High Growth Hormone Levels Research Articles

Proteomic analysis reveals sex-specific biomarker signature in postural orthostatic tachycardia syndrome

BackgroundPostural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular (CV) autonomic disorder of unknown etiology characterized by an excessive heart rate increase on standing and orthostatic intolerance. In this study we sought to identify novel CV biomarkers potentially implicated in POTS pathophysiology.MethodsWe conducted a nested case-control study within the Syncope Study of Unselected Population in Malmö (SYSTEMA) cohort including 396 patients (age range, 15–50 years) with either POTS (n = 113) or normal hemodynamic response during passive head-up-tilt test (n = 283). We used a targeted approach to explore changes in cardiovascular proteomics associated with POTS through a sequential two-stage process including supervised principal component analysis and univariate ANOVA with Bonferroni correction.ResultsPOTS patients were younger (26 vs. 31 years; p < 0.001) and had lower BMI than controls. The discovery algorithm identified growth hormone (GH) and myoglobin (MB) as the most specific biomarker fingerprint for POTS. Plasma level of GH was higher (9.37 vs 8.37 of normalised protein expression units (NPX); p = 0.002), whereas MB was lower (4.86 vs 5.14 NPX; p = 0.002) in POTS compared with controls. In multivariate regression analysis, adjusted for age and BMI, and stratified by sex, lower MB level in men and higher GH level in women remained independently associated with POTS.ConclusionsCardiovascular proteomics analysis revealed sex-specific biomarker signature in POTS featured by higher plasma level of GH in women and lower plasma level of MB in men. These findings point to sex-specific immune-neuroendocrine dysregulation and deconditioning as potentially key pathophysiological traits underlying POTS.

Early detection of insulin resistance in children with different types of intrauterine growth restriction

Relevance of the research. Intrauterine growth restriction in children is associated with an increased risk of insulin resistance and non-insulin-dependent diabetes mellitus later in life. The influence of type of intrauterine growth restriction and the mechanisms of insulin resistance are still unknown; the role of catch-up growth in this process is controversial.&#x0D; The aim of the study was to identify insulin resistance in children with different types of intrauterine growth restriction and to analyze the role of catch-up growth in this process.&#x0D; Materials and methods. The research involved 95 newborns, which were divided into groups based on birth weight and length: 60 newborns with intrauterine growth restriction (group I – 31 with asymmetrical intrauterine growth restriction; group II – 29 with symmetrical intrauterine growth restriction) and control group (group III) – 35 newborns without intrauterine growth restriction. Children also were divided into groups according to the presence of catch-up growth to 3 months old. The levels of insulin, insulin-like growth factor-1, growth hormone were measured in cord blood at birth and in blood serum at 3 months old. Glucose levels were measured in serum and insulin resistance index “the homeostasis model assessment of insulin resistance” (HOMA-IR) was calculated in children at 3 months.&#x0D; Results. The children with intrauterine growth restrictioncompared to control group had significantly lower levels of insulin-like growth factor-1 in cord blood. The differences between types of intrauterine growth restrictionhave been observed: children with symmetrical intrauterine growth restriction had higher levels of growth hormone, insulin and HOMA-IR then in asymmetrical one. Correlations between insulin and glucose in children with symmetrical intrauterine growth restriction were absent unlike to asymmetrical intrauterine growth restriction (+0.61). The negative role of catch-up growth in insulin resistance development has been defined: it was related to hyperinsulinemia and increased the frequency of insulin resistance in children either in asymmetrical or in symmetrical intrauterine growth restriction, but more in symmetrical one.&#x0D; Conclusion. Children with symmetrical intrauterine growth restriction especially with catch-up growth are at the highest risk of metabolic syndrome development in later life and require increased monitoring by pediatricians and endocrinologists.

Acromegalia y adenomas hipofisarios: una revision de la literatura

La acromegalia es una condición que engloba determinadas manifestaciones clínicas ocasionadas por altos niveles séricos de la hormona del crecimiento que, en la mayoría de los casos es debida a la presencia de adenomas hipofisarios. La temprana sospecha clínica de esta entidad y su oportuno diagnóstico permite que el tratamiento genere tasas altas de remisión de la enfermedad. Los productores de la hormona de crecimiento representan del 10 al 25%, sus manifestaciones clínicas inespecíficas, sumadas al comportamiento insidioso de la enfermedad, conducen a retraso en su diagnóstico y tratamiento, de tal forma que la sospecha de esta condición en el comienzo de aparición de signos y síntomas resulta relevante para disminuir su morbilidad.

Visfatin Levels May be an Early Marker of Atherosclerosis in Patients with Acromegaly.

The purpose of the study was to compare serum visfatin levels between patients with acromegaly and healthy controls and to evaluate the relationships between visfatin levels and epicardial fat thickness (EFT), carotid intima media thickness (cIMT), and ankle brachial index (ABI). We conducted a cross-sectional case-control study of 54 patients with acromegaly (37 females and 17 males) and 34 healthy controls (22 females and 12 males). Serum visfatin was measured by ELISA. Acromegalic and control participants and those with active or controlled acromegaly were compared with respect to their serum visfatin, clinical and metabolic parameters, EFT, cIMT, and ABI. Linear correlation was used to identify associations between these parameters and visfatin in all participants. Serum visfatin and glycated hemoglobin (HbA1c) were higher in the acromegaly group than in the control group (p<0.001 and p=0.007, respectively). There was no difference in visfatin between the active and controlled acromegaly groups, but HbA1c was higher in the active than the controlled acromegaly group (p<0.04). EFT, cIMT, and ABI were similar between the acromegaly and control groups and between the active and controlled acromegaly groups. Serum visfatin positively correlated with HbA1c, growth hormone (GH), and insulin-like growth factor-1 (IGF-1)/upper limit of normal ratio (r=0.245, p=0.024; r=0.259, p=0.017; and r=0.282, p=0.009, respectively). This study has revealed that a high visfatin level is associated with glycemic dysregulation and higher levels of GH and IGF-1 in acromegalic patients.

Emerging Mechanisms of GH-Induced Lipolysis and Insulin Resistance.

Growth hormone (GH) is a pleiotropic hormone that coordinates an array of physiological processes including growth and metabolism. GH promotes anabolic action in all tissues except adipose, where it catabolizes stored fat to release energy for the promotion of growth in other tissues. However, chronic stimulation of lipolysis by GH results in an increased flux of free fatty acids (FFAs) into systemic circulation. Hence, a sustained release of high levels of GH contributes significantly to the development of insulin resistance by antagonizing the anti-lipolytic action of insulin. The molecular pathways associated with the lipolytic effect of GH in adipose tissue however, remain elusive. Recent studies have provided molecular insights into GH-induced lipolysis and impairment of insulin signaling. This review discusses the physiological and metabolic actions of GH on adipose tissue as well as GH-mediated deregulation of the FSP27-PPARγ axis which alters adipose tissue homeostasis and contributes to the development of insulin resistance and Type 2 diabetes.

Growth hormone upregulates the pro-tumorigenic galectin 1 in mouse liver.

Transgenic mice overexpressing growth hormone (GH) spontaneously develop liver tumors, including hepatocellular carcinoma (HCC), within a year. The preneoplastic liver pathology in these mice recapitulates that observed in humans at high risk of developing hepatic cancer. Although increased expression of galectin 1 (GAL1) in liver tissue is associated with HCC aggressiveness, a link between this glycan-binding protein and hormone-related tumor development has not yet been explored. In this study, we investigated GAL1 expression during liver tumor progression in mice continuously exposed to high levels of GH. GAL1 expression was determined by Western blotting, RT-qPCR and immunohistochemistry in the liver of transgenic mice overexpressing GH. Animals of representative ages at different stages of liver pathology were studied. GAL1 expression was upregulated in the liver of GH-transgenic mice. This effect was observed at early ages, when animals displayed no signs of liver disease or minimal histopathological alterations and was also detected in young adults with preneoplastic liver pathology. Remarkably, GAL1 upregulation was sustained during aging and its expression was particularly enhanced in liver tumors. GH also induced hepatic GAL1 expression in mice that were treated with this hormone for a short period. Moreover, GH triggered a rapid increment in GAL1 protein expression in human HCC cells, denoting a direct effect of the hormone on hepatocytes. Therefore, our results indicate that GH upregulates GAL1 expression in mouse liver, which may have critical implications in tumorigenesis. These findings suggest that this lectin could be implicated in hormone-driven liver carcinogenesis.

Pasireotide and Pegvisomant Combination Treatment in Acromegaly Resistant to Second-Line Therapies: A Longitudinal Study.

The treatment of acromegaly resistant to first- and second-line therapies can be extremely challenging. We have described six patients who were successfully treated with a combination therapy of pasireotide and pegvisomant and compared them with a control group of patients resistant to conventional somatostatin analogs (SSAs), whose disease was controlled with other treatment, such as pasireotide (as monotherapy) or pegvisomant (as monotherapy or combined with conventional SSAs). In these six patients, acromegaly was controlled with combined pasireotide and pegvisomant treatment after failure of all other treatments. Compared with the 49 patients in the control group, these six patients had giant and invasive pituitary adenomas (at both the cavernous sinus and other structures). Although not statistically significant, higher growth hormone levels, more elevated Ki-67 expression, greater somatostatin receptor (SSTR) subtype 5 expression, and lower SSTR subtype 2 expression at the diagnosis of acromegaly were detected in patients receiving combination treatment with pasireotide and pegvisomant compared with the control group. Our data have reinforced the importance of personalized treatment of patients with acromegaly according to the clinical, biochemical, molecular, and morphological disease markers and suggest that combined treatment with pasireotide and pegvisomant can induce disease control in tumors with low SSTR2 expression, resistant to conventional SSAs (alone or combined with pegvisomant) and to new-generation SSAs alone (pasireotide).

Higher Growth Hormone Levels are Associated with Erectile Dysfunction in Male Patients With Acromegaly

Objective: To investigate in vivo correlates of erectile dysfunction (ED) in male patients with acromegaly. Methods: Fifty-one male patients with acromegaly were assessed by the International Index of Erectile Function-5 and Acromegaly Quality of Life (Acro-QoL) questionnaires. The measurement of serum nitric oxide (NO) were performed in patients and age-matched nonacromegalic controls. Results: Among 51 patients analyzed, 32 (62.7%) had ED. Patients with ED showed lower Acro-QoL scores regarding global (69.8 ± 17.7 versus 79.4 ± 11.2; P = .035) and personal relationship dimensions (59.6 ± 22.1 versus 76.8 ± 17.6; P = .012) than non-ED patients. ED patients were older (44.5 ± 11.2 years versus 33.2 ± 8.5 years; P = .04) and showed higher growth hormone (GH) levels (15.5 μg/L [interquartile range of 9.5 to 34.5 μg/L] versus 5.9 μg/L [interquartile range of 3.4 to 13.9 μg/L]; P = .001) compared to non-ED patients. The cutoff values for identifying ED were 7.9 μg/L for random GH and 5.3 μg/L for GH nadir after oral administration of 75 g of glucose. There was no significant difference in total testosterone levels between the two groups (6.36 ± 4.24 nmol/L versus 9.54 ± 5.50 nmol/L; P = .299). The NO levels in patients with acromegaly were significantly lower than those in nonacromegalic controls (8.77 ± 1.78 μmol/L versus 19.19 ± 5.02 μmol/L, respectively; P = .049). Furthermore, the NO levels were even lower in ED patients than those in non-ED patients (5.14 ± 0.98 μmol/L versus 12.09 ± 3.44 μmol/L; P = .027). Conclusion: Our study showed that ED is prevalent in male acromegalic patients and may be associated with systemic endothelial dysfunction induced by excessive GH. Further studies investigating the mechanism of GH and ED are required. Abbreviations: Acro-QoL = Acromegaly Quality of Life; ED = erectile dysfunction; FSH = follicle-stimulating hormone; GH = growth hormone; IGF-1 = insulin-like growth factor 1; IIEF-5 = international index of erection function-5; LH = luteinizing hormone; MRI = magnetic resonance imaging; NO = nitric oxide; OGTT = oral glucose tolerance test; QoL = quality of life; ROC = receiver operating characteristic.

SAT-181 Characterization of Adult Growth Hormone Receptor Gene-Disrupted Mice

Reduced growth hormone (GH) action can extend life- and health-span. Mice with a disrupted GHR gene since birth are dwarf and obese with low levels of IGF-1 and insulin; high levels of GH; and hold the record for the longest-lived laboratory mouse. They are also somewhat resistant to several age-related diseases including cancer and diabetes. In order to determine if disruption of GHR after birth can also extend lifespan, we previously disrupted the GHR gene at 6 weeks of age and found that females have extended maximal lifespans. In the current study, we wanted to evaluate if disrupting GH action at an adult age (6 months) will lead to the same lifelong benefits seen mice with no GH action since birth, but without dwarfism. In this study, we used the Cre-lox system to ablate the GHR in mice of 6 months (a6mGHRKO mice). Following this, we determined body weights, composition and glucose homeostatic criteria including glucose and insulin tolerance testing. We then dissected the mice 6 months after GHR disruption (1 year of age) to measure circulatory GH, Insulin growth factor 1 (IGF-1), inflammatory factors, as well as the GHR expression levels in different tissues including liver, skeletal muscle and adipose tissue. We found that, the a6mGHRKO mice were not dwarf and have decreased IGF-1 and increased circulating GH levels. We also found that the GHR gene expression was decreased in all the tissues tested, and IGF-1 mRNA levels were reduced in adipose tissue liver and heart, but not in muscle or kidneys when compared to WT mice. Also, circulatory levels of interleukin-6, tumor necrosis alpha and monocyte chemoattractant protein 1 were unchanged between a6mGHRKO mice and controls. Moreover, differences in glucose metabolism can be seen in male and female a6mGHRKO mice. While glucose tolerance was not changed between experimental mice and controls, male a6mGHRKO mice showed increased insulin sensitivity, whereas female a6mGHRKO mice showed no difference in insulin sensitivity with respect to littermate controls. Studies that assess the status of age-related mechanisms such as mechanistic target of rapamycin (mTOR) activity and oxidative stress are being performed. Finally, a separate cohort of the a6mGHRKO mice have been generated and are being evaluated for the life span of these mice. In conclusion, mice that have the GHR gene ablated at 6 months of age have a normal body length, improved insulin sensitivity in males and normal inflammatory status when compared to controls. Molecular mechanisms to determine age-related effects of GH including longevity studies are ongoing.

MON-476 Growth Hormone and the Glomerular Podocyte: Studies of Podocyte-Specific Growth Hormone Receptor Gene Deletion in Mice

Previous research has suggested a role for growth hormone (GH) in the development of kidney disease. Evidence of increased glomerular size and sclerosis in bovine GH (bGH) overproducing animals suggests that excess GH action may cause or exacerbate glomerular damage. Within the glomerulus, the podocyte plays the role of forming a filtration barrier called the slit diaphragm. This cell is known to be dysfunctional in many models of nephropathy and is also a direct target of GH. To explore the mechanisms by which GH impacts the glomerulus, we have developed a transgenic mouse, the podocyte-specific GH receptor gene-disrupted mouse (podGHR-/-). These mice were generated on a C57BL/6J background using Cre-Lox transgenic methods. To examine the effects of high GH levels on the podocyte, these mice were crossed with bovine GH (bGH) overproducing mice and studied at several time points over the course of a year, alongside wild-type control mice and podGHR-/- mice lacking bGH overexpression. Various metabolic and physiologic assays were performed on these mice, including glomerular filtration rate (GFR) testing, glucose and insulin tolerance testing, body composition analysis, and urine & serum analysis. Histological analyses were also performed. Podocyte-specific GHR gene-deletion was associated with increased GFR in male podGHR-/- mice at 54 weeks of age, and with decreased GFR in male podGHR-/- mice with bGH overexpression at 54 weeks of age. PodGHR-/- male mice exhibited significantly decreased total kidney hydroxyproline content at 54 weeks of age as well as decreased glomerular trichrome stain deposition. Both male and female podGHR-/- mice showed decreased glomerular periodic acid Schiff stain deposition at 54 weeks of age. These results suggest a role for podocyte GH activity in the regulation of GFR in the aging and diseased kidney, as well as a role for GH in directing the deposition of collagen and glycosaminoglycans in glomerulus via the podocyte.

Modulation of the somatotropic axis, adiponectin and cytokine secretion during highly pathogenic porcine reproductive and respiratory syndrome virus type 1 (HP-PRRSV-1) infection

Porcine reproductive and respiratory syndrome virus (PRRSV) is known to be clinically responsible for reproductive failure in sows and post-weaning respiratory disease in growing piglets. During the last years, highly pathogenic PRRSV isolates have been discovered. In Italy, a PRRSV-1 subtype 1 strain (namely PR40/2014) characterized by high pathogenicity was isolated and experimental infection was characterized in terms of virological/clinical features and immune modulation (Canelli et al., 2017; Ferrari et al., 2018). The present study was performed in 4-week-old pigs experimentally infected with the highly pathogenic PRRSV1_PR40/2014 (HP-PR40) or with the conventional PRRSV1_PR11/2014 (PR11). The aim was to evaluate the interrelation between plasmatic hormones and cytokines in infected pigs compared to uninfected controls in order to address potential effects on the course of an experimental infection. The time-related changes of growth hormone (GH), insulin-like growth factor-1 (IGF-1), adiponectin, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels appear to be modulated by the infection depending on the PRRSV isolate (HP-PR40 vs. PR11). In particular, in HP-PR40 infected animals, the association between high GH levels and viremia may testify the need to block the anabolic action of GH in order to shift available energy towards the immune response. This need appeared to be delayed in PR11 animals, given the lower pathogenicity of the isolate. Adiponectin, IL-6 and TNF-α course supports the hypothesis of GH resistance mechanisms to guarantee homeostasis in HP-PR40 animals and underlines the key role of energy availability in events leading to an effective response to the virus.

Excess growth hormone suppresses DNA damage repair in epithelial cells.

Growth hormone (GH) decreases with age, and GH therapy has been advocated by some to sustain lean muscle mass and vigor in aging patients and advocated by athletes to enhance performance. Environmental insults and aging lead to DNA damage, which - if unrepaired - results in chromosomal instability and tumorigenesis. We show that GH suppresses epithelial DNA damage repair and blocks ataxia telangiectasia mutated (ATM) kinase autophosphorylation with decreased activity. Decreased phosphorylation of ATM target proteins p53, checkpoint kinase 2 (Chk2), and histone 2A variant led to decreased DNA repair by nonhomologous end-joining. In vivo, prolonged high GH levels resulted in a 60% increase in unrepaired colon epithelial DNA damage. GH suppression of ATM was mediated by induced tripartite motif containing protein 29 (TRIM29) and attenuated tat interacting protein 60 kDa (Tip60). By contrast, DNA repair was increased in human nontumorous colon cells (hNCC) where GH receptor (GHR) was stably suppressed and in colon tissue derived from GHR-/- mice. hNCC treated with etoposide and GH showed enhanced transformation, as evidenced by increased growth in soft agar. In mice bearing human colon GH-secreting xenografts, metastatic lesions were increased. The results elucidate a mechanism underlying GH-activated epithelial cell transformation and highlight an adverse risk for inappropriate adult GH treatment.

Sleep apnea and cardiovascular complications of the acromegaly. Response to the medical treatment.

Acromegaly is a rare disease characterized by high levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). The excess of GH leads to the development of different manifestations in different organs, from subtle signs in the bones and soft tissues to the development of respiratory and cardiac insufficiency. In the cardiovascular system, the GH/IGF-1 axis exerts its influence on three major aspects: myocyte growth and structure, cardiac contractility and vascular function. In this article, we review the different cardiovascular and respiratory complications as well as the effects of the different treatments on these complications. Cardiovascular complications that occur in acromegaly are known as "acromegalic cardiomyopathy," and include ventricular hypertrophy, impaired diastolic and systolic function, valve diseases, coronary artery disease, and arrhythmias. Acromegaly is also associated with relevant complications of the respiratory system, mainly sleep apnea and respiratory insufficiency. Regarding treatment, there are different therapeutic strategies. Surgery is the first-choice treatment, but in general, half of patients will require adjuvant treatments, such as medical treatment (somatostatin analogues, dopamine agonists and GH receptor antagonists) or radiotherapy. The treatment can improve some complications of acromegaly, such as left ventricular hypertrophy, hypertension, or obstructive sleep apnea. On the other hand, when strict control of the disease is achieved, a reduction in mortality and cardiovascular morbidity is assured, reaching rates similar to those of the general population.

Association between male Infertility and seminal plasma levels of growth hormone and insulin-like growth factor-1.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) have been proposed to play a pivotal role in male infertility due to their anabolic effects. The aim of this study was to investigate possible associations between seminal plasma levels of GH and IGF-1 and sperm parameters. Fifty men participated in this study. Semen analysis was performed, while cell-free seminal plasma was collected following sperm centrifugation. Seminal plasma concentrations of IGF-1 and GH were determined by enzyme-linked immunosorbent assay (ELISA). Due to the presence of asthenozoospermia in all participants who presented with abnormal sperm parameters, the participants were further subdivided into normal (group A), asthenozoospermic (group B) and asthenozoospermic plus at least one additional abnormal parameter (group C). A marginally nonsignificant statistical difference (p=0.063) was revealed between the GH levels corresponding to the asthenozoospermic and the normal group with the latter presenting with higher GH levels. A statistically significant positive correlation (p<0.05) was noted between levels of GH and IGF-1 in group C. The above relationship has also been observed in men with low sperm concentration, vitality, volume and abnormal morphology. These novel findings require further investigation in order for the biological significance of those associations to be clarified.

A case of CHARGE syndrome associated with hyperinsulinemic hypoglycemia in infancy

CHARGE syndrome is a rare autosomal dominant disorder involving multiple organs. Chromodomain helicase DNA binding protein-7 (CHD7) is a major causative gene of CHARGE syndrome. We herein report a male infant born at full term with asphyxia who was diagnosed with CHARGE syndrome based on the typical anomalies. He showed a poor sucking ability and suffered from continuous hypoglycemia in early infancy, ultimately requiring tube feeding. While in a hypoglycemic status, inappropriate high insulin and low growth hormone levels were noticed. Growth hormone replacement therapy partially increased his blood glucose levels, but asymptomatic hypoglycemia with hyperinsulinemia was occasionally noticed. Additional diazoxide treatment stabilized his blood level to within the normal range. A genetic analysis of CHD7 showed the novel heterozygous monoallelic mutation c.2990delT causing a reading frameshift p.Leu997Trpfs*15 in exon 12. This case shows that patients with CHARGE syndrome caused by a CHD7 mutation may present with persistent hyperinsulinemic hypoglycemia, just like other dysmorphic syndromes genetically caused by aberrations in chromatin remodeling.

Auditory closed-loop stimulation of EEG slow oscillations strengthens sleep and signs of its immune-supportive function

Sleep is essential for health. Slow wave sleep (SWS), the deepest sleep stage hallmarked by electroencephalographic slow oscillations (SOs), appears of particular relevance here. SWS is associated with a unique endocrine milieu comprising minimum cortisol and high aldosterone, growth hormone (GH), and prolactin levels, thereby presumably fostering efficient adaptive immune responses. Yet, whether SWS causes these changes is unclear. Here we enhance SOs in men by auditory closed-loop stimulation, i.e., by delivering tones in synchrony with endogenous SOs. Stimulation intensifies the hormonal milieu characterizing SWS (mainly by further reducing cortisol and increasing aldosterone levels) and reduces T and B cell counts, likely reflecting a redistribution of these cells to lymphoid tissues. GH remains unchanged. In conclusion, closed-loop stimulation of SOs is an easy-to-use tool for probing SWS functions, and might also bear the potential to ameliorate conditions like depression and aging, where disturbed sleep coalesces with specific hormonal and immunological dysregulations.

Endoscopic Transsphenoidal Approach for Surgical Treatment of Growth Hormone Secreting Pituitary Adenoma: Endocrinological Outcome in 49 Patients Based on 2010 Consensus Criteria for Remission - Preliminary Result

Background: Nowadays, the endoscopic transsphenoidal approach is the initial option for resection of all pituitary adenomas. The current study reported the experience with endoscopic transsphenoidal surgery remission rates using the 2010 consensus criteria, predictors of remission, and the associated complications. Methods: A prospectively collected database of 49 patients with acromegaly who underwent endoscopic endonasal transsphenoidal surgery was analyzed. Tumors were classified according to size, as well as the Knosp and the Hardy-Wilson classifications. Endocrinological remission was defined as normal insulin-like growth factor (IGF)-I level and either a suppressed growth hormone (GH) level < 0.4 ng/mL during an oral glucose tolerance test, or a random GH level < 1.0 ng/mL at least 3 months after the surgery. The extent of resection was evaluated on postoperative contrast-enhanced magnetic resonance imaging (MRI). Results: Biochemical remission was achieved in 7 of 9 (77.8%) microadenoma and 28 of 40 (70%) macroadenoma. The total remission rate was 71.4% and gross total resection was achieved in 45 of 49 (91.8%) patients. Tumor size, age, gender, history of prior surgery, suprasellar extension, and sphenoid sinus invasion were not associated with remission rate. Preoperative variables predictive of remission included the Knosp score (P = 0.041) and GH levels (P = 0.047). Two patients (4.1%) experienced postoperative pan hypopituitarism, and permanent DI was observed in 3 (6.1%) patients. One patient (2%) had cerebrospinal fluid (CSF) leaks treated with serial lumbar punctures. The median follow-up period was 25.45 months; ranged from 3 to 49. Conclusions: Endoscopic transsphenoidal adenoma resection leads to a high rate of endocrinological remission in patients with low acromegaly complication. Patients with high preoperative GH levels and the Knosp scores are less likely to achieve remission.

Surgical Outcome of Growth Hormone-Secreting Pituitary Adenoma with Empty Sella Using a New Classification.

To investigate outcomes and identified risk factors affecting cure and intraoperative cerebrospinal fluid leak after transsphenoidal surgery using a new classification for growth hormone-secreting pituitary adenoma associated with empty sella. In this retrospective cohort study, 51 patients enrolled from January 2010 to June 2016 were categorized into 3 groups using a new classification scheme: grade A, whole tumor occupation area beneath a horizontal line drawn along the lowest level of empty sella; grade B, tumor occupation area that crossed the horizontal line on 1 side; and grade C, tumor occupation area that crossed the horizontal line on 2 sides. Clinical data were collected and analyzed. Cure rate for grade A patients (88.24%; 15/17) was significantly higher than cure rate for grade B (55.00%; 11/20) and grade C (50.00%; 7/14) patients. Occurrence of cerebrospinal fluid leaks in grade C patients (35.71%; 5/14) was higher than in grade A patients (5.88%; 1/17). Logistic regression analysis indicated that risk factors affecting cure included large maximum tumor diameter (P= 0.009, odds ratio [OR]= 1.222), high preoperative fasting growth hormone level (P= 0.031, OR= 1.088), and high classification (P= 0.017, OR= 4.485). Risk factor affecting intraoperative cerebrospinal fluid leak was high classification (P= 0.039, OR= 3.580). Transsphenoidal surgery is the current optimal treatment strategy. Empty sella increases the difficulty of surgery with a higher incidence of complications. The new classification scheme was better for predicting the surgical outcome for this disease.

Long term follow-up of growth hormone-secreting pituitary adenomas submitted to endoscopic endonasal surgery.

The aim of this study was to evaluate the results of the endoscopic transsphenoidal technique for growth hormone (GH)-secreting adenomas. A retrospective analysis based on medical records of 23 acromegalic patients submitted to endoscopic transsphenoidal surgery. Biochemical control was defined as basal GH < 1ng/ml, nadir GH < 0.4ng/ml after glucose load and age-adjusted IGF-1 normal at the last follow-up. The overall endocrinological remission rate was 39.1%. While all microademonas achieved a cure, just one third of macroadenomas went into remission. Suprasellar extension, cavernous sinus invasion and high GH levels were associated with lower rates of disease control. The most common complication was diabetes insipidus and the most severe was an ischemic stroke. The endoscopic transsphenoidal approach is a safe and effective technique to control GH-secreting adenomas. The transcavernous approach may increase the risk of complications. Suprasellar and cavernous sinus extensions may preclude gross total resection of these tumors.

Dietary 2-oxoglutarate prevents bone loss caused by neonatal treatment with maximal dexamethasone dose.

Synthetic glucocorticoids (GCs) are widely used in the variety of dosages for treatment of premature infants with chronic lung disease, respiratory distress syndrome, allergies, asthma, and other inflammatory and autoimmune conditions. Yet, adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Conversely, 2-oxoglutarate (2-Ox), a precursor of glutamine, glutamate, and collagen amino acids, exerts protective effects on bone development. Our aim was to elucidate the effect of dietary administered 2-Ox on bone loss caused by neonatal treatment with clinically relevant maximal therapeutic dexamethasone (Dex) dose. Long bones of neonatal female piglets receiving Dex, Dex+2-Ox, or untreated were examined through measurements of mechanical properties, density, mineralization, geometry, histomorphometry, and histology. Selected hormones, bone turnover, and growth markers were also analyzed. Neonatal administration of clinically relevant maximal dose of Dex alone led to over 30% decrease in bone mass and the ultimate strength ( P < 0.001 for all). The length (13 and 7% for femur and humerus, respectively) and other geometrical parameters (13-45%) decreased compared to the control ( P < 0.001 for all). Dex impaired bone growth and caused hormonal imbalance. Dietary 2-Ox prevented Dex influence and vast majority of assessed bone parameters were restored almost to the control level. Piglets receiving 2-Ox had heavier, denser, and stronger bones; higher levels of growth hormone and osteocalcin concentration; and preserved microarchitecture of trabecular bone compared to the Dex group. 2-Ox administered postnatally had a potential to maintain bone structure of animals simultaneously treated with maximal therapeutic doses of Dex, which, in our opinion, may open up a new opportunity in developing combined treatment for children treated with GCs. Impact statement The present study has showed, for the first time, that dietary 2-oxoglutarate (2-Ox) administered postnatally has a potential to improve/maintain bone structure of animals simultaneously treated with maximal therapeutic doses of dexamethasone (Dex). It may open the new direction in searching and developing combined treatment for children treated with glucocorticoids (GCs) since growing group of children is exposed to synthetic GCs and adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Currently proposed combined therapies have numerous side effects. Thus, this study proposed a new direction in combined therapies utilizing dietary supplementation with glutamine derivative. Impairment caused by Dex in presented long bones animal model was prevented by dietary supplementation with 2-Ox and vast majority of assessed bone parameters were restored almost to the control level. These results support previous thesis on the regulatory mechanism of nutrient utilization regulated by glutamine derivatives and enrich the nutritional science.