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Background: Greater efforts are needed to overcome the worldwide reported low achievement of LDL-c targets. This survey aimed to dissect whether and how the physician-based evaluation of patients with diabetes is associated with the achievement of LDL-c targets. Methods: This cross-sectional self-reported survey interviewed physicians working in 67 outpatient services in Italy, collecting records on 2844 patients with diabetes. Each physician reported a median of 47 records (IQR 42–49) and, for each of them, the physician specified its perceived cardiovascular risk, LDL-c targets, and the suggested refinement in lipid-lowering-treatment (LLT). These physician-based evaluations were then compared to recommendations from EAS/EASD guidelines. Results: Collected records were mostly from patients with type 2 diabetes (94%), at very-high (72%) or high-cardiovascular risk (27%). Physician-based assessments of cardiovascular risk and of LDL-c targets, as compared to guidelines recommendation, were misclassified in 34.7% of the records. The misperceived assessment was significantly higher among females and those on primary prevention and was associated with 67% lower odds of achieving guidelines-recommended LDL-c targets (OR 0.33, p < 0.0001). Peripheral artery disease, target organ damage and LLT-initiated by primary-care-physicians were all factors associated with therapeutic-inertia (i.e., lower than expected probability of receiving high-intensity LLT). Physician-suggested LLT refinement was inadequate in 24% of overall records and increased to 38% among subjects on primary prevention and with misclassified cardiovascular risk. Conclusions: This survey highlights the need to improve the physicians’ misperceived cardiovascular risk and therapeutic inertia in patients with diabetes to successfully implement guidelines recommendations into everyday clinical practice.

Background: Vertebral fractures (VFs) are a frequent complication of acromegaly, but no studies have been so far published on effectiveness of antiosteoporotic drugs in this clinical setting. Objective: To evaluate whether in real-life clinical practice bone active drugs may reduce the risk of VFs in patients with active or controlled acromegaly. Study design: Retrospective, longitudinal study including 9 tertiary care endocrine units. Patients and methods: Two hundred and forty-eight patients with acromegaly (104 males; mean age 56.00 ± 13.60 years) were evaluated for prevalent and incident VFs by quantitative morphometric approach. Bone active agents were used in 52 patients (20.97%) and the median period of follow-up was 48 months (range 12-132). Results: During the follow-up, 65 patients (26.21%) developed incident VFs in relationship with pre-existing VFs (odds ratio [OR] 3.75; P < .001), duration of active acromegaly (OR 1.01; P = .04), active acromegaly at the study entry (OR 2.48; P = .007), and treated hypoadrenalism (OR 2.50; P = .005). In the entire population, treatment with bone active drugs did not have a significant effect on incident VFs (P = .82). However, in a sensitive analysis restricted to patients with active acromegaly at study entry (111 cases), treatment with bone active drugs was associated with a lower risk of incident VFs (OR 0.11; P = .004), independently of prevalent VFs (OR 7.65; P < .001) and treated hypoadrenalism (OR 3.86; P = .007). Conclusions: Bone active drugs may prevent VFs in patients with active acromegaly.

Objective: According to the 2015 American Thyroid Association (ATA) guidelines, thyroid ablation by iodine-131 (I-131) therapy is absolutely recommended only in patients with high-risk differentiated thyroid cancer (DTC). Often distant metastases are not recognized early and they can stay silent for long time. The aim of our study was to retrospectively analyze the prevalence of metastatic disease before and after I-131 and to evaluate the influence of the new ATA guidelines in the management of DTC. Methods: We retrospectively analyzed 140 patients showing distant metastases. All metastases were detected by whole-body scan after I-131 and confirmed by histology and/or other imaging modalities. Results: In 26/140 patients metastases were detected before I-131, while in 114/140 were discovered after I-131. Comparing patients with metastases detected before and after I-131, no differences were demonstrated considering age, sex, histotype, tumor size, multifocality of cancer and metastatic localization. Metastatic DTC discovered before radioiodine had higher thyroglobulin and received a higher radioiodine total activity and number of treatments. Considering patients with distant metastases, according to the 2015 ATA guidelines, 38 patients would have been categorized as high risk, 22 as low risk and 80 as intermediate risk. Among intermediate-risk patients, only in 25 cases (31%) I-131 treatment would have been appropriate according to 2015 ATA recommendations; in the remaining 56 cases (69%), I-131 would not have been recommended. Conclusions: According to the 2015 ATA guidelines, most of metastatic patients would not have been treated after surgery, with the risk of late diagnosis and delayed treatment

Introduction: Skeletal fragility with high risk of vertebral fractures is an emerging complication of acromegaly in close relationship with duration of active disease. The aim of this cross-sectional study was to evaluate the prevalence and determinants of vertebral fractures in males and females with a history of long-standing active acromegaly undergoing treatment with Pegvisomant. Subjects and methods: Thirty-eight patients (25 females, 13 males) with acromegaly under Pegvisomant therapy were evaluated for vertebral fractures and bone mineral density at lumbar spine and femoral neck. Gonadal status, serum IGF1 levels and growth hormone receptor genotype were also assessed. Results: Vertebral fractures were detected in 12 patients (31.6%). Fractured patients had longer duration of active disease (p = 0.01) with higher frequency of active acromegaly (p = 0.04), received higher dose of Pegvisomant (p = 0.008), and were more frequently hypogonadic (p = 0.02) as compared to patients who did not fracture. Stratifying the patients for gender, vertebral fractures were significantly associated with Pegvisomant dose (p = 0.02) and untreated hypogonadism (p = 0.02) in males and with activity of disease (p = 0.03), serum insulin-like growth factor-I values (p = 0.01) and d3GHR polymorphism (p = 0.005) in females. No significant association was found between vertebral fractures and bone mineral density at either skeletal site. Conclusion: Vertebral fractures are a frequent complication of long-standing active acromegaly. When patients are treated with Pegvisomant, vertebral fractures may occur in close relationship with active acromegaly and coexistent untreated hypogonadism.

Purpose: Acromegalic osteopathy is an emerging complication of acromegaly characterized by increase in bone turnover, deterioration in bone microarchitecture and high risk of vertebral fractures (VFs). Somatostatin receptor ligands (SRLs) and pegvisomant (PegV) are used for treatment of acromegaly and there is evidence that both drugs may exert direct effects on peripheral targets regardless of biochemical control of disease. However, whether or not SRLs and PegV may directly influence skeletal health its is unknown. Methods: In this longitudinal study, we evaluated the incidence of radiological VFs in 83 patients (48 females, 35 males; median age 47 years, range 18-80 years) who were treated with SRLs alone (42 cases), PegV alone (6 cases) or in combination with SRLs (35 cases) for median period of 82 months (range 36-126). PegV was given when acromegaly was not controlled by SRLs alone. Results: During the follow-up, 29 patients (34.9%) developed incident VFs. In patients receiving PegV due to active disease during SRL therapy, incidence of VFs decreased significantly from 43.9 to 26.8% (p = 0.039). When acromegaly was controlled by PegV, the incidence of VFs was slightly but not significantly lower as compared to that observed in patients with biochemical control of disease by SRLs (10.0 vs. 26.7%; p = 0.09). In the multivariate logistic regression analysis, incident VFs were independently predicted by pre-existing VFs (odds ratio 61.0; p = 0.009), duration of active acromegaly (odds ratio 1.01; p = 0.05) and mean serum IGF-I during the follow-up (odds ratio 5.26; p = 0.03), regardless of the therapeutic regimen (odds ratio 1.05; p = 0.94). Conclusions: PegV and SRLs had comparable effects on VF risk in acromegaly. The activity of disease was the main determinant of VFs independently of the drug used to control acromegaly.

Vertebral fractures are an emerging complication of acromegaly but their prediction is still difficult occurring even in patients with normal bone mineral density. In this study we evaluated the ability of high-resolution cone-beam computed tomography to provide information on skeletal abnormalities associated with vertebral fractures in acromegaly. 40 patients (24 females, 16 males; median age 57 years, range 25–72) and 21 healthy volunteers (10 females, 11 males; median age 60 years, range: 25–68) were evaluated for trabecular (bone volume/trabecular volume ratio, mean trabecular separation, and mean trabecular thickness) and cortical (thickness and porosity) parameters at distal radius using a high-resolution cone-beam computed tomography system. All acromegaly patients were evaluated for morphometric vertebral fractures and for mineral bone density by dual-energy X-ray absorptiometry at lumbar spine, total hip, femoral neck, and distal radius. Acromegaly patients with vertebral fractures (15 cases) had significantly (p < 0.05) lower bone volume/trabecular volume ratio, greater mean trabecular separation, and higher cortical porosity vs. nonfractured patients, without statistically significant differences in mean trabecular thickness and cortical thickness. Fractured and nonfractured acromegaly patients did not have significant differences in bone density at either skeletal site. Patients with acromegaly showed lower bone volume/trabecular volume ratio (p = 0.003) and mean trabecular thickness (p < 0.001) and greater mean trabecular separation (p = 0.02) as compared to control subjects, without significant differences in cortical thickness and porosity. This study shows for the first time that abnormalities of bone microstructure are associated with radiological vertebral fractures in acromegaly. High-resolution cone-beam computed tomography at the distal radius may be useful to evaluate and predict the effects of acromegaly on bone microstru

Acromegaly is associated with an increased prevalence of vertebral fractures (VFs) in close relationship with GH hypersecretion. Two isoforms of the GH receptor (GHR) have been identified; the two isoforms differ or not by the expression of the protein fragment encoded by exon 3 of the GHR gene. Deletion of the exon 3 may influence the functional properties of the GHR and affect fracture risk in acromegalic patients.

Cross-sectional studies showed an elevated prevalence of vertebral fractures in acromegaly. However, no data are available on incident vertebral fractures in this clinical setting.

Objective: In this study, the effect of high-dose octreotide LAR on glucose metabolism in patients with acromegaly was investigated. Design: A post-hoc analysis of a clinical trial enrolling 26 patients with acromegaly not controlled by standard maximal somatostatin analog (SSAs) dose and randomized to receive high-dose (60 mg/28 days) or high-frequency (30 mg/21 days) octreotide i.m. injection (octreotide LAR) for 6 months. Methods: Glucose metabolic status was defined as worsened when a progression from normoglycemia to impaired fasting glucose (IFG) or from IFG to diabetes occurred or when an increase of HbAlc by at least 0.5% was demonstrated. An improvement of glucose metabolism was defined in the presence of a regression from IFG to normoglycemia and/or when HbAlc decreased by at least 0.5%. Results: Glucose metabolic status remained unchanged in a majority of patients (16/26 patients, 65.3%), worsened in six patients, and improved in four patients. Pre-existing metabolic status did not predict worsening of glucose metabolism, which, conversely, was significantly related to persistent biochemical activity of the disease. In fact, patients with worsened glucose metabolism exhibited a less frequent decrease in serum GH and IGF1 levels, compared with patients with improved or unchanged glucose metabolism (2/6 vs 18/20; P=0.01). Conclusion: An increase in octreotide LAR dose or frequency did not impact on glucose metabolism in most patients. Worsening of glucose metabolic status occurred in close relation with persistently uncontrolled acromegaly. © 2011 European Society of Endocrinology.

Hyperprolactinemia may cause bone loss but data on fractures are scanty. The aim of this study was to evaluate the prevalence of vertebral fractures in women with prolactin (PRL)-secreting adenoma. In this cross-sectional study, 78 women (median age 45.5 years, range: 20-81) with PRL-secreting pituitary adenoma (66 with microadenoma and 12 with macroadenoma) and 156 control subjects, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 25 patients with PRL-secreting adenoma (32.6%) and in 20 controls (12.8%, P < 0.001). Fractured patients were significantly older (P < 0.001) and had lower BMD T-score (P < 0.001), longer duration of disease (P < 0.001), higher serum PRL (P = 0.004) and lower serum IGF-I (P < 0.001) values as compared to patients who did not fracture. The prevalence of vertebral fractures was significantly (P < 0.001) higher in post-menopausal women with PRL-secreting adenoma as compared to pre-menopausal patients. Fractures occurred more frequently (P = 0.01) in patients with untreated hyperprolactinemia versus patients treated with cabergoline. Logistic regression analysis demonstrated that duration of disease maintained a significant correlation with vertebral fractures (odds ratio 1.16, C.I. 95% 1.02-1.33) even after correction for age, menopausal status, treatment with cabergoline, BMD, serum IGF-I and serum PRL values. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in women with PRL-secreting adenoma. © 2011 Springer Science+Business Media, LLC.

BACKGROUND: Sensitivity to pegvisomant therapy is highly variable in patients with acromegaly but determinants of this variability are still unknown. Lack of exon 3 (d3-) of the growth hormone (GH) receptor (GHR) has been associated with increased biological activity of GH. OBJECTIVE: To assess whether the presence of d3-GHR haplotype may have a role in predicting dose regimen and response to pegvisomant in acromegaly. DESIGN: Case series. Setting Institutional referral center at a tertiary care hospital. Patients Nineteen acromegalic patients with active disease after unsuccessful neurosurgery and somatostatin analog therapy. MEASUREMENTS: Before and 1, 3, 6 and 12 months after treatment with pegvisomant, IGF-I; GH receptor genotype, determined from peripheral blood by polymerase chain reaction. All patients started treatment with pegvisomant at 10 mg/daily and then increased the dose, according to a fixed schedule, during a 12-month follow-up until normalization of IGF-I levels. RESULTS: d3-GHR patients required a significant lower dose of pegvisomant and shorter treatment time to normalize IGF-I. CONCLUSION: The GHR genotype could be useful in predicting dose and individual response to pegvisomant in acromegaly.

Objective: In acromegaly, 25-50% of patients respond inadequately to conventional long-acting somatostatin analogue (SSA) therapy. Response may be improved by increasing SSA frequency or dose. This study evaluated the biochemical efficacy and safety of high-dose octreotide in patients with acromegaly. Design: A 24-week prospective, multicentre, randomised, open-label trial conducted from 12 December 2005 to 23 October 2007 in patients with persistently uncontrolled acromegaly despite ≥6 month conventional SSA therapy. Methods: Patients with ≥ 50% reduction in GH levels during previous SSA treatment were randomised to high-dose (60 mg/28 days) or high-frequency (30 mg/21 days) octreotide i.m. injection. Primary end-points were week 12 and 24 reduction in serum IGF1 and GH from baseline. Secondary end points included IGF1 normalisation and tumour shrinkage rates, and safety/tolerability evaluations. Results: Significantly, more patients (10 out of 11) achieved week 24 IGF1 reduction in the high-dose than the high-frequency group (8 out of 15; P < 0.05). In the high-dose group only, week-24 IGF1 values were significantly reduced (P = 0.02) versus baseline. Normalisation of IGF1 occurred only with the high-dose regimen (4/11; P = 0.02). Out of 14 patients experiencing adverse events, 5 reported drug-related gastrointestinal effects. No dose-response relationship was seen. Safety parameters were similar between treatment groups, apart from a slight decrease in HbA1c in the high-dose group only. Conclusion: High-dose octreotide treatment is safe and effective (normalisation of IGF1 levels) in a subset of patients with active acromegaly inadequately controlled with long-term SSA. Individualised octreotide doses up to 60 mg/28 days may improve outcomes of SSA therapy. © 2009 European Society of Endocrinology.

CONTEXT: Data on osteoporotic fractures in acromegaly are limited. An increased prevalence of radiological vertebral fractures was already observed in postmenopausal women with active acromegaly. It is unknown whether this observation may reflect a more general increased risk of fractures in acromegaly. DESIGN: This was a cross-sectional study. SETTING: The study was conducted at referral centers. PATIENTS AND CONTROL SUBJECTS: Subjects included 40 males with acromegaly (25 patients with controlled disease and 15 patients with active disease) and 31 control males, with age and gonadal status comparable with the patients. INTERVENTIONS: Evaluation of vertebral fractures (quantitative morphometric analysis) and bone mineral density (BMD) at lumbar spine and total hip (dual energy X-ray absorptiometry) was done. MAIN OUTCOME MEASURE: Vertebral fractures were assessed. RESULTS: Although BMD was not significantly different between acromegalic patients and control subjects, the prevalence of vertebral fractures was higher in acromegalic patients as compared with the control subjects (57.5 vs. 22.6%; chi(2): 8.7; P = 0.003). Fractured and nonfractured acromegalic patients showed no significant difference in age and BMD Z-score. However, acromegalic patients with fractures had serum IGF-I values significantly higher and duration of active disease significantly longer with respect to patients without fractures. Moreover, patients with fractures showed significantly longer untreated hypogonadism as compared with patients without fractures. In a multivariate logistic regression analysis, the duration of active acromegaly was the only risk factor significantly correlated with the occurrence of fractures (odds ratio 1.1, confidence interval 1.04-1.6). CONCLUSIONS: This study reports for the first time a high prevalence of osteoporotic vertebral fractures in an unselected acromegalic male population generally considered at low risk of osteoporosis, suggesting that complicated ost

Growth hormone deficiency (GHD) in adult patients is associated with marked decrease in bone turnover, low bone mass and high risk of clinical and subclinical fractures. We investigated whether the prevalence of spinal deformities in adults with GHD was related to the gonadal status of patients. A total of 89 adult hypopituitary patients with severe GHD were evaluated for bone mineral density (BMD) and vertebral deformities (quantitative morphometric analysis). At the study entry, 54 patients were eugonadic whereas 35 patients were hypogonadic without replacement treatment. Radiological spinal deformities were found in 55 patients (61.8%) with higher prevalence in untreated (56 cases) versus treated (33 cases) GHD patients. Eugonadic and hypogonadic patients showed no significant difference in spinal deformities although T-score was significantly lower in hypogonadic as compared with eugonadic patients. Gonadal function was not correlated with the occurrence of spinal deformities which was instead inversely correlated with rhGH treatment. In conclusion, gonadal status may influence BMD in adult patients with GHD without affecting the risk to develop vertebral deformities. Conversely, rhGH replacement treatment seems to be the only factor influencing the risk to develop vertebral deformities in adult GHD patients.

Several recent studies have reported beneficial effects of pegvisomant monotherapy on glucose homeostasis for acromegalic patients resistant to somatostatin analogs (SSA). The aim of our longitudinal study was to test whether these beneficial effects on glucose homeostasis would also occur during combined pegvisomant + SSA treatment amongst partially SSA-resistant acromegalic patients. Ten non-diabetic, partially SSA-resistant acromegalic patients underwent a 12-month SSA+pegvisomant treatment after SSA-only therapy. Glucose homeostasis was evaluated at disease diagnosis, at the end of the SSA treatment and after 6 and 12 months of combined SSA+pegvisomant treatment. The addition of pegvisomant treatment was accompanied by a significant improvement in insulin and glycemic responses to the oral glucose tolerance test, without any significant changes in fasting plasma glucose, glycosylated haemoglobin, homeostatic model assessment-derived insulin resistance index and homeostatic model assessment-derived beta-cell function. Moreover, the number of patients with glucose intolerance did not significantly change during the 12-month combined treatment, notwithstanding the significant decrease in serum IGF-1 values. Therefore, our findings suggest that the combined pegvisomant and SSA treatment may not be able to restore normal clinical and biochemical glycometabolic features occurring in acromegalic patients resistant to SSA, while a slight but significant improvement in some biochemical features may be expected.

This cross-sectional study shows that a high number of untreated adult patients with GHD develop radiological vertebral deformities. Patients undergoing GH replacement treatment showed a significantly lower prevalence of vertebral deformities versus treated patients in the presence of similar BMD, as assessed by DXA. INTRODUCTION: In this cross-sectional study, we investigated whether the prevalence and degree of spinal deformities in adults with growth hormone deficiency (GHD) were related to the age of patients, degree of bone turnover, BMD, and recombinant human GH (rhGH) replacement therapy. MATERIALS AND METHODS: One hundred seven adult hypopituitary patients (67 males and 40 females; mean age, 47 years; range: 16-81 years) with severe GHD and 130 control subjects (39 males, 91 females; mean age: 58.9 years; range: 26-82 years) were evaluated for BMD (DXA) and vertebral deformities (quantitative morphometric analysis). At study entry, 65 patients were on replacement therapy with rhGH, whereas 42 patients had never undergone rhGH. RESULTS: Vertebral fractures were significantly more frequent in GHD patients versus control subjects (63.6% versus 37.7%; chi2 15.7; p < 0.001). The fracture prevalence, as well as the fracture number, was significantly higher in untreated versus treated patients (78.6% versus 53.8%; chi2: 6.7; p = 0.009), although the two groups of patients did not show any significant difference in median T score. In untreated GHD patients, the prevalence of vertebral deformities was correlated with T score (p = 0.002) and duration of disease (p = 0.003). In treated GHD patients, the prevalence of spinal deformities was correlated only with the timing of the beginning of rhGH replacement. CONCLUSIONS: This cross-sectional study reports high prevalence of vertebral radiological deformities in adult patients with untreated GHD. The replacement treatment of GHD leads to a significant decrease in fracture rate.

In healthy subjects, parathyroid hormone (PTH) is secreted in a dual fashion, with low-amplitude and high-frequency pulses superimposed on tonic secretion. These 2 components of PTH secretion seem to have different effects on target organs. The aim of our study was to evaluate whether growth hormone excess in acromegaly may modify the spontaneous pulsatility of PTH. Five male patients with newly diagnosed active acromegaly and 8 healthy subjects were evaluated by 3-minute blood sampling for 6 hours. Plasma PTH concentrations were evaluated by multiparameter deconvolution analysis. Plasma PTH release profiles were also subjected to an approximate entropy (ApEn) estimate, which provides an ensemble measure of the serial regularity or orderliness of the release process. In acromegalic patients, baseline serum PTH values were not significantly different from those measured in the healthy subjects, as well as tonic PTH secretion rate, number of bursts, fractional pulsatile PTH secretion, and ApEn ratio. Conversely, PTH pulse half-duration was significantly longer in acromegalic patients vs healthy subjects (11.8+/-0.95 vs 6.9+/-1.6 minutes; P=.05), whereas PTH pulse mass showed a tendency (P=.06) to be significantly greater in acromegalic patients. These preliminary data suggest that growth hormone excess may affect PTH secretory dynamics in patients with acromegaly. Potentially negative bone effects of the modifications of PTH secretory pattern in acromegaly should be investigated.

This cross-sectional study shows that high numbers of postmenopausal women with acromegaly develop vertebral fractures in relation to the activity of disease. In patients with active acromegaly, vertebral fractures occur even in presence of normal BMD, whereas in patients with controlled acromegaly, vertebral fractures are always accompanied by a pathological BMD. INTRODUCTION: We studied the frequency of radiological vertebral fractures in a cohort of postmenopausal women with active or controlled acromegaly. MATERIALS AND METHODS: Thirty-six postmenopausal acromegalic patients (15 with active and 21 with controlled disease) were evaluated for BMD, bone metabolism (serum 25-hydroxyvitamin D, PTH, bone-specific alkaline phosphatase [BSALP], and urinary deoxypyridinoline [Dpd]), and vertebral quantitative morphometry. Thirty-six nonacromegalic postmenopausal women, matched for age, were selected among the patients consulting the Bone Center as a control group for BMD evaluation and vertebral quantitative morphometry. RESULTS: Vertebral fractures were shown in 19 patients (52.8%) and 11 controls (30.6%; chi2: 3.7; p=0.06). Fractured acromegalic women were older and had higher serum IGF-1, Dpd, and BSALP and lower T score and serum vitamin D values compared with nonfractured patients. Moreover, the fractured women had a longer diagnosis and were in the postmenopausal period for a longer period than the nonfractured women. The fracture rate was significantly higher in active than in controlled acromegaly (80% versus 33.3%; chi2: 7.6; p=0.008). The patients with active acromegaly who fractured (12 cases) had significantly higher serum IGF-1 values (356 ng/ml; range: 212-950 versus 120 ng/ml; range: 84-217; p<0.001) and T scores (-1.3 SD, range: -2.9 to +1.3 versus -2.7 SD, range: -3.4 to -1.5, p=0.04) compared with the fractured women whose disease was controlled (7 cases). All fractured women with controlled acromegaly had T scores<-1.0 SD (57.1% of them had osteoporosi