in smokers and 2.20 in nonsmokers (P<.01). There were no relationships between T4 or FT4I and parity, race, or iodine-containing multivitamin use.nnnCONCLUSIONnTPO-Ab status of pregnant women should be considered when constructing trimester-specific reference ranges because elevated serum TPO-Ab levels are associated with higher TSH and lower T4 values.

CD6+ Donor Marrow T-Cell Depletion as the Sole Form of Graft-Versus-Host Disease Prophylaxis in Patients Undergoing Allogeneic Bone Marrow Transplant From Unrelated Donors

PURPOSEnThe role of donor marrow T-cell depletion (TCD) in preventing graft-versus-host disease (GVHD) after transplantation of unrelated allogeneic marrow remains undefined. Because different TCD methodologies differ in the degree and specificity with which T cells are removed, it is likely that transplant outcomes would depend on which technique is used. Herein, we report results in the first 48 recipients of unrelated marrow using CD6+ TCD as the sole form of GVHD prophylaxis.nnnPATIENTS AND METHODSnMedian age of patients was 46 years (20 to 58 years). Donors were matched at A/B HLA loci. Ablation consisted of cyclophosphamide and fractionated total-body irradiation (TBI; 14 Gy). To facilitate engraftment, patients also received 7.5 Gy (22 patients) [corrected] or 4.5 Gy (26 patients) [corrected] of total lymphoid irradiation (TLI) before admission. No additional immune suppressive prophylaxis was administered. Granulocyte colony-stimulating factor was administered daily from day +1 to engraftment.nnnRESULTSnAll 48 patients demonstrated neutrophil engraftment. An absolute neutrophil count of 500 x 10(6)/L was achieved at a median of 12 days (range, 9 to 23 days). There were no cases of late graft failure. The number of CD34+ cells infused/kg was associated with speed of platelet and neutrophil recovery. The dose of TLI did not influence engraftment. Grades 2-4 acute GVHD occurred in 42% of patients (95% confidence interval [CI], 0.28 to 0.57). Mortality at day 100 was 19%. There have been only five relapses. Estimated 2-year survival was 44% (95% CI, 0.28 to 0.59) for the entire group, 58% for patients less than 50 years of age. In multivariable analysis, age less than 50 years (P =.002), cytomegalovirus seronegative status (P =.04), and early disease status at bone marrow transplant (P =.05) were associated with superior survival.nnnCONCLUSIONnCD6+ TCD does not impede engraftment of unrelated bone marrow after low-dose TLI, cyclophosphamide, and TBI. CD6+ TCD as the sole form of GVHD prophylaxis results in an incidence of GVHD that compares favorably with many adult studies of unrelated transplantation using unmanipulated marrow and immune-suppressive medications, especially in light of the median age of our patients (46 years). Although event-free survival in patients less than 50 years of age is very encouraging, older patients experience frequent transplantation-related complications despite TCD.

Radioactive iodine therapy.

Purpose of reviewReview of the management decisions that must be made by the endocrinologist during the use of radioactive iodine (RAI) therapy of hyperthyroidism and differentiated thyroid cancer. Recent findingsSince the 1940s radioactive 131I (RAI) therapy has been a major component of the treatment of hyperthyroidism and differentiated thyroid cancer. RAI is the most common definitive treatment of hyperthyroidism. Pretherapy decisions including use of antithyroid medication and low-iodine diet will be discussed with the relevant supportive literature. The method of semi-quantitative calculation used for RAI treatment of hyperthyroidism will be described. Evidence-based guideline for the management of differentiated thyroid cancer by the American Thyroid Association, new drug development and recent randomized controlled trials have changed current practice of how RAI is used for remnant ablation and adjuvant therapy of differentiated thyroid cancer. SummaryRAI is a common tool for the endocrinologist in the management of hyperthyroidism and differentiated thyroid cancer. Review of the management decisions and practice of RAI therapy will educate the endocrinologist of the literature supporting current RAI use in hyperthyroidism and new developments in limiting the radiation exposure to the patients with differentiated thyroid cancer.

Prediction of hypocalcemia after using 1- to 6-hour postoperative parathyroid hormone and calcium levels:an analysis of pooled individual patient data from 3 observational studies

Parathyroid hormone (PTH) levels up to 6 hours postthyroidectomy have been shown to have excellent predictive power in determining hypocalcemia. In this study, we investigate the usefulness of combining calcium and PTH to increase the predictive power.

Initial Staging of Differentiated Thyroid Carcinoma: Continued Utility of Posttherapy 131I Whole-Body Scintigraphy

PURPOSEnTo retrospectively compare pretherapy iodine 123 ((123)I) and posttherapy iodine 131 ((131)I) sodium iodide whole-body scintigraphy of patients with newly diagnosed differentiated thyroid cancer to determine if there is significant and clinically relevant discordance of nonphysiologic iodide-avid foci (IAFs) between the two examinations.nnnMATERIALS AND METHODSnThis study was approved by the Institutional Review Board, the requirement for informed consent was waived, and the study complied with HIPAA. The authors identified 108 patients (88 women, 20 men; age range, 16-86 years; mean, 47.5 years; 45 patients younger than 45 years, 63 patients 45 years and older) who previously had undergone total or near-total thyroidectomy for differentiated thyroid carcinoma. Each patient had undergone a pretherapy ( 123)I whole-body scan followed by a posttherapy ( 131)I whole-body scan. The number and location of IAFs were recorded on both scans. Data were compared by using a Wilcoxon signed rank test for paired data and assessed clinical relevance based on changes in tumor staging.nnnRESULTSnPosttherapy ( 131)I whole-body scans revealed additional IAFs outside the thyroid bed not detected on pretherapy ( 123)I scans in 21 (19%, P < .001) of 108 patients. Nineteen (90%) of these 21 had IAFs in new locations (P < .001), with tumor upstaging of 11 (59%, 10% of total) of those 19 patients; six (55%, 6% of total) of those 11 had scintigraphic patterns consistent with unsuspected metastatic disease. Concordant scintigraphic patterns were observed in 87 (81%) of 108.nnnCONCLUSIONnIn patients with newly diagnosed differentiated thyroid cancer who had undergone thyroidectomy and ( 131)I ablation, posttherapy ( 131)I whole-body scintigraphy revealed new IAFs in 18% and clinical upstaging occurred in 10% of patients compared with pretherapy ( 123)I whole-body scintigraphy. Therefore, posttherapy ( 131)I whole-body scintigraphy provides incremental clinically relevant information as it helps to establish the true extent of IAFs and may contribute to altering of staging.