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: This study aimed to clinically validate the global skeletal uptake (GSU) of 99mTc-methylene diphosphonate (99mTc-MDP), and to compare it with a marker of bone formation (i.e. serum osteocalcin or OC) and an index of bone resorption (i.e. urinary deoxypyridinoline or U-DPD) in different endocrine disorders affecting the skeleton. We studied 29 female patients with thyrotoxicosis (TT), 27 with primary hyperparathyroidism (PHPT), 16 with acromegaly (AC), 15 with Cushing’s syndrome (CS), and altogether 110 healthy women matched for age, BMI and menstrual status. In all subjects total body digital scan images (TBDS) were acquired at 5 min and at 4 h after the administration of 99mTc-MDP; the whole body retention (WBR) of the tracer was measured by counting two identical sets of rectangular ROIs, and GSU was subsequently calculated by drawing an irregular ROI on 4 h TBDS images. Serum OC was assessed by IRMA and urinary DPD by fluorometric detection after reverse phase high pressure chromatography. In TT patients GSU (40.0 ± 5.1 vs 36.5 ± 4.8%), OC (19.1 ± 11.8 vs 7.1 ± 2.9 mg/l) and U-DPD (62.4 ± 42.7 vs 19.5 ± 5.3 pmol/pmol) were significantly (p<0.01) higher than in controls. PHPT patients showed GSU (47.2 ± 6.6 vs 37.8 ± 5.3%), OC (38.6 ± 40.9 vs 8.2 ± 2.5 mg/l), and U-DPD (55.0 ± 51.3 vs 21.9 ± 6.1 pmol/pmol) values significantly (p<0.001) higher than controls. In CS patients, GSU (39.6 ± 6.4 vs 32.7 ± 3.5%; p<0.01) and U-DPD (22.8 ± 8.4 vs 16.5 ± 2.7 pmol/pmol; p<0.05) were higher, whereas OC (3.6 ± 2.4 vs 5.2 ± 1.9 mg/l; p<0,05) was lower than in controls. In AC patients, GSU (34.9 ± 5.3 vs 35.2 ± 3.4%) did not differ significantly from controls, whereas OC (16.8 ± 8.8 vs 6.9 ± 2.9 mg/l; p<0.001) and U-DPD (30.9 ± 13.6 vs 21.0 ± 5.7 pmol/pmol; p<0.01) were higher. Stepwise multivariate linear regression analysis was performed with disease activity, creatinine clearance, age, and years since menopause as predictor variables and GSU or OC or U-DPD as dependent variables. The significant partial regression coefficients (r) were: in TT, free triiodothyronine (fT3) with GSU (r = 0.37; p<0.005), Ln OC (r = 0.30; p = NS), Ln U-DPD (r = 0.76; p<0.0001), respectively; in PHPT, PTH with GSU (r = 0.74; p<0.001), Ln OC (r = 0.50; p<0.05), Ln U-DPD (r = 0.64; p<0.001); in CS Ln urinary free cortisol with OC (r = -0.68; p<0.001) and U-DPD (r = 0.66; p<0.05). Our data suggest that GSU could represent a valuable clinical tool for evaluating bone turnover rate in PHPT, CS, TT but not in AC. The behavior of GSU and OC and U-DPD is non-uniform in disorders characterized by a marked uncoupling between bone formation and resorption. [ABSTRACT FROM AUTHOR]

Gastric emptying of two different test liquid meals (500 ml isotonic saline and 500 ml skimmed milk, 1.8% fat) has been measured in 10 (saline) and in 19 (milk) normal volunteers by means of real-time ultrasonography (RUS) and scintigraphy, employed simultaneously. In each subject, saline and milk contained 37 MBq of diethylenetriaminopentacetic acid (DPTA) marked with 99mTc. Determinations were made thereafter every 5 min up to 45 min with saline and every 30 min up to a maximum of 220 min with milk. The determination of gastric emptying by RUS was obtained indirectly through the measurement of gastric dimensions, with a single scan performed at the epigastrium, while the subject was kept in a standing position. At each observation, the percent decrease of gastric measurements and the decay in radioactivity over the gastric region were calculated, blind, by two independent examiners. Linear regression and correlation coefficient were subsequently computed for gastric measurements and decay in radioactivity. The results show that the values obtained with RUS do not differ grossly from the ones obtained with scintigraphy. This suggests that the ultrasonographic determination of gastric dimensions with a single section of the stomach may be a valuable method for use in the evaluation of gastric emptying of liquids. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Recent sun exposure should correlate with circulating 25-hydroxyvitamin D [25(OH)D] due to ultraviolet B (UVB)-catalyzed cutaneous synthesis of vitamin D. Methods: A Sun Exposure Score was calculated for healthy adults using a recall questionnaire assessing daily Time in Sun (<5min, 5–30min, >30min) and Skin Exposure (face/hands; face/hands and arms; face/hands and legs; and “bathing suit”) for 1 week in each of the winter and summer (n =47 and 23, respectively; n =18 participated in both). Concentrations of 25(OH)D were measured by DiaSorin RIA on end-of-week sera. Results: Mean serum 25(OH)D was higher in summer than winter (58.6±16.5nmol/L vs. 38.8±29.0nmol/L, respectively, P =0.003 unpaired). The calculated Sun Exposure Score correlated strongly with serum 25(OH)D during summer (Spearman''s rho=0.59, P =0.003); based on the Pearson coefficient of determination, summer Sun Exposure Score explained 38% of the variability in summer serum 25(OH)D. The Sun Exposure Score did not correlate with 25(OH)D in the winter (rho=0.19, P =0.210). The summer correlation was largely explained by the Time in Sun (rho=0.58, P =0.004) rather than area of Skin Exposed (rho=0.10, P =0.660). Although there was a correlation between winter and summer Sun Exposure Scores (rho=0.63, P =0.005), there was no summer vs. winter correlation in serum 25(OH)D (rho=0.08, P =0.76). Conclusion: This simple 1-week sun exposure recall questionnaire predicted summer serum 25(OH)D concentrations, accounting for 38% of the variability in 25(OH)D among healthy Italian adults. [Copyright &y& Elsevier]

Background: Congenital erythropoietic porphyria (CEP) is a rare autosomal recessively inherited disorder with chronic and relatively stable presentation. Till now brain blood flow derangements have been described only in acute hepatic porphyrias. We describe the first findings of brain perfusion defects, studied by single photon emission tomography/computed tomography (SPET/CT), in two patients affected by CEP, by using a semi-quantification anatomic-standardized voxel-based program compared with magnetic resonance imaging (MRI) results., Subjects and Methods: Two Pakistanis brothers were investigated for CEP confirmed by a genetic test. The disease was severe with: skin burning, mood depression and haemolytic anemia. Considering depression, patients underwent brain SPET/CT and MRI. Single photon emission tomography/CT images were processed by neurostat semi-quantitative software. Data obtained were compared to a normal database and z-score images were generated., Results: In both patients we found several perfusion defects evident in transaxial slices and in z-score images obtained by neurostat processing. Magnetic resonance imaging was negative in both patients. Biochemical mechanisms inducing localized brain hypoperfusion are uncertain. However, mismatch between SPET/CT data and MRI was probably due to absence of necrosis., Conclusion: In our opinion, SPET/CT could have a key role in this setting of patients due to its high sensitivity and reliability in mild-to-moderate brain perfusion defects detection. Moreover, the quantitative analysis by using neurostat may allow to recognize even mild brain perfusion alterations, difficult to detect only visually.

Primary hyperparathyroidism (PHPT) is associated with hypovitaminosis D as assessed by serum total 25-hydroxyvitamin D (TotalD) levels. The aim of this study is to evaluate whether this is also the case for the calculated bioavailable 25-hydroxyvitamin D (BioD) or free 25-hydroxyvitamin D (FreeD), and whether the vitamin D status is influenced by genetic background. We compared vitamin D status of 88 PHPT patients each with a matched healthy family member sharing genetic background, i.e., first-degree relative (FDR), or not, namely an in-law relative (ILR). We compared TotalD and vitamin D-binding protein (DBP), using the latter to calculate BioD and FreeD. We also genotyped two common DBP polymorphisms (rs7041 and rs4588) likely to affect the affinity for and levels of vitamin D metabolites. TotalD was lower (p < 0.001) in PHPT (12.3 ± 6.6 ng/mL) than either family member group (FDR: 19.4 ± 12.1 and ILR: 23.2 ± 14.1), whether adjusted for DBP or not. DBP levels were also significantly lower (p < 0.001) in PHPT (323 ± 73 mg/L) versus FDR (377 ± 98) or ILR (382 ± 101). The differences between PHPT and control groups for TotalD, BioD, and FreeD were maintained after adjustment for season, gender, and serum creatinine. 25-hydroxyvitamin D, evaluated as total, free, or bioavailable fractions, is decreased in PHPT. No difference was seen between first-degree relative and in-law controls, suggesting that neither genetic nor non-genetic background greatly influences the genesis of the hypovitaminosis D seen in PHPT.

Unlabelled: The aim of the study was to assess the diagnostic contribution of hybrid SPECT/CT lymphoscintigraphy compared to planar imaging for the correct identification of sentinel lymph nodes (SLN) in breast cancer (BC) patients., Materials and Methods: 73 planar and SPECT/CT lymphoscintigraphies were performed in 70 consecutive patients with BC (70 women, mean age 55.7±12.0 years, range 26-84) for pre-surgical SLNs research. Cohen'K was performed to evaluate the agreement between both techniques; their diagnostic capability was evaluated by the Student's t-test for paired data., Results: In 54/73 (73.9%) lymphoscintigraphies, SLNs were detected both on planar and SPECT/CT images. In 19/73 (26.1%) discordant cases, planar technique showed a higher number of SLNs in 4/19 lymphoscintigraphies, while SPECT/CT in 15/19. Radio-guided surgery confirmed SPECT/CT findings. Concordance between the two techniques was poor (K=-0.095). Overall, SPECT/CT detected 13 SLNs more than planar imaging (p=0.07). Furthermore, in 17/73 (23.2%) lymphoscintigraphies, SPECT/CT defined the exact SLNs anatomical localization, equivocal on planar images., Conclusions: SPECT/CT demonstrated added value over planar imaging, providing more information for the best surgical approach. It is useful especially in patients with negative or doubt planar imaging.

Background: Hereditary Coproporphyria (HCP) is characterized by abdominal pain, neurologic symptoms and psychiatric disorders, even if it might remain asymptomatic. The pathophysiology of both neurologic and psychiatric symptoms is not fully understood. Therefore, aiming to evaluate a possible role of brain blood flow disorders, we have retrospectively investigated cerebral perfusion patterns in Single Photon Emission Computed Tomography (SPECT) studies in HCP patients., Materials & Methods: We retrospectively evaluated the medical records of patients diagnosed as being affected by HCP. A total of seven HCP patients had been submitted to brain perfusion SPECT study with 99mTc-Exametazime (hexamethylpropyleneamine oxime, HMPAO) or with its functionally equivalent 99mTc-Bicisate (ECD or Neurolite) according with common procedures. In 3 patients the scintigraphic study had been repeated for a second time after the first evaluation at 3, 10 and 20 months, respectively. All the studied subjects had been also submitted to an electromyographic and a Magnetic Resonance Imaging (MRI) study of the brain., Results: Mild to moderate perfusion defects were detected in temporal lobes (all 7 patients), frontal lobes (6 patients) and parietal lobes (4 patients). Occipital lobe, basal ganglia and cerebellar involvement were never observed. In the three subjects in which SPECT study was repeated, some recovery of hypo-perfused areas and appearance of new perfusion defects in other brain regions have been found. In all patients electromyography resulted normal and MRI detected few unspecific gliotic lesions only in one patient. Discussion & Conclusions: Since perfusion abnormalities were usually mild to moderate, this can probably explain the normal pattern observed at MRI studies. Compared to MRI, SPECT with 99mTc showed higher sensitivity in HCP patients. Changes observed in HCP patients who had more than one study suggest that transient perfusion defects might be due to a brain artery spasm possibly leading to psychiatric and neurologic symptomatology, as already observed in patients affected by acute intermittent porphyria. This observation, if confirmed by other well designed studies aiming to demonstrate a direct link between artery spasm, perfusion defects and related symptoms could lead to improvements in HCP treatments.

Objective: To describe the biochemical effects of an over-supplementation of vitamin D3 in two patients with primary hyperparathyroidism (PHPT)., Design: Two patients (A and B) with PHPT took erroneously 2,400,000 U (300,000 U/day for 8 days) and 4,500,000 U (300,000 U/day for 15 days) of cholecalciferol, respectively. They were followed for 4 months and ionized calcium, creatinine, PTH, 25 hydroxy-vitamin D, 1,25(OH)₂D and urinary calcium/creatinine levels were measured. Finally, the patients were operated on and a parathyroid adenoma was removed in both., Results: One week after the last dose of vitamin D, serum ionized calcium (iCa) rose from 1.35 to 1.41 mMol/L (n.r. 1.14-1.31) for patient A, and from 1.43 to 1.62 for patient B, while fasting urinary Calcium/Creatinine (uCa/Cr) augmented from 0.31 to 0.50 mg/mg, and from 0.32 to 0.55, respectively. During the follow-up, the average levels of iCa were 1.37 ± 0.03 and 1.48 ± 0.07 mMol/L, while those of uCa/Cr were 0.29 ± 0.13 and 0.32 ± 0.13, both iCa and uCa/Cr levels returning to baseline values within 4 months., Conclusions: The unintentional over-supplementation of vitamin D in the two PHPT patients caused a moderate and temporary increase of hypercalcemia and hypercalciuria and was not associated with clinical signs of toxicity.

Background: Somatostatin (SS) acts as a universal endocrine off-switch, and also inhibits the growth of neuroendocrine tumours through its specific receptors (SSTRs). Somatostatin receptors are G-protein-coupled receptors, which are encoded by five separate genes (SSTR1-5). Short peptide analogues demonstrate specific binding only for the subgroup consisting of SSTR2a, SSTR3 and SSTR5. Moreover, previous studies reported that expression of mRNA for SSTR2a correlated with therapeutic outcome in patients with carcinoid tumours treated with somatostatin analogs., Purpose: To develop and apply a Real Time Quantitative PCR technique (RT-qPCR) to compare and contrast the mRNA levels of SSTR2a, SSTR3 and SSTR5 in Neuroendocrine Lung Cancer affected patients., Methods: Peripheral blood samples from 21 neuroendocrine lung cancer affected patients (14 SCLC, 6 LC and 1 LCNEC) subjected to scintigraphy with (111)In-DTPA-D-Phe(1)-octreotide (OctreoScan) and 24 healthy blood donors were investigated by RT-qPCR. mRNA levels for SSTR2a, SSTR3 and SSTR5 were measured in peripheral blood samples with a relative quantification method using plasmid dilutions as calibration curves and GAPDH as reference gene., Results: A statistically significant increase in target genes/GAPDH copy number ratio was found for SSTR2a (median 38; IQR 22-141) and SSTR5 (median 51; IQR 19-499) in neuroendocrine lung cancer affected patients as compared with samples from healthy blood donors (P ≤ 0.0003 and P ≤ 0.0005). Since low levels of expression were detected in the control group for all three genes, optimal cut-off values were assessed using ROC curve analyses and were equal to 9.05 for SSTR2a and 16.97 for SSTR5. These cut off values resulted in a sensitivity of 86% (95%IC 65-95) for both markers and a specificity of 83% (95%IC 64-93%) and 79% (95%IC 60-91%) for SSTR2a and SSTR5 respectively. Comparison between OctreoScan results and RT-qPCR analysis demonstrated agreement in 76% of the cases., Conclusions: Our results suggest that SSTR2a and SSTR5 mRNAs are detectable in peripheral blood of neuroendocrine lung cancer affected patients using real-time quantitative PCR, with a good agreement with OctreoScan. The high sensitivity of this non-invasive molecular technique suggests that this method could represent a useful tool in the clinical management of neuroendocrine lung cancers.

Introduction: Previous papers investigating vitamin D status have often outlined the significant relationships between serum parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD), but the influence of ionized calcium levels has not been concomitantly considered., Design: Cross-sectional., Materials and Methods: In 1050 healthy men (547) and women (503), serum ionized calcium (iCa), creatinine (Cr), albumin, 25OHD, and PTH were measured. After conventional analysis, a regression tree was fitted on the data set., Results: 25OHD and PTH values showed significant opposite seasonal changes. 25OHD levels negatively correlated with PTH, which in turn negatively correlated with iCa. A regression tree was fitted to the whole data set using PTH as the response variable and 25OHD and iCa as covariates. PTH concentration depended on that of iCa only in subjects with 25OHD levels>16.35 ng/mL, while for 25OHD<16.35 ng/mL it depended on 25OHD values., Conclusions: Our results indicated that PTH levels were highly conditioned by those of 25OHD in subjects with 25OHD values lower than 16.35 ng/mL and by those of iCa only for higher 25OHD concentration., (Copyright 2010 Elsevier Inc. All rights reserved.)