Variations in serum thyroxine concentrations with time after an oral replacement dose

Serum thyroxine concentrations were measured sequentially in eight healthy male volunteers after the oral administration of one of two brand name, commercially available thyroxine tablets. In all cases, levels peaked at 2 hours and did not return to baseline values until 24 hours after dosing. From 2 through 10 hours, statistically significant elevations in serum thyroxine concentrations were observed. Such fluctuations may be important in evaluating laboratory results in patients receiving replacement doses of thyroxine.     

Outcomes of patients with differentiated thyroid carcinoma following initial therapy.

This analysis was performed to determine the effect of initial therapy on the outcomes of thyroid cancer patients. The study setting was a prospectively followed multi-institutional registry. Patients were stratified as low risk (stages I and II) or high risk (stages III and IV). Treatments employed included near-total thyroidectomy, administration of radioactive iodine, and thyroid hormone suppression therapy. Outcome measures were overall survival, disease-specific survival, and disease-free survival. Near-total thyroidectomy, radioactive iodine, and aggressive thyroid hormone suppression therapy were each independently associated with longer overall survival in high-risk patients. Near-total thyroidectomy followed by radioactive iodine therapy, and moderate thyroid hormone suppression therapy, both predicted improved overall survival in stage II patients. No treatment modality, including lack of radioactive iodine, was associated with altered survival in stage I patients. Based on our overall survival data, we confirm that near-total thyroidectomy is indicated in high-risk patients. We also conclude that radioactive iodine therapy is beneficial for stage II, III, and IV patients. Importantly, we show for the first time that superior outcomes are associated with aggressive thyroid hormone suppression therapy in high-risk patients, but are achieved with modest suppression in stage II patients. We were unable to show any impact, positive or negative, of specific therapies in stage I patients.     

A multisite study to examine the efficacy of the otoacoustic emission/automated auditory brainstem response newborn hearing screening protocol: results of visual reinforcement audiometry

PURPOSE: This 3rd of 4 articles on a study of the efficacy of the 2-stage otoacoustic emission/automated auditory brainstem response (OAE/A-ABR) newborn hearing screening protocol describes (a) the behavioral audiometric protocol used to validate hearing status at 8-12 months of age, (b) the hearing status of the sample, and (c) the success of the visual reinforcement audiometry (VRA) protocol across 7 sites. METHOD: A total of 973 infants who failed OAE but passed A-ABR, in one or both ears, during newborn screening were tested with a VRA protocol, supplemented by tympanometry and OAE screening at age 8-12 months. RESULTS: VRA audiograms (1.0, 2.0, and 4.0 kHz) were obtained for 1,184 (82.7%) of the 1,432 study ears. Hearing loss was ruled out in another 100 ears by VRA in combination with OAE, for a total of 88.7% of the study sample. Permanent hearing loss was identified in 30 ears of 21 infants. Sites differed in their success with the VRA protocol. CONCLUSIONS: Continued monitoring of hearing beyond the newborn period is an important component of early detection of hearing loss. Using a structured protocol, VRA is an appropriate test method for most, but not all, infants. A battery of test procedures is often needed to adequately delineate hearing loss in infants. Examiner experience appears to be a factor in successful VRA.     

Effect of metoprolol and verapamil administered separately and concurrently after single doses on liver blood flow and drug disposition

Nine healthy males participated in a double-blind, placebo-controlled, randomized, crossover study to determine the effects of verapamil and metoprolol administered alone and concurrently on blood flow through the hepatic artery and portal and hepatic veins and to detect a possible drug interaction between the two agents. Single oral doses of placebo/placebo, metoprolol (50 mg)/placebo, verapamil (80 mg)/placebo, or verapamil/metoprolol were separated by at least 14 days. Liver blood flow through individual hepatic vessels was measured up to 8 hours after dosage administration using a duplex Doppler ultrasound technique. Cardiac output, heart rate, blood pressure, stroke volume, and total peripheral resistance were measured for 3 hours after drug doses were given. In 5 subjects, pharmacokinetic parameters for total drug as well as S- and R-enantiomers were also measured. Verapamil given alone caused a rapid and intense increase in liver blood flow (hepatic artery = 50%, portal vein = 42%, hepatic vein = 55%) 0.75 to 1 hour after administration because of a decrease in total peripheral resistance and an increase in heart rate, stroke volume, and cardiac output. Metoprolol given alone caused a slow but prolonged decrease in liver blood flow (maximum decrease: hepatic artery = -54%, portal vein = -21%, hepatic vein = -27%) 4 hours after administration because of a decrease in heart rate and cardiac output. When the two agents were given together, a composite of the changes noted after separate administration was noted: a brief peak increase in liver blood flow at 0.33 to 1 hour followed by a slow, prolonged decrease that reached its maximum decline 4 to 5 hours postdose. During the combined phase, metoprolol and its enantiomers had an increased AUC and Cmax, while verapamil and its enantiomers had an increased AUC and t1/2. These pharmacokinetic changes were consistent with the magnitude and time course of liver blood flow changes through the hepatic artery and portal or hepatic veins.     

The continuing impact of thyroid scintigraphy on the diagnosis of thyroid enlargement

The impact of thyroid scintigraphy on the working diagnosis was evaluated in 204 consecutive patients referred for thyroid testing. The a priori and a posteriori diagnoses were discordant about one third of the time. The differences were highly significant (P less than 0.001) in the cases of uninodular and multinodular goiter.     

A commercial digoxin radioassay modified for use as an emergency ("stat") procedure.

A recent "stat" procedure recommended by the manufacturer for use with a commercial digoxin radioassay involves doubling the amount of antibody used in the regular procedure, to compensate for the decrease in binding that results from use of a shorter (10 min) incubation. This has two obvious disadvantages: increased material cost and decreased sensitivity because of the increase in the binding capacity of the assay. In our modified procedure, we kept the binding capacity constant by decreasing the volume of the incubation mixture without increasing the amount of antibody. Total binding and the rate of binding on 10-min incubation are 50.4 and less than 1.3% per minute, respectively. Results by our modified stat procedure compare well with those by the manufacturer's suggested regular procedure in terms of sensitivity, accuracy, and precision, and are more sensitive and economical than those by the manufacturer's suggested stat procedure.     

Imaging modalities in the follow-up of non-lodine avid thyroid carcinoma

Introduction: The treatment of primary thyroid cancer requires protracted follow-up because of to the possibility of the development of recurrent metastases many years after the initial diagnosis. Often such follow-up involves imaging at regular intervals with diagnostic I-131 studies. However, not all thyroid cancer concentrates I-131. The purpose of this article is to review the efficacy of alternative diagnostic imaging modalities for follow-up of thyroid carcinomas that do not concentrate radioiodine.Materials and Methods: These procedures include the use of nuclear medicine imaging with thallium-201 (Tl-201), Tc-99m-sestamibi, Tc-99m pentavalent dimercaptosuccinic acid (DMSA), radiolabeled anti-carcinoembryonic antigen antibodies, and radioiodinated-131 meta-iodobenzyl guanidine, as well as computerized x-ray tomography, magnetic resonance imaging (MRI), and ultrasound (US).Results and Conclusion: Thallium-201, MRI, and pentavalent DMSA provide adequate sensitivity for follow-up of selected patients with suspected recurrent noniodine concentrating thyroid carcinoma.