Global skeletal uptake of 99mTc-methylene diphosphonate (GSU) in patients affected by endocrine diseases: comparison with biochemical markers of bone turnover.

This study aimed to clinically validate the global skeletal uptake (GSU) of (99m)Tc-methylene diphosphonate ((99m)Tc-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 (99m)Tc-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 microg/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 microg/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 microg/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.

Different patterns of global and regional skeletal uptake of 99mTc-methylene diphosphonate with age: relevance to the pathogenesis of bone loss.

UNLABELLED: Bone turnover changes with age have been shown by both histomorphometric and scintimetric methods; fewer studies have been performed on the regional differences of bone remodeling in the aging skeleton. To noninvasively investigate this issue, we evaluated the age-related patterns of global and regional bone uptake of 99mTc-methylene diphosphonate (MDP) in a large sample of healthy women. METHODS: In a group of 84 healthy women (33 pre- and 51 postmenopausal), the uptake of 99mTcMDP was semiquantitatively measured in 5 regions of interest. Total-body digital scans (TBDSs) were acquired at 5 min and at 4 h. Five regions of interest were drawn on the skeleton as a whole, on the lumbar spine, on the iliac wing, on the femoral neck, and on the femoral diaphysis of the 4-h TBDS. Regional skeletal uptake of the lumbar spine (LS-RSU), of the iliac wing (IL-RSU), of the femoral neck (FN-RSU), and of the femoral diaphysis (FD-RSU) was calculated as percentage injected dose retained in these skeletal segments at 4 h. RESULTS: As expected, in postmenopausal women the global skeletal uptake (GSU) values were higher than those in premenopausal women (40.7 +/- 5.9 percentage injected dose [%ID] versus 35.1 +/- 4.2 %ID; P < 0.0001). GSU correlated positively with age (r = 0.70; P < 0.001), but the addition of years since menopause to the regression model did not ameliorate the regression. On the other hand, LS-RSU (r = -0.55; P < 0.0001), IL-RSU (r = -0.45; P < 0.0001), and FN-RSU (r = -0.22; P < 0.005) decreased significantly, whereas FD-RSU increased significantly (r = 0.39; P < 0.001) with age; the same regressions were not influenced significantly by the addition of menopausal duration to the regression model. The strongest correlation among the different RSUs was that found between LS-RSU and IL-RSU (r = 0.63; P < 0.001). Moreover, the linear regression coefficients of the various RSUs with age were all significantly different from each other (P < 0.001). CONCLUSION: Our data show that the GSU of 99mTc-MDP increases with age, whereas different skeletal segments display a variable degree of turnover activation at different ages. This could ultimately induce the different rates of bone loss of different skeletal segments at various ages and, consequently, their variable propensity to fracture.

Clinical validation of a new immunoradiometric assay for intact human osteocalcin.

The purpose of this study was to estimate clinical validity of a new available immunoradiometric assay for circulating intact human BGP (N-tact Osteo SP) by measuring this protein in a large number of normal subjects and patients with the most common metabolic bone diseases. One hundred normal subjects were studied in order to obtain our normal ranges (4.9 +/- 1.7 ng/ml). The mean values found in 28 patients with primary hyperparathyroidism (17.5 +/- 22.8 ng/ml, P < 0.001), 15 glucocorticoid-treated patients (1.9 +/- 1.5, P < 0. 001), 10 patients with hypoparathyroidism (1.5 +/- 0.7, P < 0.001), 9 with hyperthyroidism (8.3 +/- 3.8, P < 0.001), 8 with skeletal metastases (7.2 +/- 2.3, P < 0.001), and 4 with humoral hypercalcemia of malignancy (2.42 +/- 1.91, P < 0.005) were significantly different from mean values found in normal subjects. Mean decrease of serum osteocalcin T-score values was significantly greater when evaluated by N-tact Osteo SP assay in 15 steroid-treated patients (-1.4 +/- 1.0) and 19 primary hyperparathyroid (PHPT) patients (3.6 +/- 1.9), compared with the mean values obtained with the Elsa-Osteo assay (-0.67 +/- 1.2, P < 0. 002 and 4.3 +/- 2.8, P < 0.04, respectively). We found significant correlations between the global skeletal uptake of 99mTc-methylendiphosphonate and serum BGP levels assayed by both N-tact Osteo SP (P < 0.01) and Elsa-Ost-Nat assay (P < 0.05). Our results indicate that this new immunoradiometric assay for the intact human osteocalcin has the potential for good discrimination between normal subjects and patients with both low and high bone turnover. Furthermore, our findings emphasize the fact that, in the absence of available standardized commercial assays, one should rely on only one assay because different results are obtained by different assays under different clinical conditions.

Efficacy of 51Cr-EDTA clearance to tailor a carboplatin therapeutic regimen in ovarian cancer patients.

AIM: The aim of this study was to evaluate the efficacy of 51Cr-EDTA clearance to tailor the carboplatin dose in two different therapeutic regimens of advanced epithelial ovarian cancer. MATERIALS AND METHODS: 14 patients entered the study, eight treated by carboplatin (C) alone and six by C and paclitaxel (P). The dose of C was calculated from the Calvert formula [DOSE(mg) = desired AUC x (GFR + 25)] based on the Glomerular filtration rate (GFR) figure; in our protocol desired Area under the curve (AUC) figure was 5 mg/ml x min. The method used to calculate the GFR requires only 4 blood samples taken in the late part of the disappearance plasmatic curve and conjugates accuracy to an acceptable clinical compliance. RESULTS: In only 5 courses a significant hematological toxicity (HT) was present (4 courses grade 2, 1 course grade 3); it was necessary to delay only 2 courses; no treatment was discontinued because of HT. CONCLUSION: We concluded that there is no summation toxicity of C and P if administered simultaneously and that the assessment of GFR by 51Cr-EDTA clearance is an optimal tool to predict an acceptable toxicity.

Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer.

This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine (l-T4) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer (DTC). Twenty female (14 premenopausal and 6 postmenopausal) patients receiving l-T4 suppressive therapy for DTC were studied. The sample was selected in such a way as to avoid factors influencing bone metabolism other than l-T4. All patients were monitored by sensitive thyroid-stimulating hormone, free triiodothyronine and free thyroxine assays throughout the follow-up. Nineteen healthy (12 premenopausal and 7 postmenopausal) matched women served as controls. In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99m methylene diphosphonate (GSU); bone mineral density (BMD) was measured by quantitative computed tomography at the lumbar spine (LS) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites: the femoral neck, Ward's triangle and the greater trochanter. No significant difference was found in either GSU or BMD between patients (treated for an average period of 68 months) and controls in the whole sample or in any subgroup. Furthermore, no correlations were found between either GSU or BMD and the duration of therapy, daily doses of l-T4 or results of thyroid function tests. Our data show that carefully monitored l-T4 therapy does not influence skeletal turnover (directly reflected by GSU) or the bone density of the spine and femur.

Age-related changes in the global skeletal uptake of technetium-99m methylene diphosphonate in healthy women.

A short-term evaluation of global skeletal uptake (GSU) of technetium-99m methylene diphosphonate (MDP) was performed in 40 healthy female subjects with a wide age range in order to investigate the clinical performance of the technique and to detect the age-related changes in bone turnover. The results obtained were compared with measurements of the main biochemical markers of skeletal metabolism. We found that GSU increases progressively with age, independently of concomitant changes in renal function; significant correlations with biochemical markers of bone formation were also found. Therefore, the method appears to provide useful information concerning the bone turnover rate, and is also applicable to elderly people owing to its simplicity.

In vivo visualization of pituitary dopaminergic receptors by iodine-123 methoxybenzamide (IBZM) correlates with sensitivity to dopamine agonists in two patients with macroprolactinomas.

We performed in two patients with macroprolactinoma, pituitary scintigraphy with 123 iodine-methoxybenzamide (IBZM), a dopaminergic antagonist that specifically binds to the D2 dopaminergic receptors. In a 34-yr-old woman with basal PRL levels of about 2000 ng/mL, 7.5 mg/day of Bromocriptine (Br) for a month neither reduced PRL levels nor affected tumor size; in this patient single photon emission tomography SPECT failed to show any pituitary accumulation of the tracer. In the other patient, a 27-yr-old man presenting with cerebrospinal fluid rhinorrhea, basal PRL levels were at 5000 ng/mL; magnetic resonance imaging (MRI) demonstrated a huge pituitary tumor, and SPECT showed a very intense concentration of IBZM at the level of the adenoma. PRL levels fell dramatically to 530 ng/mL with only 2.5 mg/day of Br after 4 days; after 6 days with 7.5 mg/day Br, PRL levels were 63 ng/mL, and the patient underwent surgery to correct cerebrospinal fluid leakage. We conclude that, in these two patients, the pituitary scintigraphy with IBZM has given information on the density of dopamine receptors on the adenoma and has correlated with the inhibitory effect of Br on PRL secretion. Whether this tool might be of value in identifying patients with pituitary tumors potentially responsive to Br treatment is still to be investigated.

Considerations of brain death on a SPECT cerebral perfusion study.

Brain death imaging is often a diagnostic challenge. Cerebral angioscintigraphy is extensively used for this analysis, but this test does not allow the perfusion evaluation of the posterior fossa. The authors report a case in which a SPECT study showed persistence of blood flow in infratentorial structures with total absence of cerebral (supratentorial) perfusion. This finding excluded the diagnosis of brain death.

[Increase of plasma levels of beta-endorphin during maximum bicycle ergometry effort in sedentary and trained subjects]. / Incremento dei livelli plasmatici di beta-endorfina durante sforzo massimale al cicloergometro in sedentari ed allenati.

Plasmatic levels of beta-endorphin during maximal graded bicycle stress test were measured by RIA on extracted plasma in 10 well-trained (A group) and in 8 untrained subjects (C group). Blood samples were obtained at rest, at peak work load and at the third, 10th and 90th min of recovery. For every stress test the following were evaluated: exercise time, maximum work load, total work load, maximum double product and mean K (an index of velocity of heart rate recovery during the first three minutes after the exercise). Both groups A and C showed a significant rise in beta-endorphin activity at the third minute of recovery; the increase was significantly greater in trained rather than in sedentary subjects (p less than 0.01). Beta-endorphin release was closely related to mean K; no relationship was found between exercise time, maximum work load, total work load, maximum double product and beta-endorphin rise. Our data shows that a release of beta-endorphin occurs during the initial phase of recovery after a maximal stress test; beta-endorphin rise is greater in trained subjects and correlates with the speed of heart rate recovery, but has no relationship with the duration and the grade of the effort. Whether beta-endorphin increase plays a role in the rapid decrease of adrenergic tone which occurs after exercise or represents a secondary phenomenon remains to be determined.