Risk In Acromegaly Research Articles

Cardiovascular remodeling in active and controlled acromegaly: association with sleep-disordered breathing.

We hypothesized that anunfavorable cardiovascular profile in acromegaly is associated with sleep-disordered breathing (SDB), while acromegaly control improves both respiratory sleep characteristics and thecardiovascular profile. The patients underwent the assessment of breathing during sleep and cardiovascular profileassessment atthe start of the studyincluding arterial stiffness, blood pressure, echocardiography, nocturnal heart rate variability (HRV). The assessment was repeated in patients withacromegaly at 1 year after transsphenoidal adenectomy (TSA). A total of 47 patients with acromegaly and 55 control subjects were enrolled. At one year after TSA, 22 patients with acromegaly were reassessed.Multiple linear regression analysis with adjustment for age, sex and body mass index (BMI) showed the associations of insulin growth-like factor 1 (IGF-1) with obstructive apnea index (OAI: β=0.035/h, p<0.001), but not with cardiovascular parameters, in patients withacromegaly. The analysis of combined acromegaly and control dataset with adjustment for age, sex and BMI showed the association the presence of acromegaly with diastolic blood pressure (DBP; β=17.99 mmHg, p<0.001), ejection fraction (EF; β=6.23%, p=0.009), left heart remodeling (left ventricle posterior wall: β=0.81 mm, p=0.045) and the association of the presence of SDB (apnea-hypopnea index≥15/h) with left ventricular function (EF: -4.12%, p=0.040; end systolic volume: 10.12 ml, p=0.004). Control of acromegaly was accompanied by the decrease in OAI (5.9 [0.8, 14.5]/h and 1.7 [0.2, 5.1]/h, p=0.004) and nocturnal heart rate (66.1 [59.2, 69.8] bpm and 61.7 [54.0, 67.2] bpm, p=0.025) and by the increase in blood pressure (DBP: 78.0 [70.3, 86.0] mm Hg and 80.0 [80.0, 90.0] mm Hg, p=0.012). The comorbidities of acromegaly, including sleep-disordered breathing, appear to have a long-term effect on cardiovascular remodeling in active acromegaly. Future studies should investigate the applicability of the treatment of SDBfor the reduction of cardiovascular risk in acromegaly.

Cardiovascular Risk in Acromegaly

Abstract Acromegaly is associated with cardiovascular disease, the principal cause of increased mortality. Direct cardiac effects of GH/IGF-1 are cardiomyocyte growth and cardiac contractility, cardiac remoddeling. Other important risk factors in acromegaly are hypertension, valvular diseases, arrhytmias. Older patients with long-term uncontrolled disease may develop congestive heart failure as end-stage of acromegalic cardiomyopathy. Early treatment of acromegaly is essential for evolution and prognosis of cardiovascular complications.

Association of Epicardial Adipose Tissue Thickness with Cardiovascular Risk in Acromegaly

Objective:Acromegaly is a rare disease associated with increased mortality. Reports on coronary artery disease in acromegaly are controversial. This study aimed to investigate the possible association of epicardial adipose tissue thickness with cardiovascular risk in patients with acromegaly.Methods:The study included 38 patients followed up with the diagnosis of acromegaly and 29 healthy controls. Patients with acromegaly were divided into controlled and uncontrolled acromegaly groups based on insulin-like growth factor-1 levels. Epicardial adipose tissue thickness measurements were obtained from chest computed tomography, and laboratory data were extracted from patient files.Results:Twenty-nine patients (76.3%) had controlled acromegaly. Eleven patients with acromegaly had diabetes mellitus (28.9%), 18 (47.4%) had hypertension, and 27 (71%) had a concomitant chronic disease. Epicardial adipose tissue thickness was significantly increased in the acromegaly group (p<0.001). No significant difference was observed between the controlled and uncontrolled acromegaly groups in terms of the epicardial adipose tissue thickness. Age was the only parameter that was significantly correlated with the epicardial adipose tissue thickness. When the Framingham risk score was calculated, the 10-year cardiovascular risk of patients with acromegaly was 5.63%.Conclusions:The epicardial adipose tissue thickness is increased in acromegaly. However, this increase may not have clinical relevance in terms of cardiovascular risk.

Incidence of Benign and Malignant Tumors in Patients With Acromegaly Is Increased: A Nationwide Population-based Study.

Whether cancer risk in acromegaly is increased remains controversial, and the risk of benign tumors has been little studied. To investigate the incidence of benign and malignant tumors in acromegaly in a nationwide population-based study. Adult patients diagnosed with acromegaly between 1987 and 2017 were identified in the Swedish National Patient Registry. The diagnoses of benign and malignant tumors were recorded. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) for neoplasms with 95% CIs were calculated using the Swedish general population as reference. The study included 1296 patients (52% women). Mean (SD) age at diagnosis was 51.6 (14.7) years. Median (range) follow-up time was 11.7 (0-31) years. Overall, 186 malignancies were identified in acromegalic patients compared with 144 expected in the general population (SIR 1.3; 95% CI 1.1-1.5). The incidence of colorectal and anal cancer (SIR 1.5; 95% CI 1.0-2.2), and renal and ureteral cancer (SIR 4.0; 95% CI 2.3-6.5) was increased, whereas the incidence of malignancies of the respiratory system, brain, prostate, and breast was not. Only 3 cases of thyroid cancer were recorded. Mortality due to malignancies was not increased (SMR 1.1; 95% CI 0.9-1.4). Incidence of benign tumors was increased more than 2-fold (SIR 2.4; 95% CI 2.1-2.7). Patients with acromegaly had an increased risk of both benign and malignant tumors, including colorectal and anal cancer, and renal and ureteral cancer. Whether this is associated with acromegaly itself or due to more intensive medical surveillance remains to be shown.

Correlations between Arteriograph-Derived Augmentation Index and Disease Activity in Acromegaly Patients.

Objective: The high prevalence of cardiovascular diseases in acromegaly patients attracted attention to the association between the growth hormone and cardiovascular system. New markers such as the augmentation index (AIx) and central aortic pressure (CAP) have recently been introduced to the clinical practice for a variety of diagnostic and monitoring purposes in predicting arterial stiffness and associated endothelial dysfunction. In this present study, we aimed to determine the condition of the vascular system using the non-invasive arterial stiffness marker; AIx measured using by the Arteriograph device and to evaluate the relationship between these markers and the disease activity in acromegaly patients. Methods: This was a cross-sectional study. The study included 53 acromegaly patients and 20 individuals age and sex matched as controls. The arterial stiffness was evaluated to estimate the AIx and CAP with a low-frequency suprasystolic waveform analysis in the occluded brachial artery, performed by using a Cardio Scope II Arteriograph device, which was adapted from a standard sphygmomanometer. Results: The mean augmentation index was statistically significantly different between the three groups, being 98% in the active acromegaly (AA) group, 92% in controlled acromegaly (CA) and 79.5% in the control group (p=0.001). In the acromegaly group, the results of the regression analysis indicated a strong correlation of the arterial stiffness parameters with HbA1c and the platelet counts, however, the levels of IGF-1 and GH were not correlated Conclusion: It might be thought that AIx may have an important role in predicting the cardiovascular risk in acromegaly.

Serum Levels of Asprosin, a Novel Adipokine, Are Significantly Lowered in Patients with Acromegaly.

Background Asprosin is a novel identified adipokine secreted mainly by white adipose tissue, which is elevated in metabolic diseases such as diabetes and obesity. Acromegaly is a syndrome caused by pituitary growth hormone (GH) cell adenoma with excessive GH secretion. Serum adipocytokines levels may be involved in abnormal glycolipid metabolism in acromegaly patients. Objectives To investigate serum asprosin levels in acromegaly patients and its correlation with high GH levels and glucolipid metabolic parameters. Methods A retrospective case-control study was conducted and 68 acromegaly patients and 121 controls were included in this study. Clinical information and laboratory examinations were collected and serum asprosin levels were measured by commercial ELISA kits. Results Serum asprosin levels in acromegaly patients were significantly lower than controls (P < 0.001). Serum asprosin levels in patients with the course of acromegaly ≥5 years (compared with <5 years), high area under curve of growth hormone (GH-AUC) after 75 g oral glucose tolerance test (OGTT) (compared with low GH-AUC patients), and high IGF-1 SDS group (compared with low IGF-1 SDS group) were significantly reduced (all P < 0.05). Serum asprosin levels in acromegaly patients were negatively correlated with the course of acromegaly, IGF-1 SDS, nadir growth hormone value (GH-Nadir), and GH-AUC after OGTT. Multiple stepwise linear regression indicated that acromegaly was an independent influencing factor of serum asprosin levels. According to serum asprosin levels tertiles, the risk of acromegaly in the lowest group was 2.67 times higher than the highest group (OR ＝ 3.665, 95% CI 1.677 ∼ 8.007, P=0.001), and the increased risk of the lowest group still existed after adjusting for gender, age, BMI, and TC (Model 2). Conclusions Serum asprosin levels in acromegaly patients are lowered, which may be related to increased blood glucose and reduced body fat mass caused by long-term high GH levels exposure.

Klotho gene G395A and C1818T polymorphisms in acromegaly: Association with clinical presentation and comorbidities.

Klotho is a new identified anti-ageing gene with tumour suppressor activities. Current data suggest that there is a tight relationship between Klotho protein and growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis. This study aimed to investigate the possible association of Klotho gene polymorphisms with acromegaly and to assess whether these polymorphisms contribute to clinical characteristics, comorbidities and biochemical variables in these patients. The study included 52 patients with acromegaly and 52 unrelated healthy subjects. The Klotho G395A and C1818T polymorphisms were assessed by Sanger sequencing. Serum levels of sKlotho were determined by ELISA method. Subjects carrying GA genotype of Klotho G395A polymorphism had 3.27 times higher risk of developing acromegaly [odds ratio (OR), 3.27; 95% confidence interval (CI): 1.37-7.81; p=.023]. The A allele of G395A was significantly associated with acromegaly risk (OR, 2.27; 95% CI: 1.1-4.72; p=.022). No association was observed between the studied polymorphisms and disease characteristics including age at acromegaly diagnosis, size of adenoma, baseline GH and IGF-1 concentrations, and final outcome. G395A polymorphism was associated with the presence of malignancy (OR, 2.24, 95% CI: 1.63-3.08; p=.019) and colorectal polyps (OR, 1.99; 95% CI: 1.02-3.88; p=.047) in patients with acromegaly. Serum sKlotho levels were significantly higher and correlated with GH and IGF-1 levels among acromegaly patients. There was no association between the studied polymorphisms and sKlotho levels. Klotho G395A polymorphism is associated with acromegaly susceptibility and increased risk of malignancy and colorectal polyps in these patients.

Trabecular bone score as a useful tool for assessment of fracture risk in acromegaly

Trabecular bone score as a useful tool for assessment of fracture risk in acromegaly

Cardiometabolic Risk in Acromegaly: A Review With a Focus on Pasireotide.

Acromegaly is a disease due to chronic GH excess and a consequent rise in IGF-1 levels. This rare endocrine condition is associated with metabolic alterations such as hyperglycaemia, dyslipidaemia, and systemic arterial hypertension, which, in addition to GH excess-related cardiovascular changes, play critical roles in increasing cardiovascular risk and mortality rates. Biochemical control of acromegaly, achieved by means of surgical, and/or medical treatment, positively impacts on cardiovascular risk factors and metabolic alterations, reducing overall patient mortality. However, treatment modalities of acromegaly and disease control differently impact on glucose homeostasis and lipid changes, and consequently on cardiometabolic risk. In this regard, pasireotide was shown to significantly influence glucose metabolism. This review summarizes the cardiometabolic consequences of acromegaly and its treatment, focusing on available data around the effects of medical therapy with pasireotide on factors that influence cardiometabolic risk.

Hip Structure Analyses in Acromegaly: Decrease of Cortical Bone Thickness After Treatment: A Longitudinal Cohort Study.

ABSTRACTLong‐standing growth hormone (GH) excess causes the skeletal clinical signs of acromegaly with typical changes in bone geometry, including increased cortical bone thickness (CBT). However, a high prevalence and incidence of vertebral fractures has been reported. The aim of this study was to assess the course of cortical bone dimensions in the hip by comparing patients with acromegaly and clinically nonfunctioning pituitary adenomas (NFPAs) at baseline and 1 year after pituitary surgery (1‐year PO) in a longitudinal cohort study. DXA was performed in patients with acromegaly (n = 56) and NFPA (n = 47). CBT in the femoral neck (CBTneck), calcar (CBTcalcar), and shaft (CBTshaft) were determined by hip structural analysis (HSA). CBT at baseline and the change to 1‐year PO were compared. Test results were adjusted for differences in gender distribution, age, and gonadal status. Cortical thickness analyses showed higher values [mm] at baseline in patients with acromegaly compared with NFPA: CBTneck median [25th; 75th] 6.2 [4.7; 8.0] versus 5.1 [4.1; 6.4] (p = 0.006), CBTcalcar 4.8 [4.2, 5.7] versus 4.0 [3.2, 4.5] (p < 0.001), CBTshaft 6.2 [5.1, 7.2] versus 5.2 [4.6, 6.0], (p = 0.003). In acromegaly, GH was correlated with CBTneck (r = 0.31, p = 0.020), whereas IGF‐1 was correlated with CBTcalcar (r = 0.39, p = 0.003) at baseline. In acromegaly, CBTneck decreased by 11.2%, p = 0.002 during follow‐up. Finally, the decrease in CBTneck and CBTcalcar in acromegaly was significant compared with NFPA (p = 0.023 and p = 0.017, respectively). Previous observations of increased CBT in acromegaly were confirmed with DXA‐derived HSA in a large, well‐defined cohort. The decline in CBT in acromegaly could contribute to the increased fracture risk in acromegaly despite increased bone dimensions and disease control. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Exon 3-deleted growth hormone receptor isoform is not related to worse bone mineral density or microarchitecture or to increased fracture risk in acromegaly.

Acromegaly is a cause of secondary osteoporosis and is associated with increased risk of vertebral fractures (VFs). The influence of exon 3-deleted isoform of growth hormone receptor (d3-GHR) on bone microarchitecture has not been studied in acromegaly. The aim of this study was to analyze the associations between d3-GHR isoform and bone mineral density (BMD), bone microarchitecture, and VFs in acromegaly patients. Consecutive acromegaly patients treated at a single reference center were included. BMD was analyzed using dual-energy X-ray absorptiometry (DXA) and bone microarchitecture was analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT). The presence of moderate to severe VFs was assessed by thoracic and lumbar X-ray. GHR genotyping was analyzed by PCR, and full-length isoform of GHR (fl-GHR) was represented by a 935-bp fragment and d3-GHR by a 532-bp fragment. Eighty-nine patients were included [56 females; median age at diagnosis: 43years (17-78)]. Disease was uncontrolled in 63% of patients. At least one d3-GHR allele was present in 60% of patients. Frequency of active disease (p = 0.276) and hypogonadism (p = 1.000) was not different between patients with fl-GHR and those with at least one d3-GHR. There was no difference in any DXA or HR-pQCT parameters between patients with fl-GHR and those with d3-GHR. Significant VFs were observed in 14% of patients, but there was no difference in frequency between patients with fl-GHR and those with at least one d3-GHR allele (p = 0.578). Presence of d3-GHR was not associated with worse BMD or bone microarchitecture or with higher frequency of significant VFs.

Cardiovascular manifestations and risk in acromegaly: experience of diabetology-endocrinology department of Oujda's Mohammed VI university hospital

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

SAT-472 Increased Thyroid Cancer Risk in Acromegaly: A Report of 3 Cases

Introduction: There is a high incidence of thyroid cancer in patients with acromegaly. We present three patients who were diagnosed with acromegaly and thyroid cancer within a short time interval. Case 1: A 34-year-old female who had uvulopalatopharngoplasty for sleep apnea presented for evaluation of elevated IGF-1 1226 ng/mL (88-246). She reported increased shoe size, growth of facial hair, and increased hand size causing her to resize her wedding band multiple times. GH did not suppress on oral glucose tolerance testing (OGTT) and MRI revealed a 2.2 cm pituitary macroadenoma. On initial exam, she was noted to have to have thyromegaly and ultrasound showed a 1.3 cm solid nodule with microcalcifications. She underwent transsphenoidal hypophysectomy (TSSH) and a month later was sent for FNA biopsy of the nodule which was consistent with papillary carcinoma (PTC). She underwent total thyroidectomy two months later with 1 cm PTC on final pathology. Case 2: A 60-year-old female presented for evaluation of thyroid nodules. An ultrasound revealed a right solid 2.2 cm isoechoic nodule and a left 1.2cm solid nodule with calcifications. At the initial encounter, physical exam was notable for prominence of the forehead and jawline and sausage digits. History was significant for carpal tunnel syndrome, osteoarthritis, DM2, excessive perspiration and snoring. Screening IGF-1 was elevated 771 ng/mL (81-225) and GH failed to suppress on OGTT. FNA biopsy of the left nodule showed PTC. Pituitary MRI revealed an 8mm microadenoma. She underwent TSSH and then a total thyroidectomy three months later with a 1cm PTC, follicular variant on final pathology. Case 3: A 30-year-old female presented with amenorrhea, increased hand/foot size and changes in the jaw. IGF-1 was 729 ng/mL(63-373) and GH failed to suppress on OGTT. MRI showed a 2.5cm pituitary adenoma with cavernous sinus invasion. She underwent TSSH and was on medical treatment for acromegaly for about two years when she was noted to have a thyroid nodule on palpation. Ultrasound showed a 10 mm isthmus solid isoechoic nodule and a 15 mm left midpole solid hypoechoic nodule. FNA of the isthmus nodule was consistent with PTC. Total thyroidectomy pathology showed a 0.7cm PTC. Conclusion: Carcinomas are the third most frequent cause of mortality in acromegalic patients, after vascular and respiratory diseases. Sustained secretion of GH and IGF-1 is known to induce proliferation and inhibit apoptosis. Thyroid nodular disease is more frequent in acromegalic patients, and thyroid cancer is one of the most commonly detected cancers in acromegaly. It remains controversial whether acromegaly increases the risk of malignant transformation of thyroid nodules. In all of our patients with acromegaly, stage I PTC was likely present at the time of diagnosis. Periodic thyroid ultrasound exam should be considered an important part of monitoring patients with acromegaly.

Association between acromegaly and a single nucleotide polymorphism (rs2854744) in the IGFBP3 gene

BackgroundIt has been reported that the single nucleotide polymorphism (SNP) rs2854744 at the − 202 locus of insulin-like growth factor binding protein-3 (IGFBP3) is associated with serum levels and a number of malignancies. However, the effect of IGFBP3 gene polymorphism on acromegaly is less clear. Therefore, in the current study, we aimed to investigate whether the −202A/C polymorphism of IGFBP3 constitutes a risk factor for acromegaly.MethodsThe study included 102 acromegalic patients and 143 control subjects in Beijing Tiantan Hospital. The genotyping of IGFBP3 was carried out using the MassARRAY method. Serum IGFBP3 concentrations were also determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations of genetic polymorphisms with the development of acromegaly and its different subtypes.ResultsThe study revealed that the C allele of rs2854744 was associated with a reduced risk of acromegaly (OR 0.594, 95% CI 0.388–0.909), as well as with the female (OR 0.385, 95% CI 0.206–0.72), macroadenoma (OR 0.557, 95% CI 0.347–0.893) and monotherapy (OR 0.512, 95% CI 0.316–0.828) subgroups under the additive model. A higher serum IGFBP3 level was observed in patients with the AA genotype, but this difference was not significant (P = 0.331).ConclusionThis study is one of the first to show that the IGFBP3 polymorphism may have an influence on serum levels and that the C allele of rs2854744 is associated with a reduced risk of acromegaly. This correlation was more prominent in females, those with large tumours and those treated with monotherapy in a Chinese population. Genetic polymorphism of IGFBP3 may be involved in the development of acromegaly.

Non-classical factors of cardiovascular risk in acromegaly

Non-classical factors of cardiovascular risk in acromegaly

Effects of pegvisomant and somatostatin receptor ligands on incidence of vertebral fractures in patients with acromegaly.

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. In this longitudinal study, we evaluated the incidence of radiological VFs in 83 patients (48 females, 35 males; median age 47 years, range 18-80years) who were treated with SRLs alone (42 cases), PegV alone (6 cases) or in combination with SRLs (35 cases) for median period of 82months (range 36-126). PegV was given when acromegaly was not controlled by SRLs alone. 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). 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.

Endothelial Dysfunction in Acromegalic Patients: A Case-Control Study

Assessing cardiovascular risk in patients with acromegaly using traditional cardiovascular risk factors is inadequate. Endothelial dysfunction seems to be a much better indicator for assessing cardiovascular risk in acromegaly. The study aims to compare from this point of view two groups of patients, with hypertension and with acromegaly. The first group consists of 54 patients with acromegaly and the second group of 64 hypertensive patients. Endothelial dysfunction was evaluated by the FMD method. The relationship between endothelial dysfunction, specific humoral markers of acromegaly and traditional cardiovascular risk factors was analysed in both groups. Although the presence of cardiovascular risk factors was statistically significantly higher in the group of hypertensives (the most important were age, blood pressure, glycemia, hypertriglyceridemia and SCORE), the presence of endothelial dysfunction was higher in the acromegaly group (61.10% vs. 32.10%, p=0.02). The best correlation with endothelial dysfunction in acromegaly group was the level of GH (28.9±28 vs. 11.7±10.3, p=0.003). The presence of endothelial dysfunction in patients with acromegaly is highly dependent on the level of GH and traditional cardiovascular risk factors are less important. In these patients the cardiovascular risk should not be evaluated in the same way as in normal population.

Coronary microvascular dysfunction may be related to IGF-1 in acromegalic patients and can be restored by therapy

Background and aimsAcromegaly increases the risk of cardiovascular mortality. Data on the cardiovascular risk in asymptomatic acromegaly are limited. In particular, data on coronary microvascular abnormalities are lacking. We assessed coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic acromegaly. MethodsWe studied 40 acromegalic patients (23 male, age 52 ± 11 years) without clinical evidence of cardiovascular disease, and 40 control subjects matched for age and sex. Coronary flow velocity in the left anterior descending coronary artery was detected by transthoracic Doppler echocardiography, at rest, and during adenosine infusion. CFR was the ratio of hyperaemic to resting diastolic flow velocity. ResultsCFR was lower in patients than in controls (2.9 ± 0.8 vs. 3.7 ± 0.6, p < 0.0001) and was abnormal (≤2.5) in 13 patients (32.5%) compared with any control subjects (0%) (p < 0.0001). CFR was inversely related to insulin-like growth factor 1 (IGF-1) levels (r = −0.5, p < 0.004). In patients with CFR≤2.5, IGF-1 was higher (756 [381–898] μg/l versus 246 [186–484] μg/l, p < 0.007) whereas growth hormone (GH) levels were similar (6.3 [2.8–13.7] μg/l versus 5 [2.8–8.9] μg/l, p = 0.8). In multivariable linear regression analysis, IGF-1 was independently associated with CFR (p < 0.0001). In multiple logistic regression analysis, IGF-1 independently increased the probability of CFR≤2.5 (p = 0.009). In four patients with active disease (all with CFR<2.5), treatment with somatostatin analogues normalized CFR. However the other four patients with active disease were not responder. ConclusionsAcromegalic patients have coronary microvascular dysfunction that may be restored by therapy with somatostatin analogues. IGF-1 independently correlates with the coronary microvascular impairment, suggesting the pivotal role of this hormone in explaining the increased cardiovascular risk in acromegaly.

Understanding and predicting fracture risk in acromegaly

Understanding and predicting fracture risk in acromegaly

Cystatin-C and epicardial adipose tissue as noninvasive predictors of cardiovascular risk in acromegaly.

Acromegaly (ACRO) is associated with elevated cardiovascular risk, although the prevalence of coronary artery disease (CAD) is unclear. Increased epicardial adipose tissue (EAT) and elevated cystatin-C (Cys-C) levels are cardiovascular risk factors, also related to the progression of CAD in several populations. To measure the severity and extent of CAD in patients with ACRO and to determine whether either EAT or Cys-C reflect higher cardiovascular risk in patients with ACRO than in healthy controls. Case-control study, of 35 patients with ACRO (19 males, 17 with active disease) and 35 age-, gender- and body mass index (BMI)-matched healthy controls; mean age was 48·1 ± 8·1 years and mean BMI was 27·6 ± 4·8 kg/m2 . Cys-C was measured by an immunoturbidimetric assay. The 10-year risk of developing a coronary event was calculated using the Framingham Risk Score (FRS). EAT index (volume indexed to body surface area), and severity and extent of CAD were measured using a 256-slice multidetector computed tomography scanner (iCT-256 Philips Healthcare, Amsterdam). Coronary artery disease lesions, EAT index and severity/extent of CAD were similar between patients with ACRO and controls. Forty-four per cent of patients with ACRO had mild coronary lesions associated with greater EAT index (ß = 0·022, P = 0·036). Cys-C levels correlated with both EAT index (ρ = 0·386, P = 0·031) and FRS (ρ = 0·477, P = 0·004) in patients with ACRO only, despite similar prevalence of traditional cardiovascular risk factors. In a multiple linear regression model, both Cys-C levels (ß = 0·369, P = 0·007) and EAT index (ß = 0·29, P = 0·025) predicted FRS (R2 = 0·613). In patients with ACRO, both Cys-C and EAT index might be used as noninvasive predictors of cardiovascular risk.