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Biomedical subjects

Kenneth A Woeber

Publications and source records attributed to Kenneth A Woeber.

7 recordsLinked to original sources

A phase II trial of rosiglitazone in patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer.

BACKGROUND: Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that has been shown to induce differentiation, cell cycle arrest, and apoptosis in a variety of human cancers including thyroid cancer. METHODS: Ten patients with differentiated thyroid cancer were enrolled in an open-label, phase II trial of oral rosiglitazone treatment (4 mg daily for 1 week, then 8 mg daily for 7 weeks). The levels of PPARgamma receptor mRNA and protein expression were determined in the patient's neoplasm. RESULTS: Of 10 patients, 4 had positive radioiodine scans after rosiglitazone therapy with uptake in the neck in 3 patients and in the pelvis in 1 patient. After treatment, the serum thyroglobulin level decreased in 2 patients, increased in 5 patients, and was stable in 3 patients. No patient developed clinically important toxicity associated with rosiglitazone treatment. We found no relationship in the level of PPARgamma mRNA and protein expression in patients who had radioiodine uptake compared with those who did not. CONCLUSIONS: Our findings suggest that rosiglitazone treatment may induce radioiodine uptake in some patients with thyroglobulin-positive and radioiodine-negative differentiated thyroid cancer. We found no relationship between the expression level of the PPARgamma mRNA and protein in the neoplasm and radioiodine uptake status after rosiglitazone therapy, questioning the potential pathway of effect.

Adult↗

Triiodothyronine production in Graves' hyperthyroidism.

OBJECTIVE: To quantify the relative contributions of thyroid secretion and peripheral generation to triiodothyronine (T(3)) production in untreated Graves' hyperthyroidism. PATIENTS, DESIGN, AND MEASUREMENTS: Thirty-one patients with hyperthyroidism, of whom 6 had T(3) toxicosis, and 21 surgically and radioiodine ablated patients with thyroid cancer on thyroid stimulating hormone-suppressive therapy in whom serum T(3) should reflect peripheral generation alone were compared with respect to serum free thyroxine (T(4)) and serum free T(3) concentrations. MAIN OUTCOMES: Serum free T(4)/free T(3) molar ratios were virtually identical in the patients with T(4)+T(3) toxicosis (2.7 +/- 0.4) and those with T(3) toxicosis (2.6 +/- 0.4) and were significantly lower than in the patients with thyroid cancer (4.0 +/- 0.4) (p < 0.001). In the hyperthyroid patients, peripherally generated T(3) was calculated as the quotient of the individual serum free T(4) concentration and the free T(4)/free T(3) molar ratio in thyroid cancer; this value was subtracted from the individual measured free T(3) concentration to derive the value for secreted T3. Secreted T(3) accounted for 33 +/- 6% of T(3) production in T(4)+T(3) toxicosis and 34 +/- 10% in T(3) toxicosis. CONCLUSIONS: This study indicates that about one third of T3 production in untreated Graves' hyperthyroidism, irrespective of whether presenting as T4+T3 toxicosis or T3 toxicosis, arises from thyroid secretion as compared to about 20% in normal individuals.

Adult↗

Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is rare but is one of the most aggressive human malignancies. Several prognostic factors have been observed in patients with ATC, and some experts advocate aggressive multimodal therapy in selected patients. However, it is unclear whether such an approach significantly improves survival. The authors analyzed prognostic factors and treatment outcomes in patients with ATC reported in the National Cancer Institute's Surveillance, Epidemiology, and End Results data base. METHODS: The cohort consisted of 516 patients with ATC reported to 12 population-based cancer registries between 1973 and 2000. Demographic, pathologic, and treatment data were used for univariate and multivariate survival analyses. RESULTS: The mean patient age at diagnosis was 71.3 years, and there were 171 men and 345 women. Eight percent of patients had intrathyroidal tumors, 38% had extrathyroidal tumors and/or lymph node invasion, and 43% of patients had distant metastasis. The average tumor size was 6.4 cm (range, 1-15 cm). Sixty-four percent of patients underwent surgical resection of their primary tumor, and 63% received external beam radiotherapy. The overall cause-specific mortality rate was 68.4% at 6 months and 80.7% at 12 months. Univariate analysis showed that age < 60 years, female gender, intrathyroidal tumor, external beam radiotherapy, surgical resection, and combined surgical resection of tumor and radiotherapy were associated with a lower cause-specific mortality. On multivariate analysis, only age < 60 years, an intrathyroidal tumor, and the combined use of surgical and external beam radiation therapy were identified as independent predictors of lower cause-specific mortality. CONCLUSIONS: Although most patients with ATC had an extremely poor prognosis, patients < 60 years old with intrathyroidal tumors survived longer. Surgical resection with external beam radiotherapy for ATC was associated with lower cause-specific mortality.

Adolescent↗

Extent of disease and practice patterns for medullary thyroid cancer.

BACKGROUND: There have been significant improvements in the management of medullary thyroid cancer (MTC), and consensus treatment guidelines have been established by numerous international and national societies. It is unclear if the advances in diagnosis and treatment of MTC have led to earlier diagnosis and more complete initial treatment of patients with MTC. STUDY DESIGN: Patients with MTC (n=1,070) were identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database from 12 population-based cancer registries between 1973 and 2000. Four equal-time quartiles (group I=1973 to 1979, group II=1980 to 1986, group III=1987 to 1993, and group IV=1994 to 2000) were compared for changes in demographics, extent of disease, and treatment. RESULTS: Mean tumor size was significantly larger in 1988 than in 1989 through 2000 (p=0.044), but there was no significant trend toward smaller tumor size. The number of patients having total or near total thyroidectomy increased significantly in the latter two quartiles (p < 0.001) but not the number of patients having cervical lymph node dissection. Unfortunately, 15% of patients in group IV still had less than total or near total thyroidectomy, and 41% had no cervical lymph node dissection. There were no significant differences in age, gender, rate of lymph node or distant metastasis, SEER stage, TNM stage, and cause-specific mortality among the four time groups and annually. CONCLUSIONS: There was no significant trend toward earlier stage of disease at diagnosis and treatment and no significant increase in the survival of patients with MTC during a 28-year period. A high proportion of patients continue to receive less than optimal initial surgical treatment.

Adolescent↗

Observations concerning the natural history of subclinical hyperthyroidism.

OBJECTIVE: To examine the natural history of a subnormal serum thyroid-stimulating hormone (TSH) concentration with normal concentrations of both serum free thyroxine (FT4) and free triiodothyronine (FT3) (subclinical hyperthyroidism). PATIENTS, DESIGN, AND MEASUREMENTS: A retrospective analysis was undertaken and yielded 16 ambulatory patients who had presented with subclinical hyperthyroidism and were longitudinally followed with measurements of serum TSH and both FT4 and FT3 for a cumulative follow-up of 11 to 36 months. Seven of the patients had subclinical Graves' hyperthyroidism as judged from the presence of thyroid-stimulating immunoglobulins (TSI) in serum, and 9 had multinodular goiter confirmed with ultrasound and no TSI. RESULTS: In the 7 patients with TSI, serum TSH reverted to normal in 5 patients, with disappearance or decrease of TSI in 4, within 3 to 19 months. In 1 patient, subnormal serum TSH accompanied by both normal FT4 and FT3 has persisted for 15 months, and in a second patient serum TSH reverted to normal within 9 months, but at follow-up 27 months later overt hyperthyroidism had emerged. In the 9 patients with multinodular goiter, subnormal serum TSH accompanied by both normal FT4 and FT3 persisted during cumulative follow-up that ranged from 11 to 36 months. CONCLUSIONS: This study suggests that the natural history of subclinical hyperthyroidism is variable, resolving or occasionally evolving in subclinical Graves' disease and persisting unchanged in multinodular goiter.

Adult↗

Methimazole-induced hepatotoxicity.

OBJECTIVE: To present the case of a patient with Graves' hyperthyroidism in whom treatment with methimazole led to severe cholestasis. METHODS: A detailed case report and an overview of previously published cases of methimazole- and carbimazole-induced hepatotoxicity, found in a MEDLINE search with use of methimazole, carbimazole, thionamides and antithyroid agents as subject headings, are provided. RESULTS: In a 36-year-old woman with severe hyperthyroidism, treatment with methimazole (20 mg twice daily) was initiated. Nineteen days later, pruritus, scleral icterus, dark urine, and abdominal discomfort prompted discontinuation of the therapy. Laboratory investigations and abdominal ultrasonography showed findings consistent with a cholestatic reaction to methimazole. Recovery was slow but complete. Of the 30 previously published cases of hepatotoxicity related to treatment with methimazole or carbimazole in which the nature of the hepatic injury was described, 19 were also cholestatic. CONCLUSION: Physicians should be aware that thionamide drugs can be associated with hepatotoxicity. Analysis of the known cases suggests that older age of the patient and higher dose of the drug are risk factors for cholestatic injury.

Adult↗

Evaluation of a "formal" endocrinology curbside consultation service: advice by means of internet, fax, and telephone.

OBJECTIVE: To describe the development, implementation, and assessment of an Internet- and fax-based endocrinology curbside consultation service. METHODS: An Internet- and fax-based endocrinology consultation service was designed by developing a simple Web site so that requesting physicians could complete a form about the patient. Community and academic-based primary-care physicians were invited to use the service. One month after each consultation, a follow-up questionnaire about the effectiveness and use of the Internet and fax consultation service was sent to each physician who had requested the consultation. RESULTS: During the 5-month period in which the service was offered, 67 physicians requested a total of 85 "formal" endocrinology curbside consultations. Of these 85 requests, 46 were by e-mail, 31 by fax, and 8 by telephone. Follow-up questionnaires were returned by 61 of the 67 physicians who used the service. One hundred percent of the physicians found the service to be useful, and about 33% noted formal consultation had been avoided. In approximately 55% of the consultations, physicians indicated that the response caused them to alter the treatment of their patient. Consultation questions encompassed the full spectrum of endocrinology. The issues were approximately equally distributed among test interpretation, medication, and management. CONCLUSION: We successfully designed and implemented an Internet- and fax-based endocrinology curbside consultation service. This form of consultation was used by physicians and brought about change in the management of their patients.

Attitude of Health Personnel↗