Executive functions and adaptive behaviour in individuals with Down syndrome.

BACKGROUND: Previous research has explored executive functions (EFs) and adaptive behaviour in children and adolescents with Down syndrome (DS), but there is a paucity of research on the relationship between the two in this population. This study aims to shed light on the profile of EFs and adaptive behaviour in DS, exploring the differences by age and investigating the relationship between these two domains. METHOD: Parents/caregivers of 100 individuals with DS from 3 to 16 years old participated in the study. The sample was divided into preschoolers (3-6.11 years old) and school-age children (7-16 years old). Parents/caregivers completed either the Preschool Version of the Behaviour Rating Inventory of Executive Function (for children 2-6.11 years old) or the Second Edition of the same Inventory (for individuals 7 + years old). Adaptive behaviour was assessed with the Vineland Adaptive Behaviour Scale - Interview, Second Edition. RESULTS: Findings suggest that individuals with DS have overall difficulties, but also patterns of strength and weakness in their EFs and adaptive behaviour. The preschool-age and school-age children's EF profiles differed slightly. While both age groups showed Emotional Control as a relative strength and Working Memory as a weakness, the school-age group revealed further weaknesses in Shift and Plan/Organise. As concerns adaptive behaviour, the profiles were similar in the two age groups, with Socialisation as a strength, and Communication and Daily Living Skills as weaknesses, but with a tendency for preschoolers to obtain intermediate scores for the latter. When the relationship between EFs and adaptive behaviour was explored, Working Memory predicted Communication in the younger group, while in the older group the predictors varied, depending on the adaptive domains: Working Memory was a predictor of Communication, Inhibit of Daily Living Skills, and Inhibit and Shift of Socialisation. CONCLUSION: As well as elucidating the EF profiles and adaptive behaviour in individuals with DS by age, this study points to the role of EFs in adaptive functioning, providing important information for targeted interventions.

Lenvatinib as a salvage therapy for advanced metastatic medullary thyroid cancer.

PURPOSE: Patients with advanced progressive metastatic medullary thyroid cancer (MTC), show poor prognosis and few available systemic therapeutic options. After the loss of clinical benefit with other tyrosine kinase inhibitors (TKI), we evaluated the use of lenvatinib as salvage therapy. METHODS: Ten patients who experienced the loss of clinical benefit after treatment with at least one previous TKI, were treated with lenvatinib. We assessed patient's response immediately before, at the first (first-EV) and last (last-EV) evaluation, after the beginning of treatment. RESULTS: At first-EV, one patient died, while all the remaining 9 showed a stable disease (SD) in the target lesions. At last-EV, SD was still observed in seven patients, while partial response (PR) and progressive disease (PD), in one patient each. Conversely, analyzing all target and non-target lesions, at first-EV, we observed PR in one patient and SD in eight patients. At last-EV, PR was shown in two patients and SD was shown in seven. Bone metastases showed stable disease control at both first-EV and last-EV in only approximately 60% of cases. Tumor markers (CTN and CEA) decreased at first-EV, while they increased at last-EV. Seven patients experienced at least one dose reduction during treatment with lenvatinib. CONCLUSIONS: In this real-life clinical experience, lenvatinib showed interesting results as salvage therapy in patients with advanced progressive metastatic MTC patients. Its usefulness could be effective in patients without any other available treatment, because previously used or unsuitable, especially with negative RET status with no access to the new highly selective targeted therapies.

Bone metastases from differentiated thyroid carcinoma: current knowledge and open issues.

Bone represents the second most common site of distant metastases in differentiated thyroid cancer (DTC). The clinical course of DTC patients with bone metastases (BM) is quite heterogeneous, but generally associated with low survival rates. Skeletal-related events might be a serious complication of BM, resulting in high morbidity and impaired quality of life. To achieve disease control and symptoms relief, multimodal treatment is generally required: radioiodine therapy, local procedures-including surgery, radiotherapy and percutaneous techniques-and systemic therapies, such as kinase inhibitors and antiresorptive drugs. The management of DTC with BM is challenging: a careful evaluation and a personalized approach are essential to improve patients' outcomes. To date, prospective studies focusing on the main clinical aspects of DTC with BM are scarce; available analyses mainly include cohorts assembled over multiple decades, small samples sizes and data about BM not always separated from those regarding other distant metastases. The aim of this review is to summarize the most recent evidences and the unsolved questions regarding BM in DTC, analyzing several key issues: pathophysiology, prognostic factors, role of anatomic and functional imaging, and clinical management.

Clinico-pathological features, treatments and survival of malignant insulinomas: a multicenter study.

INTRODUCTION: Management of malignant insulinomas is challenging due to the need to control both hypoglycaemic syndrome and tumor growth. Literature data is limited to small series. AIM OF THE STUDY: To analyze clinico-pathological characteristics, treatments and prognosis of patients with malignant insulinoma. MATERIALS AND METHODS: Multicenter retrospective study on 31 patients (male: 61.3%) diagnosed between 1988 and 2017. RESULTS: The mean age at diagnosis was 48 years. The mean NET diameter was 41 ± 31 mm, and 70.8% of NETs were G2. Metastases were widespread in 38.7%, hepatic in 41.9% and only lymph nodal in 19.4%. In 16.1% of the cases, the hypoglycaemic syndrome occurred after 46 ± 35 months from the diagnosis of originally non-functioning NET, whereas in 83.9% of the cases it led to the diagnosis of NET, of which 42.3% with a mean diagnostic delay of 32.7 ± 39.8 months. Surgical treatment was performed in 67.7% of the cases. The 5-year survival rate was 62%. Overall survival was significantly higher in patients with Ki-67 ≤10% (P = 0.03), insulin level <60 µU/mL (P = 0.015) and in patients who underwent surgery (P = 0.006). Peptide Receptor Radionuclide Therapy (PRRT) was performed in 45.1%, with syndrome control in 93% of patients. CONCLUSIONS: Our study includes the largest series of patients with malignant insulinoma reported to date. The hypoglycaemic syndrome may occur after years in initially non-functioning NETs or be misunderstood with delayed diagnosis of NETs. Surgical treatment and Ki67 ≤10% are prognostic factors associated with better survival. PPRT proved to be effective in the control of hypoglycaemia in majority of cases.

Amylose molecular fine structure dictates water-oil dynamics during deep-frying and the caloric density of potato crisps.

The fine structure of extractable amylose (E-AM) in potato flakes dictates oil uptake during the production of deep-fried crisps from dough made from the flakes, and thus their caloric density. High levels of short E-AM chains increase the extent of amylose crystallization during dough making and increase water binding. Time-domain proton NMR analysis showed that they also cause water to be released at a low rate during deep-frying and thus restrict dough expansion and, most importantly, oil uptake. X-ray micro-computed tomography revealed that this results in high thickness of the crisp solid matrix and reduced pore sizes. Thus, the level of short E-AM chains in potato flakes impacts amylose crystal formation, dough strength and expansion, as well as the associated oil uptake during deep-frying. Based on these results, we advise potato crisp manufacturers to source potato cultivars with high levels of short amylose chains for the production of reduced-calorie crisps and to make well-reasoned process adaptations to control the extractability of potato amylose.

Real-world efficacy and safety of lenvatinib: data from a compassionate use in the treatment of radioactive iodine-refractory differentiated thyroid cancer patients in Italy.

BACKGROUND: Lenvatinib is a multi-kinase inhibitor approved for patients with radioactive iodine (RAI)-resistant differentiated thyroid cancer (DTC). Before the drug approval from the Italian National Regulatory Agency, a compassionate use programme has been run in Italy. This retrospective study aimed to analyse data from the first series of patients treated with lenvatinib in Italy. METHODS: The primary aim was to assess the response rate (RR) and progression-free survival (PFS). Secondary end-points include overall survival (OS) and toxicity data. RESULTS: From November 2014 to September 2016, 94 patients were treated in 16 Italian sites. Seventeen percent of patients had one or more comorbidities, hypertension being the most common (60%). Ninety-eight percent of patients were treated by surgery, followed by RAI in 98% of cases. Sixty-four percent of patients received a previous systemic treatment. Lenvatinib was started at 24 mg in 64 subjects. Partial response and stable disease were observed in 36% and in 41% of subjects, respectively; progression was recorded in 14% of patients. Drug-related side-effects were common; the most common were fatigue (13.6%) and hypertension (11.6%). Overall, median PFS and OS were 10.8 months (95% confidence interval [CI], 7.7-12.6) and 23.8 months (95% CI, 19.7-25.0) respectively. CONCLUSION: Lenvatinib is active and safe in unselected, RAI-refractory, progressive DTC patients in real-life setting. RR and PFS seem to be less favourable than those observed in the SELECT trial, likely due to a negative selection that included heavily pretreated patients or with poor performance status.

Donor transmission intestinal carcinoma after kidney transplantation: case report.

Tumor transmission is a rare complication of organ transplantation. Despite several improvements in excluding donor malignant disease, there continue to be reports of unknown tumors in the donors. The risk of having a donor with an undetected malignancy ranges between 1.3% and 2%. The cases of two kidney transplant recipients who had intestinal carcinoma transmitted from the same deceased donor are described. The clinical presentation, previous data, and management options are discussed. As a result of the increase in the overall donor pool, using extended criteria donors, donors of extreme ages, donors with prolonged intensive care admission, and donors who may potentially transmit disease to their recipients, the risk of tumor transmission and also infections should be considered.

Single center experience with elective surgical patients as living kidney donors.

PURPOSE: To report a single center experience with elective surgical patients as living kidney donors. METHODS: We retrospectively analyzed a prospective database of 458 living kidney donors from September 2005 to May 2011. Fifteen (3.2%) of them were elective surgical patients simultaneously undergoing living donor nephrectomy. We reviewed age, gender, operative time, intraoperative blood transfusion, intra- and postoperative complications, as well as length of hospital stay. Recipients were evaluated for delayed graft function. Four hundred forty-three patients undergoing living donor nephrectomy alone composed the control group. RESULTS: Among the elective surgical patients group, the mean (range) operative time was 155 (90 to 310) minutes and mean (range) length of hospital stay was 3 (2 to 9) days. One (6.7%) recipient displayed delayed graft function. Among the regular living kidney donors group, the mean (range) operative time was 100 (70 to 150) minutes, mean (range) length of hospital stay was 3 (2 to 5) days, and delayed graft function was observed in 5.6% of recipients. Only operative time (P = .03) was significantly different between the groups. CONCLUSIONS: Elective surgical patients are potential donors who may be treated at the same time as the living donor nephrectomy.

Interplay between serum osteocalcin and insulin sensitivity in primary hyperparathyroidism.

Osteocalcin (OC) has been proposed as a regulator of insulin sensitivity in both humans and other animals. Primary hyperparathyroidism (PHPT) is characterized by high OC levels and insulin resistance. The aim of this study was to evaluate whether in PHPT the link between OC levels and blood markers of insulin resistance was maintained. In a consecutive series of 219 adult PHPT patients, serum OC as well as fasting insulin and glucose levels were measured. Insulin sensitivity was estimated by homeostatic model assessment (HOMA2-S%). The same parameters were evaluated in a subgroup of 45 patients after parathyroidectomy (PTX). PHPT patients were characterized by markedly high OC levels. After subdividing them according to glucose tolerance, it was found that OC was similar in subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT), while diabetic subjects had lower serum OC than those with NGT (P < 0.02) or IGT (P < 0.04). OC was negatively associated with fasting glucose and positively associated with HOMA2-S%. OC independently predicted HOMA2-S% in a multivariate analysis. In the subgroup of surgically cured PHPT patients, OC levels significantly decreased after PTX, while HOMA2-S% did not change. Our findings indicate that in PHPT there is a positive relationship between OC and glucose metabolism, OC being one of the predictors of insulin sensitivity. However, data in surgically cured patients, showing OC normalization in spite of unchanged HOMA2-S%, suggest that OC does not likely play a major role in affecting insulin sensitivity in PHPT.

Surgical treatment of anaplastic thyroid carcinoma. Our experience.

BACKGROUND: In anaplastic thyroid carcinoma (ATC) surgical resection associated to radiotherapy and chemotherapy can ameliorate local disease control with occasional long-term survivals. PATIENTS AND METHODS: Resection of the tumor was accomplished in 20 ATC patients, with no macroscopic (13 cases) or minimal residual neck disease infiltrating vital structures (7 cases). Ten of these patients (50%) had distant metastases. Sixteen cases were also treated with radiotherapy and chemotherapy, while in one patient only chemotherapy was possible; 2 patients refused further therapy; the last one is starting adjuvant treatment. Morbidity and survival were analysed, and compared with other 15 ATCs submitted to partial tumor debulking or not operated at all (control group). RESULTS: Function of at least one laryngeal recurrent nerve was preserved in all 20 patients; none experienced permanent hypoparathyroidism. At last follow-up examination 17 patients had died and 3 were alive 1, 6 and 80 months after the operation, the latter being free of disease. Survival of dead patients ranged from 3 to 28 months (mean: 8 months). In the control group all patients died, survival ranging from 1 to 13 months (mean: 4 months). Actuarial analysis of survival showed a significant difference between the two groups (p = 0.0112); multivariate analysis of several prognostic factors confirmed that complete or near complete tumour resection was the most relevant. CONCLUSIONS: Surgical resection is an important component of the multimodal treatment of ATC and should be attempted whenever possible.

Multifocal renal allograft biopsy: impact on therapeutic decisions.

OBJECTIVE: There are no data to support the suggestion that samples removed from one segment of the transplanted kidney are representative of the whole graft. The aim of this study was to compare the histological differences between biopsies obtained from different portions of the renal allograft and their impact on treatment recommendations. PATIENTS AND METHODS: Two hundred percutaneous biopsies were performed on kidney allografts and samples were collected from the upper and lower poles (100 kidneys). All samples were randomized and blindly reviewed. We obtained the discordance rates between the poles for the grading of acute rejection and for the diagnosis of nephrotoxicity due to immunosuppression. We also checked if the differences found were sufficient to call for different clinical recommendations. These values were compared with the intrapathologist variation rates. RESULTS: In 70 kidneys adequate sampling was obtained from both poles. The diagnosis of acute rejection were made in 17. The discordance rate between the upper and lower poles was 82.3% (kappa = 0.34), higher than the intrapathologist variation (P = .002). Nephrotoxicity was found in 14 kidneys. The discordance rate between the upper and lower poles was 28.6% (kappa = 0.88), with no difference compared with the intrapathologist variation. In 14 of the 70 kidneys (25.7%), discordances between poles had impact on clinical recommendations, most of these cases due to different gradings of acute rejection (78%). This number was higher than the intrapathologist variation (P = .04). CONCLUSIONS: The histopathological changes in the kidney allograft are not always homogeneous. This heterogeneity may affect the therapeutic recommendations.

A rare case of adulthood-onset growth hormone deficiency presenting as sporadic, symptomatic hypoglycemia.

Symptomatic hypoglycemia is described in children with severe GH deficiency (GHD), but is rare in adults with GHD. We describe the case of a 62- yr-old man, referred for recurrent hypoglycemic events. He reported a previous head trauma at the age of 20 yr and a diagnosis of reactive hypoglycemia at the age of 50 yr. In the last months, during a period of job-related stress, the hypoglycemic episodes became more frequent and severe (glucose <2.2 mmol/l), finally requiring hospitalization. On admission, the patient was in good general health, with normal renal and hepatic function. During hospitalization, no hypoglycemic episodes were recorded, also during a 72-h fasting test. Biochemical data and abdominal computed tomography (CT) excluded insulinoma. A tumor-induced hypoglycemia was ruled out. The 4-h oral glucose tolerance test (OGTT) showed an impaired glucose tolerance with a tendency toward asymptomatic hypoglycemia. Hormonal study disclosed low levels of GH (0.2 ng/ml) and IGF-I (51 ng/ml); the response of GH to GHRH plus arginine confirmed a severe GHD (GH peak 2.7 ng/ml). Other pituitary and counterregulation hormones were within the normal range and magnetic resonance imaging (MRI) of the pituitary gland was normal. Replacement therapy with a low dose of rhGH induced an increase of IGF-I up to low-normal values, accompanied by lasting regression of hypoglycemic events. In conclusion, hypoglycemia was the main clinical symptom of isolated adult onset GHD, in the present case. The possible pathogenesis of isolated adult onset GHD and the association of GHD with conditions predisposing to hypoglycemia are considered and discussed.

Proinsulin-secreting neuroendocrine tumor of the pancreas.

Insulinoma is characterized by spontaneous fasting hypoglycemia. Diagnosis relies on inappropriately increased insulin levels (>6 microU/ml), high insulin/glucose ratio (IGR >0.3), raised proinsulin values (>5 pMol/l). A 74-yr-old man was referred to us for episodes of symptomatic hypoglycemia without hyperinsulinemia and imaging [abdominal computed tomography (CT) and magnetic resonance scans] negative for neuroendocrine tumor (NET). During hospitalization severe hypoglycemic crises persisted requiring continuous glucose iv infusion. Insulin values (immunofluorimetric method) were not inappropriately increased, accordingly IGR was normal but C-peptide was in the upper-normal range. Proinsulin levels measured with specific radioimmunoassay were remarkably high. Octreoscan study was negative whereas endoscopic ultrasound disclosed a 10 mm lesion in the body of the pancreas, confirmed by rapid spiral CT scanning with dynamic images. Increased proinsulin levels allowed diagnosis of a secreting NET. After removal of the lesion, the patient experienced hyperglycemia. Histology confirmed a benign NET positively staining for insulin. In conclusion, proinsulin assay is of particular help when immunoreactive insulin, measured by specific new immunometric assays (immunoenzymometric and immunofluorimetric assays), is normal. These methods have good precision and specificity (no cross reactivity with intact or Des 31,32 proinsulin), but rare insulinomas secreting most, or all, of their insulin-like activity as proinsulins would go undetected if insulin levels alone were measured.

The oral glucose tolerance test reveals a high frequency of both impaired glucose tolerance and undiagnosed Type 2 diabetes mellitus in primary hyperparathyroidism.

AIMS: To evaluate the frequency of impaired glucose tolerance (IGT)and undiagnosed diabetes mellitus together with the indices of insulin resistance (IR) in primary hyperparathyroidism (pHPT). METHODS: Out of 105 consecutive pHPT patients (F/M 78/27, asymptomatic/symptomatic 68/37, age (mean +/- s.d.) 60.7 +/- 12.7 years,body mass index 25.2 +/- 3.8 kg/m2, ionized calcium (iCa) 1.49 +/- 0.16 mmol/l,parathormone 200.4 +/- 233.9 pg/ml),59 without known diabetes mellitus and controls (n = 60) underwent an oral glucose tolerance test (OGTT, 75 g os). As indices of IR, homeostasis model assessment (HOMAIR)or OGTT data (insulin sensitivity index composite (ISI comp)) were evaluated. RESULTS: In pHPT the prevalence of IGT (mean, 95% confidence intervals (CI), 40.7%, 27.8-53.6) was higher than in controls (25.0%, 13.7-36.3, P < 0.03). Similarly,the prevalence of undiagnosed diabetes mellitus was higher in pHPT(15.3%, 5.8-24.7) than in controls (5.0%, 0-10.7, P < 0.05). Moreover,the prevalence of IGT and undiagnosed diabetes was higher in pHPT than that previously reported in the general population of Northern Italy(8.5% and 3.2%, respectively). The indices showed that insulin resistance was higher in pHPT than in controls: HOMAIR (median, 95% CI,2.6, 2.5-3.9 vs. 1.7, 1.6-2.5, respectively; P < 0.003); ISI comp (3.5, 3.4-4.6 vs. 5.1, 4.9-7.2, respectively; P < 0.002). CONCLUSIONS: Our data in a large and modern day pHPT series, with a preponderance of asymptomatic patients, confirm increased insulin resistance and pre-valence of IGT and undiagnosed diabetes.

Left ventricular hypertrophy in primary hyperparathyroidism. Effects of successful parathyroidectomy.

OBJECTIVE: The association between primary hyperparathyroidism (PHPT) and increased mortality mainly from cardiovascular disease is still debated. The increased mortality previously reported in PHPT was not confirmed in a recent population based study. A high prevalence of left ventricular (LV) hypertrophy was, however, reported in this disease. Although arterial hypertension is regarded as the principal factor, the pathogenesis of LV hypertrophy in PHPT is complex and not completely defined, moreover the effects of successful parathyroidectomy (PTX) are not fully elucidated. The aims of this study were: to ascertain the prevalence of LV hypertrophy in a series of patients with PHPT in comparison to a control population, to seek for relationship between biochemical markers of disease, blood pressure (BP) levels and LV measurements and to evaluate the effects of successful PTX on LV hypertrophy during short-term follow-up. SUBJECTS AND DESIGN: Forty-three patients affected by active PHPT (16 males and 27 females, mean age 60.2 +/- 12.7 years) and 43 controls age- and sex-matched with the same prevalence of arterial hypertension were studied in a case-control analysis. Each subject underwent a M- and 2D mode echocardiographic evaluation and repeated BP measurement. In 21 PHPT submitted to surgery the echocardiographic measurement was repeated 6 months after successful PTX. MEASUREMENTS: Serum concentrations of parathyroid hormone (PTH), total-(Ca) and ionized calcium (iCa), phosphate, creatinine, total alkaline phosphatase (TALP) were measured in patients with PHPT at diagnosis and six months after PTX in the subgroup operated on; BP values were measured in three different occasion; mono and 2D echocardiographic evaluation was performed in control subjects and patients with PHPT either before and after PTX. RESULTS: LV hypertrophy, measured by LV mass index (LVMI), was present in 28/43 PHPT patients (65.1%) and in 15/43 (34.8%) controls, P < 0.05; among hypertensive subjects, 21/21 (100%) PHPT patients and 13/21 (61.9%) controls P < 0.05 were hypertrophic while among normotensive subjects, these figures were 7/22 (31.8%) for PHPT patients and 2/22 (9%) for controls, P = 0.67. At multiple regression analysis in a model including biochemical parameters and BP values, serum PTH levels were associated with LVMI values as the strongest predicting variable (0.46, P < 0.02). Six months after PTX, LVMI decreased (137.8 +/- 37.3 vs 113.0 +/- 28.5, P < 0.05) without changes in mean BP values and ratio of hypertensive patients. CONCLUSION: The present data confirm the high prevalence of LV hypertrophy in primary hyperparathyroidism also in a group of patients with an asymptomatic clinical presentation. The correlation between PTH values and left ventricular mass index suggests an action of the hormone in the pathogenesis of LV hypertrophy confirmed also by the decrease of left ventricular mass index after the reduction of PTH levels. The reversal of left ventricular mass index after parathyroidectomy could affect mortality in primary hyperparathyroidism. An echocardiographic study could be suggested in the clinical work-up of primary hyperparathyroidism in order to evaluate heart involvement and the response to successful parathyroidectomy.

Comparison of assay of total and bone-specific alkaline phosphatase in the assessment of osteoblast activity in patients with metastatic bone disease.

The evaluation of response of osseous metastases to systemic treatments is often low as a consequence of the different radiologic appearances that make objective assessment not only difficult but sometimes impossible. Radiographic evidence of recalcification, the UICC criterion of response, is often evident for 6 months and sometimes may be delayed even more. This accounts for lower response rates in bone with respect to other metastatic sites in clinical trials. A transient rise in bone formation indices may provide an early indication of bone healing and, along with measurement of symptomatic changes, could ameliorate the response evaluation. Among the biochemical markers of bone formation, total alkaline phosphatase (TALP) is widely employed, but it lacks specificity. Estimation of bone isoenzyme (E-BALP) by electrophoretic techniques is time consuming and semiquantitative. The immunoradiometric assay (I-BALP) seems to overcome these limitations. In this study, we compared the two methods of bone isoenzyme estimation with each other and with the levels of bone gla protein (BGP) and carboxyterminal propeptide of type I procollagen (PICP) in a group of 136 cancer patients with bone metastases stratified as having lytic or mixed and blastic lesions at X-ray, and in 62 cancer patients without apparent bone involvement. The same indices were also evaluated prospectively in a patient subset submitted to chemotherapy associated with pamidronate. The aims of the study were to evaluate whether I-BALP is superior to E-BALP and whether both methods of bone isoenzyme estimation are more advantageous than TALP, BGP, and PICP in the assessment of osteoblast activity either in baseline conditions or in response to treatment. In bone metastatic patients with lytic appearances, values above the cut-off limit were observed in 32.1%, 23.3%, 48.9%, 32.9%, and 14% for, TALP, E-BALP, I-BALP, PICP, and BGP, while the corresponding percentages in those with blastic/mixed appearances were 74.0%, 84.8%, 76.9%, 51.9%, and 43.8%, respectively. In the patients without bone involvement, values within the normal range were 90.2%, 98.2%, 89.6%, 71.7%, and 90.2%, respectively. Levels of TALP, E-BALP, and I-BALP were reciprocally correlated in the three groups examined. In bone metastatic patients, however, the degree of correlation of the enzymes with PICP and BGP was weak. Liver isoenzyme of alkaline phosphatase (LALP) was found to correlate with E-BALP, but not with I-BALP, in patients with mixed/blastic lesions. Thirty-eight patients were submitted to pamidronate therapy (60 mg every 3 weeks, administered 4 times) in association with cytotoxic treatment. Osteoblastic markers were determined before any administration. Serum TALP, E-BALP, and I-BALP showed a transient rise in 9 cases, a progressive reduction in 12, no change in 2, and a progressive increase in 6. Changes in E-BALP and I-BALP from baseline were greater than those of TALP. A divergent pattern between TALP and both I-BALP and E-BALP was found in 9 patients, whereas a divergent temporal profile between the two methods of bone isoenzyme estimation was recorded in only 3 patients. Eight out of 38 cases obtained a partial recalcification of lytic and mixed lesions. Seven of them showed the concomitant early increase in TALP, E-BALP, and I-BALP followed by a gradual decline (osteoblastic flare), whereas 1 patient demonstrated the flare of E-BALP and I-BALP but not of TALP. No relationship was found between response and temporal changes in in BGP and PICP serum levels. We conclude that I-BALP is a useful marker for detecting excess osteoblastic activity in patients who have at imaging "pure" lytic bone metastases. In the longitudinal evaluation of patients receiving multiple pamidronate infusions plus chemotherapy, TALP, E-BALP, and I-BALP, but not BGP and PICP, appeared to be useful to identify responders in bone. (ABSTRACT TRUNCATED)

Serum markers of bone and collagen turnover in patients with Cushing's syndrome and in subjects with adrenal incidentalomas.

The aim of this study was to assess serum levels of some markers of bone turnover and collagen synthesis in 22 patients with adrenal incidentalomas (AI), a model of silent glucocorticoid excess, and to compare the results with those obtained in 18 patients with Cushing's syndrome (CS). Osteocalcin (BGP), bone isoenzyme of alkaline phsophatase, carboxy-terminal propeptide of type I procollagen, and carboxy-terminal cross-linked telopeptide of type I collagen were measured as biochemical indexes of bone turnover, and amino-terminal propeptide of type III procollagen was determined as an index of collagen synthesis. Two groups of healthy volunteers evenly matched for sex, age, and menstrual status were used for a case-control analysis of AI and CS groups, respectively. Patients with AI showed a slight, albeit significant, reduction in serum BGP and a mild increase in carboxy-terminal cross-linked telopeptide of type I collagen levels compared with controls [median, 6.6 vs. 7.8 ng/mL (P < 0.05) and 4.2 vs. 3.1 micrograms/L (P < 0.01), respectively]. No significant differences were found when comparing the other markers. Patients with CS had BGP, bone isoenzyme of alkaline phosphatase, and amino-terminal propeptide of type III procollagen levels significantly lower than control values [median, 3.0 vs. 7.3 ng/mL (P < 0.0001); 4.4 vs. 11.5 micrograms/L (P < 0.01); 2.2 vs. 4.3 micrograms/L (P < 0.0001), respectively], but no significant difference in the other markers. These results confirm a clear inhibition of osteoblastic activity in CS and could suggest an enhanced bone metabolism in patients with AI. The degree of impairment of bone turnover in patients with AI does not seem enough to recommend surgery (removal of the adrenal adenoma) in the absence of other indications.