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Gilbert H Daniels

Publications and source records attributed to Gilbert H Daniels.

10 recordsLinked to original sources

A comparison of short-term changes in health-related quality of life in thyroid carcinoma patients undergoing diagnostic evaluation with recombinant human thyrotropin compared with thyroid hormone withdrawal.

CONTEXT: Thyroid carcinoma requires lifelong monitoring with serum thyroglobulin, radioactive iodine whole body scanning, and other imaging modalities. Levothyroxine (L-T4) withdrawal for thyroglobulin measurement and whole body scanning increases these tests' sensitivities but causes hypothyroidism. Recombinant human TSH (rhTSH) enables testing without L-T4 withdrawal. OBJECTIVE: Our objective was to examine the impact of short-term hypothyroidism on the health-related quality of life (HRQOL) of patients after rhTSH vs. L-T4 withdrawal. DESIGN, SETTING, AND PATIENTS: In this multicenter study, the SF-36 Health Survey was administered to 228 patients at three time points: on L-T4, after rhTSH, and after L-T4 withdrawal. INTERVENTIONS: INTERVENTIONS included administration of rhTSH on L-T4 and withdrawal from thyroid hormone. MAIN OUTCOME MEASURES: Mean SF-36 scores were compared during the two interventions and with the U.S. general population and patients with heart failure, depression, and migraine headache. RESULTS: Patients had SF-36 scores at or above the norm for the general U.S. population in six of eight domains at baseline on L-T4 and in seven of eight domains after rhTSH. Patients' scores declined significantly in all eight domains after L-T4 withdrawal when compared with the other two periods (P < 0.0001). Patients' HRQOL scores while on L-T4 and after rhTSH were at or above those for patients with heart failure, depression, and migraine in all eight domains. After L-T4 withdrawal, patients' HRQOL scores were significantly below congestive heart failure, depression, and migraine headache norms in six, three, and six of the eight domains, respectively. CONCLUSIONS: Short-term hypothyroidism after L-T4 withdrawal is associated with a significant decline in quality of life that is abrogated by rhTSH use.

Female↗

Elevation of thyroid cancer risk among cutaneous melanoma survivors.

Recent molecular studies have identified recurrent BRAF mutations in both cutaneous melanoma and thyroid malignancies. This relatively selective shared genetic vulnerability raises the possibility that these 2 tumors are connected through a common undisclosed pathogenic mechanism. To assess for possible associations between these 2 genetically related tumors at the population level, we calculated standardized incidence ratios (SIRs) for thyroid cancer (TC) among cutaneous melanoma (CM) survivors and CM among TC survivors using the National Cancer Institute's Surveillance, Epidemiology and End Result (SEER) database. Between 1973 and 2000, there were 73,274 and 27,138 cases of CM and TC cases, respectively. Overall, we found a 2.17-fold increase (p < 0.0000001) in the risk of TC after a diagnosis of CM. This augmented risk of TC is somewhat higher for males, for those diagnosed more recently and for the first 3 years after the CM diagnosis. We also detected a considerably smaller and borderline significant increased risk of CM (25%, p = 0.063) among the post-TC survivors. Of note, TC patients who received radiation therapy had a 57% increased risk of a subsequent CM (p = 0.034). Our study documents a strong unilateral risk of TC after CM. More studies are clearly needed to better delineate this mechanism.

Adult↗

Multiple endocrine neoplasia 2A due to a unique C609S RET mutation presents with pheochromocytoma and reduced penetrance of medullary thyroid carcinoma.

OBJECTIVE: We have identified a large kindred with multiple endocrine neoplasia 2A (MEN 2A) due to a mutation at RET codon 609 that results in a cysteine to serine substitution, a mutation previously identified in only one case in the literature. We characterized the clinical phenotype of the kindred and the biochemical mechanism of this new mutation. PATIENTS AND DESIGN: The index case, a 42-year-old woman, presented with pheochromocytoma. We screened 29 family members for the presence of the mutation. Of the 15 mutation-positive family members, 11 agreed to undergo further evaluation by physical examination, calcium and pentagastrin-stimulated calcitonin levels, measurement of urinary metanephrines, adrenal imaging and serum calcium levels. Biochemical characterization of the mutation was by transient transfection of human neuroblastoma cells and Western blot analysis. RESULTS: This kindred demonstrated an inheritance pattern consistent with autosomal dominant pheochromocytoma. Strikingly, no clinically evident case of medullary thyroid cancer (MTC) was observed among mutation-positive family members. Thyroidectomy in six cases revealed C-cell hyperplasia in all and microscopic MTC in two cases. Transfection experiments using human neuroblastoma cells showed that the mutant RET, unlike the wild-type receptor, is constitutively phosphorylated in the absence of ligand, and thus resembles other previously characterized MEN 2A mutations. CONCLUSIONS: The identification of a new mutation causing a MEN 2A phenotype that features pheochromocytoma and the surprising absence of clinically apparent MTC has significant implications for carriers of this mutation and provides further insights into the genotype-phenotype correlation in MEN 2A.

Adolescent↗

The thyrotropin reference range should remain unchanged.

CONTEXT: Recent recommendations to decrease the upper limit of the TSH reference range from 4.5 to 2.5 mIU/liter, based on the high proportion of normal people whose serum TSH is less than 2.5 mIU/liter and the observation that those with TSH between 2.5 and 4.5 mIU/liter [upper reference range (URR)] have increased risk of progression to overt hypothyroidism (Whickham, 20-yr data), have not been subjected to critical analysis. STUDY SUBJECTS: The study subjects were from the Reference Group of NHANES III, 14,333 people more than 12 yr old, without known thyroid disease or antithyroid antibodies; 85% had TSH levels below 2.5 mIU/liter, and 2.3% had subclinical hypothyroidism (SCH). An additional 9.7% had URR TSH, representing 20.6 million Americans, who would also be identified as SCH if the upper TSH limit were decreased. Many with URR TSH do not have thyroid disease. INTERVENTION: The time of phlebotomy is important, because the TSH level varies throughout the day, with early morning values greater than later ones, and is accentuated by sleep deprivation, strenuous exercise, or working during the night or evening shifts. Repeated measurements in the same individual vary considerably over months. RESULTS: About half of those with URR TSH probably have thyroid disease, but most with thyroid disease, antithyroid peroxidase antibodies, have TSH below 2.5 mIU/liter. Those with URR TSH with thyroid disease probably have minimal thyroid deficiency, without any reported adverse health consequences or benefit of treatments with levothyroxine. CONCLUSION: Because routine levothyroxine treatment is not recommended for SCH, it is certainly not warranted in individuals with URR TSH. For all patients with URR TSH, it is reasonable to determine serum TSH every 1-2 yr.

Humans↗

Thyroid carcinoma.

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Biomarkers, Tumor↗

Subclinical thyroid disease: scientific review and guidelines for diagnosis and management.

CONTEXT: Patients with serum thyroid-stimulating hormone (TSH) levels outside the reference range and levels of free thyroxine (FT4) and triiodothyronine (T3) within the reference range are common in clinical practice. The necessity for further evaluation, possible treatment, and the urgency of treatment have not been clearly established. OBJECTIVES: To define subclinical thyroid disease, review its epidemiology, recommend an appropriate evaluation, explore the risks and benefits of treatment and consequences of nontreatment, and determine whether population-based screening is warranted. DATA SOURCES: MEDLINE, EMBASE, Biosis, the Agency for Healthcare Research and Quality, National Guideline Clearing House, the Cochrane Database of Systematic Reviews and Controlled Trials Register, and several National Health Services (UK) databases were searched for articles on subclinical thyroid disease published between 1995 and 2002. Articles published before 1995 were recommended by expert consultants. STUDY SELECTION AND DATA EXTRACTION: A total of 195 English-language or translated papers were reviewed. Editorials, individual case studies, studies enrolling fewer than 10 patients, and nonsystematic reviews were excluded. Information related to authorship, year of publication, number of subjects, study design, and results were extracted and formed the basis for an evidence report, consisting of tables and summaries of each subject area. DATA SYNTHESIS: The strength of the evidence that untreated subclinical thyroid disease is associated with clinical symptoms and adverse clinical outcomes was assessed and recommendations for clinical practice developed. Data relating the progression of subclinical to overt hypothyroidism were rated as good, but data relating treatment to prevention of progression were inadequate to determine a treatment benefit. Data relating a serum TSH level higher than 10 mIU/L to elevations in serum cholesterol were rated as fair but data relating to benefits of treatment were rated as insufficient. All other associations of symptoms and benefit of treatment were rated as insufficient or absent. Data relating a serum TSH concentration lower than 0.1 mIU/L to the presence of atrial fibrillation and progression to overt hyperthyroidism were rated as good, but no data supported treatment to prevent these outcomes. Data relating restoration of the TSH level to within the reference range with improvements in bone mineral density were rated as fair. Data addressing all other associations of subclinical hyperthyroid disease and adverse clinical outcomes or treatment benefits were rated as insufficient or absent. Subclinical hypothyroid disease in pregnancy is a special case and aggressive case finding and treatment in pregnant women can be justified. CONCLUSIONS: Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few. The consequences of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0 mIU/L) are minimal and we recommend against routine treatment of patients with TSH levels in these ranges. There is insufficient evidence to support population-based screening. Aggressive case finding is appropriate in pregnant women, women older than 60 years, and others at high risk for thyroid dysfunction.

Humans↗

Subclinical thyroid disease: clinical applications.

Subclinical hypothyroidism and hyperthyroidism are diagnoses based on laboratory evaluation with few if any clinical signs or symptoms. Subclinical hypothyroidism is defined as an elevation in serum thyroid-stimulating hormone (TSH) above the upper limit of the reference range (0.45-4.5 mIU/L) with normal serum FT4 concentration; subclinical hyperthyroidism is defined as a decrease in serum TSH below the reference range with normal serum FT4 and T3 concentrations. Though these conditions represent the earliest stages of thyroid dysfunction, the benefits of detecting and treating subclinical thyroid disease are not well established. Most persons found to have subclinical thyroid disease will have TSH values between 0.1 and 0.45 mIU/L or between 4.5 and 10 mIU/L, for which the benefits of treatment are not clearly established; treatment may be beneficial in individuals with serum TSH lower than 0.1 mIU/L or higher than 10 mIU/L. This article illustrates approaches to managing patients with subclinical hypothyroidism and hyperthyroidism through 5 case scenarios that apply the principles of evidence-based medicine. Because of the substantial uncertainty concerning the consequences of untreated subclinical hypothyroidism and hyperthyroidism, as well as the benefit of initiating treatment, patient preferences are important in deciding on management of subclinical disease.

Adult↗

Radioactive iodine lobe ablation as an alternative to completion thyroidectomy for follicular carcinoma of the thyroid.

We performed a retrospective record review of patients who received large lobar remnant ablation after surgery for well-differentiated thyroid carcinoma including 30 with papillary carcinoma, 14 with follicular carcinoma, and 6 with Hürthle cell carcinoma. We compared these 50 patients to a group of patients who underwent total or near-total thyroidectomy for well-differentiated thyroid carcinoma. The ablation group was treated with single outpatient doses of 29.9 mCi (131)I to prepare for whole-body radioiodine scanning. Subsequent serum thyrotropin (TSH) concentration during thyroid hormone withdrawal was greater than 25 microU/mL in 94% of patients. The mean TSH in this population (76 microU/mL) was not statistically different from a group of 50 patients who underwent total or near-total thyroidectomy (mean, TSH 71 microU/ml p = 0.84). Twenty-four hour radioiodine uptake post-29.9 mCi (131)I ablation was less than 1% in 80% of patients. The mean radioiodine uptake (0.8%) in the lobe ablation population was significantly lower than in patients treated with total thyroidectomy (mean, 2.4%, p < 0.001). There was minimal morbidity after 29.9 mCi (131)I ablation of large lobar remnants. Outpatient 29.9 mCi (131)I ablation is a safe, effective, and less costly alternative to completion thyroidectomy in selected patients. Although we included patients with both papillary and follicular carcinoma in our review, we recommend this method for patients with minimally invasive follicular carcinoma requiring whole body scanning, even with large postsurgical remnants in place.

Adolescent↗

Cystic lymph node metastases in papillary thyroid carcinoma.

OBJECTIVE: The aim of this study was to illustrate and discuss the sonographic spectrum of surgically proven cystic nodal metastases from papillary thyroid carcinoma. By correlative evaluation of the sonographic imaging findings to gross pathology and histology, our purpose was to provide useful hints to differentiate cystic lymph node metastases from other benign cystic neck lesions such as branchial cysts. MATERIALS AND METHODS: Sonographic examinations of 74 patients (47 women, 27 men; mean age, 49 years) with 97 histologically confirmed cystic lymph nodes metastases from papillary thyroid carcinoma were included in the study. The anatomic relationship of the nodes relative to the primary tumor was recorded, and all cystic nodes were qualitatively categorized as either simple (purely cystic) or complex (thickened outer wall, internal nodules, internal septations, and calcifications). All imaging findings were compared with gross pathologic specimens. RESULTS: Most of the cystic metastases were ipsilateral to the primary tumor (87.8%) and located in the mid or lower jugular chain (73.2%). In 14.9% of all patients, cystic lymph node metastases were the initial manifestation of disease. Only 6.2% of all lymph node metastases were purely cystic (all of these occurred in patients less than 35 years old). Of the 91 complex metastases, a thickened outer wall was present in 35.2% of patients, internal nodules in 42.9%, and internal septations in 57.1%. No calcifications were seen in the 91 complex metastases, and two or more findings were seen in 23.1%. All sonographic findings were verified by surgery. CONCLUSION: In most of the patients, cystic lymph node metastases are characterized sonographically by the presence of a thickened outer wall, internal echoes, internal nodularity, and septations. However, in younger patients, the lymph nodes might appear purely cystic, thereby mimicking branchial cysts and thus requiring biopsy for final diagnosis and therapy planning.

Adult↗