119 research outputs found
Somatostatin Receptor Scintigraphy in Medullary Thyroid Cancer
Medullary thyroid cancer (MTC) is a neuroendocrine tumor originating from the calcitonināsecreting C cells. Surgery, consisting of a total thyroidectomy and an extensive lymph node dissection, is the only effective treatment in MTC; however, metastases are frequently found in the regional cervical lymph. The biochemical marker for MTC is calcitonin, and this is frequently used for the detection of persistent/residual/metastatic tumor. The value of 111Inālabeled somatostatin receptor scintigraphy (SRS) in patients with MTC is limited, with sensitivity ranging between 0 and 75%. Other scintigraphic imaging techniques such as 18FāFDG PET, 18FāDOPA PET, and PET imaging with 68Gaālabeled DOTA peptides combined with CT imaging are upcoming. Treatment of patients with metastatic disease with the current available somatostatin analogues, octreotide and lanreotide, does not seem to have an effect on survival but may be considered to control flushing and diarrhea in some patients. Experience with peptide receptor radionuclide therapy is limited in this patient group and disappointing. New therapies in the treatment of metastatic MTC use target tyrosine kinase receptors inhibitors belonging to the same family group of proteins as RET
Clinical implications of the oncometabolite succinate in SDHx-mutation carriers
Succinate dehydrogenase (SDH) mutations lead to the accumulation of succinate, which acts as an oncometabolite. Germline SDHx mutations predispose to paraganglioma (PGL) and pheochromocytoma (PCC), as well as to renal cell carcinoma and gastro-intestinal stromal tumors. The SDHx genes were the first tumor suppressor genes discovered which encode for a mitochondrial enzyme, thereby supporting Otto Warburg's hypothesis in 1926 that a direct link existed between mitochondrial dysfunction and cancer. Accumulation of succinate is the hallmark of tumorigenesis in PGL and PCC. Succinate accumulation inhibits several Ī±-ketoglutarate dioxygenases, thereby inducing the pseudohypoxia pathway and causing epigenetic changes. Moreover, SDH loss as a consequence of SDHx mutations can lead to reprogramming of cell metabolism. Metabolomics can be used as a diagnostic tool, as succinate and other metabolites can be measured in tumor tissue, plasma and urine with different techniques. Furthermore, these pathophysiological characteristics provide insight into therapeutic targets for metastatic disease. This review provides an overview of the pathophysiology and clinical implications of oncometabolite succinate in SDHx mutations
Blood sampling for metanephrines comparing venipuncture vs. indwelling intravenous cannula in healthy subjects
Background: To diagnose pheochromocytoma or sympathetic paraganglioma, guidelines recommend blood sampling after at least 30 min of supine rest and using an indwelling intravenous cannula is preferred. Although blood sampling by venipuncture is more convenient and cost-effective, it is unknown whether venipuncture affects plasma concentrations of free metanephrines (MNs). We therefore investigated whether there is a difference in plasma concentrations of free MNs collected by venipuncture or by an intravenous cannula. Methods: We included 22 healthy participants (12 men and 10 women, median age 26 years). We collected blood using an indwelling cannula and venipuncture to determine plasma concentrations of free MNs and catecholamines, and calculated the median of the individually calculated absolute and relative differences. Results: Plasma concentrations of free MN, normetanephrine (NMN) and epinephrine were higher with blood sampling using venipuncture compared to that when using an indwelling cannula. The median (interquartile range [IQR]) difference was MN 0.020 (Ć¢'0.004 to 0.040) nmol/L, median percentage difference 20.5% (Ć¢'2.4 to 35.2%), NMN 0.019 (Ć¢'0.004 to 0.077) nmol/L, median percentage difference 4.6% (Ć¢'1.1 to 25.4%) and epinephrine 0.022 (0.007-0.079) nmol/L, median percentage difference 24.9% (7.8-83.3%). When the two sampling conditions were compared, plasma-free 3-methoxytyramine (3-MT), norepinephrine and dopamine concentrations did not differ. Conclusions: Blood sampling by venipuncture resulted in statistically significant higher concentrations of MN, NMN and epinephrine compared to sampling by means of an indwelling cannula. However, differences were small. For most patients it seems justifiable to collect blood via venipuncture
The Value of Pre-Ablative I-131 Scan for Clinical Management in Patients With Differentiated Thyroid Carcinoma
BACKGROUND: A diagnostic I-131 (Dx) scan is used to detect a thyroid remnant or metastases before treatment of differentiated thyroid cancer (DTC) with I-131. The aim of this study is to specify in which patients with DTC a Dx scan could have an additional value, by studying the effect of the Dx scan on clinical management. METHODS: Patients with DTC, treated with I-131 after thyroidectomy were included in this retrospective cohort study. Twenty-four hours after administration of 37 MBq I-131 a whole body Dx scan and an uptake measurement at the original thyroid bed were performed. Outcomes of the Dx scan and the subsequent changes in clinical management, defined as additional surgery or adjustment of I-131 activity, were reported. Risk factors for a change in clinical management were identified with a binary logistic regression. RESULTS: In 11 (4.2%) patients clinical management was changed, including additional surgery (n=5), lowering I-131 activity (n=5) or both (n=1). Risk factors for a change in clinical management were previous neck surgery (OR 5.9, 95% CI: 1.4-24.5), surgery in a non-tertiary center (OR 13.4, 95% CI: 2.8 ā 63.8), TSH <53.4 mU/L (OR 19.64, 95% CI: 4.94-78.13), thyroglobulin ā„50.0 ng/L (OR 7.4, 95% CI: 1.6-34.9) and free T4 ā„4.75 pmol/L (OR 156.8, 95% CI: 128.4-864.2) CONCLUSION: The Dx scan can potentially change clinical management before treatment with I-131, but the yield is low. A Dx-scan should only be considered for patients with a high pre-scan risk of a change in management, based on patient history and prior center-based surgical outcomes
The effect of metformin on cardiovascular risk profile in patients without diabetes presenting with acute myocardial infarction:data from the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) trial
Objective: In patients with diabetes mellitus, metformin treatment is associated with reduced mortality and attenuation of cardiovascular risk. As a subanalysis of the Glycometabolic Intervention as adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) study, we evaluated whether metformin treatment in patients with ST-segment elevation myocardial infarction (STEMI) without diabetes improves the cardiovascular risk profile. Methods: A total of 379 patients, without known diabetes, presenting with STEMI were randomly allocated to receive metformin 500 mg twice daily or placebo for 4 months. Results: After 4 months, the cardiovascular risk profile of patients receiving metformin (n= 172) was improved compared with placebo (n= 174); glycated hemoglobin (5.83% (95% CI 5.79% to 5.87%) vs 5.89% (95% CI 5.85% to 5.92%); 40.2 mmol/mol (95% CI 39.8 to 40.6) vs 40.9 mmol/mol (40.4 to 41.2), p= 0.049); total cholesterol (3.85 mmol/L (95% CI 3.73 to 3.97) vs 4.02 mmol/L (95% CI 3.90 to 4.14), p= 0.045); low-density lipoprotein cholesterol (2.10 mmol/L (95% CI 1.99 to 2.20) vs 2.3 mmol/L (95% CI 2.20 to 2.40), p= 0.007); body weight (83.8 kg (95% CI 83.0 to 84.7) vs 85.2 kg (95% CI 84.4 to 86.1), p= 0.024); body mass index (26.8 kg/m(2) (95% CI 26.5 to 27.0) vs 27.2 kg/m(2) (95% CI 27.0 to 27.5), p= 0.014). Levels of fasting glucose, postchallenge glucose, insulin, high-density lipoprotein cholesterol, and blood pressure were similar in both groups. Conclusions: Among patients with STEMI without diabetes, treatment with metformin for 4 months resulted in a modest improvement of the cardiovascular risk profile compared with placebo
Hypocalcemia induced by tyrosine kinase inhibitors:targeted treatment with 'untargeted' side effects
Experimentele farmacotherapi
Impact of the Introduction of Calcimimetics on Timing of Parathyroidectomy in Secondary and Tertiary Hyperparathyroidism
Hyperparathyroidism (HPT), both secondary and tertiary, is common in patients with end-stage renal disease, and is associated with severe bone disorders, cardiovascular complications, and increased mortality. Since the introduction of calcimimetics in 2004, treatment of HPT has shifted from surgery to predominantly medical therapy. The aim of this study was to evaluate the impact of this change of management on the HPT patient population before undergoing (sub-)total parathyroidectomy (PTx). Overall, 119 patients with secondary or tertiary HPT undergoing PTx were included in a retrospective, single-center cohort. Group A, who underwent PTx before January 2005, was compared with group B, who underwent PTx after January 2005. Patient characteristics, time interval between HPT diagnosis and PTx, and postoperative complications were compared. Group A comprised 70 (58.8 %) patients and group B comprised 49 (41.2 %) patients. The median interval between HPT diagnosis and PTx was 27 (interquartile range [IQR] 12.5-48.0) and 49 (IQR 21.0-75.0) months for group A and B, respectively (p = 0.007). Baseline characteristics were similar among both groups. The median preoperative serum parathyroid hormone (PTH) level was 936 pg/mL (IQR 600-1273) for group A versus 1091 pg/mL (IQR 482-1373) for group B (p = 0.38). PTx resulted in a dramatic PTH reduction (less than twofold the upper limit: A, 80.0 %; B, 85.4 %), and postoperative complication rates were low in both groups (A: 7.8 %; B: 10.2 %) [p = 0.66]. The introduction of calcimimetics in 2004 is associated with a significant 2-year delay of surgery with continuously elevated preoperative PTH levels, while parathyroid surgery, even in a fragile population, is considered a safe and effective procedure
Localization of parathyroid adenomas using 11C-methionine pet after prior inconclusive imaging
Purpose: Minimally invasive parathyroidectomy (MIP) is the recommended treatment in primary hyperparathyroidism (pHPT) for which accurate preoperative localization is essential. The current imaging standard consists of cervical ultrasonography (cUS) and MIBI-SPECT/CT. 11C-MET PET/CT has a higher resolution than MIBI-SPECT/CT. The aim of this study was to determine the diagnostic performance of 11CMET PET/CT after initial inconclusive or negative localization.Ā Methods: We performed a retrospective single center cohort study of patients with pHPT undergoing parathyroid surgery after prior negative imaging and later localization by means of 11C-MET PET/CT between 2006 and 2014. Preoperative localization by 11C-MET PET/CT was compared with later surgical localization, intraoperative quick PTH (IOPTH), duration of surgery, histopathology, and follow-up data. Also, differences in duration of surgery between the groups with and without correct preoperative localization were analyzed.Ā Results: In 18/28 included patients a positive 11C-MET-PET/CT result corresponded to the surgical localized adenoma (64%). In 3/28 patients imaging was false positive and no adenoma was found. In 7/28 patients imaging was false negative at the side of the surgically identified adenoma. Sensitivity of 11C-MET PET/ CT was 72% (18/25). Duration of surgery of correctly localized patients was significantly shorter compared to falsely negative localized patients (p = 0.045).Ā Conclusion: In an intention to treat 11C-MET-PET/CT correctly localized the parathyroid adenoma in 18/28 (64%) patients, after previous negative imaging. A preoperatively correct localized adenoma leads to a more focused surgical approach (MIP) potentially reducing duration of surgery and potentially healthcare costs
Use of Salivary Iodine Concentrations to Estimate the Iodine Status of Adults in Clinical Practice
BACKGROUND: Measurement of the 24-h urinary iodine concentration or urinary iodine excretion (UIE) is the gold standard to determine iodine status; however, this method is inconvenient. The use of salivary iodine could be a possible alternative since salivary glands express the sodium-iodine symporter. OBJECTIVES: We aimed to establish the correlation between the salivary iodine secretion and UIE, to evaluate the clinical applicability of the iodine saliva measurement. METHODS: We collected 24-h urine and saliva samples from 40 participantsĀ ā„18 y: 20 healthy volunteers with no specific diet (group 1), 10 patients with differentiated thyroid cancer with a low dietary intake (<50Ā Ī¼g/d, group 2), and 10 patients with a high iodine status as the result of the use of amiodarone (group 3). Urinary and salivary iodine were measured using a validated inductively coupled plasma MS method. To correct for differences in water content, the salivary iodine concentration (SIC) was corrected for salivary protein and urea concentrations (SI/SP and SI/SU, respectively). The intra- and inter-individual CVs were calculated, and the Kruskal-Wallis test and Spearman's correlation were used. RESULTS: The intra-individual CVs for SIC, SI/SP, and SI/SU were 63.8%, 37.7%, and 26.9%, respectively. The inter-individual CVs for SIC, SI/SP, and SI/SU were 77.5%, 41.6% and 47.0%, respectively. We found significant differences (PĀ <Ā 0.01) in urinary and salivary iodine concentrations between all groups [the 24-h UIE values were 176 Ī¼g/d (IQR, 96.1ā213 Ī¼g/d), 26.0 Ī¼g/d (IQR, 22.0ā37.0 Ī¼g/d), and 10.0*10(3) Ī¼g/d (IQR, 7.57*10(3)ā11.4*10(3) Ī¼g/d) in groups 1ā3, respectively; the SIC values were 136 Ī¼g/L (IQR, 86.3ā308 Ī¼g/L), 71.5 Ī¼g/L (IQR, 29.5ā94.5 Ī¼g/L), and 14.3*10(3) Ī¼g/L (IQR, 10.6*10(3)ā25.6*10(3) Ī¼g/L) in groups 1ā3, respectively]. Correlations between the 24-h UIE and SIC, SI/SP, and SI/SU values were strong (Ļ = 0.80, Ļ = 0.90, and Ļ = 0.86, respectively; PĀ <Ā 0.01). CONCLUSIONS: Strong correlations were found between salivary and urinary iodine in adults with different daily iodine intakes. A salivary iodine measurement can be performed to assess the total iodine body pool, with the recommendation to correct for salivary protein or urea
Unilateral and Bilateral Adrenalectomy for Pheochromocytoma Requires Adjustment of Urinary and Plasma Metanephrine Reference Ranges
Context: Follow-up after adrenalectomy for pheochromocytoma is recommended because of a recurrence risk. During follow-up, plasma and/or urinary metanephrine (MN) and normetanephrine (NMN) are interpreted using reference ranges obtained in healthy subjects. Objective: Because adrenalectomy may decrease epinephrine production, we compared MN and NMN concentrations in patients after adrenalectomy to concentrations in a healthy reference population. Design: A single-center cohort study was performed in pheochromocytoma patients after adrenalectomy between 1980 and 2011. Subjects: Seventy patients after unilateral and 24 after bilateral adrenalectomy were included. Main Outcome Measures: Plasma-free and urinary-deconjugated MN and NMN determined at 3 to 6 months and annually until 5 years after adrenalectomy were compared with concentrations in a reference population. Data are presented in median (interquartile range). Results: Urinary and plasma MN concentrations 3 to 6 months after unilateral adrenalectomy were lower compared with the reference population (39 [31-53] mu mol/mol creatinine and 0.14 [0.09-0.18] nmol/L vs 61 [49-74] mu mol/mol creatinine and 0.18 [0.13-0.23] nmol/L, respectively, both P <.05). Urinary MN after bilateral adrenalectomy was reduced even further (7 [1-22] mu mol/mol creatinine; P <.05). Urinary and plasma NMN were higher after unilateral adrenalectomy (151 [117-189] mu mol/mol creatinine and 0.78 [0.59-1.00] nmol/L vs 114 [98-176] mu mol/mol creatinine and 0.53 [0.41-0.70] nmol/L; both P <.05). Urinary NMN after bilateral adrenalectomy was higher (177 [106-238] mu mol/mol creatinine; P <.05). Changes in urinary and plasma MNs persisted during follow-up. Conclusion: Concentrations of MN are decreased, whereas NMN concentrations are increased after unilateral and bilateral adrenalectomy. Adjusted reference values for MN and NMN are needed in the postsurgical follow-up of pheochromocytoma patients. (J Clin Endocrinol Metab 98:1076-1083, 2013
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