Active Acromegaly Research Articles

"Silent" thyrotropin (TSH) expression in acromegaly and clinically non-functioning pituitary adenomas.

The pituitary adenomas secreting thyrotropin (TSH) are considered the rarest type of hormonally active pituitary tumour. In spite of that, many cases are described in the literature. On the other hand, the observations of the co-expression of TSH with other pituitary hormones (mostly with growth hormone [GH]) and "silent" expression of TSH in clinically non-functioning pituitary adenomas (CNFPA) are rather scarce. Among 93 examined pituitary adenomas, 22 of them were diagnosed as active acromegaly and 71 as clinically non-functioning pituitary adenomas (CNFPA). All of them were immunostained with antibodies against pituitary hormones, including the anti-TSH antibody. TSH-immunopositive adenomas are immunostained also to detect somatostatin receptor subtypes (SSTR 1-5). TSH immunopositivity was found in 4.2% of CNFPA (3/71 tumours) and in 13.6% (3/22) cases of somatotropinomas manifesting as active acromegaly. All of the examined TSH-immunopositive adenomas expressed SSTR subtypes except SSTR4. The symptoms of hyperthyroidism were not observed in any of the acromegalic patients co-expressing TSH with GH. Our data confirm the relative rarity of TSH expression or co-expression of TSH in pituitary tumours. In most cases TSH is co-expressed with GH in patients with acromegaly and is not accompanied by hyperthyroidism. The "silent" expression of TSH may occur also, although rarely in CNFPA. The strong expression of SSTR in TSH-immunopositive CNFPA ("silent thyrotropinoma") indicates the possibility of the treatment of these tumours with somatostatin analogues. (Endokrynol Pol 2016; 67 (5): 515-518).

The impact of diabetes mellitus on the survival of patients with acromegaly.

An increased risk of mortality in patients with uncontrolled acromegaly has been reported in several studies. We aimed to assess the impact of co-morbidities on the survival of patients with acromegaly after long-term treatment and follow-up. A retrospective analysis was performed for 285 patients with active acromegaly, who were admitted to the Chang Gung Memorial Hospital, Taiwan between 1978 and 2012. Of these patients, 106 (37.2%) were diagnosed with diabetes mellitus (DM). During the follow-up period, 21 cases of histological proved malignant in acromegalic patients, and DM with acromegaly had a higher incidence of malignancy (13.2% vs. 3.8%; p < 0.01). The 5-, 10-, and 20-year survival rates were 93.1%, 86.9%, and 84.7% for the DM group, respectively, and 96.5%, 96.5%, and 96.5% for the non-DM group, respectively. After a mean follow-up of 15.1 ± 0.6 years, age, DM, coronary heart disease, and malignancy were found to be significant factors of mortality. Control of growth hormone and IGF-1 levels also conferred a marginal survival benefit. DM and malignancy significantly influence the survival of patients with acromegaly; thus, these patients need close follow-up and appropriate therapy. (Endokrynol Pol 2016; 67 (5): 501-506).

The effects of high serum growth hormone and IGF-1 levels on bone mineral density in acromegaly

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) play a major role in bone homeostasis. In this study, we aimed to assess bone mineral density (BMD) in active acromegaly. A total of 29patients with active acromegaly (age 46.10± 13.27years; body mass index [BMI]: 29.51± 4.91kg/m2) and 42 healthy individuals matched for age and BMI (age: 40.35± 11.74years; BMI: 28.18± 7.35kg/m2) were included in the study. BMD was measured by DXA. The mean levels of GH and IGF-1 were found to be 12.61± 11.34ng/ml and 676.47± 316.19ng/ml in acromegaly, respectively, while the mean levels of GH and IGF-1 were found to be 0.59± 0.81ng/ml (p= 0.0001) and 178.17± 57.11ng/ml (p= 0.0001) in the control group, respectively. Only total hip t‑score was determined to be significantly lower in acromegaly compared to the control group (p= 0.037). No significant differences were found between the other parameters in DXA and only a positive correlation was found between IGF-1 levels and L1-L4 BMD (r= 0.259, p= 0.029). Although GH and IGF-1 levels were increased in acromegalic patients, no significant difference was found in terms of vertebral BMD. Only hip t‑scores were found to be lower in acromegalic patients, but this low hip t‑score did not reach the osteopenic level. The positive correlation between IGF-1 and lumbar vertebral BMD suggested a more prominent effect of IGF-1 on BMD compared to GH.

Bone turnover is significantly increased in patients with active acromegaly while bone mineral density remains normal

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

The negative effect of GH/IGF-1 excess on NAD- and NADP-dependent blood lymphocytes dehydrogenases activity in acromegaly

Background. Acromegaly is a rare serious condition characterized by chronic hypersecretion of growth hormone (GH) from a pituitary adenoma and induces the synthesis of insulin-like growth factor I (IGF-1). The idea of the crucial GH importance not only in the control of cell proliferation and differentiation, but, also, in the regulation of immune cells metabolism allows to think that chronic excess GH/IGF-I in acromegaly is the potent effector distortion of the immune response mechanisms. Aim. To study the NAD(P)-dependent dehydrogenases level in blood lymphocytes and their interaction with GH/IGF-1 concentration in patients with active acromegaly.Methods. The level of NAD(P)-dependent dehydrogenases in blood lymphocytes was studied in a group of 88 patients with active acromegaly, mean age 51.0±12.5 years. The NAD(P)-dependent dehydrogenases activity was determined by biochemiluminescence method. The concentrations of GH and IGF-1 were measured by ELISA.Results. Studying the activity of mitochondrial NAD(P)-dependent dehydrogenases found a decrease in all NAD-dependent oxidoreductase: NADIDH, NADGDH, and MDH (P&lt;0.01), which allows to state the low level flow in the tricarboxylic acid cycle. In active acromegaly were revealed the decreasing activity of all studied oxidoreductases: glucose-6-phosphate dehydrogenase (P&lt;0.01), NAD–lactate dehydrogenase (LDH) (P&lt;0.001), NADH–LDH (P&lt;0.001), NAD–malate dehydrogenase (MDH) (P&lt;0.001), NADH–MDH (P&lt;0.001), NADP–MDH (P&lt;0.001), NAD–glutamate dehydrogenases (GDH) and NADH–GDH (P&lt;0.001), NADP–GDH and NADPH–GDH (P&lt;0.001), NAD–isocitrate dehydrogenases (IDH) and NADP–IDH (P&lt;0.01 and P&lt;0.001 respectively), and, also, glutathione reductase (P&lt;0.001). Our data observed that decreasing activity of NADP–GDH positively correlated with the basal GH level (r=+0.23, P=0.04) and NADP–MDH activity with IGF-1 level (r=+0.30, P=0.008). The low NADH–MDH activity negatively correlated to the basal GH concentration (r=−0.23, P=0.04).Conclusion. The chronic excess of GH/IGF-1 causes a significant depletion of metabolic lymphocytes reserves and may play an important role in several systems malignancies of acromegaly patients. This pathway continues to attract interest as a potentially useful target for therapeutic design of acromegaly.

Successful treatment of residual pituitary adenoma in persistent acromegaly following localisation by 11C-methionine PET co-registered with MRI.

To determine if functional imaging using 11C-methionine positron emission tomography co-registered with 3D gradient echo MRI (Met-PET/MRI), can identify sites of residual active tumour in treated acromegaly, and discriminate these from post-treatment change, to allow further targeted treatment. Twenty-six patients with persistent acromegaly after previous treatment, in whom MRI appearances were considered indeterminate, were referred to our centre for further evaluation over a 4.5-year period. Met-PET/MRI was performed in each case, and findings were used to decide regarding adjunctive therapy. Four patients with clinical and biochemical remission after transsphenoidal surgery (TSS), but in whom residual tumour was suspected on post-operative MRI, were also studied. Met-PET/MRI demonstrated tracer uptake only within the normal gland in the four patients who had achieved complete remission after primary surgery. In contrast, in 26 patients with active acromegaly, Met-PET/MRI localised sites of abnormal tracer uptake in all but one case. Based on these findings, fourteen subjects underwent endoscopic TSS, leading to a marked improvement in (n = 7), or complete resolution of (n = 7), residual acromegaly. One patient received stereotactic radiosurgery and two patients with cavernous sinus invasion were treated with image-guided fractionated radiotherapy, with good disease control. Three subjects await further intervention. Five patients chose to receive adjunctive medical therapy. Only one patient developed additional pituitary deficits after Met-PET/MRI-guided TSS. In patients with persistent acromegaly after primary therapy, Met-PET/MRI can help identify the site(s) of residual pituitary adenoma when MRI appearances are inconclusive and direct further targeted intervention (surgery or radiotherapy).

Predictive value of T2 relative signal intensity for response to somatostatin analogs in newly diagnosed acromegaly.

The difficulty of predicting the efficacy of somatostatin analogs (SSA) is not fully resolved. Here, we quantitatively evaluated the predictive value of relative signal intensity (rSI) on T1- and T2-weighted magnetic resonance imaging (MRI) for the short-term efficacy (3months) of SSA therapy in patients with active acromegaly and assessed the correlation between MRI rSI and expression of somatostatin receptors (SSTR). This was a retrospective review of prospectively recorded data. Ninety-two newly diagnosed patients (37 males and 55 females) with active acromegaly were recruited. All patients were treated with pre-surgical SSA, followed by reassessment and transspenoidal surgery. rSI values were generated by calculating the ratio of SI in the tumor to the SI of normal frontal white matter. The Youden indices were calculated to determine the optimal cutoff of rSI to determine the efficacy of SSA. The correlation between rSI and expression of SSTR2/5 was analyzed by the Spearman rank correlation coefficient. T2 rSI was strongly correlated with biochemical sensitivity to SSA. The cutoff value of T2 rSI to distinguish biochemical sensitivity was 1.205, with a positive predictive value (PPV) of 81.5% and a negative predictive value (NPV) of 77.3%. No correlation was found between MRI and tumor size sensitivity. Moreover, T2 rSI was negatively correlated with the expression of SSTR5. T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly.

"Micromegaly": an update on the prevalence of acromegaly with apparently normal GH secretion in the modern era.

Approximately 25% of cases of clinically active acromegaly cases treated in our academic center between 1996 and 2000, were diagnosed in patients who had elevated plasma IGF-1 levels, but apparently "normal" 24-h mean plasma GH levels. The current study served to update the data for patients with acromegaly referred to our facility, after increasing awareness of this "normal" GH subpopulation throughout the medical community. A retrospective chart review was conducted on 157 patients with acromegaly who underwent resection of a confirmed somatotroph pituitary adenoma at the University of Michigan Health System between the dates of 1 Jan 2001 to 23 Sept 2015. Overall prevalence of acromegalic patients with "normal" GH levels, defined as GH <4.7ng/mL, was 31%. Over time, the percentage of patients with "normal" GH at diagnosis did not decline: 26% from 2001 to 2005, 19% from 2006 to 2010, and 47% from 2011 to 2015. Mean pituitary tumor size was 1.8±0.1cm for the group with elevated GH, and 1.2±0.1cm for the group with "normal" GH (p<0.001). Percent microadenomas was higher in a group with "normal" GH as compared to those with elevated GH (48 vs. 12%, p<0.001), and tumors >2cm in the maximal diameter were encountered more frequently in the group with elevated GH (43 vs. 14%, p<0.001). Our data show that a substantial percentage of patients with clinical acromegaly have "normal" GH, and therefore strengthens the growing body of evidence which supports the leading role of IGF-1 levels in diagnostic evaluation. At the present time, questions about the natural course of "micromegaly" and treatment benefits compared to the subpopulation with elevated GH levels remain unanswered, but research continues to build on our understanding of the heterogeneous population of individuals.

Treatable glomerular hyperfiltration in patients with active acromegaly.

The glomerular filtration rate (GFR) is increased in patients with active acromegaly. The aim of this study is to elucidate whether renal function deteriorates in patients with acromegaly and whether this deterioration is reversible after surgical remission. A case-control study of 48 acromegalic patients who were surgically cured (cases) and 48 patients with nonfunctioning pituitary adenomas (NFomas, controls) was conducted. We performed clinical and biochemical examinations before surgery and 3months post-surgery. The GFR of each patient was estimated (estimated GFR, eGFR) using their serum creatinine, age, sex, and body surface area, and postoperative changes in the eGFR were assessed. The preoperative eGFR was significantly higher in patients with acromegaly than in those with NFoma (99.8 vs 75.1mL/min respectively, P<0.01). In acromegalic patients, surgical remission was accompanied by a significant decline in the eGFR (from 99.8 to 86.2mL/min, P<0.01). Conversely, in patients with NFoma, the postoperative eGFR did not change significantly (from 75.1 to 81.9mL/min, P=0.12). Among the acromegalic patients, the postoperative decreases in the eGFR were more prominent in patients with a preoperatively high or normal vs low eGFR. Our data demonstrated a significant post-surgical eGFR decrease in patients with acromegaly, but not in patients with NFomas. This change in the eGFR was reversible in acromegalic patients with a high/normal preoperative eGFR, but not in those with a low preoperative eGFR. This suggests that the reversible pathophysiological change in some patients is functional but not organic.

Three-dimensional soft tissue analysis of the hand: a novel method to investigate effects of acromegaly.

BackgroundAcral overgrowth is a highly common clinical sign in patients with active acromegaly. To what extent this overgrowth persists after long-term remission of acromegaly is largely unknown. Using the new imaging technique of three-dimensional (3D) stereophotogrammetry, it is possible to accurately investigate soft tissue changes of the hand. The aim of the recent study was to compare the 3D soft tissue characteristics of the hands of patients in long-term remission of acromegaly to those of a healthy pair matched control group.MethodsA case-control study was performed at a tertiary referral center. Twelve patients in remission of acromegaly (58 % male, mean age 58.3 years, mean BMI 29.6 kg/m2) were compared to twelve age-, gender-, ethnicity-, and BMI-matched control subjects. Of each individual, 3D photographs of both hands were acquired and analyzed using a 3D computer software program.ResultsThe patients in long-term remission of acromegaly have overgrowth of soft tissue of the hand compared to matched control subjects, with a larger length and width of the hand (p = 0.0025, p = 0.0017, respectively). Furthermore, the diameters measured at the proximal interphalangeal (PIP) joints of the individual fingers are larger in the acromegaly patients.ConclusionsSignificant soft tissue overgrowth of the hand persists in former acromegaly patients, even after long-term remission. Analysis of 3D hand photographs is an accurate and easy tool to evaluate the acral soft tissue patterns in acromegaly.Level of Evidence: Level III, diagnostic study.

Serum Myokines Levels in Patients with Endogenous Cushing Syndrome and Acromegaly: Cross-Sectional Case−Control Study

Myokines are produced and released by muscle cells in response to muscular contractions. Endogenous Cushing syndrome (CS) and acromegaly cause significant changes in muscle tissue leading to atrophy or hypertrophy. However, there is no data whether these endocrine abnormalities influence myokine secretion. To evaluate serum levels of myostatin, interleukin-6 (IL6) and irisin in patients with CS and acromegaly. Fasting serum samples were taken and stored in aliquot at ≤-20°C from consecutive subjects with clinically evident and biochemically confirmed active CS, acromegaly and healthy volunteers matched by age, sex and body mass index (BMI). Commercially available kits were used to assay serum myokine levels. Grip strength was measured by a dynamometer. Insulin-like growth factor-1 (IGF1) was measured by immunochemiluminescence assay (Liaison), twenty-four hours urine free cortisol (24hUFC) ― by immunochemiluminescence assay (Vitros ECi), salivary free cortisol ― by electrochemiluminescence assay (Cobas). One-way ANOVA was utilized to assess the difference between groups. We enrolled 88 subjects: 30 patients suffered from CS (group 1), 28 ― acromegaly (2) and 30 matched healthy controls (3) with no difference among the groups in sex, age and BMI (p=0.492, 0.062 and 0.174 respectively). Mean 24hUFC in subjects with CS and mean IGF1 in subjects with acromegaly were significantly higher as compared to other groups (p<0.001). Right-hand grip strength was lower in patients with CS as compared to both patients with acromegaly and healthy subjects (p=0.04). However, among these young adults we did not find statistically significant differences in measured myokines levels: irisin ― p=0.15; IL6 ― p=0.34; myostatin ― p=0.50. There was a significant correlation between myostatin and irisin in the whole group of people and in every separately analyzed subset of patients (p<0.001), but no correlation was found between any measured myokines and 24hUFC or IGF1. Hypercortisolism or supraphysiological IGF1 levels do not significantly influence serum levels of myostatin, IL6 and irisin in young adults.

The possible role of mRNA expression changes of GH/IGF-1/insulin axis components in subcutaneous adipose tissue in metabolic disturbances of patients with acromegaly.

We explored the effect of chronically elevated circulating levels of growth hormone (GH)/insulin-like-growth-factor-1 (IGF-1) on mRNA expression of GH/IGF-1/insulin axis components and p85alpha subunit of phosphoinositide-3-kinase (p85alpha) in subcutaneous adipose tissue (SCAT) of patients with active acromegaly and compared these findings with healthy control subjects in order to find its possible relationships with insulin resistance and body composition changes. Acromegaly group had significantly decreased percentage of truncal and whole body fat and increased homeostasis model assessment-insulin resistance (HOMA-IR). In SCAT, patients with acromegaly had significantly increased IGF-1 and IGF-binding protein-3 (IGFBP-3) expression that both positively correlated with serum GH. P85alpha expression in SCAT did not differ from control group. IGF-1 and IGFBP-3 expression in SCAT were not independently associated with percentage of truncal and whole body fat or with HOMA-IR while IGFBP-3 expression in SCAT was an independent predictor of insulin receptor as well as of p85alpha expression in SCAT. Our data suggest that GH overproduction in acromegaly group increases IGF-1 and IGFBP-3 expression in SCAT while it does not affect SCAT p85alpha expression. Increased IGF-1 or IGFBP-3 in SCAT of acromegaly group do not appear to contribute to systemic differences in insulin sensitivity but may have local regulatory effects in SCAT of patients with acromegaly.

Fatigue and subjective complaints in patients with active and controlled acromegaly: a cross sectional multi-center study

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

Optimizing Blood Sampling Protocols in Patients With Acromegaly for the Estimation of Growth Hormone Secretion.

Optimal blood sampling schemas of GH for the estimation of the 24-hour secretion rate have not been established in acromegalic patients. By censoring available 24-hour GH serum profiles, we investigated the reliability of such simplified schemas. Design, Subjects, and Methods: We used 24-hour serum GH concentration profiles obtained with 10-minute sampling in a large cohort of healthy subjects (n = 130; mean age, 42; range, 18-77 years) and acromegalic patients (n = 87; mean age, 48; range 18-72 years). Patient categories were active disease, surgically cured, and somatostatin analog-treated individuals. The regression coefficients of determination (R(2)) and the linear slopes (β) between 24-hour secretion rates or mean concentrations (144 samples) on the one hand and mean values with less frequent sampling on the other, decreased in controls and in patients a short (1-2 weeks) or long (2-5 years) time after successful surgery. By contrast, the regression parameters remained essentially unchanged in patients with active acromegaly and those under GH suppressive treatment. Excellent correlations (R(2) ≥ 0.90) without GH underestimation existed between mean GH of daytime profiles and mean GH of 24-hour profiles and GH secretion rates estimated by deconvolution in patients with active acromegaly and patients treated with somatostatin analogs. Simplified sampling schemes, particularly a day profile, can be used for the estimation of GH secretion in patients with active acromegaly and under medical treatment. However, in healthy controls and patients after successful surgery, prolonged and frequent sampling schemes, at least at 2-hour intervals, reliably reflect 24-hour secretion.

Arterial properties in acromegaly: relation to disease activity and associated cardiovascular risk factors.

Acromegaly is associated with increased cardiovascular morbidity and mortality when inadequately treated, which may be secondary to associated comorbidities or to direct IGF-1 effects on the cardiovascular system. By using a control group carefully matched for traditional cardiovascular risk factors, we aimed to assess the direct contribution of disease activity and IGF-1 levels to arterial damage as assessed by measurements of arterial stiffness and endothelial function. Twenty-nine subjects with acromegaly (11 males, 52±14year; 15 active acromegaly) and 24 matched controls underwent evaluation of large and small artery compliance using applanation tonometry, pulse wave velocity (PWV), augmentation index (Alx), carotid ultrasonography intima-media thickness, (IMT) and flow-mediated dilatation (FMD). IGF-1 expressed as times the upper limit of the normal range (x ULN) was 2.2±1.1 in patients with active disease versus 0.7±0.2 in patients in remission. Irrespective of disease activity, FMD was lower in patients with acromegaly than in control subjects, (3.4±2.7% in active acromegaly, 4.4±3.3% in controlled acromegaly and 7.5±3.8% in controls; p=0.004). There were no significant differences in PWV, Alx, and IMT between groups. A positive correlation was found between IGF-1× ULN and IMT (r=0.4; P=0.02). Asymmetric dimethylarginine (ADMA), a novel cardiovascular risk factor, was positively correlated to arterial stiffness (r=0.46; p=0.017) and negatively with small vessel compliance (r=-0.44, p=0.02). Patients with acromegaly have significantly impaired endothelial function as assessed by FMD, but other tested vascular parameters were similar to a control group that was adequately matched for cardiovascular risk factors.

MEAN PLATELET VOLUME AND PLATELET FUNCTION ANALYSIS IN ACROMEGALIC PATIENTS BEFORE AND AFTER TREATMENT.

Mean platelet volume (MPV) and platelet function analysis have been studied before in acromegaly, but the effect of treatment on both parameters has not been evaluated. We aimed to investigate MPV and platelet function analysis in acromegalic patients after six-months of treatment. Forty patients with active acromegaly and 36 healthy subjects were included in the study. Plasma glucose and lipids, fibrinogen, GH, IGF-1 levels, MPV and platelet function analysis were measured. All patients with acromegaly were re-evaluated six months after treatment. Fasting blood glucose (FBG), GH, IGF-1, fibrinogen levels and MPV values were significantly higher in acromegalic group compared with the control. Platelet function was enhanced significantly (pcol-ADP: 0.002, pcolepinephrine: 0.002). After 6 months of treatment FBG, serum GH, IGF-1, fibrinogen and MPV decreased and collagen/ADP- and collagen/epinephrine-closure times (CT) were increased. Acromegalic patients that were in remission with long-acting SSA after surgery had significantly higher fibrinogen levels and MPV and decreased collagen/epinephrine-CT with respect to the controls (pfibrinogen: 0.001, pMPV: 0.026, pcol-epinephrine: 0.037). Acromegaly was associated with increased MPV and enhanced platelet activity. Although growth hormone hypersecretion was controlled by surgery and medical treatment, these parameters did not improve - indicating a still increased risk for cardiovascular events.

Effects of Somatostatin Analogues on Glucose Metabolism in Acromegaly: Friend of Foe?

Effects of Somatostatin Analogues on Glucose Metabolism in Acromegaly: Friend of Foe?

Reduction of trabecular and cortical volumetric bone mineral density at the proximal femur in patients with acromegaly.

Data on dual energy absorptiometry (DXA)-measured bone mineral density (BMD) at the level of the total hip (TH) and femoral neck (FN) in patients with acromegaly (ACRO) are conflicting. Increase in bone size associated with ACRO may limit the reliability of DXA. Our objective is to evaluate trabecular and cortical volumetric BMD (vBMD) across the proximal femur in ACRO patients. Cross sectional study in a clinical research center. Thirty-five ACRO patients (19 males; mean age, 48±7 years; BMI, 27.5±4.4 kg/m(2); 17 with active disease) and 35 age, gender, and BMI-matched controls. vBMD was assessed by quantitative computed tomography at the level of the TH, FN, trochanter (TR), and intertrochanteric (IT). Trabecular vBMD was lower in both total and active ACRO as compared with controls (P<0.01). Cortical vBMD was lower in ACRO patients (active and controlled) vs controls at both TH and TR sites (P<0.05). These findings were confirmed when only eugonadal patients were analyzed. Both total cross sectional area (CSA) and average cortical thickness (ACT) were greater in ACRO patients vs controls (P<0.05). An inverse association between disease duration and trabecular vBMD at TH (r=-0.42, P=0.023) and IT (r=-0.41, P=0.026) was also found. Both cortical and trabecular vBMD are reduced at the proximal femur in ACRO patients, regardless of gender, gonadal status, and disease activity. Disease duration is negatively associated with trabecular vBMD at the TH and IT.

Soluble α-Klotho - a new marker of acromegaly?

Klotho is a transmembrane protein that attenuates insulin/insulin-like growth factor-1 (IGF-1) signalling and appears to be involved in ageing. Recent data suggest that soluble a-Klotho (sKlotho) is also elevated in acromegaly. The aim of this study was to assess serum levels of sKlotho in patients in relation to the activity of the disease and to compare with the control group. We studied 55 patients with acromegaly and 29 healthy controls (CG). Patients were divided into three subgroups according to minimal GH (growth hormone) concentration during the oral glucose tolerance test (OGTT) and the IGF-1 concentration: a surgically cured acromegalic group (SCA), well-controlled acromegalic group (WCA), and active acromegaly group (AA). In all subjects, blood samples were taken to assess the concentration of sKlotho, GH, IGF-1, and biochemical markers. Soluble a-Klotho was highest in the AA group and lowest in the SCA group. The differences in sKlotho levels were statistically significant when the AA group was compared to the SCA, WCA, and CG groups (p = 0.000, p = 0.002, p = 0.001, respectively). There were no significant differences in sKlotho levels among the SCA, WCA, and CG groups. sKlotho positively correlated with GH levels in the WCA and WCA + SCA groups (r = 0.666, p = 0.009; r = 0.366, p = 0.047, respectively) and with the IGF-1 level in the AA group (r = 0.589, p = 0.021). sKlotho is increased in active acromegaly and normalises after successful treatment. It could be a new biomarker of acromegaly activity. (Endokrynol Pol 2016; 67 (4): 390-396).

Low Frequency of Cardiomyopathy Using Cardiac Magnetic Resonance Imaging in an Acromegaly Contemporary Cohort.

Left ventricular hypertrophy (LVH) and myocardial fibrosis are considered common findings of the acromegaly cardiomyopathy in echocardiography studies. To evaluate the frequency of LVH, systolic dysfunction and myocardial fibrosis was undertaken in patients with acromegaly using cardiac magnetic resonance imaging (CMRi) before and after 12 months of octreotide long-acting repeatable treatment. Consecutive patients with active acromegaly submitted to biochemical analysis and CMRi before and after 12 months of treatment. Additionally, echocardiography was performed before treatment. Forty consecutive patients were evaluated using CMRi at baseline and 30 patients were reevaluated after 12 months of treatment. Additionally, 29 of these patients were submitted to echocardiography. Using CMRi, the frequency of LVH was 5%. The mean left ventricular mass index (LVMi) was 61.73 ± 18.8 g/m(2). The mean left ventricular ejection fraction (LVEF) was 61.85 ± 9.2%, and all patients had normal systolic function. Late gadolinium enhancement was present in five patients (13.5%), and one patient (3.5%) had an increased extracellular volume. After treatment, 12 patients (40%) had criteria for disease control. No clinically relevant differences in cardiac variables before and after treatment were observed. Additionally, there was no difference in LVMi and LVEF among patients with and without disease control. Using echocardiography, 31% of the patients had LVH, mean LVMi was 117.8 ± 46.3 g/m(2) and mean LVEF was 67.3 ± 4.4%. All patients had normal systolic function. We demonstrated by CMRi, the gold-standard method, that patients with active acromegaly might have a lower prevalence of cardiac abnormalities than previously reported.