Dosage assessment for radioiodine therapy in benign thyroid disorders

The general aim of this thesis was to investigate the value and the shortcomings of the becquerel-per-gram method for radioiodine therapy in various benign thyroid disorders. The history of this treatment form, which goes back to the late 1940s, is described in Chapter 1. Almost fifty years after the discovery of radioactivity, the first clinical experiences with 131 I-treatment were reported in the United States. A simple and effective treatment form had emerged as an alternative to surgery and antithyroid drug (ATD) therapy in Graves disease. The efficacy of radioiodine was initially tested and demonstrated in patients who could not be cured with ATD medication. With increasing experience in the management of Graves disease, it became apparent that the outcome of radio-iodine treatment was difficult to predict. No more than half of all patients treated became euthyroid with one 131 I administration. Higher or lower dosage protocols made the difference for the outcome in the other 50%. In other words, there was the choice between a greater risk of early hypothyroidism or persistent hyper-thyroidism. The development of different schools with regard to the desired therapy outcome (i.e., rapid cure of hyperthyroidism, or restoring euthyroidism) did not hamper the furthering of radioiodine therapy. By the late 1980s, radioiodine had replaced surgery as the first choice for the curation of Graves hyperthyroidism, toxic adenoma and toxic multinodular goiter. After this introduction, a number of items relevant to radioiodine treat-ment are reviewed: the physical and radiobiologic properties of iodine-131; pros and cons of different therapeutic aims; and factors influencing the outcome of radioiodine therapy. A statement of the aims of this thesis concludes Chapter 1. In Chapter 2, we present the clinical follow-up results of radioiodine treatment in patients with toxic adenoma and in patients with toxic multinodular goiter. The prevalence of both these disorders is relatively low in comparison with dif-fuse toxic goiter (Graves disease), and consequently the number of cases in-cluded in this investigation is limited. Because of their similar histopathologic and clinical profiles, they have been studied as one group. A standardized dos-age of 3.7 MBq per gram thyroid tissue was applied in patients with multinodu-lar goiter, and a dosage of 7.4 MBq per gram adenomatous tissue was used in patients with toxic adenoma. With a single radioiodine treatment good clinical results were obtained in patients with toxic adenoma (75% euthyroidism, 11% hypothyroidism, 14% relapse) over a follow-up period varying between one and eight years. In patients with toxic multinodular goiter, 70% became euthyroid, 22% suffered a relapse of thyrotoxicosis and 8% became hypothyroid. Repeat radioiodine therapy (3 for TA, 11 for TMNG) was successful in all patients with a relapse. Most other researchers have found somewhat fewer relapses and higher hypothyroidism rates for toxic multinodular goiter; the recurrence rate for TMNG varied between 2% and 52%. The lowest failure rate was obtained with a fixed dosage of 740 MBq (20 mCi). It seems contradictory that with that regimen also the hypothyroidism rate (6%) was slightly lower than what we found. At this stage, a fixed dosage regimen seems preferable over the more laborious indi-vidualized regimen. The underperformance of the individualized protocol could possibly be explained by inaccurate volume measurements, especially in toxic adenoma. Further optimization of the standardized regimen for these disorders may be expected from T3 suppression medication and from lithium co-medica-tion. Both may have the ability to increase the effect of a given amount of 131 I, although the mechanisms of action are entirely different. The aim of radioiodine therapy in patients with nontoxic goiter is the reduction of goiter size, while simultaneously preserving the normal thyroid function. This item is dealt with in Chapter 3. In 27 patients with sporadic nontoxic goiter, a therapeutic dose of 3.7 MBq per gram functioning thyroid tissue led to sub-stantial objective reduction of the goiter mass (by 34% on average). The subjec-tive results were more than adequate: 85% of all patients reported substantial improvement or complete relief of their complaints. Hypothyroidism resulted in 3/27 (11%) of the patients. Thyroid volume measurements with 99m Tc-pertech-netate scintigraphy were carried out for therapy dosage calculations as well as for follow-up measurements. For an objective assessment of the goiter reduc-tion, CT-scanning was used as the gold standard. It was concluded that the accu-racy of planar scintigraphic volume determinations in nontoxic goiter is suffi-cient for dosage calculation purposes if the thyroid volume does not exceed 200 ml. However, as the therapy results were no less in patients with thyroid vol-umes over 200 ml than in patients with smaller goiters, the accuracy of these measurements does not seem to carry much weight. Recently, other researchers have reported equally satisfying results in the reduction of goiter size. It seems that the indication for radioiodine therapy in patients with nontoxic goiter may be broader than has thus far been assumed. In Chapter 4, a summary is given of the radioiodine therapy results using a standardized megabecquerel-per-gram dosage protocol in patients with Graves disease. The overall results are in compliance with the results of other research groups. We found a cure rate of 70% (including 39% hypothyroidism), and re-current hyperthyroidism in 30%. The thyroids radioiodine uptake capacity and the thyroids mass appeared to be important factors with regard to the progno-sis of the therapy outcome. Patients with thyroid weights > 60 g more often suffered a recurrence of hyperthyroidism, whereas those with thyroid weights < 60 g appeared to be prone to a hypothyroid therapy outcome. Likewise, pa-tients with radioiodine uptake values < 60% had a higher risk of becoming hy-pothyroid than those with uptake values > 80%. From the preceding four chapters we may conclude that the standard therapy dosage formula D = W ´ (100%/U) ´ 3.7 MBq (where D is the therapy dosage in MBq, W is the thyroid weight in grams, and U is the 24-h radioiodine uptake percentage) is adequate for radioiodine therapy in all thyroid conditions under consideration, except in Graves disease. It remained unclear what particular dynamics of Graves disease make the prediction of the therapy outcome so much more difficult than in other thyroid disorders. We have looked into the technical, biologic and logistic aspects of the two cornerstones of the radioiodine dosage calculation, viz. the iodine uptake measurement and the scintigraphic thyroid volume measurement. Chapter 5 sets off with a survey of the clinical practice in The Netherlands, of radioiodine uptake measurements that are used for therapeutic 131 I dosage calculations in patients with Graves hyperthyroidism. From the response to a nation-wide questionnaire it was concluded that at most departments the radioiodine uptake was measured (and the therapy dosage was computed) several days or even weeks before the actual therapy date. Large dif-ferences prevailed between institutions. This survey is followed by an analysis of the clinical consequences of said practice. Variations in radioiodine uptake of over 10% occurred within a short time in more than half the patient popula-tion (62% of all patients with regard to the 5-hr 131 I uptake and 51% with regard to the 24-hr uptake). The radioiodine turnover rate, too, was recognized as a relevant parameter for the dosage calculation. The incidence of increased radio-iodine turnover as earlier reported in the literature (about 16%) was confirmed in our study, but in 14% of all patients the turnover rate had changed from normal to increased or vice versa during an interval of 6 weeks on average. The results of radioiodine treatment in patients with Graves hyperthyroidism were again reviewed; in comparison with the methods as used in Chapter 4 only one variable was altered, viz. the time-point of the 131 I uptake measurements. In the repeat study, described in Chapter 6, the uptake was measured on the day before therapy. The results differed significantly from those in the historic con-trols. A significant shift occurred from hypothyroidism to persisting hyper-thyroidism. The outstanding significance of the radioiodine turnover rate as a predictor of the clinical outcome was also recognized in this investigation. For patients who had become euthyroid after radioiodine therapy, the radioiodine turnover rates (i.e., 5/24-h 131 I uptake ratios) were 0.76-0.84 (95% confidence interval, C.I.), whereas in patients with persisting hyperthyroidism the turn-over rates were 0.84-0.92 (95% C.I.). There was some overlap between patients with euthyroid and hypothyroid outcomes (rates 0.69-0.79, 95% C.I.), but the differences were still highly significant. It seems that the radioiodine turnover rate has great predictive potential with regard to the therapy outcome. On the basis of the present data, proper quantitative dosage corrections can not yet be performed, but indicatively 131 I therapy dosage adaptations may be realized. The second cornerstone of classic 131 I therapy dosage calculations, the thyroid volume, forms the center of interest in Chapters 7 and 8. Based on our earlier experience with CT-scanning in patients with nontoxic goiter, this modality was also chosen as the gold standard in a pilot study of 5 patients with Graves disease (Chapter 7). However, adequate manual segmentation was not feasible with native CT in 4 out of 5 patient studies. As CT with contrast enhancement is contra-indicated when radioiodine treatment is scheduled, it was concluded that CT is not suited for thyroid volume measurements under these conditions. It was argued that the discrepancies between the results in patients with non-toxic goiter and in patients with Graves disease may be caused by the relatively small thyroidal iodine pool in the latter. The lower iodine content would cause a lower signal intensity on CT, and less contrast between the thyroid gland and the surrounding tissues. In 25 patients with Graves disease, a direct comparison was made between pla-nar scintigraphy, ultrasound (US), and SPECT (with attenuation correction and scatter correction, using standard commercial hardware and software), while MRI was used as the gold standard. In this investigation (Chapter 8), it was con-cluded that MRI, SPECT, or US may be pursued for thyroid volume measurements. Planar scintigraphy is very inaccurate, and should be discarded as a means of pretherapeutic thyroid volume measurements. SPECT can be used as an alterna-tive to planar scintigraphy for the qualitative functional diagnosis; MRI or US should only be used as an add-on to scintigraphy. A general discussion of radioiodine therapy for benign thyroid disorders is pre-sented in Chapter 9. In view of the good results in all nodular thyroid disorders under study, it was concluded that adjustments to the standard dosage formula are not indicated. In patients with Graves disease, it is much harder to make an accurate prognosis of the therapy outcome. It is argued that attempts to pre-serve normal endogenous thyroid function through a patient-tailored model is to be preferred over the quick induction of hypothyroidism and subsequent levothyroxine substitution. Generalized proposals are made for adjustments to the standard radioiodine therapy dosage formula, making use of all optimiza-tion factors that were found in the investigations described in Chapters 2-7. This chapter is concluded by proposals for future research, primarily aimed at optimization of radioiodine dosage calculations in patients with Graves dis-ease. Dosimetric models and computer algorithms are needed to adjust for vari-ations in thyroid volume, 131 I uptake and radioiodine turnover rate. SPECT meas-urements of the 131 I concentration within the thyroid gland, instead of the thy-roid volume and the absolute amount of 131 I in the thyroid gland, deserve fur-ther investigation. Because of the clinical implications, we also propose a study of very-short-term variations in radioiodine uptake. The influence of antithy-roid drugs on the radioiodine turnover rate warrants further study, as well as a quantification of the dose-effect relationship of lithium co-medication in pro-longing the retention of radioiodine in the thyroid. Other proposed medication studies include the investigation of the clinical value of triiodothyronine (T 3 ) suppression therapy in autonomous thyroid disease, and of the clinical value of low-dose recombinant human thyrotropin (rhTSH) in patients with nontoxic goiter. Finally, it seems worthwhile from an endocrinologic viewpoint to do an open-label study of the merits of combined T 3 /T 4 medication versus T 4 alone in patients who have become hypothyroid after radioiodine therapy

Thyroid Disorders

The thyroid disorders are one of the most common and exciting areas of endocrinology. Hypothyroidism, multinodular goiter, hyperthyroidism and thyroid cancer are only few of the several implications that the thyroid disorders have in health. In fact, thyroid hormones regulate not only metabolism process, but also many other molecular and physiological systems. From this point of view, hyperthyroidism complications are a good example of the significance of thyroid hormone actions. This book aims to provide a general view of thyroid disorders, and a deeper explanation of hyperthyroidism and its complications and impact in health

Goiter

The thyroid gland is a commonly diseased endocrine organ of human body. The disorders affecting the thyroid gland are varied but are very much amenable to treatment. The enlargement of the thyroid is termed goiter. It can affect the whole gland or only part of it. The disease is perplexing but in-depth knowledge of the pathophysiology helps in elucidating causes and thereby treating the disease. In this book, the diffuse and nodular goiter has been addressed as well as the functional abnormalities of the gland and its implications on the body are discussed in various chapters. The relevant updated information is included. To address a few of these current issues and recent updated information, authors have put in a lot of effort to organize the book

Risk Stratification of Thyroid Nodule: From Ultrasound Features to TIRADS

Since the 1990s, ultrasound (US) has played a major role in the assessment of thyroid nodules and their risk of malignancy. Over the last decade, the most eminent international societies have published US-based systems for the risk stratification of thyroid lesions, namely, Thyroid Imaging Reporting And Data Systems (TIRADSs). The introduction of TIRADSs into clinical practice has significantly increased the diagnostic power of US to a level approaching that of fine-needle aspiration cytology (FNAC). At present, we are probably approaching a new era in which US could be the primary tool to diagnose thyroid cancer. However, before using US in this new dominant role, we need further proof. This Special Issue, which includes reviews and original articles, aims to pave the way for the future in the field of thyroid US. Highly experienced thyroidologists focused on US are asked to contribute to achieve this goal

Patterns of injury and violence in Yaoundé Cameroon: an analysis of hospital data.

BackgroundInjuries are quickly becoming a leading cause of death globally, disproportionately affecting sub-Saharan Africa, where reports on the epidemiology of injuries are extremely limited. Reports on the patterns and frequency of injuries are available from Cameroon are also scarce. This study explores the patterns of trauma seen at the emergency ward of the busiest trauma center in Cameroon's capital city.Materials and methodsAdministrative records from January 1, 2007, through December 31, 2007, were retrospectively reviewed; information on age, gender, mechanism of injury, and outcome was abstracted for all trauma patients presenting to the emergency ward. Univariate analysis was performed to assess patterns of injuries in terms of mechanism, date, age, and gender. Bivariate analysis was used to explore potential relationships between demographic variables and mechanism of injury.ResultsA total of 6,234 injured people were seen at the Central Hospital of Yaoundé's emergency ward during the year 2007. Males comprised 71% of those injured, and the mean age of injured patients was 29 years (SD = 14.9). Nearly 60% of the injuries were due to road traffic accidents, 46% of which involved a pedestrian. Intentional injuries were the second most common mechanism of injury (22.5%), 55% of which involved unarmed assault. Patients injured in falls were more likely to be admitted to the hospital (p &lt; 0.001), whereas patients suffering intentional injuries and bites were less likely to be hospitalized (p &lt; 0.001). Males were significantly more likely to be admitted than females (p &lt; 0.001)DiscussionPatterns in terms of age, gender, and mechanism of injury are similar to reports from other countries from the same geographic region, but the magnitude of cases reported is high for a single institution in an African city the size of Yaoundé. As the burden of disease is predicted to increase dramatically in sub-Saharan Africa, immediate efforts in prevention and treatment in Cameroon are strongly warranted

Fusion, 2020

https://hsrc.himmelfarb.gwu.edu/smhs_fusion/1012/thumbnail.jp

Sodium Iodide Symporter Location, Expression and Regulation in Red Dru, Sciaenops Ocellatus

Iodine, a non-metallic trace element, is one of the heaviest elements essential for normal biological function. Vertebrate animals must obtain iodine from the environment to manufacture thyroid hormones and sufficient iodine supply is thus critical for normal endocrine function. In mammals, iodine uptake from the environment is achieved by the sodium iodide symporter (NIS), but little is known outside a few mammalian orders about how animals obtain iodine. Because the basic biochemical pathways for thyroid hormone synthesis and receptor activation appear conserved in vertebrates, the mechanisms through which non-mammalian species accumulate iodine for thyroid hormone manufacture have also been assumed to be similar. However, few studies have identified the NIS gene or characterized the regulation of its activity in fish. The perciform teleost fish, red drum (Sciaenops ocellatus) is easily obtained from hatcheries and has been used extensively for nutritional and thyroid hormone research, therefore providing an informative species in which to study the mechanisms of iodide uptake and utilization in a nonmammalian species. I developed a fast, non-lethal methodology using Positron Emission Tomography and Computed Tomography PET/CT imaging of 124I injected fish to produce three dimensional images identifying areas of active radioiodide uptake in the subpharyngeal region of red drum, thus allowing me to establish a methodology for consistently obtaining thyroid tissue. I then confirmed that an NIS homolog is expressed in red drum thyroid, stomach and intestine, but found little evidence for its expression in gills. Utilizing quantitative RT-PCR, I demonstrated that thyroid stimulating hormone stimulated nis expression in red drum subpharyngeal thyroid tissue but not any other nis expressing tissue, similar to mammalian thyroid NIS. nis expression in red drum subpharyngeal, stomach, intestine, and gill tissues was relatively unchanged during feeding, salinity transfer, and environmental iodide exposure, suggesting that these fish have physiological mechanisms of dietary iodine uptake, thyroid hormone synthesis, and iodide recycling similar to those described in mammals. Minimal nis expression in gills across a variety of osmotic environments and nutritional conditions suggests that this transporter does not serve as a mechanism for direct environmental iodide uptake via gills

Entwicklungen und Untersuchungen zur Bildgebung der Schilddrüse: 124Iod-PET/CT, 3D-Ultraschall und nuklearmedizinisch-sonographische Bildfusion

In der etablierten Schilddrüsenbildgebung existieren trotz des bereits hohen Standards begrenzende Faktoren. Methodische und technische Neuerungen erscheinen mithin sinnvoll und geboten. Die vorliegende Habilitationsschrift stellt die Entwicklung und Erprobung neuer Konzepte der Schilddrüsendiagnostik in drei Teilgebieten vor: *Durch die 124Iod-Niedrigaktivitäts-PET/Niedrigdosis-CT wird (i) die Ortsauflösung der herkömmlichen Szintigraphie übertroffen und die Detektierbarkeit kleinerer Strukturen sowie anatomischer Details verbessert. Durch den parallel akquirierten CT-Datensatz können (ii) zusätzliche Erkenntnisse zur Schilddrüse sowie deren Beziehung zu Nachbarorganen gewonnen werden. Darüber hinaus sind (iii) im Rahmen der Vorbereitung von Radiojodtherapien prätherapeutische Uptake-Messungen möglich. *Der 3D-US ermöglicht (i) den lückenlosen Scan der Schilddrüse und (ii) die vollständige digitale Archivierung des Untersuchungsvolumens im PACS. Dadurch ergeben sich auf Schnittbildworkstations die Vorteile (iii) des Second Readings, (iv) des Side-by-Side-Vergleichs mit vorangegangenen 3D-US-Studien und anderen Schnittbildverfahren. Darüber hinaus kann (v) eine nachträgliche Datenverarbeitung (Processing) erfolgen. *Die Einbeziehung des Ultraschalls in das Konzept der Fusions- bzw. Hybridbildgebung hat gezeigt, dass die räumliche Verknüpfung und bildliche Überlagerung der morphologisch-sonographischen Informationen mit den nuklearmedizinisch-funktionellen Bilddaten erfolgen kann. Aus dem klinischen Potential der Methoden einerseits, sowie den geschilderten Limitationen andererseits ergeben sich Implikationen für die Zukunft. Zunächst sind die apparativ-technische Weiterentwicklung der Verfahren sowie eine Optimierung der informationstechnischen Einbindung notwendig. Darüber hinaus muss eine Entwicklung hin zu einer zeitsparenden und einfachen Anwendbarkeit erfolgen, um einen rationellen klinischen Workflow zu ermöglichen und personelle Ressourcen zu schonen

Full Issue: Volume 14, Number 2, Spring 2021

Complete .pdf file of Volume 14, Number 2 of The Science Journal of the Lander College of Arts and Sciences. Published Spring 2021