Frederik A Verburg

University Hospital RWTH Aachen, Aachen, North Rhine-Westphalia, Germany

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Publications (128)441 Total impact

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    ABSTRACT: To compare and outline the beneficial skills of combined 68Ga-DOTATATE positron emission tomography (PET) with concurrent contrast enhanced X-ray computed tomography (ceCT) against stand-alone ceCT in 54 patients with neuroendocrine tumours (NET).
  • F A Verburg
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    ABSTRACT: Thyroid surgery is one of the more common surgical procedures in Germany. This is in contrast with the situation in some other countries, where this procedure is performed comparatively rarely. In this paper the number of thyroid surgeries in Germany is compared with other western countries (Netherlands, USA, England). In contrast to e. g. the USA and England the number of thyroid surgeries in Germany is declining, however with approximately 109/100 000/year in 2012 is still elevated (Netherlands: 16/100 000/year, USA: at least 42/100 000/year, England: at least 27/100 000/year). Possible contributing factors to this higher number of thyroid surgeries in Germany are explored. These factors include iodine deficiency, the frequent use of advanced diagnostics such as ultrasound, insufficient use of preoperative diagnostic measures such as fine needle biopsy and the practice of "defensive medicine". How much each of these factors contributes is however unclear.
    Nuklearmedizin 06/2015; 54(3):101-5. · 1.67 Impact Factor
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    ABSTRACT: In adult differentiated thyroid cancer (DTC) patients, successful ablation and the number of (131)I therapies needed carry a prognostic significance. The goal was to assess the prognosis of DTC in children and adolescents treated in our centre in relation to the number of treatments needed and to establish the determinants of both complete remission (CR) and successful ablation. Seventy-six DTC patients <21 years of age at diagnosis were included. Recurrence and death rates, rates of CR (=negative stimulated thyroglobulin, negative neck ultrasound and negative (131)I whole-body scintigraphy) and successful ablation (=CR after initial (131)I therapy) were studied. No patients died of DTC. Seven patients were treated by surgery alone and did not show signs of recurrence during follow-up. Of the 69 patients also treated with (131)I therapy, 47 patients achieved CR, 25 of whom had successful ablation. In multivariate analysis, female gender and the absence of distant metastases were independent determinants of a higher CR rate. Female gender, lower T stage and higher (131)I activity (successful ablation, median activity 3.1 GBq, unsuccessful ablation 2.6 GBq) were determinants of a higher rate of successful ablation. After (131)I therapy no patient showed recurrence after reaching CR or disease progression if CR was not reached. In our paediatric DTC population prognosis is extremely good with no deaths or recurrences occurring regardless of the number of (131)I therapies needed or whether CR was reached. The determinants of CR and successful ablation can be used to optimize the chance of therapy success.
    European Journal of Nuclear Medicine 06/2015; DOI:10.1007/s00259-015-3076-8 · 5.22 Impact Factor
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    ABSTRACT: to determine whether the first three months after 131I ablation is too early to perform radioiodine diagnostic whole body scintigraphy (dxWBS) in differentiated thyroid carcinoma patients. The files of 462 patients who were treated for DTC in our hospital were reviewed. All patients underwent surgical thyroidectomy. 146 patients had data available on a. a dxWBS which was performed less than four months (max 120 days) after 131I ablation with concurrent stimulated TSH stimulated thyroglobulin (Tg) measurement without further therapeutic measures between ablation and dxWBS and b. a second dxWBS or 131I therapy (rxWBS) within 1.5 years after ablation. A discordance between the initial and follow-up scan was found in 25/129 (19%) patients: of 54 patients with a positive initial dxWBS, scan results of a second dxWBS or rxWBS obtained with a suitable distance to the initial scan contradicted the initial one in 15 patients (27%). New lesions were discovered in 10/74 negative first dxWBS cases (14%). A discordance between the initial and follow-up stimulated Tg was found in 5/129 (4%) patients: 2/90 (2%) of patients with a negative stimulated Tg at initial dxWBS subsequently showed a positive results whereas 3/29 (10%) patients with an initially positive Tg showed a negative Tg level at the second procedure. Less than four months after 131I ablation is too early to perform radioiodine diagnostic whole body scintigraphy with concurrent TSH stimulated Tg measurement. The identification of the right, later, timepoint however requires further research.
    Nuklearmedizin 06/2015; 54(4). DOI:10.3413/Nukmed-0733-15-03 · 1.67 Impact Factor
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    ABSTRACT: BACKGROUND: Fatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells' increased demands for membrane, energy, and protein production. METHODS: We investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. FASN inhibition's impact on cell viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection enzyme-linked immunosorbent assay, immunoblotting, and 18 F-fluoromethylcholine uptake measurement, respectively. RESULTS: Relative to that in healthy fallopian tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell lines and primary cultures had 11-fold-100-fold mRNA and protein overexpression. In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression and cell viability and induced apoptosis. Unlike concomitant administration, sequential cerulenin/cisplatin treatment reduced cisplatin's half maximal inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed lower 18 F-fluoro-methylcholine uptake than did cisplatin-sensitive cells, suggesting that metabolic imaging might help guide therapy. CONCLUSIONS: FASN inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian cancer cells and may reverse cisplatin resistance.
    Journal of Translational Medicine 05/2015; 13(1). · 3.99 Impact Factor
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    ABSTRACT: Fatty acid synthase (FASN) is crucial to de novo long-chain fatty acid synthesis, needed to meet cancer cells' increased demands for membrane, energy, and protein production. We investigated FASN overexpression as a therapeutic and chemosensitization target in ovarian cancer tissue, cell lines, and primary cell cultures. FASN expression at mRNA and protein levels was determined by quantitative real-time polymerase chain reaction and immunoblotting and immunohistochemistry, respectively. FASN inhibition's impact on cell viability, apoptosis, and fatty acid metabolism was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide assay, cell death detection enzyme-linked immunosorbent assay, immunoblotting, and (18) F-fluoromethylcholine uptake measurement, respectively. Relative to that in healthy fallopian tube tissue, tumor tissues had 1.8-fold average FASN protein overexpression; cell lines and primary cultures had 11-fold-100-fold mRNA and protein overexpression. In most samples, the FASN inhibitor cerulenin markedly decreased FASN expression and cell viability and induced apoptosis. Unlike concomitant administration, sequential cerulenin/cisplatin treatment reduced cisplatin's half maximal inhibitory concentration profoundly (up to 54%) in a cisplatin-resistant cell line, suggesting platinum (re)sensitization. Cisplatin-resistant cells displayed lower (18) F-fluoro-methylcholine uptake than did cisplatin-sensitive cells, suggesting that metabolic imaging might help guide therapy. FASN inhibition induced apoptosis in chemosensitive and platinum-resistant ovarian cancer cells and may reverse cisplatin resistance.
    Journal of Translational Medicine 05/2015; 13(1):146. DOI:10.1186/s12967-015-0511-3 · 3.99 Impact Factor
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    ABSTRACT: AimInternational guidelines significantly diverge on the effectiveness of thyroid scintigraphy (TS) in the initial work-up of thyroid nodules. In particular, the role of TS to detect or exclude the presence of autonomously functioning thyroid nodules (AFTN) in patients with normal serum thyrotropin (TSH) is still a matter to debate. Here we aimed to review the literature on the prevalence of normal TSH value out of patients with AFTN, and meta-analyze data of the retrieved eligible papers.MethodsA comprehensive literature search of studies published from January 2000 to December 2014 on AFTN detected by TS was performed. Records reporting serum TSH values in AFTN were selected. Pooled prevalence of AFTN with normal TSH values was calculated on a per-patient analysis including 95% confidence intervals (95%CI).ResultsEight records including 2761 AFTN were selected for the meta-analysis. Pooled prevalence of AFTN with normal TSH detected by TS was 50% (95%CI: 32-68%). Selection bias in the included studies and heterogeneity among studies were potential limitations of the meta-analysis.Conclusions Present meta-analysis shows that about one in two patients with AFTN demonstrated by TS has a TSH value within normal references. As a consequence, TSH measurement may not be considered as effective as a single tool to detect or exclude AFTN, and TS remains mandatory.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 05/2015; DOI:10.1111/eci.12456 · 2.83 Impact Factor
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    ABSTRACT: The prostate-specific membrane antigen (PSMA) has recently emerged as a target for radionuclide imaging and therapy of prostate cancer [1, 2]. However, PSMA expression was also shown on the cell membrane of endothelial cells of tumour neovasculature in a number of other cancers such as renal cell carcinoma [3, 4], colon carcinoma, neuroendocrine tumours, melanoma or breast cancer [3]. However, to our knowledge no study has yet investigated the expression of PSMA in the neovasculature of differentiated thyroid cancer (DTC).[68Ga]PSMA-HBED-CC can be used for positron emission tomography (PET)/CT-based staging of prostate cancer [1] as well as for eligibility screening for and monitoring of PSMA-targeted radionuclide therapy [2].Considering the limited number of therapeutic options currently available for patients with metastasized, 131I-negative, [18F]-2-fluorodeoxyglucose-positive DTC [5], we hypothesized that PSMA expression could be present in DTC as well. This would provide an intere ...
    European Journal of Nuclear Medicine 04/2015; DOI:10.1007/s00259-015-3065-y · 5.22 Impact Factor
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    ABSTRACT: Many prognostic systems have been developed for differentiated thyroid cancer. It is unclear which one of these performs "best". Our aim was to compare staging systems applicable to our patient database to identify which best predicts DTC related loss of life expectancy and DTC specific mortality. Database study of DTC patients treated in our centre between 1978 (earliest available data) up to and including July 1, 2014. All were staged in accordance with the AMES, Clinical Class, Memorial Sloan Kettering, Ohio State University, TNM versions 5 and 6/7, University of Alabama, University of Münster and qTNM systems. 2257 differentiated thyroid cancer patients. loss of life expectancy expressed as relative survival and thyroid cancer specific mortality. Comparison was based on p values of univariate Cox regression analyses as well as analysis of the proportion of variance explained (PVE). Median available follow-up time was 7.2 years (range: 0-35.1 years). 327 patients died, 149 of whom died of DTC. Version 7 of the TNM system was best for predicting DTC related mortality (p=7.1*10(-52) ; PVE=0.296), followed by TNM version 5 (p=6.7*10(-44) ; PVE=0.255). For prediction of loss of life expectancy, version 7 of the TNM system was also best, closely followed by the Clinical Class system (p both < 2*10(-16) ). The UICC/AJCC TNM-system version 7 outperforms other prognostic classification systems based on extent of disease at the start of treatment both for prediction of differentiated thyroid cancer related death and for prediction of loss life expectancy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 03/2015; DOI:10.1111/cen.12765 · 3.35 Impact Factor
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    ABSTRACT: Aim: To compare uptake measurements and different methods for the pretherapeutic determination of the effective thyroidal 131I half life (Teff) to the results of posttherapeutic dosimetric measurements. Patients, methods: Retrospective study of 1538 patients who received their first RIT in our department for autonomous thyroid nodules (ATN), autonomous multinodular goiter (AMG) or Graves' disease (GD) between November 1999 and January 2011. Pretherapeutic measurements were performed at any combination of 24 h, 48 h and 6 days after 131I administration. Post-therapy dosimetric measurements were performed in 12 h intervals until discharge. Teff was determined through monoexponential curve fitting. Results: Pretherapeutic Teff values based on measurements at 24 h and 48 h, 24 h and 6 d, 48 h and 6 d as well as on day 24 h, 48 h and 6 d yielded implausible (< 2 d or > 8 d) values for Teff, in 60.4%, 25.7%, 29.1 and 21.4% of available calculations, respectively. The plausible results showed significant, clinically relevant and sometimes considerable overestimations of Teff. Using empirically determined fixed disease specific Teff values resulted in a better congruence between the pre- and posttherapeutic dosimetry results. 24 h measurements were marginally more accurate than 48 h ones in AMG and GD whereas 48 h measurements were marginally more accurate in ATN; these differences are however not clinically relevant. 6 d measurements are clearly less accurate than those after 24 h or 48 h. Conclusion: In ATN, AMG and GD, pretherapeutic dosimetry can be performed by a single uptake measurement at 24 h or 48 h using a fixed, disease specific value for Teff. Additional later measurements do not yield a further clinically relevant contribution to accuracy of pretherapeutic dosimetry.
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    ABSTRACT: The aim of this study is to evaluate the impact of a high resolution (HR) image reconstruction with a voxel size of 2mm in comparison to the most routinely used standard reconstruction with 4mm voxels in patients suffering from prostate cancer having undergone (18)F-methylcholine PET/CT. Phantom studies were performed using a Jaszczak phantom and a custom made phantom containing small hot lesions (size 2-10mm). Clinical evaluation was performed on PET/CT scans of 50 patients. Images were reconstructed with 4mm and 2mm voxel size and analyzed quantitatively using AMIDE and MATLAB. Clinical images were judged by two observers concerning TNM staging, image quality and the correlation of PET and CT data. Phantom studies revealed increased SUVmean and SUVmax values in the HR images (P<0.01). The lower detection limit was approximately 3mm in the HR and 4-5mm in the conventional images. Lower FWHM values were found in the HR images. No significant difference was found concerning the image quality and the correlation of PET and CT (each P>0.5). For both reconstructions, a comparable total amount of lesions was reported (P>0.5) with no impact on the TNM staging. In conclusion, the HR PET reconstruction provides semi-quantitative advantages in the sense of an improved lower detection limit and increased semi-quantitative tumour-to-background ratios. In the setting of choline PET/CT for prostate cancer the high resolution reconstruction could be implemented clinically as there are no relevant qualitative differences between this and the conventional image resolution in terms of image quality, assessment confidence and lesion identification rate.
    Hellenic journal of nuclear medicine 11/2014; DOI:10.1967/s002449910145 · 0.93 Impact Factor
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    ABSTRACT: Abstract Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. The initial treatment consists of total thyroidectomy followed by ablation of thyroid remnants by radioiodine in most cases. As thyroid cells are the only source of thyroglobulin (Tg), circulating Tg serves as a biochemical marker of persistent or recurrent disease in the follow-up of DTC. Due to the suboptimal clinical detection rate of older Tg assays endogenous or exogenous thyrotropin (TSH) stimulations are recommended for unmasking occult disease. However, the development of new Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations, reflecting minimal amounts of thyroid tissue, even without the need for TSH stimulation. Even if the use of these assays still has not found its way in current clinical guidelines, such assays are now increasingly used in clinical practice. As serum Tg measurement is a technically challenging assay and criteria to define a 'highly sensitive' assay may be different, a good knowledge of the technical difficulties and interpretation criteria is of paramount importance for both clinical thyroidologists, laboratory physicians and scientists involved in the care of DTC patients.
    Clinical Chemistry and Laboratory Medicine 10/2014; DOI:10.1515/cclm-2014-0813 · 2.96 Impact Factor
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    ABSTRACT: Context: Recent trial results have revived interest in low activity initial I-131 therapy (RIT) of differentiated thyroid cancer (DTC) Objective: compare different initial I-131 activities for outcome. Design: Database study Setting: University hospital Patients: 1298 (698 low risk, 434 high risk M0 and 136 M1) DTC patients, grouped according to ablation activity (I: ≤2000 MBq (54 mCi), II: 2000-3000 MBq (54-81 mCi) and III: >3000 MBq (81 mCi)), subdivided by age (<45 and ≥45 years at diagnosis). Main outcome measures: Complete remission (CR: Tg below functional sensitivity combined with visually negative I-131 diagnostic whole body scintigraphy), recurrence and DTC specific mortality rates, life expectancy. Results: Low risk patients: in patients <45 a lower median cumulative activity was required to achieve CR in group III (3590 MBq) than in groups I (8050 MBq) and II (6300 MBq). In patients ≥45 DTC specific mortality was significantly higher in group I than in groups II and III (15-year:16.1±7.7%, 0.8±0.8% and 7.2±5.5%, respectively; p=0.004). High risk M0 patients: In patients ≥45 the recurrence rate (15-year: 44.4±16.6%, 24.1±7.6% and 8.6±3.9%; p=0.001) and DTC specific mortality (15-year: 51.8±15.8%, 13.2±4.4% and 9.5±3.7%; p=0.004) were significantly higher in group I than in groups II and III. M1 patients: There were no significant differences in survival results between different activity groups in either age category. Conclusion: Before adopting low initial activity RIT for, especially older, low risk patients, results of long-term follow-up should be regarded critically. Low-activity RIT in older high-risk patients is not to be recommended.
    Journal of Clinical Endocrinology &amp Metabolism 09/2014; 99(12):jc20141631. DOI:10.1210/jc.2014-1631 · 6.31 Impact Factor
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    ABSTRACT: Purpose To determine the frequency of seemingly pathological retroperitoneal uptake in the location of the coeliac ganglia in patients undergoing [68Ga]PSMA-HBED PET/CT. Methods The study included 85 men with prostate cancer referred for [68Ga]PSMA-HBED PET/CT. The PET/CT scans were evaluated for the local finding in the prostate and the presence of lymph node metastases, distant metastases and coeliac ganglia. The corresponding standardized uptake values (SUV) were determined. SUVmax to background uptake (gluteal muscle SUVmean) ratios were calculated for the ganglia and lymph node metastases. Immunohistochemistry was performed on the ganglia. Results In 76 of the 85 patients (89.4 %) at least one ganglion with tracer uptake was found. For the ganglia, SUVmax and SUVmax to background SUVmean ratios were 2.97 ± 0.88 and 7.98 ± 2.84 (range 1.57-6.38 and 2.83-30.6), respectively, and 82.8 % of all ganglia showed an uptake ratio of >5.0. For lymph node metastases, SUVmax and SUVmax to background SUVmean ratios were 8.5 ± 7.0 and 23.31 ± 22.23 (range 2.06-35.9 and 5.25-115.8), respectively. In 35 patients (41.2 %), no lymph node metastases were found but tracer uptake was seen in the ganglia. Immunohistochemistry confirmed strong PSMA expression in the ganglia. Conclusion Coeliac ganglia show a relevant [68Ga]PSMA-HBED uptake in most patients and may mimic lymph node metastases.
    European journal of nuclear medicine and molecular imaging 09/2014; 42(2). DOI:10.1007/s00259-014-2915-3 · 5.22 Impact Factor
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    ABSTRACT: Differentiated thyroid cancer is a rare malignancy, but leaves numerous survivors for life-long follow-up. The cornerstone in current guidelines for follow-up is by measuring the thyroid specific tumour marker, thyroglobulin in serum. Most patients can be followed by this method, but some thyroid cancer patients have antithyroglobulin antibodies in serum, both at diagnosis and after treatment, where follow-up is commenced. These antibodies interfere technically in the immunological methods for measuring thyroglobulin, and the antithyroglobulin antibody positive patients are thus eliminated from following current guidelines. In recent years studies have indicated that following the concentration of antithyroglobulin antibodies in serum may be a surrogate marker for recurrence of the thyroid carcinoma. This has recently resulted in publication of an expert position paper, providing a flow scheme for these particular patients. The current review summarises the literature which is the basis for the paper.
    Current Medicinal Chemistry 08/2014; DOI:10.2174/0929867321666140826120844 · 3.85 Impact Factor
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    ABSTRACT: To assess the risk of differentiated thyroid cancer (DTC) recurrence, DTC-related mortality and life expectancy in relation to the number of courses of (131)I therapy (RIT) and cumulative (131)I activities required to achieve complete remission (CR).
    European journal of nuclear medicine and molecular imaging 07/2014; 41(12). DOI:10.1007/s00259-014-2851-2 · 5.22 Impact Factor
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    ABSTRACT: Context: The determinants of successful I-131 therapy of Graves' disease (GD) are unclear. Objective: To relate dosimetry parameters to outcome of therapy in order to identify significant determinants eu- and/or hypothyroidism after I-131 therapy, in GD patients. Design: Retrospective study. Setting: University hospital. Patients: 206 GD patients treated in our hospital between November of 1999 and January of 2011. All received I-131 therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Main outcome measures: Post-therapy dosimetric thyroid measurements were performed twice daily until discharge; from these measurements thyroid I-131 half-life, the total thyroid absorbed dose and the maximum dose rate after I-131 administration were calculated. Results: 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after I-131 therapy. In univariate analysis non-hyperthyroid and hyperthyroid patients only differed by gender. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal I-131 half life and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (p<0.001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Conclusion: Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.
    Journal of Clinical Endocrinology &amp Metabolism 07/2014; DOI:10.1210/jc.2014-1347 · 6.31 Impact Factor
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    ABSTRACT: A 51-year-old man with a history of metastatic medullary thyroid cancer (MTC) presented with high adrenocorticotropin (ACTH) and urinary free cortisol levels. The diagnosis of ectopic ACTH production, a rare MTC complication, was established in this patient. PET/CT using the somatostatin analogue DOTA-(Tyr)-octreotate labeled with gallium (Ga-DOTATATE) was performed, showing positive radionuclide uptake in multiple MTC metastases. After this therapy with the novel somatostatin analogue, pasireotide was initiated after which urinary free cortisol and ACTH levels decreased. The present case thus illustrates a potential theranostic use of Ga-DOTATATE PET/CT in MTC.
    Clinical Nuclear Medicine 07/2014; DOI:10.1097/RLU.0000000000000522 · 2.86 Impact Factor
  • Markus Luster, Theresia Weber, Frederik A Verburg
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    ABSTRACT: The concept of individualized therapy is rapidly gaining recognition in the management of patients with differentiated thyroid cancer (DTC). This Review provides an overview of the most important elements of this paradigm shift in DTC management and discusses the implications for clinical practice. In the majority of patients with DTC who have an inherently good prognosis, the extent of surgery, the dosage of (131)I therapy and the use of levothyroxine therapy are all aspects suitable for individualization, on the basis of both the stage of disease and the response to treatment. In individuals with advanced disease, newer imaging techniques, advances in (131)I therapy and the use of targeted molecular therapies (such as multitargeted kinase inhibitors) have provided new options for the personalized care of patients, for whom until recently no effective therapies were available. Individualized therapies could reduce adverse effects, including the sometimes debilitating hypothyroidism that used to be required before initiation of (131)I treatment, and major salivary gland damage, a common and unpleasant side effect of (131)I therapy. Highly individualized interdisciplinary treatment of patients with DTC might lead to improved outcomes with reduced severity and frequency of complications and adverse effects. However, in spite of ongoing research, personalized therapies remain in their infancy.
    Nature Reviews Endocrinology 07/2014; 10(9). DOI:10.1038/nrendo.2014.100 · 12.96 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the changes in the thyroid axis setpoint after long-term suppressive levothyroxine therapy for differentiated thyroid carcinoma and the resulting changes in levothyroxine requirement. Ninety-nine differentiated thyroid cancer patients were reviewed. All patients had at least one known TSH-level≥0.01 mU/l (lower detection limit) and <1.0 mU/l within 2 years of initial treatment (time 1) and had at least one TSH-value≥0.01 mU/l and <1.0 mU/l after continuous LT4 therapy for a minimum of 5 years (time 2).At time 2 the mean LT4 dosage/kg body weight, TSH, FT3, and FT4 levels were significantly lower than at time 1, while body weight was higher. At time 2, the FT3/FT4 ratio rate had dropped significantly (p<0.001). At time 1, patients would require 2.96 μg/kg body weight to reach total TSH suppression. The dose of levothyroxine/kg required for suppression can be lowered by about 0.05 μg/kg body weight for each year of suppressive therapy. After a median of 12.7 years of continuous suppressive levothyroxine therapy, patients would require 2.25 μg/kg body weight (-23.5%) to reach total TSH-suppression. At least part of this reduction was independent of aging. As a result of changes in thyroid hormone metabolism and thyroid axis setpoint, long-term TSH-suppressive therapy contributes to a reduction in the dosage of levothyroxine per kilogram body weight required for full TSH suppression over time.
    Hormone and Metabolic Research 05/2014; 46(11). DOI:10.1055/s-0034-1375678 · 2.04 Impact Factor

Publication Stats

762 Citations
441.00 Total Impact Points

Institutions

  • 2012–2015
    • University Hospital RWTH Aachen
      • Department of Neurology
      Aachen, North Rhine-Westphalia, Germany
    • Universität Ulm
      • Clinic of Nuclear Medicine
      Ulm, Baden-Wuerttemberg, Germany
  • 2009–2015
    • University of Wuerzburg
      • Department of Nuclear Medicine
      Würzburg, Bavaria, Germany
    • Department of Nuclear Medicine
      Nyitra, Nitriansky, Slovakia
  • 2014
    • Universitätsklinikum Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2011–2014
    • Maastricht University
      Maestricht, Limburg, Netherlands
  • 2012–2013
    • Maastricht Universitair Medisch Centrum
      Maestricht, Limburg, Netherlands
  • 2011–2013
    • RWTH Aachen University
      Aachen, North Rhine-Westphalia, Germany
  • 2010–2013
    • Ente Ospedaliero Cantonale
      Bellinzona, Ticino, Switzerland
  • 2009–2010
    • St. Antonius Ziekenhuis
      • Department of Nuclear Medicine
      Nieuwegen, Utrecht, Netherlands
  • 2004–2009
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands