Active Acromegalic Patients Research Articles

Increased Risk of Arrhythmias in Active Acromegaly with Complications and Persistent Uncontrolled Active Acromegaly

Objective: Previous studies showed acromegaly have significant higher prevalence of ventricular arrhythmias and often complicated by diabetes mellitus (DM) and hypertension (HT). Both HT and DM are notoriously associated with the development of arrhythmias. However, the effect of complication (DM and/or HT) in acromegaly on ventricular arrhythmias and the risk of ventricular arrhythmias in acromegaly accept therapy but no control is largely unknown. Methods: A cross-sectional study with 307 acromegaly and 303 patients with non-functional pituitary adenoma as control group. All subjects divided into acromegaly with/without complication and controls with/without complication. In the longitudinal study, 30 persistent uncontrolled active acromegaly with at least three months follow-up. Electrocardiographic Measurements, laboratory examination, and clinical data collection performed in all subjects. QT interval corrected for heart rate (QTc) analysed among groups. Results: QTc in acromegaly population significantly increased compared to controls (p<0.001). Factorial design twoway ANOVA correcting age revealed significant main effects of complication (p=0.016) and acromegaly (p<0.0001), as well as positive interactions between complication and acromegaly (P<0.038) on QTc. Persistent uncontrolled active acromegalic patients after therapy showed QTc significantly increase in follow-up relative to pre-treatment (p<0.0001). The normalized GH level (r=0.11, p<0.05) and complication (r=0.25, p<0.0001) have a significant positive correlation with QTc in acromegaly. Conclusions: Acromegaly is an independent risk factor for ventricular arrhythmias and acromegaly with complication have an elevated risk for ventricular arrhythmia. Persistent uncontrolled acromegaly, who have significantly decreased in serum GH/IGF-1 levels relative to pre-treatment, also enhance the risk of ventricular arrhythmia.

Active acromegaly is associated with enhanced left ventricular contractility: Results from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study

IntroductionAcromegaly is a relatively rare chronic hormonal disease resulting in disfigurement. In 90% of cases, acromegaly is caused by a benign pituitary monoclonal human growth hormone-secreting tumor. The aim of the present study was to determine the presence of left ventricular (LV) deformation abnormalities using three-dimensional speckle-tracking echocardiography in a group of acromegalic patients. MethodsThirty-eight acromegalic patients were involved in the study. Thirteen patients were excluded due to inadequate image quality. The mean age of the remaining patients was 57.2±13.6 years and seven were male. Their data were compared to an age- and gender-matched control population, which consisted of 34 healthy volunteers (mean age: 52.7±4.9 years, 15 male). ResultsGlobal and mean segmental LV radial strain (RS) (33.2±13.4% vs. 25.2±10.8%, p=0.01 and 36.0±12.1% vs. 28.2±10.0%, p=0.009, respectively) proved to be significantly higher in acromegaly compared to controls. Active acromegalic patients had significantly higher global and mean segmental LV-RS (35.5±14.4% vs. 25.2±10.8%, p=0.03 and 37.9±13.3% vs. 28.2±10.0%, p=0.03, respectively) compared to controls. Between the active and inactive acromegaly groups, only basal LV circumferential strain (-30.2±4.8% vs. -26.7±4.1%, p=0.02) was found to be significantly different. ConclusionThe presented clinical, demographic, therapeutic and echocardiographic features demonstrate that active acromegaly is associated with enhanced LV RS as compared to healthy controls and those with inactive acromegaly.

Caracterización de tumores secretores de hormona de crecimiento de acuerdo al patrón granular y su rol en el pronóstico

Classification of growth hormone (GH) - secreting tumors by the granular pattern might predict their clinical behavior in acromegalic patients. There are several other prognostic factors. To compare the features at presentation and cure rates of patients with GH secreting tumors according to the granular pattern, and to define independent prognostic factors for surgical treatment in these patients. A retrospective, observational study of 85 active acromegalic patients surgically treated in two medical centers. Seventy-four patients (87%) were classified as having densely granulated (DG) and 11 (13%) as sparsely granulated (SG) tumors. The latter were less active biochemically, had a higher rate of macroadenoma and cavernous sinus invasion and had a lower rate of biochemical cure than the DG group. Several characteristics were associated with disease persistence but only age (Odds ratio (OR) = 0.93) and cavernous sinus invasion (OR = 21.7) were independently associated in the logistic regression model. The sparsely granulated pattern is associated with a more aggressive behavior, but the main determinants of prognosis are age and cavernous sinus invasion.

Evaluation of the natural course of thyroid nodules in patients with acromegaly

To investigate the nodular thyroid disease (NTD) and the natural course of thyroid nodules in patients with acromegaly. 138 patients with acromegaly (73F/65M), whose initial thyroid ultrasonography performed in our university hospital, were included in this study. The frequencies of NTD, papillary thyroid cancer (PTC) and associated factors on nodule formation were investigated at initial assessment. Patients who had NTD continued to follow-up (n = 56) were re-evaluated with a ultrasonography performed after a mean 7-years follow-up period. The nodule size changes were compared with the initial data and the factors affecting nodule growth were investigated. The frequency of NTD was found 69%. Patients with NTD were older (p = 0.05), with higher baseline IGF-1%ULN (upper limit of normal) (p = 0.01). In patients with NTD, the majority had similar nodule size (45%), decreased nodule size in 30% and nodule growth in 25%. In patients with active acromegaly at last visit, nodule growth was more significant (p < 0.001). For one unit change in the IGF-1 levels, nodule growth increased by 1.01 folds and presence of active acromegaly disease was related with ninefolds increase in nodule growth. The frequency of PTC was 14% in patients with nodule growth and PTC was diagnosed 11% of all acromegalic patients. Both NTD and nodule growth is more frequent in active acromegalic patients. Thyroid nodules may show dynamic changes according to the disease activity and nodule growth should be closely monitored due to the risk of malignancy in patients with active acromegaly disease.

Assessment of Nasal Carriage of Staphylococcus Aureus and Axillar Flora in Patients With Acromegaly.

Recent study showed that patients with acromegaly have typical skin findings including increased sebum secretion, decreased transepidermal water loss, more alkaline, and colder skin surface correlated with serum growth hormone and insulin-like growth factor 1 levels. Different anatomic localizations and texture of the skin differ in bacterial concentrations.Nasal carriage of Staphylococcus aureus and axillar flora in patients with acromegaly was compared with normal population with regard to duration of acromegaly as well as the growth hormone and insulin-like growth factor 1 levels. This patient-control prospective study was conducted in university hospitals in Mersin, Turkey. The study consisted of 30 active acromegalic patients and 60 healthy adults who had no previously diagnosed chronic illness as a control group. A total of 90 volunteers were enrolled in this study; nasal and axillar cultures were obtained. Axillar and nasal specimens from anterior nares of the individuals were taken using sterile swabs. Nasal colonization of Staphylococcus aureus was 13.3% in acromegalic patients, but 43.4% in control group. This difference was statistically significant (P = 0.004). Patients and control group compared according to axillar cultures, the authors determined proteus colonization 16.7% in patients with acromegaly but no proteus colonization in control group. This result was statistically significant (P = 0.001). Proteus colonization was negatively correlated only with disease duration in acromegalic patients (P = 0.017). The authors demonstrated that compared with healthy subjects, acromegalic patients had low percentage of nasal carriage of Staphylococcus aureus and more gram-negative basili in the axillar flora. These nasal and axillar flora changes should be considered for prophylactic antibiotics use before surgery and ampiric antibiotics use after surgery.

Patients with Active Acromegaly are at High Risk of 25(OH)D Deficiency.

Acromegaly is a chronic disease characterized by hypersecretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Electrolyte disturbances such as hypercalcemia and hyperphosphatemia are reported in patients with this disorder. There is limited data on vitamin D status in subjects with acromegaly. The aim of the study was to determine calcium, inorganic phosphate, magnesium, alkaline phosphatase, and 25(OH)D levels with regard to the activity of the disease. We also studied correlations of 25(OH)D and IGF-1, GH, body mass, body mass index, and age. A study group consisted of 55 acromegalic patients, and was divided into three subgroups: active acromegaly (AA), well-controlled acromegaly (WCA), cured acromegaly (CA). We enrolled 29 healthy subjects to a control group (CG). Vitamin D deficiency was recorded in all AA patients, 13 WCA patients (92.86%), 10 CA patients (62.5%), and 13 controls (54.17%). The highest 25(OH)D levels were found in the CG group and the lowest in the AA group (p = 0.012). The dose of octreotide did not influence serum 25(OH)D levels. A significant positive correlation between IGF-1 and 25(OH)D levels was observed in the AA group (r = 0.58, p = 0.024). Inorganic phosphate levels were the highest in the AA group. In conclusion, active acromegalic patients have lower 25(OH)D levels in comparison with the CG and are at higher risk of vitamin D deficiency.

Tamoxifen as a therapeutic agent in acromegaly

Administration of high doses of estrogens to patients with acromegaly has been shown to improve symptomatology of acromegaly and glucose tolerance more than 50 years ago. Selective estrogen receptor modulators (SERMs) mimic the effects of estrogen in bone, liver and the cardiovascular system, but function as an anti-estrogen in endometrial and breast tissue. In this study, we evaluated hormonal effects of a SERM, tamoxifen, in active acromegalic patients with particular emphasis on its use in males. We studied 15 men and 2 post-menopausal women with biochemically-active acromegaly despite the fact that other modalities were ineffective in normalizing their insulin-like growth factor-1 (IGF-1) levels. All patients were treated with tamoxifen 20-40 mg daily for 2-11 months (median of 4 months). IGF-1 and growth hormone (GH) levels were assessed immediately before the beginning of treatment and at 2-4 monthly intervals thereafter. Baseline and treatment levels of total and bioavailable testosterone were measured in men. Tamoxifen did not affect basal GH secretion, but it decreased circulating IGF-I in 14 patients (82%) by an average of 90 ± 4 mcg/L, (p = 0.005), and normalized plasma IGF-I in 8 patients (47%). Total and bioavailable testosterone levels increased in all evaluable men (n = 8). Tamoxifen was well tolerated. Tamoxifen might be useful in the treatment of patients with biochemically-mild active acromegaly, but longer term studies are warranted.

Differential patterns of regional neuroadrenergic cardiovascular drive in acromegalic disease

It has been shown that acromegaly is characterized by an autonomic imbalance and by marked sympathoinhibition. However, there is no information available as to whether adrenergic inhibition is confined to selected vascular districts or, rather, is generalized. We examined 17 newly diagnosed active acromegalic patients without hyperprolactinaemia, pituitary hormone deficiencies, obstructive sleep apnoea and cardiac hypertrophy and 14 healthy subjects matched for age, sex and body mass index. For each subject, we collected information regarding anthropometric parameters and echocardiography, and collected plasma samples to investigate anterior pituitary function, glucose and lipid metabolism and plasma leptin levels. Beat-to-beat mean arterial pressure, heart rate and efferent post-ganglionic muscle and skin sympathetic nerve traffic (MSNA and SSNA, respectively; determined by microneurography) were measured. Both MSNA and SSNA were recorded in a randomized sequence over two 30min periods. Measurements also included evaluation of SSNA responses to emotional stimulus. In addition to significant reductions in plasma leptin levels, acromegalic patients had markedly decreased MSNA compared with the healthy controls. There were no significant differences in SSNA between the two groups, either under basal conditions or in responses to arousal stimuli. There was a significant and direct correlation between MSNA and plasma leptin levels, but not between plasma leptin and SSNA. These data provide the first evidence that the sympathetic inhibition characterizing the early phase of acromegaly is not generalized to the entire cardiovascular system.

Reduced arterial stiffness in patients with acromegaly: non-invasive assessment by the cardio-ankle vascular index (CAVI)

In patients with acromegaly, cardiovascular diseases are the most common cause of death. Arterial stiffness is increasingly recognized as a valuable surrogate marker for predicting cardiovascular events. To evaluate the vascular status of acromegalic patients, we used the cardio-ankle vascular index (CAVI) to reflect the arterial stiffness from the heart to the ankles. We analyzed 21 acromegalic patients, comprising five patients with untreated active acromegaly, one patient treated with medication and 15 patients who underwent transsphenoidal surgery. Among the 15 patients with surgery, 10 received additional therapies with dopamine agonists and/or somatostatin analogs. All patients with acromegaly unexpectedly showed significant reductions in the CAVI, indicating reduced arterial stiffness, compared with age- and sex-matched controls, regardless of whether they underwent surgery. There was a significant negative correlation between the CAVI and the serum insulin-like growth factor (IGF)-I level in these patients. Active acromegalic patients were associated with lower CAVI than controlled patients. Sequential measurements of the CAVI and serum IGF-I before and after treatment with octreotide and transsphenoidal surgery revealed that a reduced IGF-I level after treatment was accompanied by CAVI elevation. The present findings indicate that the CAVI is negatively correlated with the serum IGF-I level in acromegaly. These findings are consistent with previous reports indicating that the GH/IGF-I axis reduces peripheral vascular resistance. This non-invasive assessment can reflect the present vascular status and would be a useful marker for evaluation of therapeutic effects in patients with acromegaly.

QT dispersion in patients with acromegaly

Acromegaly is a rare condition caused by a pituitary adenoma that secretes growth hormone. The mortality rate is 72% higher in patients with acromegaly than in the general population according to meta-analyses. Mortality analysis has shown as many as 60% of acromegalic patients die due to cardiovascular disease. Sudden cardiac death may occur in patients with acromegaly and malignant ventricular arrhythmia may play an important role in this fatal complication; however, the precise mechanism is not fully known. QT dispersion (dQT) is an electrophysiological factor known to be associated with a tendency for ventricular arrhythmia and sudden cardiac death. This study aimed to evaluate dQT as an early predictor of ventricular tachyarrhythmia, as sudden cardiac death commonly occurs in acromegalic patients. This cross-sectional case-control study enrolled 20 patients (10 female and 10 male) with acromegaly and 20 healthy controls (11 female and 9 male) after exclusion criteria were applied. Each participant underwent 12-lead electrocardiography, including≥3 QRS complexes, at a speed of 25mm/s after a 15-min rest. In each participant, the QT interval (beginning of the Q wave to the end of the T wave) was corrected (QTc) for heart rate using Bazett's formula [Formula: see text] QTc dispersion (dQTc) (QTc max - QTc min) was also calculated. There was no significant difference in median dQTc between the acromegalic patients (0.79s) and the controls (0.45s) (p>0.05). Active acromegalic patients (n=14) were estimated to have a median dQTc of 0.82s, after excluding from the analysis six patients that were under full biochemical control, and that had randomly obtained growth hormone levels<0.4ng/mL, GH<1ng/mL based on oral glucose tolerance test, and normal IGF-I for age and gender. A significant difference was noted in median dQTc between the active acromegalic patients and the controls (p=0.015). The dQT in active acromegalic patients was longer than that in the control group, which indicates that patients with active acromegaly might have an elevated risk for ventricular arrhythmia. We think that a non-invasive, simple and inexpensive marker-measurement of dQT-as part of cardiac monitoring could be valuable for screening complications in acromegalic patients.

Magnetic Resonance Imaging as a Predictor of Response to Somatostatin Analogs in Acromegaly after Surgical Failure

Transsphenoidal surgery is considered first-line therapy for acromegaly; however, there is often a need for adjunctive therapy. Somatostatin analogs (SSA) have greatly improved the effectiveness of medical treatment, but one third of patients are resistant. The aim was to evaluate whether magnetic resonance imaging (MRI) signal could predict long-term response to SSA in patients with active acromegaly after neurosurgery. Sixty-two patients who were active acromegalic after surgery were included in this retrospective study. Remaining pituitary tumor was classified as hyper-, iso-, or hypointense by evaluating T2-weighted MRI signal. Treatment with SSA at maximal effective doses was prescribed and evaluated at 6 and 12 months by monitoring IGF-I, GH, and T2 MRI. Complete response to SSA treatment (defined as normal IGF-I) at 6 months was observed in 30%, partial response (defined as IGF-I between 2 and 3 sd score) in 15%, and no response in 55% of patients. At 12 months, 28, 20, and 52% were observed, respectively. MRI signal was hypointense in 40%, hyperintense in 48%, and isointense in 12%. At 6 months, complete response to SSA was observed in 71% of cases having hypointense MRI signal and in 20% of hyperintense (P = 0.04). At 12 months, 62% of hypointense remained well controlled, whereas in the hyperintense group, good, partial, or no response results did not change from that observed at 6 months (P = 0.04). In active acromegalic patients after surgery, a hypointense T2-weighted MRI signal is associated with a better response to SSA treatment at 6 and 12 months.

Changes in the expression of suppressor of cytokine signalling (SOCS) 2 in the colonic mucosa of acromegalic patients are associated with hyperplastic polyps

Acromegalic patients have increased prevalence of colonic polyps. Development of hyperplastic polyps was related to suppressor of cytokine signalling (SOCS) 2 haploinsufficiency in animal models of acromegaly. To evaluate whether variations in SOCS2 expression in the colonic mucosa of acromegalic patients might be associated to hyperplastic polyps, patients with active acromegaly or disease in remission with or without hyperplastic polyps were studied; controls were non-acromegalic subjects age- and sex- matched with or without polyps. Expression of SOCS1-3 was evaluated by RT-PCR, immunofluorescence and Western blot in the colonic mucosa. Coimmunoprecipatiton was used to evaluate multimeric protein complexes. Acromegalic patients with active disease and hyperplastic polyps had higher levels of SOCS2 transcripts; on the contrary, SOCS1 and SOCS3 transcripts did not differ among the study groups. While the expression of SOCS2 and SOCS3 protein was indistinguishable with that of the corresponding transcripts, SOCS1 protein expression was reduced in active acromegalic patients with polyps. SOCS1 protein was reduced owing to its increased proteasome degradation mediated by SOCS2. The increased SOCS2 and reduced SOCS1 led to increased STAT5b expression, suggesting a higher GH signalling transduction. Acromegalic patients with active disease and hyperplastic polyps have high levels of SOCS2 and increased SOCS1 degradation, leading to reduced negative feedback on GH signalling, likely favouring a hyperplastic polyps phenotype.

Influence of Growth Hormone Receptor d3 and Full-Length Isoforms on Biochemical Treatment Outcomes in Acromegaly

In acromegaly, a discrepancy between what are defined as "normal" levels of GH and IGF-I for every given patient is observed in up to 35% of subjects at diagnosis and during the follow-up. The aim of the study was to evaluate the impact of GH receptor (GHR) polymorphism on the biochemical assessment of the treatment of acromegaly and on prevalence of discordant levels of GH and IGF-I. The study was performed in an institutional referral center at a tertiary care hospital. We studied prospectively and retrospectively 84 consecutive acromegalic patients with active disease after neurosurgery and treated them with somatostatin analogs. The GHR genotype (flfl, fld3, or d3d3) was determined from peripheral blood. Lack of exon 3 of GH receptor (d3-GHR) was found in 40 of 84 patients (47.6%). After neurosurgery, 67 subjects (79.8%) of the study population, concordant active acromegalic patients, had high IGF-I and mean GH levels above 2 ng/ml, whereas the remaining 17 patients (20.2%, discordant active acromegalic patients) showed discordance between these two parameters (high IGF-I and GH levels < or = 2 ng/ml). Overall, 70.6% of discordant patients were carriers of the d3-GHR. After somatostatin analogs, discordant active acromegalic patients increased to 30.9%, 69.2% of whom were carriers of the d3-GHR. Logistic regression analysis demonstrated that d3-GHR carriers maintained the significant correlation with discordant GH and IGF-I values either after neurosurgery or after somatostatin analog treatment, independently of the effects of age, sex, duration of acromegaly, serum GH, and IGF- I values either at diagnosis of acromegaly or after neurosurgery. The GHR polymorphism seems to have a relevant impact on the posttreatment biochemical assessment of acromegaly. Moreover, the d3-GHR isoform could be an independent predictor of GH and IGF-I discrepancy during the follow-up in acromegaly.

11β-Hydroxysteroid dehydrogenase activity in acromegalic patients with normal or impaired carbohydrate metabolism

The 11β-hydroxysteroid dehydrogenase isoenzymes (11β-HSD) catalyse the interconversion of cortisol (F) and cortisone (E). Earlier studies demonstrated that growth hormone (GH) and insulin resistance may exert opposite effects on the conversion of E to F by 11β-HSD type 1. Therefore, in the present study we determined F and E concentrations in 562 plasma samples obtained from acromegalic patients during an active phase (76 patients) and after cure of the disease (68 patients). In addition, we examined whether type 2 diabetes mellitus or impaired glucose tolerance, which are frequently associated with active acromegaly could influence plasma F and E levels in these patients. We found that plasma F concentrations were similar in patients with active acromegaly and in those who were cured with pituitary surgery, irradiation and/or medical therapy (mean ± S.E., 12.4 ± 0.3 and 12.7 ± 0.4 μg/dl, respectively). However, plasma E levels were significantly higher in patients with active compared to those with cured acromegaly (2.8 ± 0.1 and 2.2 ± 0.1 μg/dl, respectively; p < 0.001), resulting in a lower F/E ratio in patients with active disease (4.6 ± 0.1 vs. 5.9 ± 0.2 in the cured group of patients; p < 0.001). When the effect of altered carbohydrate homeostasis on plasma F and E was analysed, the results indicated significantly lower plasma E levels and higher F/E ratios in active acromegalic patients with type 2 diabetes mellitus or impaired glucose tolerance compared to those with normal carbohydrate metabolism (E, 2.5 ± 0.1 and 3.0 ± 0.1 μg/dl, respectively; F/E, 5.1 ± 0.2 and 4.4 ± 0.1; p < 0.001), whereas plasma F concentrations were similar in these two groups (12.1 ± 0.4 and 12.6 ± 0.3 μg/dl, respectively). These findings indicate that disease activity exerts a significant impact on 11β-HSD in acromegalic patients, which is further modified with altered carbohydrate homeostasis, frequently present in patients with active disease.

Analyses of Factors Influencing the Acute Effect of Octreotide in Growth Hormone-secreting Adenomas

Somatostatin analogues such as octreotide are used to treat active acromegalic patients by reducing serum growth hormone (GH) levels. However, the acute effect of octreotide on GH secretion differs among patients. To elucidate factors influencing the acute effect of octreotide, we collected data from 56 patients with somatotroph adenoma from two institutions. We analyzed the correlation of the following factors with the acute effect of octreotide: immunohistochemical staining of somatostatin receptor subtype 2A (SSTR 2A), presence of gsp mutation, proliferative potentials analyzed by Ki-67 staining index (SI). We found that the acute effect of octreotide significantly correlated with two factors: Ki-67 SI and the plasma membrane-dominant staining pattern of SSTR 2A. Monovariate analysis revealed a statistically significant inverse relation of Ki-67 SI with the reduction of GH by octreotide. We assessed the contribution of each factor on the acute effect of octreotide by multivariate analysis. Significant multiple regression was confirmed with p value of 0.003. Post-test revealed that the plasma membrane-dominant staining pattern of SSTR 2A was significantly related to the reduction of GH by octreotide. These results show that the acute effect of octreotide is positively related to SSTR 2A staining on the plasma membrane.

Alterations in biomarkers of cardiovascular disease (CVD) in active acromegaly

In acromegalic patients, cardiovascular and metabolic comorbidities contribute to enhance mortality. Available data on the lipoprotein profile of these patients are controversial. Our aim was to characterize the lipoprotein profile and emergent biomarkers of cardiovascular disease in active acromegalic patients in comparison with sex- and age-matched healthy controls. Eighteen patients with active acromegaly and 18 controls were studied. Glucose levels, hormonal status, lipoprotein profile and C reactive protein (CRP) were evaluated by standardized methods. Cholesteryl ester transfer protein (CETP) and lipoprotein-associated phospholipase A(2 )(Lp-PLA(2)) were measured by radiometric techniques, endothelin-1 and vascular cell adhesion molecule (VCAM)-1 by enzyme-linked immunosorbent assay, and leucocytes CD18, CD49d and CD54 by flow cytometry. After adjusting for body mass index (BMI), acromegalic patients presented a more atherogenic lipoprotein profile, consisting of higher levels of triglycerides and apolipoprotein B and alterations in the ratios which estimate insulin resistance and atherogenic risk. CETP activity was significantly increased in acromegalic patients as compared to controls (168 +/- 17 vs. 141 +/- 30% per ml h, respectively; P < 0.05). Endothelin-1 levels evidenced an increase in the patients' group (0.9 +/- 0.2 vs. 0.7 +/- 0.2 ng/l, respectively; P < 0.01) and showed positive and significant correlations with GH, IGF-1 and IGFBP-3 (r = 0.45, 0.42 and 0.44, respectively; P < 0.01 for all of them; with BMI as a fixed variable). Lymphocytes from acromegalic patients showed increased CD49d content (282 +/- 59 vs. 246 +/- 48 arbitrary units, respectively; P < 0.05). Taken together, the alterations described seem to contribute to constituting a state of higher propensity for the development of atherosclerotic cardiovascular disease, which adds to the presence of specific cardiomyopathy.

Ghrelin and leptin serum levels during an oral glucose tolerance test in active and inactive acromegalic patients

Ghrelin and leptin serum levels during an oral glucose tolerance test in active and inactive acromegalic patients

Improvement of intrinsic myocardial contractility and cardiac fibrosis degree in acromegalic patients treated with somatostatin analogues: a prospective study

Acromegalic patients have increased left ventricular (LV) mass (M) and impaired diastolic function. Using ultrasonic cardiac tissue characterization, we evaluated the early changes in cardiac fibrosis (IBS) and intrinsic myocardial contractility (CVI) as well as their reversibility after treatment with somatostatin analogues (SMSA) in patients with acromegaly. Twenty-two acromegalic patients with active untreated disease (Acro(UNTR)) underwent conventional Doppler echocardiography and integrated backscattering; 25 healthy subjects (controls) and eight patients with acromegaly in remission after pituitary adenomectomy (Acro(REM)) served as controls. As expected, Acro(UNTR) at baseline had higher LVM than controls or Acro(REM) (P < 0.001); LVM reduced in acromegalic patients after SMSA (P < 0.005 vs. baseline) while LV ejection fraction did not change. LV diastolic function was reduced in all acromegalic patients, either at baseline or after SMSA therapy (E/A ratio, 0.96 +/- 0.3 and 1.1 +/- 0.3, respectively, P < 0.002 vs. controls, 1.6 +/- 0.3). CVI was reduced in Acro(UNTR) (14.3 +/- 5.8%, P < 0.003 vs. controls, 28.7 +/- 7.5%) and greatly improved after SMSA (22.5 +/- 4.5%, P < 0.003 vs. baseline). Cardiac fibrosis was increased in Acro(UNTR) (IBS(MSI), 53.7 +/- 5.3%P < 0.002 vs. controls) and reduced after SMSA (43.7 +/- 4.2%P < 0.002 vs. baseline) albeit not reaching values observed in controls. More importantly, five of 22 (23%) Acro(UNTR) patients had normal LVM, but increased cardiac fibrosis as revealed by back scattering. IBS values and CVI% were related with serum GH and IGF-1 (P < 0.0001) levels, and the estimated duration of disease (P < 0.005). The present study demonstrated that active acromegalic patients had early impairment of systolic function and increased cardiac fibrosis; increased fibrosis may precede LV hypertrophy; these changes are related to the activity of disease and might improve during treatment with SMSA.

Efficacy and safety of 48 weeks of treatment with octreotide LAR in newly diagnosed acromegalic patients with macroadenomas: An open-label, multicenter, non-comparative study

The aim of the present multicentric, open-label, non-comparative study was to evaluate the role of octreotide long-acting repeatable (LAR) as primary therapy for the treatment of GH-secreting pituitary macroadenomas. The patients received octreotide LAR 20 mg every 4 weeks for 12 weeks; afterwards the dose was confirmed or adjusted at 30 mg every 4 weeks, for the remaining 12 weeks, for responder or non-responder patients, respectively. Responder patients continued the study until 48 weeks. Twenty-one naive active acromegalic patients were enrolled. In all patients, GH profile, IGF-I levels and magnetic resonance imaging (MRI) were evaluated at baseline and during treatment. The ability of octreotide LAR to decrease mean GH < 2.5 microg/I and/or normalize IGF-I levels, adjusted for age and gender, was defined respectively as total or partial success. Total success was achieved in 5/21 (23.8%), 6/20 (30%) and 4/14 (28.6%) patients after 12, 24 and 48 weeks; partial success in 7/21 (33.3%), 9/20 (45%) and 9/14 (64%) patients at 12, 24 and 48 weeks according to GH levels, while according to IGF-I levels in 7/21 (33.3%), 7/20 (35%) and 5/14 (35.7%) patients at 12, 24 and 48 week. Tumor size was notably decreased after treatment with octreotide LAR: in 16 macroadenoma patients completing the study, the tumor sizes were 1609 +/- 1288, 818 +/- 616 (49.1 +/- 23.7%) and 688 +/- 567 mm3 (54.6 +/- 24.4%) at baseline, 24 and 48 weeks. This study shows that octreotide LAR is effective in suppressing GH/IGF-I secretion and inducing tumor shrinkage in GH-secreting macroadenomas in a 48-week treatment. Octreotide LAR could be used as primary therapy in patients harbouring large pituitary tumors, who are less likely to be cured by neurosurgery.

Efficacy of Octreotide LAR in Acromegalic Patients

Background: Octreotide (OC)-LAR is a long-acting preparation of octreotide which has been effectively used to suppress GH/IGF-1 hypersecretion in acromegalic patients. The clinical response, biochemical outcomes, and safety of OC-LAR were evaluated in 27 active acromegalic patients. Method: 27 patients with an active disease status (according to the clinical picture, GH >5 μg/L and elevated age-matched IGF-1), and previously treated with bromocriptine after surgery, comprised the study population. OC-LAR was given (20 mg, i.m., every 4 week for 3 injections, then the doses were titrated individually) and the acromegalic symptoms and adverse reactions recorded. The serum levels of GH and IGF-1 were evaluated every 12 week. The acromegalic symptoms including headache, fatigue and arthralgia, improved in all patients. Results: Gastrointestinal side effects were transient and mild. The levels of GH significantly decreased, from 8.9 ± 3.5 to 2.9 ± 2.2 μg/L at 12 weeks (P < 0.001, vs. baseline), to 2.9 ± 2.1 μg/L after 24 weeks (P < 0.001) and to 2.5 ± 1.3 μg/L at 48 weeks (P < 0.001). The levels of IGF-1 significantly decreased, from 753.7 ± 213.6 to 429.7 ± 253.4 μg/L at 12 weeks (P < 0.001, vs. at baseline), to 405.7 ± 213.3 μg/L at 24 weeks (P < 0.001) and to 348.9 ± 144.7 μg/L at 48 weeks (P <0.001). The safelevel of GH is less than 2.5 μg/L and normal age-matched IGF-1 levels were achieved in 63 and 52% of the patients, respectively. Conclusion: Octreotide-LAR was well tolerated and effective as an adjuvant treatment in lowering the levels of GH and IGF-1 in active acromegalic patients (J Kor Soc Endocrinol 20:344～352, 2005).