Robert Dudczak

Severe Hyperglycemia: Effects of Rehydration on Endocrine Derangements and Blood Glucose Concentration

Diabetic ketoacidosis is associated with an excess secretion of counterregulatory hormones. The effect of rehydration on these endocrine derangements before insulin administration is unknown. Therefore, we measured the effect of rehydration with hypoosmolal fluid (220 mosmol/kg) on blood glucose (BG), immunoreactive insulin (IRI), immunoreactive C-peptide (IRCP), immunoreactive glucagon (IRG), human pancreatic polypeptide (hPP), growth hormone (GH), prolactin (PRL), cortisol, aldosterone, renin (PRC), epinephrine, norepinepnrine, and parathyroid hormone (PTH) in ketoacidotic diabetic patients [pH 7.03 ± 0.05 (SEM); n = 8] and in patients (n = 2) with nonketotic hyperglycemia (BG, 29.8 mmol/L and 46.8 mmol/L). The cumulative net fluid balance after rehydration was 4364 ± 690 ml. Basal insulin was inappropriately low, and IRCP was below the normal range (1.5 ± 0.5 ng/ml). Serum osmolality fell during hypoosmolal rehydration (n = 9) from 335 ± 11 to 315 ± 9 mosmol/kg. Rehydration with hypoosmolal fluid with bicarbonate added at a pH of less than 7.2 induced a fall in BG ranging from 6.1 mmol/L to 22.6 mmol/L, or of 16.7% to 79.8% of the initial BG level, as well as a decrease in plasma lactate and urinary glucose. These effects were paralleled by a decrease in IRG, cortisol, epinephrine, norepinephrine, aldosterone, and PRC. No fall in BG was seen in one patient whose dehydrated state was maintained by infusion of isotonic saline. Low dose insulin treatment was initiated in all patients immediately when no further fall in blood glucose levels was achieved. We conclude that rehydration improves the metabolic situation in severe diabetic hyperglycemia and ketoacidosis by reducing (a) the availability of counterregulatory hormones and (b) peripheral insulin resistance on a cellular level. Thus, proper rehydration will support the beneficial action of simultaneous low dose insulin treatment in patients with severe hyperglycemia.

Long‐term follow‐up of patients with bone metastases from differentiated thyroid carcinoma – surgery or conventional therapy?

objective Surgery of bone metastases from differentiated thyroid carcinoma seems indicated in individual patients. This study was performed (1) to analyse retrospectively patients with bone metastases from differentiated thyroid carcinoma and (2) to evaluate the impact of surgery of bone metastases on survival.

11C-Acetate Positron Emission Tomography Imaging and Image Fusion With Computed Tomography and Magnetic Resonance Imaging in Patients With Recurrent Prostate Cancer

PURPOSE To assess the clinical value of computed tomography (CT) and magnetic resonance imaging (MRI) image fusion with 11C-acetate (AC) positron emission tomography (PET) imaging for detection and exact location of clinically occult recurrences. PATIENTS AND METHODS Fifty prostate cancer patients with elevated/increasing serum prostate-specific antigen levels after radical therapy underwent whole-body AC PET. Uptake was initially interpreted as normal, abnormal, or equivocal. In case of abnormal or equivocal uptake, additional conventional imaging techniques, such as CT, MRI, and bone scans, were performed. To precisely define the anatomic location of abnormal uptake and to improve characterization of equivocal lesions, a software-assisted image fusion (CT-PET, MRI-PET) was performed and evaluated as site-by-site analysis of 51 abnormal (n = 37) or equivocal (n = 14) sites of all 50 patients. In 17 patients, additional histopathologic evaluation was available. RESULTS In five (10%), 13 (26%), and 32 (64%) of the 50 patients, AC PET studies demonstrated AC uptake judged as normal, equivocal, and abnormal, respectively. Image fusion changed characterization of equivocal lesions as normal in five (10%) of 51 sites and abnormal in nine (18%) of 51 sites. It precisely defined the anatomic location of abnormal uptake in 37 (73%) of 51 sites. AC PET findings did influence patient management in 14 (28%) of 50 patients. CONCLUSION Retrospective fusion of AC PET and CT/MRI is feasible and seems to be essential for final diagnosis. This is particularly true in patients with AC uptake in the prostate region.

Pharmacoresistance in epilepsy: A pilot PET study with the p-glycoprotein substrate R-[(11)C]verapamil

Summary:  Purpose and Methods: Regional overexpression of the multidrug transporter P‐glycoprotein (P‐gp) in epileptic brain tissue may lower target site concentrations of antiepileptic drugs and thus contribute to pharmacoresistance in epilepsy. We used the P‐gp substrate R‐[11C]verapamil and positron emission tomography (PET) to test for differences in P‐gp activity between epileptogenic and nonepileptogenic brain regions of patients with drug‐resistant unilateral temporal lobe epilepsy (n = 7). We compared R‐[11C]verapamil kinetics in homologous brain volumes of interest (VOIs) located ipsilateral and contralateral to the seizure focus. Results: Among different VOIs, radioactivity was highest in the choroid plexus. The hippocampal VOI could not be used for data analysis because it was contaminated by spill‐in of radioactivity from the adjacent choroid plexus. In several other temporal lobe regions that are known to be involved in seizure generation and propagation ipsilateral influx rate constants K1 and efflux rate constants k2 of R‐[11C]verapamil were descriptively increased as compared to the contralateral side. Parameter asymmetries were most prominent in parahippocampal and ambient gyrus (K1, range: −3.8% to +22.3%; k2, range: −2.3% to +43.9%), amygdala (K1, range: −20.6% to +31.3%; k2, range: −18.0% to +38.9%), medial anterior temporal lobe (K1, range: −8.3% to +14.5%; k2, range: −14.5% to +31.0%) and lateral anterior temporal lobe (K1, range: −20.7% to +16.8%; k2, range: −24.4% to +22.6%). In contrast to temporal lobe VOIs, asymmetries were minimal in a region presumably not involved in epileptogenesis located outside the temporal lobe (superior parietal gyrus, K1, range: −3.7% to +4.5%; k2, range: −4.2% to +5.8%). In 5 of 7 patients, ipsilateral efflux (k2) increases were more pronounced than ipsilateral influx (K1) increases, which resulted in ipsilateral reductions (10%–26%) of R‐[11C]verapamil distribution volumes (DV). However, for none of the examined brain regions, any of the differences in K1, k2 and DV between the epileptogenic and the nonepileptogenic hemisphere reached statistical significance (p > 0.05, Wilcoxon matched pairs test). Conclusions: Even though we failed to detect statistically significant differences in R‐[11C]verapamil model parameters between epileptogenic and nonepileptogenic brain regions, it cannot be excluded from our pilot data in a small sample size of patients that regionally enhanced P‐gp activity might contribute to drug resistance in some patients with temporal lobe epilepsy.

Positron emission tomography imaging of adrenal masses: 18F-fluorodeoxyglucose and the 11β-hydroxylase tracer 11C-metomidate

Purpose11C-metomidate (MTO), a marker of 11β-hydroxylase, has been suggested as a novel positron emission tomography (PET) tracer for adrenocortical imaging. Up to now, experience with this very new tracer is limited. The aims of this study were (1) to evaluate this novel tracer, (2) to point out possible advantages in comparison with 18F-fluorodeoxyglucose (FDG) and (3) to investigate in vivo the expression of 11β-hydroxylase in patients with primary aldosteronism.Methods Sixteen patients with adrenal masses were investigated using both MTO and FDG PET imaging. All patients except one were operated on. Five patients had non-functioning adrenal masses, while 11 had functioning tumours(Cushing’s syndrome, n=4; Conn’s syndrome, n=5; phaeochromocytoma, n=2). Thirteen patients had benign disease, whereas in three cases the adrenal mass was malignant (adrenocortical cancer, n=1; malignant phaeochromocytoma, n=1; adrenal metastasis of renal cancer, n=1).ResultsMTO imaging clearly distinguished cortical from non-cortical adrenal masses (median standardised uptake values of 18.6 and 1.9, respectively, p<0.01). MTO uptake was slightly lower in patients with Cushing’s syndrome than in those with Conn’s syndrome, but the difference did not reach statistical significance. The expression of 11β-hydroxylase was not suppressed in the contralateral gland of patients with Conn’s syndrome, whereas in Cushing’s syndrome this was clearly the case. The single patient with adrenocortical carcinoma had MTO uptake in the lower range.ConclusionMTO could not definitely distinguish between benign and malignant disease. FDG PET, however, identified clearly all three study patients with malignant adrenal lesions. We conclude: (1) MTO is an excellent imaging tool to distinguish adrenocortical and non-cortical lesions; (2) the in vivo expression of 11β-hydroxylase is lower in Cushing’s syndrome than in Conn’s syndrome, and there is no suppression of the contralateral gland in primary aldosteronism; (3) for the purpose of discriminating between benign and malignant lesions, FDG is the tracer of choice.

Myocardial m-[123I]Iodobenzylguanidine Scintigraphy for the Assessment of Adrenergic Cardiac Innervation in Patients With IDDM: Comparison With Cardiovascular Reflex Tests and Relationship to Left Ventricular Function

Cardiac imaging using m-[123I]iodobenzylguanidine (mIBG) reflects sympathetic myocardial innervation. In patients with insulin-dependent diabetes mellitus (IDDM), the following were studied: 1) the prevalence of derangements of cardiac autonomic innervation as detected by mIBG scintigraphy in comparison with cardiovascular reflex tests and 2) the relationship between adrenergic cardiac innervation and left ventricular (LV) function. Twenty-four patients with IDDM without overt heart disease were studied after silent coronary artery disease was excluded by 201Tl scintigraphy. Cardiac innervation was evaluated by both mIBG scintigraphy (tomographic imaging) and cardiovascular reflex tests. Systolic (ejection fraction [EF] percentage) and diastolic (peak filling rate [PFR] defined as end-diastolic volumes per second [EDV/s]) LV function were determined by equilibrium radionuclide angiography at rest and during bicycle exercise. mIBG scintigraphy was also performed in 10 control subjects. All control subjects exhibited a normal myocardial mIBG distribution. Among diabetic patients, only six had normal mIBG scans (group 1), whereas 18 had evidence of regional adrenergic denervation (group 2). Reflex tests suggested cardiac autonomic neuropathy in only seven of these patients (P < 0.01 vs. mIBG). All patients had a normal EF at rest. However, group 2 showed an impaired response to exercise as indicated by a smaller increase in EF (5 ± 6 vs. 13 ± 5%, P < 0.05) and a lower PFR (5.9 ± 0.8 vs. 7.3 ± 1.2 EDV/s, P < 0.01). Myocardial mIBG scintigraphy reveals that in patients with IDDM, sympathetic myocardial dysinnervation is much more common than previously thought. Furthermore, subclinical LV dysfunction is related to derangements of adrenergic cardiac innervation.

FDG-PET in adrenocortical carcinoma.

Adrenal cortical carcinoma (ACC) is a rare malignant neoplasm with a poor prognosis. Radical surgery of the primary tumor and of local as well as of distant recurrence is the only effective treatment, and requires accurate and early localization of recurrent tumors. In this regard, we prospectively scanned 10 patients with ACC, 8 during follow-up and 2 at primary work-up. In all patients PET scans from the neck to the upper thighs were obtained 45 minutes after injection of 370 MBq [18F]FDG. Reading was done visually, with the investigator blinded to the results of other diagnostic modalities. All known sites of ACC lesions showed markedly increased FDG uptake. In 3 patients, previously unknown lesions were identified by PET in the lung (one lesion), the abdomen (3 lesions), and the skeleton (multiple), respectively. One false positive liver focus was shown by PET aside from the true positive lung metastases in the same patient. The sensitivity/specificity of PET based on different organs was 100/97%, that based on the number of PET-detected lesions (N = 23) was 100/95%. PET altered or influenced the tumor stage in 3/10 patients, modifying the subsequent therapeutic management in 2/10 patients. We conclude that FDG-PET is highly useful in ACC and should be included in the work-up for initial staging as well as for follow-up.

No Immunological Benefit of Selenium in Consecutive Patients with Autoimmune Thyroiditis

BACKGROUND Recently it has been demonstrated that after selenium (Se) supplementation in autoimmune thyroiditis (AIT) patients, there was a significant decrease of thyroid peroxidase (TPO) autoantibody (TPOAb) levels. The aim of our study was to evaluate the immunological benefit of Se administration in unselected AIT patients and thus address the question whether Se administration should generally be recommended for AIT patients. METHODS Thirty-six consecutive AIT patients (aged 19-85 years) were included in the present study. In addition to their levothyroxine (LT(4)) treatment, 18 patients received 200 microg (2.53 micromol) sodium selenite per day orally for the time span of 3 months, whereas 18 patients received placebo. All patients had measurement of thyroid hormones, thyrotropin (TSH), autoantibodies (thyroglobulin antibodies [TgAb] and TPOAb), Se levels, and intracellular cytokine detection in CD4(+) and CD8(+) T cells of peripheral blood mononuclear cells (PBMC) by flow cytometry before and after Se or placebo administration. RESULTS No significant difference in the TPOAb levels was found after Se administration (524 +/- 452 vs. 505 +/- 464 IU/mL; p > 0.05). Furthermore, we found no significant differences in the CD4(+) or CD8(+) cytokine pattern (IFN-gamma, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, TNF-alpha, TNF-beta) in patients before and after Se administration, in patients before and after placebo administration and between Se group and placebo group before and after Se vs. placebo administration. CONCLUSION We demonstrate that Se administration in our AIT patients cohort does not induce significant immunological changes, either in terms of cytokine production patterns of peripheral T lymphocytes or of TPOAb levels. Our data suggest that AIT patients with moderate disease activity (in terms of TPOAb and cytokine production patterns) may not (equally) benefit as patients with high disease activity.

Isotopic renal function studies in severe hypothyroidism and after thyroid hormone replacement therapy.

Aim: To investigate the possible changes in the renal tubular function in severe short-term hypothyroidism using 99mTc-MAG3 renography. Methods: 27 consecutive thyroidectomized patients (7 males and 20 females) aged 19–79 (mean 53) years were included in the present study. 99mTc-MAG3 renography was performed in all patients before and after thyroid hormone replacement therapy. In addition, 51Cr-EDTA clearance and serum creatinine concentrations were determined. Results: The serum creatinine concentrations were significantly increased in hypothyroidism as compared with the concentrations after thyroxine substitution (1.30 ± 0.44 vs. 1.04 ± 0.32 mg/dl, p < 0.05). According to the 51Cr-EDTA clearance, the glomerular filtration rate was significantly lower in hypothyroidism than after treatment (61 ± 18 vs. 75 ± 23 ml/min). In contrast, we did not find any significant change in the renographic parameters for 99mTc-MAG3 before and after treatment (total excreted activity 20 min after administration 51 ± 12 vs. 54 ± 14%; Tmax left:right 4.2 ± 1.77 : 3.91 ± 1.06 min vs. 4.1 ± 1.66 : 4.4 ± 1.96 min). Conclusions: We did not find any influence of thyroid hormones on the outcome of 99m Tc-MAG3 renography. As 99mTc-MAG3 reflects the tubular function, it seems that the renal hemodynamic changes in severe hypothyroidism mainly affect the glomerular function. In general, the glomerular filtration rate reduction seems to be reversible after hormone substitution therapy; however, care has to be taken in patients with renal insufficiency.

Diagnostic imaging in Merkel cell carcinoma: Lessons to learn from 16 cases with correlation of sonography, CT, MRI and PET ☆

OBJECTIVE The authors report imaging findings in a series of 16 patients with MCC, a rare tumour which is often managed primarily by a dermatologist. To our knowledge, no equivalent series of MCC has been described in the nuclear medicine literature. MATERIAL AND METHODS In this IRB-approved retrospective noncomparative case series 16 patients with biopsy-proven Merkel cell carcinoma were included between January 1999 and October 2007. Twenty-nine whole body PET scans (18F-FDG n=24, 18F-FDOPA n=5) in 16 patients were retrospectively reviewed with regard to tracer uptake in six anatomical sites per patient. For 127/144 of FDG-PET evaluated regions and 68/144 of regions depicted by conventional imaging methods, a valid standard of reference could be obtained. A combined standard of reference was applied, which consisted of histopathology (lymphadenectomy or biopsy) or clinical or radiological follow-up for at least 12 months. RESULTS the mean FDG uptake over the clinicopatholigical verified FDG avid areas was 4.7 SUV (1.5-9.9 SUV). The region based assessment of diagnostic value, in consideration of the standard of reference, resulted in a sensitivity of 85.7% and a specificity of 96.2% of FDG-PET (n=127) and in a combined sensitivity of 95.5% and a specificity of 89.1% for morphological imaging methods (n=68). Differences between methods did not reach statistical significance (p=1.00, p=0.18). CONCLUSIONS FDG-PET is a highly useful whole body staging method of comparable value compared to conventional imaging methods with restricted field of view. The lessons learned from case series are discussed.