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Shireen Fatemi

Bio: Shireen Fatemi is an academic researcher from Kaiser Permanente. The author has contributed to research in topics: Thyroglobulin & Thyroid cancer. The author has an hindex of 12, co-authored 14 publications receiving 1655 citations. Previous affiliations of Shireen Fatemi include University of Southern California.

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Journal ArticleDOI
TL;DR: The RIA method used in this study provided more clinically appropriate serum Tg values in the group of TgAb-positive patients with metastatic DTC and may be an additional clinically useful tumor marker parameter for following T gAb- positive patients.
Abstract: The prevalence of circulating thyroid autoantibodies (TgAb or antithyroid peroxidase) was increased nearly 3-fold in patients with differentiated thyroid cancers (DTC) compared with the general population (40% vs. 14%, respectively). Serum TgAb (with or without antithyroid peroxidase) was present in 25% of DTC patients and 10% of the general population. Serial postsurgical serum TgAb and serum Tg patterns correlated with the presence or absence of disease. Measurements of serum Tg were made in 87 TgAb-positive sera by a RIA and two immunometric assay (IMA) methods to study TgAb interference. TgAb interference, defined as a significant intermethod discordance (>41.7% coefficient of variation) between the Tg RIA and Tg IMA values relative to TgAb-negative sera, was found in 69% of the TgAb-positive sera. TgAb interference was characterized by higher Tg RIA vs. IMA values and was, in general, more frequent and severe in sera containing high TgAb concentrations. However, some sera displayed marked interference when serum TgAb was low (1-2 IU/mL), whereas other sera with very high TgAb values (>1000 IU/mL) displayed no interference. An agglutination method was found to be too insensitive to detect low TgAb concentrations (1-10 IU/mL) causing interference. Exogenous Tg recovery tests were an unreliable means for detecting TgAb interference. Specifically, the exogenous Tg recovered varied with the type and amount of Tg added and the duration of incubation employed. Further, recoveries of more than 80% were found for some sera displaying gross serum RIA/IMA discordances. The measurement of serum Tg in DTC patients with circulating TgAb is currently problematic. It is important to use a Tg method that provides measurements that are concordant with tumor status. IMA methods are prone to underestimate serum when TgAb is present, increasing the risk that persistent or metastatic DTC will be missed. The RIA method used in this study provided more clinically appropriate serum Tg values in the group of TgAb-positive patients with metastatic DTC. Furthermore, as serial serum TgAb measurements paralleled serial serum Tg RIA measurements, TgAb concentrations may be an additional clinically useful tumor marker parameter for following TgAb-positive patients. Disparities between serial serum Tg and TgAb measurements might alert the physician to the possibility of TgAb interference with the serum Tg measurement and prompt a more cautious use of such data for clinical decision-making.

515 citations

Journal ArticleDOI
TL;DR: Specificity differences, suboptimal sensitivity, hook effects, and an inability to reliably detect interfering T gAb compromise the clinical utility of current Tg and TgAb methods.
Abstract: Context: Changes in thyroglobulin (Tg) and/or Tg antibody (TgAb) methods can disrupt the serial monitoring of differentiated thyroid carcinoma (DTC) patients. Objective: This study compared Tg measurements made in TgAb-negative and TgAb-positive sera using four RIA and 10 immunometric assay (IMA) methods. Design: TgAb detection using a panel of 12 direct methods was contrasted with four Tg recovery tests. Sera from 110 normal euthyroid subjects (68 TgAb negative/42 TgAb positive) and 131 TgAb-negative DTC patients had Tg and/or TgAb analyses made by 10 laboratories in four countries. Euthyroid controls were used to compare Tg and TgAb ranges, sensitivities, and TgAb interference, whereas DTC patients were used to study Tg assay specificities, hook effects, and the influence of high Tg levels on TgAb measurements. Results: Tg methods had high between-method variability [47 ± 3% (±sem)] that was only marginally reduced by CRM-457 standardization (37 ± 3%). All methods had suboptimal sensitivity, and some fa...

251 citations

Journal ArticleDOI
01 May 1999-Thyroid
TL;DR: Serum Tg measurements should be interpreted relative to the TSH status of the patient, and the optimal degree of TSH suppression for a patient should be based on clinical judgment, relative to tumor staging and the risks from iatrogenic hyperthyroidism.
Abstract: Thyroglobulin (Tg) measurement is primarily used to monitor patients with differentiated thyroid carcinoma (DTC) for tumor recurrence. Serum Tg levels principally integrate 3 variables: the mass of thyroid tissue present (benign or neoplastic); the degree of thyrotropin (TSH) receptor stimulation and tumor's intrinsic ability to synthesize and secrete Tg--a factor that needs to be assessed by a preoperative serum Tg determination. Serum Tg measurements should be interpreted relative to the TSH status of the patient. When TSH is low (on levothyroxine [LT4] therapy) basal serum Tg may be undetectable and recombinant human thyrotropin (rhTSH) administration may be needed to increase serum Tg into the measureable range. The Tg fold response to rhTSH (rhTSH-stimulated Tg/basal Tg) is an index of the tumor's sensitivity to TSH. Normal thyroid remnant and well-differentiated thyroid tumors display a greater (>10-fold) serum Tg response to TSH stimulation compared with less well-differentiated tumors (<3-fold). The factors influencing the response include the magnitude and chronicity of the serum TSH elevation, the mass of thyroid tissue and the TSH receptor status of the tumor. Technical problems still compromise the clinical utility of serum Tg measurement. Thyroglobulin autoantibodies are present in approximately 20% of all DTC patients and cause either underestimation or overestimation of serum Tg measurements made by immunometric assay (IMA) and radioimmunoassay (RIA) methods, respectively. Other technical problems include poor interassay precision, "hook" effects (IMA methods), intermethod standardization differences, and suboptimal sensitivity for detecting small amounts of tumor during TSH suppression. When TSH is suppressed, the basal serum Tg provides an integrated index of thyroid tissue mass and its capability to secrete Tg. Serial measurements of basal Tg concentrations can be used to monitor tumor progression or regression. The development of a low (<1 ng/mL) serum Tg (on LT4 therapy) by the second postoperative year signifies a low 5-year recurrence risk whereas a rising serum Tg in the face of TSH suppression is an abnormal response consistent with recurrence. The optimal degree of TSH suppression for a patient should be based on clinical judgment, relative to tumor staging and the risks from iatrogenic hyperthyroidism. Despite current technical limitations, serum Tg measurement is the cornerstone of long-term monitoring for most DTC patients. For optimal use of serum Tg, it is necessary to understand the pathophysiology of Tg secretion, the limitations of Tg methods and the use of rhTSH to overcome the insensitivity of current Tg methods.

198 citations

Journal ArticleDOI
TL;DR: The results demonstrate that mild Mg depletion can impair mineral homeostasis and may be implicated as risk factor for osteoporosis in disorders such as chronic alcoholism and diabetes mellitus, in which Mg deficiency and osteopsorosis are both common.
Abstract: Magnesium (Mg) deficiency in man may result in hypocalcemia, impaired PTH secretion, and low serum concentrations of 1,25-dihydroxyvitamin D [1,25-(OH)2D]. To determine whether these changes are due to selective Mg depletion, we studied 26 normal subjects before and after a 3-week low Mg (less than 1 meq/day) diet. This diet induced Mg deficiency, as demonstrated by a fall in pre- to postdiet serum Mg levels from 0.80 +/- 0.01 to 0.61 +/- 0.02 mmol/L (P less than 0.001), an increase in Mg retention from 11 +/- 4% to 62 +/- 4% (P less than 0.001), and a fall in red blood cell free Mg2+ from 205 +/- 10 to 162 +/- 7 microM (P less than 0.001). Serum calcium (Ca) fell significantly from 2.36 +/- 0.02 to 2.31 +/- 0.03 mmol/L (P less than 0.05), and serum 1,25-(OH)2D fell from 55 +/- 4 to 43 +/- 3 pmol/L (P less than 0.05). PTH secretion was impaired, as demonstrated by a fall or no change in serum PTH in 20 of 26 subjects despite a fall in the serum Ca and Mg. In addition, an iv injection of Mg in eight subjects after the diet resulted in a significant rise in PTH from 15 +/- 2 to 19 +/- 2 ng/L (P less than 0.01), whereas a similar injection given to six of the subjects before the diet resulted in a significant fall from 28 +/- 5 to 13 +/- 3 ng/L (P less than 0.001). The fall in serum 1,25-(OH)2D may be due to both the decrease in PTH secretion and a renal resistance to PTH. PTH resistance was suggested, as no increase in serum 1,25-(OH)2D was observed in the six subjects in which the PTH concentration rose by mean of 68% after the diet. Also, the rise in serum 1,25-(OH)2D after a 6-h human PTH-(1-34) infusion was significantly less after Mg deprivation. The results demonstrate that mild Mg depletion can impair mineral homeostasis and may be implicated as risk factor for osteoporosis in disorders such as chronic alcoholism and diabetes mellitus, in which Mg deficiency and osteoporosis are both common.

186 citations

Journal ArticleDOI
TL;DR: TgAb methods were too qualitatively and quantitatively variable to establish conversion factors that would allow a change in method without disrupting serial TgAb monitoring, and it is recommended that assay AS limits be used to detect Tg Ab to minimize false-negative misclassifications.
Abstract: A comparison of four thyroglobulin autoantibody methods found that the use of manufacturer-recommended cut-offs was unreliable for detecting interfering thyroglobulin autoantibodies.

143 citations


Cited by
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01 Nov 2009-Thyroid
TL;DR: Evidence-based recommendations are developed to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer and represent, in the authors' opinion, contemporary optimal care for patients with these disorders.
Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

10,501 citations

Journal ArticleDOI
04 Nov 2009-Thyroid
TL;DR: Evidence-based recommendations in response to the 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 represent, in the authors' opinion, contemporary optimal care for patients with these disorders.
Abstract: Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's 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. Methods: Relevant 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. Results: The 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, a...

7,525 citations

01 Jan 2014
TL;DR: Lymphedema is a common complication after treatment for breast cancer and factors associated with increased risk of lymphedEMA include extent of axillary surgery, axillary radiation, infection, and patient obesity.

1,988 citations

Journal ArticleDOI
TL;DR: The approach to treatment of papillary and follicular cancer is usually very similar, and DTC is more likely to be completely resected and ablated with iodine-131 (I), an approach that has become more popular in the past several decades when discovered at an early stage.
Abstract: Papillary and follicular thyroid cancer, together referred to as differentiated thyroid cancer (DTC), is usually curable when discovered at an early stage. Its management, however, is often a challenge because there have been no prospective randomized trials of treatment and none are likely to be done, given its typically prolonged course and relative infrequency. Instead, clinicians rely on large patient cohort studies in which therapy has not been randomized, leading to some disagreement about management. Nonetheless, thyroid cancer mortality rates have fallen significantly (20%, P , 0.05) in the United States between 1973 and 1996 (1), almost certainly due to early diagnosis and effective treatment of DTC, which comprises 90% of thyroid cancers and 70% of the thyroid cancer deaths (2). The decline in mortality, however, occurred only in women (1), perhaps because they undergo routine medical examinations more than men, in whom thyroid cancer is typically discovered at an older age (1). DTC is more likely to be completely resected and ablated with iodine-131 (I), an approach that has become more popular in the past several decades, when discovered at an early stage (3, 4). Much of the following discussion refers to treatment of DTC because the approach to treatment of papillary and follicular cancer is usually very similar.

1,302 citations