Hyperinsulinemic Hypoglycemia in Three Generations of a Family with Glucokinase Activating Mutation, c.295T>C (p.Trp99Arg).

Familial Hyperinsulinemic Hypoglycemia (FHH) is a very rare disease with heterogeneous clinical manifestations. There are only a few reports of heterozygous activating mutations of glucokinase (GCK) attributable to FHH, with no reports describing effects in the course in pregnancy with affected mother/affected child. A large kindred with FHH and GCK:c.295T>C (p.Trp99Arg) pathogenic variant was identified in which four family members from three generations were affected. The clinical follow up in one clinical center lasted up to 30 years, with different times of diagnosis ranging from neonate period to adulthood. The severity of hypoglycemia was mild/severe and fasting was the trigger for hypoglycemia. Response to diazoxide varied from good, in the neonate, to moderate/poor, in childhood/adulthood; however, this was biased by poor compliance. Treatment with somatostatin analogues was discontinued due to side effects. Over time, patients developed clinical adaptation to very low glucose levels. During pregnancy, episodes of severe hypoglycemia in the first trimester were observed, which responded very well to steroids. The clinical course of the GCK:c.295T>C (p.Trp99Arg) mutation varied in the same family, with the development of clinical adaptation to very low glucose levels over time. Treatment with steroids might prevent hypoglycemia during pregnancy in an affected mother.

99mTc Labeled Glucagon-Like Peptide-1-Analogue (99mTc-GLP1) Scintigraphy in the Management of Patients with Occult Insulinoma.

INTRODUCTION: The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. MATERIALS AND METHODS: Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions. RESULTS: Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient). CONCLUSIONS: 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective surgical treatment. This imaging technique may eliminate the need to perform invasive procedures in case of occult insulinoma.

Optimization of image reconstruction method for SPECT studies performed using [99mTc-EDDA/HYNIC] octreotate in patients with neuroendocrine tumors.

BACKGROUND: Somatostatin receptor scintigraphy (SRS) is a useful tool in the assessment of GEP-NET (gastroenteropancreatic neuroendocrine tumor) patients. The choice of appropriate settings of image reconstruction parameters is crucial in interpretation of these images. The aim of the study was to investigate how the GEP NET lesion signal to noise ratio (TCS/TCB) depends on different reconstruction settings for Flash 3D software (Siemens). METHODS: SRS results of 76 randomly selected patients with confirmed GEP-NET were analyzed. For SPECT studies the data were acquired using standard clinical settings 3-4 h after the injection of 740 MBq 99mTc-[EDDA/HYNIC] octreotate. To obtain final images the OSEM 3D Flash reconstruction with different settings and FBP reconstruction were used. First, the TCS/TCB ratio in voxels was analyzed for different combinations of the number of subsets and the number of iterations of the OSEM 3D Flash reconstruction. Secondly, the same ratio was analyzed for different parameters of the Gaussian filter (with FWHM = 2-4 times greater from the pixel size). Also the influence of scatter correction on the TCS/TCB ratio was investigated. RESULTS: With increasing number of subsets and iterations, the increase of TCS/TCB ratio was observed. With increasing settings of Gauss [FWHM coefficient] filter, the decrease of TCS/TCB ratio was reported. The use of scatter correction slightly decreases the values of this ratio. CONCLUSIONS: OSEM algorithm provides a meaningfully better reconstruction of the SRS SPECT study as compared to the FBP technique. A high number of subsets improves image quality (images are smoother). Increasing number of iterations gives a better contrast and the shapes of lesions and organs are sharper. The choice of reconstruction parameters is a compromise between image qualitative appearance and its quantitative accuracy and should not be modified when comparing multiple studies of the same patient.

Imaging of inflamed carotid artery atherosclerotic plaques with the use of 99mTc-HYNIC-IL-2 scintigraphy in end-stage renal disease patients.

PURPOSE: Identification of vulnerable plaques remains crucial for better cardiovascular risk assessment. At least 20% of inflammatory cells within unstable (vulnerable) plaques comprise T lymphocytes, which contain receptors for interleukin-2 (IL-2); those receptors can be identified by scintigraphy with radiolabelled IL-2.The aim of this study was to identify the "inflamed" (vulnerable) plaques by scintigraphy using IL-2 labelled with (99m)Tc in the selected, high cardiovascular risk group of end-stage renal disease (ESRD) patients. METHODS: A total of 28 patients (18 men, 10 women, aged 55.2 ± 9.6 years, 17 on peritoneal dialysis, 11 on haemodialysis) underwent common carotid artery (CCA) scintigraphy with the use of (99m)Tc-hydrazinonicotinamide (HYNIC)-IL-2. In all cases, ultrasound examination of the CCA was performed and levels of selected proinflammatory factors, atherogenic markers and calcium-phosphate balance parameters were measured. Finally, the target to non-target (T/nT) ratio of IL-2 uptake in atherosclerotic plaques with intima-media thickness (IMT), classic cardiovascular risk factors and concentrations of the measured factors were compared. RESULTS: Increased (99m)Tc-HYNIC-IL-2 uptake in atherosclerotic plaques in 38/41 (91%) cases was detected. The median T/nT ratio of focal (99m)Tc-HYNIC-IL-2 uptake in atherosclerotic plaques was 2.35 (range 1.23-3.63). The mean IMT value on the side of plaques assessed by scintigraphy was 0.79 ± 0.18 mm (median 0.8, range 0.5-1.275). Correlations between T/nT ratio and homocysteine (R = 0.22, p = 0.037), apolipoprotein B (apoB) (R = 0.31, p = 0.008), apoB to apoA-I ratio (R = 0.29, p = 0.012) and triglyceride concentration (R = 0.26, p = 0.021) were detected. A lower T/nT ratio in patients with better parameters of nutritional status (haemoglobin, albumin, adiponectin) in comparison with patients with worse nutritional parameters (3.20 ± 0.5 vs 2.16 ± 0.68, p = 0.025) was revealed as well as a difference between values of T/nT ratio in groups of patients with values of apoB, soluble CD40 ligand and asymmetric dimethylarginine above and below median (3.18 ± 0.52 vs 2.16 ± 0.68, p = 0.031). No statistically significant association was found between T/nT ratio and mean value of either IMT or classic cardiovascular risk factors. CONCLUSION: Scintigraphy with the use of (99m)Tc-HYNIC-IL-2 can be a tool for inflamed atherosclerotic (vulnerable) plaque visualization within CCA in ESRD patients. Quantitative results of carotid artery scintigraphy with (99m)Tc-HYNIC-IL-2 correlate with serum concentration of selected cardiovascular risk markers.

Repeated cycles of peptide receptor radionuclide therapy (PRRT)--results and side-effects of the radioisotope 90Y-DOTA TATE, 177Lu-DOTA TATE or 90Y/177Lu-DOTA TATE therapy in patients with disseminated NET.

PURPOSE: PRRT is a known tool in the management of patients with disseminated and inoperable NETs. The aim of study was to assess the effectiveness of the repeated cycles of PRRT in patients with disseminated and inoperable NETs. MATERIAL AND METHODS: Eighty nine patients were included in the PRRT. Among them 16 patients (18%) were qualified for a repeated PRRT cycle due to progression of the disease. In one of the patients qualified for the repeated cycle, PRRT was used as neoadjuvant therapy. The results and side-effects of the repeated cycles of PRRT were analyzed. RESULTS: Disease stabilization was observed in 10 patients 6 months after the repeated PRRT cycle and in 5 patients after 12 and 18 months. Ten of the patients who had received repeated PRRT cycles died. In the case of neoadjuvant therapy, further reduction of the tumor size was observed, enabling qualification for surgery. Clinically significant reduction in the mean values of morphological parameters was not observed. Only after 12 and 18 months the mean values of creatinine levels were higher than the normal range (only in 2 patients). CONCLUSIONS: The repeated cycles of PRRT did not cause a clinically significant increase of the toxicity of PRRT. The changes in kidney and blood morphology parameters were transient. The repeated cycles of PRRT enabled stabilization of the disease.

[Fusion SPECT/CT in clinical practice]. / Fuzja SPECT/TK w praktyce klinicznej.

Fusion consists in a combination of images obtained using different diagnostic techniques, usually functional (SPECT, PET) and structural (CT, MR) imaging. It may be performed as a software fusion of images obtained not the same time by different devices or as a hardware fusion of images obtained the same time using as a hybrid system enabling both the functional and structural imaging (SPECT/CT, PET/CT). Fusion enables precise anatomical location of lesions detected by SPECT, functional verification of lesions found by CT. It is a useful tool in the assessment of effectiveness and dosimetry for radioisotopic therapy. Additionally fusion of functional and structural examinations reduces diagnostic difficulties appearing in independent interpretation. In spite of inconveniences resulting from technical aspects of software fusion (positioning differences, spontaneous movements of internal organs) it is more and more commonly used in clinical practice in centers not possessing hybrid systems.

Biokinetics of ¹³¹I after endogenous and exogenous stimulation of TSH in patients with DTC.

BACKGROUND: The effective radioiodine treatment of patients with DTC is possible only after raising the TSH value over 30 µUI/ml. This effect might be obtained by either endogenous or exogenous stimulation. The aim of this study was to evaluate differences in (131)I biokinetics of selected regions of interest (ROIs) in cases of endogenous and exogenous stimulation. MATERIAL AND METHODS: Two groups of 50 patients were enrolled in the study. All patients were treated with 3.7 GBq of ¹³¹I; the first group after thyroid hormone withdrawal (THW), the second group after rhTSH administration (rhTSH). On the basis of post-treatment images, the uptake ratios over selected ROIs (thyroid remnants, mediastinum, liver, stomach, abdomen, and whole-body) were compared between groups. RESULTS: In the case of uptake over the whole-body and the liver, statistically significant higher values were received for the THW group. For the remaining regions, the differences between groups were statistically insignificant, but uptake ratios in the rhTSH group were generally numerically lower compared to the THW group. CONCLUSIONS: The revealed difference in radioiodine biokinetics after thyroid hormone withdrawal or administration of recombinant human TSH may influence many important aspects of patients with DTC treatment, such as the choice of proper therapeutic scheme, the cost of therapy, and the dose assessment.

[Quantitative analysis of heart scintigraphy (99mTc-MIBI GSPECT) with regional myocardial wall motion and systolic thickening of left ventricle assessment for detecting myocardial damage in ethanol withdrawal patients]. / Zastosowanie analizy ilosciowej badania 99mTc-MIBI GSPECT z ocena odcinkowej ruchomosci scian i grubienia skurczowego miesnia lewej komory w aspekcie oceny stopnia uszkodzenia miesnia sercowego w zespole odstawiennym u chorych uzaleznionych od alkoholu--doniesienie wstepne.

Severe ethanol withdrawal syndrome, with psychosomatic symptoms, is life-threatening condition and if not treated can be fatal (in approximately 15% of cases). The purpose of this investigation was to assess cardiac muscle function using 99mTc-MIBI GSPECT in acute alcohol withdrawal. The group examined consisted of 10 males aged from 33 to 45 (45.7 +/- 8.82) because of alcohol withdrawal syndrome. The control group for quantitative analysis of the heart scintigraphy (GSPECT) consisted of 20 people referred for examination to the Laboratory of Nuclear Medicine, Jagiellonian University, which results of cardiac perfusion scintigraphy were assessed as normal. In acute withdrawal syndrome quantitative analysis of the heart scintigraphy (99mTc-MIBI GSPECT) revealed impaired regional wall motion and wall thickening related mainly to the lower wall segments. The abnormalities in myocardial perfusion (99mTc-MIBI GSPECT) was found in varying degrees of severity in all patients.

New forms of radionuclide therapy with (90)Y in oncology.

BACKGROUND: Currently, there is growing interest in the use of the beta emitter (90)Y in systemic therapy in oncology. For successful therapy, an appropriate ligand is chosen to carry the isotope to the place of its action. As well as performing this function, the type of the ligand influences both the course and the side effects of the treatment. For RIT of lymphomas, bone marrow becomes the critical organ; in NET patients treated with labelled somatostatin analogues, increased kidney irradiation can occur. The aim of this study was to evaluate the side effects of therapy using 90Y associated with different ligands, depending on the charge to critical organs after treatment in two groups of patients: those with neuroendocrine tumours and those with non-Hodgkin's lymphomas. MATERIAL AND METHODS: 32 patients with histopathologically confirmed NET treated with (90)Y-DOTATATE (7.4 GBq/m(2) cumulative dose) and 30 NHL patients treated with (90)Y-ibritumomab tiuxetan (1200 MBq max dose) were enrolled in the study. The kidney function and changes of blood indices were assessed during the course of the therapy. RESULTS: 59% of NET patients treated with (90)Y-DOTATATE displayed transient reduction of blood indices, the largest after cycles III and IV of therapy. After 5 months an increase in creatinine level was noticed, but no statistically important changes in creatinine level and GFR were observed. In the group of patients with NHL, the change of haematological indices after RIT concerned mainly PLT, ANC and WBC. The reduction of the average PLT and WBC values started in the first weeks after the treatment application, reaching nadir in the 6(th) week and 8(th) week, respectively. No life threatening infections were observed in either group of patients. CONCLUSIONS: After treatment with the use of the (90)Y radionuclide, no significant treatment toxicity, including disorders involving the critical organs for both types of therapies, was found in the groups of neuroendocrine tumour and non-Hodgkin's lymphoma patients.

[Evaluation of regional cerebral blood flow using 99mTc-ECD SPECT in ethanol dependent patients: pilot study]. / Ocena zaburzen regionalnego przeplywu mózgowego metoda tomografii emisyjnej Pojedynczego Fotonu z uiyciem 99mtc-ECD u pacjentów uzaleinionych od alkoholu: doniesienie wstepne.

UNLABELLED: The depressant actions of ethanol in the brain is known. SPECT is non invasive method to measure the regional cerebral blood flow (rCBF) and to evaluate indirectly the brain metabolism. The aim of the study is to evaluate morphologic and functional status of CNS using 99mTc-ECD SPECT in chronic alcoholics. MATERIAL AND METHODS: Examined group consisted of 18 male alcoholic patients aged from 28 to 52 years (x = 42.1 +/- 5.4) treated at the Ward of Toxicology and Environmental Diseaes (Detoxification Unit). Only patients without prior head injury, CNS inflammatory changes, epilepsy, migraine, diabetes mellitus or other systemic injury were included. Alcohol dependence was diagnosed according to ICD-10 criteria. The intensity of withdrawal syndrome was measured using CIWA-A scale. The regional cerebral blood flow (rCBF) was measured using 99mTc-ECD SPECT with the double head E.CAM Siemens gamma camera. The reference group, necessary to obtain a normal values for the gamma camera applied, consisted of 31 healthy subjects (33.32 +/- 10.99 y). RESULTS: The mean values of rCBF in all examined region of frontal and temporal lobes, and in basal ganglia bothsided were significantly lower in the group of alcoholic patients than in the control group. No significant difference between rCBF in occipital lobes except the occipital inferior region, and in parietal lobes except the parietal superior region. Symetrical hypoperfusion (rCBF-2SD) in the frontal lobes was stated in 11 (61.1%), in temporal lobes in 4 (22.2%), in parietal and occipital lobes in 3 (16.7%) of the patients examined. In 7 the patients examined rCBF disturbances in basal ganglia were found (bothsided in 4, leftsided in 2, and rightsided in 2 the patients). Focal rCBF changes in the parietal, frontal and temporal lobes localised mostly on the left hemisphere were stated in 27.8% of the alcoholics examined. In concusion, the metabolic disturbances and the brain morphological changes mostly in frontal and temporal lobes due to chronic alcoholism were detected in the pilot study. A further investigation on more numerous group of ethanol dependent patients and monitoring of the changes in alcoholics who maintain a long-term abstinence from alcohol is needed.