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Robert C Smallridge

Publications and source records attributed to Robert C Smallridge.

10 recordsLinked to original sources
PubMed2006

Monitoring thyroglobulin in a sensitive immunoassay has comparable sensitivity to recombinant human tsh-stimulated thyroglobulin in follow-up of thyroid cancer patients.

CONTEXT: Most thyroglobulin (Tg) assays have a sensitivity of 0.5-1 ng/ml. A minority of patients with undetectable T4-suppressed Tg levels have a recombinant human TSH (rhTSH)-stimulated Tg above 2 ng/ml and identifiable residual disease. OBJECTIVE: The objective was to determine whether a Tg assay with improved sensitivity could eliminate the need for rhTSH stimulation when baseline Tg is below 0.1 ng/ml. DESIGN: A retrospective study of two academic endocrine practices was conducted. POPULATION: A total of 194 patients undergoing rhTSH stimulation participated in the study. RESULTS: Of the 80 patients with Tg below 0.1 ng/ml, two (2.5%) had rhTSH-stimulated Tg above 2 ng/ml. One other patient with stimulation to 0.3 ng/ml and negative 123I scan had an ultrasound-detected malignant lymph node resected. None had 131I/123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. If T4-suppressed Tg was 0.1-0.5 or 0.6-2.0 ng/ml, rhTSH Tg was above 2 ng/ml in 24.2 and 82.4%, respectively. CONCLUSIONS: Patients with differentiated thyroid carcinoma and a T4-suppressed serum Tg below 0.1 ng/ml rarely have a rhTSH-stimulated Tg above 2 ng/ml, and none of these patients had 131I or 123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. We recommend monitoring such patients with a T4-suppressed Tg level and periodic neck ultrasonography. An increase in T4-suppressed serum Tg to a detectable level or the appearance of abnormal lymph nodes by physical or ultrasound exam should prompt further investigation.

Adolescent↗
PubMed2006

Molecular diagnosis of a BRAF papillary thyroid carcinoma with multiple chromosome abnormalities and rare adrenal and hypothalamic metastases.

OBJECTIVE: Molecular characterization of thyroid tumors is rarely applied to patient management. Our aim was to demonstrate the application of molecular and cell biology to patient care. DESIGN: Clinical and molecular case study. MAIN OUTCOMES: A 57-year-old man with papillary thyroid carcinoma presented with adrenal and several other presumed metastases, pulmonary nodules, and mediastinal lymphadenopathy. Bronchial carcinoma was entertained for the pulmonary lesions because of a tobacco history. Mediastinal lymph node biopsy was nondiagnostic. Cells from the biopsy were grown in tissue culture and characterized by immunocytochemical (ICC), allele-specific polymerase chain reaction (PCR), reverse transcription (RT)-PCR, DNA sequencing, and cytogenetics. A panel of agents were tested the cells for tumoricidal activity. The cells expressed thyroid-specific markers [thyroid-stimulating hormone receptor (TSH-R), thyroglobulin (TG), sodium iodide symporter (NIS)] and markers [thyroid transcription factor-1 (TTF-1), cytokeratin-7, epidermal growth factor receptor (EGF-R)] present in the primary tumor and adrenal metastasis. The BRAF V600E mutation was detected. The karyotype was 44-48,XY, + der(1) t(1;9)(p13;p13),add(9)(p13),-17,-18, + 0-3mar[cp20]. Lovastatin, gefitinib, paclitaxel, depsipeptide, and 17-AAG inhibited the growth of the cultured cells. Combinations of two or three drugs produced additive or synergistic effects depending upon the combination. CONCLUSIONS: Unusual metastases may be associated with multiple molecular and cytogenetic abnormalities. Thus, molecular and cell-biological studies can allow otherwise difficult thyroid tumor diagnosis and may be used for targeted, individualized selection of potential treatments.

Adrenal Gland Neoplasms↗
PubMed2006

Prevalence of postpartum thyroid dysfunction: a quantitative review.

Estimates of the prevalence of postpartum thyroid dysfunction (PPTD) vary widely because of variations in study design, populations, and duration of screening. Our objective was to estimate the prevalence of PPTD among general and high-risk women, across geographical regions and in women with antithyroid peroxidase antibodies (TPOAbs). We conducted a systematic review and pooled analysis of the published literature (1975-2004), simultaneously accounting for sample size, study quality, percentage follow-up, and duration of screening. Data sources were MEDLINE and the bibliography of candidate studies. Two reviewers independently extracted data. Of 587 studies identified, 21 articles (8081 subjects) met the study criteria. The pooled prevalence of PPTD, defined as an abnormal thyroid-stimulating hormone (TSH) level, for the general population was 8.1% (95% confidence interval [CI] 6.6%-10.0%). The risk ratios for the development of PPTD among women with TPOAbs compared to women without TPOAbs ranged between 4 and 97 with a pooled risk ratio of 5.7 (95% CI: 5.3-6.1). Global prevalence varied from 4.4% in Asia to 5.7% in the United States. Prevalence among women with type 1 diabetes mellitus was 19.6% (95% CI 19.5%-19.7%). PPTD occurs in 1 of 12 women in the general population worldwide, 1 of 17 women in the United States and is 5.7 times more likely to occur in women with TPOAbs. The high prevalence may warrant routine screening TPOAbs, but the benefits, cost, and risks related to subsequent therapy must be weighed.

Databases, Bibliographic↗
PubMed2005

Thyroid function inside and outside of pregnancy: what do we know and what don't we know?

A workshop entitled, "The Impact of Maternal Thyroid Diseases on the Developing Fetus: Implications for Diagnosis, Treatment, and Screening," was held in Atlanta, Georgia, January 12-13, 2004. This paper reports on the session that examined the prevalence of thyroid dysfunction in reproductive-age women and the factors associated with abnormal function. For this session the following papers were presented: "Thyroidal Economy in the Pregnant State: An Overview," "The Prevalence of Thyroid Dysfunction in Reproductive-Age Women- United States," and "Risk Factors for Thyroid Disease: Autoimmunity and Other Conditions." These presentations were formally discussed by invited respondents and by others in attendance. Salient points from this session about which there was agreement include the following: physiologic changes associated with pregnancy require an increased availability of thyroid hormones by 40% to 100% in order to meet the needs of mother and fetus during pregnancy. In the first trimester of gestation the fetus is wholly dependent on thyroxine from the mother for normal neurologic development. For the maternal thyroid gland to meet the demands of pregnancy it must be present, disease-free, and capable of responding with adequate stores of iodine. Thyroid autoimmunity is common and may contribute to miscarriages, as well as to hypothyroidism. With sufficient iodine nutrition, autoimmune thyroid disease (AITD) is the most common cause of hypothyroidism. As of 1994, iodine nutrition in the United States appeared to be adequate, but its continued monitoring is essential.

Age Distribution↗
PubMed2005

2004 where do we go from here?--Summary of working group discussions on thyroid function and gestational outcomes.

A workshop entitled, "The Impact of Maternal Thyroid Diseases on the Developing Fetus: Implications for Diagnosis, Treatment, and Screening," was held in Atlanta, Georgia, January 12-13, 2004. This paper reports points of agreement among the attendees based on the scientific rigor of material presented. At the end of the workshop, participants were divided into four smaller groups to discuss and determine areas of agreement on issues associated with thyroid insufficiency, identify research needs and gaps, and recommend research strategies and policy needs. Discussion included: problems for the mother and the pregnancy; neuropsychological/developmental performance in offspring of women with thyroid deficiency; issues of diagnosis and treatment for the pregnant women with overt and subclinical hypothyroidism; the issues involved with screening women who are pregnant or who are planning pregnancy; and the status of Iodine Nutrition in the United States. The group then identified research needs and gaps. The results of these discussions are outlined in the paper with recommended research strategies and public health action.

Female↗
PubMed2005

Racial comparisons of thyroid function and autoimmunity during pregnancy and the postpartum period.

OBJECTIVE: To evaluate thyroid function and the prevalence of thyroid peroxidase (TPO) antibody and autoimmunity in African-American and white women during pregnancy and the postpartum period. METHODS: Five hundred eighty-nine women were evaluated prospectively. Serum thyroid-stimulating hormone (TSH), free thyroxine (T4), and TPO, Ro, and La antibodies were obtained during pregnancy, at delivery, and postpartum. Levels of hCG were determined during pregnancy. Urinary iodine levels were evaluated in the third trimester in another group of women. All TPO antibody-positive patients were to be followed up at 3 and 6 months postpartum. RESULTS: African-American women had lower TSH values than white women at all times. Thyroid-stimulating hormone increased, and free T4 decreased from the first to third trimester of pregnancy for both groups. African Americans had higher hCG levels than whites in the first trimester but not in the third trimester. There was no difference in urine iodine excretion between African-American and white women. Finally, there was no difference in TPO antibody seropositivity between African-American and white women. Overall, 5 patients (0.8%) were diagnosed with subclinical hypothyroidism during pregnancy. CONCLUSION: Fluctuations in TSH and free T4 during pregnancy parallel reported obstetric values. African Americans demonstrated consistently lower TSH levels than whites. These differences were unexplained by racial differences in either TPO antibody seropositivity, iodine status, or chorionic gonadotropin levels.

Adult↗
PubMed2004

Human telomerase reverse transcriptase gene expression and the surgical management of suspicious thyroid tumors.

PURPOSE: Patients with a preoperative cytologic diagnosis of a suspicious thyroid nodule present a therapeutic dilemma because surgery differs for benign and malignant lesions. To address this issue, several molecular markers, including human telomerase reverse transcriptase (TERT), have been tested as markers of thyroid cancer. Because most studies select cases falling into well-defined categories to test new markers, they may overestimate their discriminatory power when applied to samples that are difficult to classify. Fine-needle aspirates (FNAs) of the thyroid with indeterminate cytology are an example of such cases. EXPERIMENTAL DESIGN: We examined whether assessing TERT mRNA by reverse transcription-PCR could have improved the surgical management in a cohort of 100 patients undergoing thyroidectomy for indeterminate FNA results. RESULTS: Ninety percent of 48 cancers were TERT positive, as were 35% of 52 benign lesions. When 10 cases with concomitant lymphocytic thyroiditis were excluded, the overall sensitivity of TERT was 91% (95% confidence interval, 80-98%) and specificity was 79% (64-90%). No clinical or tumor variable contributed to the predictive ability of TERT except for tumor size, which added only marginally. Basing the surgical approach on the TERT assay alone would have reduced lobectomies performed for malignant disease from 11 to 4 cases and reduced total thyroidectomies for benign lesions from to 15 to 9, an overall 50% reduction in suboptimal treatment. CONCLUSIONS: The overall performance of preoperative differential diagnosis for thyroid tumors with indeterminate FNA results can be substantially improved by the inclusion of molecular markers such as TERT.

Adenocarcinoma, Follicular↗
PubMed2004

Targeting the ERK pathway: novel therapeutics for thyroid cancer.

Over the past two decades significant progress has been made in elucidating the pathogenesis of thyroid cancer. The ongoing identification of mutations in cellular signaling pathways has revolutionized the field of thyroid cancer biology and has led to the development of novel new therapeutic agents. One of the signaling cascades implicated in the oncogenic process is the ERK pathway that normally functions to transmit mitogenic signals from the cell membrane to the nucleus. Genetic alterations of key components of this cascade, namely RET, Ras and Raf, are thought to result in constitutive activation of the pathway and subsequent thyroid tumorigenesis. Targeting of these components with pharmaceutical agents holds the potential of providing newer and more effective treatment modalities for thyroid cancer. Several such drugs are currently being developed to inhibit RET, Ras, Raf, as well as other factors impacted by the ERK pathway. These include a vast array of agents such as antisense compounds, small molecule inhibitors as well as inhibitors of farnesyl transferase, heat shock proteins, matrix metalloproteinases and histone deacetylases. Some of these drugs have already entered preclinical and clinical testing with promising anti-tumor effects. These as well as even newer agents may offer exciting possibilities for the future treatment of thyroid cancer.

Animals↗
PubMedDate not supplied

Effect of thyroid hormone replacement on methionine-stimulated homocysteine levels in patients with subclinical hypothyroidism: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine whether treatment of subclinical hypothyroidism with levothyroxine would improve homocysteine metabolism. METHODS: Twenty-four patients with subclinical hypothyroidism who had thyrotropin (thyroid-stimulating hormone or TSH) levels between 5 and 10 microIU/mL and normal free thyroxine concentrations were recruited from a primary care clinic and were randomized to receive levothyroxine (N = 12) or placebo (N = 12) for a period of 6 months in a double-blind, placebo-controlled study. Homocysteine was measured during fasting and after methionine challenge at the beginning and the end of the study in all patients treated with levothyroxine or placebo. RESULTS: The 12 patients treated with levothyroxine had normal TSH levels at the end of the study, with a median value of 1.8 microIU/mL. The 12 patients receiving placebo had a median TSH of 6.0 microIU/mL after the 6-month study period. The ratio of fasting homocysteine at 6 months in comparison with baseline was 1.16 (95% confidence interval, 0.90 to 1.63) for the levothyroxine-treated group and 1.00 (0.88 to 1.29) for the placebo group (P = 0.95). The ratio of post-methionine homocysteine at 6 months in comparison with baseline was 1.00 (95% confidence interval, 0.92 to 1.35) for the levothyroxine-treated group and 0.89 (0.68 to 1.05) for the placebo group (P = 0.081). CONCLUSION: In this study, levothyroxine treatment of patients with subclinical hypothyroidism did not alter homocysteine levels in the fasting or post-methionine states.

Adult↗