Basal Growth Hormone Levels Research Articles

VITAMIN D AND SOME GROWTH PARAMETERS IN CHILDREN WITH DIFFERENT FORMS OF SHORTISH STATURE

The aim of study – to analyze the level of 25(OH)D in the blood plasma of children withdifferent forms of shortish stature according to the state of the growth hormone (GH)/insulin-like growth factor (IGF-1) system.Materials and methods. In the Department of Pediatric Endocrine Pathology of the StateInstitution «V. P. Komisarenko Institute of Endocrinology and Metabolism of the NationalAcademy of Medical Sciences of Ukraine» 129 children with shortish stature werestudied. The following data were considered: sex and age of the patient, anthropometricdata, vitamin D level in blood (excluding summer months of recruitment), bone age, GHlevel before and after stimulation tests (clonidine, insulin), and IGF-1 level.The results of the study were statistically analyzed in Excel.Results. All groups of subjects had growth retardation ranging from minus 2.19±0.49 tominus 2.83±0.12 SDS. In children with biologically inactive growth hormone syndromeand idiopathic shortish stature (ISS), bone age retardation was within 1.84 years.In patients with intrauterine development delay (IDD), the bone age was practically thesame as the passport age, and children with growth hormone delete (GHD) had a delayin bone age of 2.44 years.The basal level of GH was low in all patients, but the lowest level was observed in childrenwith GHD and the highest in patients with syndrome of biologically inactive growthhormone (BIGHS). During the stimulation tests with clofelin and insulin, the maximumrelease of GH in the blood of the subjects was obtained. At the same time, in children withGHD it was low, indicating this pathology, in all other groups the level of GH increasedto normal values (more than 10 ng/ml). Conclusions. Basal GH levels were the lowest in children with GHD and the highest in patientswith BIGHS. The lowest IGF-1 levels were observed in children with IDD. The majority(60.87 %) of children with BIGHS were vitamin D deficient. Vitamin D deficiency was found inpatients with IDD: vit. D insufficiency in 52.94 % and vit. D deficiency in 47.06 %. The largestgroup of children with ISS and GHD had vit. D deficiency (48.57 % and 47.22 %, respectively).

Growth hormone increase by luteinizing hormone-releasing hormone reflects gonadotroph-related characteristics in acromegaly

PurposeWe previously showed the clinical characteristics of acromegaly with a paradoxical growth hormone (GH) response to oral glucose or thyrotropin-releasing hormone. However, the clinical characteristics of acromegaly with an increased GH response to luteinizing hormone-releasing hormone (LHRH responders) remain unclear. The aim of the present study was to evaluate the clinical characteristics, especially gonadotroph-related characteristics of LHRH responders in acromegaly.MethodsThe clinical characteristics of 33 LHRH responders and 81 LHRH nonresponders were compared.ResultsNo differences in age, sex or basal serum levels of GH, insulin-like growth factor-1 (IGF-1), and gonadotropin were observed between the two groups. Steroidogenic factor 1 (SF-1), gonadotropin-releasing hormone receptor (GnRHR), and LH expression was more frequently observed in LHRH responders (P < 0.05). In addition, a greater increased rate of GH after LHRH loading, and the proportion of GnRHR and gonadotropin expression was observed in pituitary tumor with SF-1 expression than that without the expression (P < 0.01). LHRH responders showed a greater GH decrease in the octreotide test and a greater IGF-1 decrease after first-generation somatostatin ligand than LHRH nonresponders (P < 0.05). Furthermore, the proportion of hypointense pituitary tumors on T2-weighted magnetic resonance imaging and tumors with densely granulated type was higher in LHRH responders than in LHRH nonresponders, respectively (P < 0.05). No difference between the two groups was observed in either somatostatin receptor 2 or 5 expression.ConclusionsThe increased GH response to LHRH is associated with the gonadotroph-related characteristics. This response may reflect the biological characteristics of somatotroph tumors.

The Preoperative Paradoxical GH Response to Oral Glucose Load Predicts a low Risk of Recurrence in Acromegaly.

a paradoxical growth hormone (GH) response to oral glucose load (OGTT) in acromegaly is associated with a milder phenotype. To study whether the GH response to OGTT predicts the risk of recurrence after initial surgical cure. Retrospective, observational study. Two tertiary care centers. We investigated 254 patients with acromegaly who were cured by surgery. All patients underwent OGTT at diagnosis before pituitary surgery. A peak-to-basal GH ratio ≥ 120% within 90 minutes was used to distinguish paradoxical (GH-Par) from non-paradoxical acromegalic patients (GH-NPar). Cox analysis was used to investigate whether the paradoxical GH response to OGTT was associated with the risk of disease recurrence. A paradoxical GH response to OGTT occurred in 87 patients (34.3%, termed GH-Par group). Recurrence of acromegaly occurred in three patients of the GH-Par group (3.4%) and in 20 patients in the GH-NPar group (12.0%). In the multivariate analysis, the paradoxical GH response to OGTT was significantly associated with the risk of recurrence (HR 0.18, 95% CI, 0.05-0.63; P = 0.007). Basal GH level at diagnosis was the only other variable associated with the risk of disease recurrence (HR 1.58, 95% CI, 1.01-2.47; P = 0.04). our study demonstrates that a paradoxical GH response to OGTT in the preoperative setting predicts a lower risk of disease recurrence after initial surgical cure. The pattern of GH responsiveness to OGTT is, therefore, useful to predict the long-term outcome of patients with acromegaly.

Ідіопатична низькорослість: особливості поліморфізму Taql гена VDR рецептора вітаміну D

The causes of idiopathic short stature (IS) are diverse and not well understood, including polymorphisms of the vitamin D receptor (VDR) gene, dysfunction of growth hormone (GH) secretion, or certain structural abnormalities of the GH cannot be denied. The Taql polymorphism is located at the exon-intron junction and can potentially affect the stability of the VDR gene mRNA and, consequently, the child's height. Purpose - to study of the influence of the Taql polymorphism of the VDR gene in children with IS on certain indicators of bone metabolism. Materials and methods. We studied 22 children aged 10.68±3.28 years diagnosed with idiopathic short stature. The following data were taken into account: sex and age of the patient, anthropometric data, blood vitamin D level, bone age, basal and after stimulation tests, and Taql polymorphism of the VDR gene. All data were analyzed by non-parametric methods of variational statistics using the computer program MedCals (2006). Results. All children with IS had low vitamin D levels, regardless of the Taql polymorphic locus of the vitamin D receptor gene. All children with IS, regardless of the Taql polymorphic locus of the vitamin D receptor gene, were found to have low vitamin D levels. The basal level of GH in all patients was low, while the stimulated level of GH was normal in all patients. Conclusions. In the group of patients with IS, the frequency of the T/C (TaqI T/C, g.65058 T&gt;C) genotype is 1.63 times higher than in the group of healthy subjects. Carriage of allele C of the polymorphic locus rs731236 Tagl of the VDR gene is significantly associated with the risk of developing idiopathic short stature - OR (Odds ratio) =1.68 (95% CI (confidence interval): 1.41-2.01; p&lt;0.001), and in the presence of the T/C genotype the risk of this pathology is significantly high - OR=3.78 (95% CI: 1.23-11.63; p&lt;0.02). Vitamin D deficiency was found in children with the T/T polymorphism, and vitamin D deficiency was found in patients with the T/C and C/C polymorphisms. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Endocrine Outcomes and Associated Predictive Factors for Somatotrophin Pituitary Adenoma after Endoscopic Endonasal Transsphenoidal Surgery: 10 Years of Experience in a Single Institute.

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level ( p = 0.166), basal GH level ( p = 0.001), and nadir GH level ( p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891-0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

Laron syndrome in South Indian children – A descriptive study

Objectives: The objectives of this study were to describe the clinical and biochemical features of five children with Laron syndrome (LS) from South India. Material and Methods: This is a prospective descriptive case series of five children with clinical and biochemical features of LS managed over 5 years. Results: Five children (two girls and three boys) with LS with the mean age group of 5.9 ± 1.7 years and the mean age at diagnosis of 2.7 ± 0.8 years are described. All children were born out of consanguinity and all had typical phenotypic facies of LS. The mean Z-scores of height, weight, and body mass index on follow-up for the cohort were −7.0 ± 1.6, −5.9 ± 2.8, and −0.1 ± 0.7, respectively, and they were within ± 2 SD of the mean for children in LS chart. The median basal growth hormone level for age was 13 ng/mL and the median growth hormone levels at 30 min, 60 min, 90 min, and 120 min post-stimulation test were 35 ng/mL, 35 ng/mL, 44 ng/mL, and 50 ng/mL, respectively. All of them had insulin-like growth factor-1 (IGF-1) levels less than the 3rd percentile and no increment during the IGF-1 generation test. The prevalence of micropenis was 100% and one child had symptomatic hypoglycemic episodes. Genetic analysis was performed in two boys and both harbored variants in the growth hormone receptor gene. Conclusion: LS should be suspected in children with clinical features of growth hormone deficiency along with elevated growth hormone levels and low IGF-1 levels with no increment of IGF-1 in the IGF-1 generation test.

GENETIC FEATURES OF CHILDREN WITH IDIOPATHIC SHORT STATURE.

The aim: To investigate the clinical and genetic characteristics of children with idiopathic short stature, taking into account the polymorphism of the vitamin D receptor (VDR) BsmI gene. Materials and methods: Eighteen children diagnosed with of idiopathic short stature who were treated at the State Institution «V.P. Komisarenko Institute of Endocrinology and Metabolism of the National Academy of Medical Sciences of Ukraine» were examined. The following values were taken into account: the patient's sex and age, anthropometric data, vitamin D level in the blood (excluding summer months of patient recruitment), bone age, basal growth hormone (GH) level and its level after stimulation tests (clonidine, insulin), IGF-1 levels, blood levels of total and ionized calcium and VDR gene polymorphism. Results: The A allele carriers of the polymorphic locus BsmI (rs1544410) of the VDR gene are significantly associated with the risk of developing idiopathic short stature OR = 4.47 (95% CI 2.11-9.48; p <0.05). The risk of idiopathic short stature is significantly higher OR = 9.33 (95% CI 3.09-28.16; p <0.05) in children with the presence of the G/A genotype. Vitamin D deficiency (43.83 ± 6.47 nmol/l) was found in children with the BsmI polymorphic variant G/G VDR, and vitamin D insufficiency was found in children with BsmI polymorphic variants G/A and A/A VDR (58.14 ± 20.05 and 51.58 ± 22.84 nmol/l, respectively). Conclusions: The data obtained regarding the polymorphic locus BsmI (rs1544410) of the of VDR gene cannot exclude it's the involvement in the pathogenesis of idiopathic short stature.

Short-term and long-term remission after endoscopic transnasal adenomectomy in patients with acromegaly

Neurosurgery is the most effective treatment for acromegaly. As most of the patients present with macroadenomas, surgical treatment is not always successful, even with the expert level of a neurosurgeon. Assessment of the postoperative remission rates in acromegaly preoperative predictors of treatment efficacy is an urgent task of modern research. To assess the short-term and long-term remission of acromegaly after endoscopic transnasal adenomectomy in a tertiary medical center and assess preoperative predictors of the treatment effectiveness. A single-center, prospective, uncontrolled study was conducted. We included patients with active acromegaly who did not receive medical therapy with somatostatin analogues and were referred for endoscopic transsphenoidal adenomectomy. Plasma miRNA expression was assessed by quantitative reverse transcription PCR. Postoperative samples of adenomas were sent for study, with the determination of the immunohistochemical staining for somatostatin receptors 2 and 5 subtypes and morphology was performed on postoperative adenoma samples. The study included 44 patients: 32.8% men, median age 47.0 [34.0; 55.0], IGF-1 744.75 ng/ml [548.83;889.85], growth hormone 9.5 ng/ml [4.94; 17.07]. Tumor volume 832 mm3 [419.25; 2532.38]. Early postoperative remission was achieved in 35 patients (79.5%). Patients who achieved short-term remission had higher IGF-1 and basal growth hormone levels. Median follow-up was 19.0 months [12.5;29.0]. Long-term remission was achieved in 61.4% (27 patients), no remission in 9 (20.5%), recurrency in 2 patients (4.5%), 6 patients were to follow-up (13.6%). In patients with long-term remission, we observed lower growth hormone and IGF-1 levels. No differences in miRNA expression was observesd. The predictive value of basal GH before surgery for long-term remission was assessed: area under the curve 0.811 (95% CI: 0.649; 0.973). A cut-off value of 15.55 ng/mL corresponded to a sensitivity of 70.0% (34.8%; 93.3%), a specificity of 85.7% (67.3%; 96.0%), an accuracy of 81.6% (65 .7%; 92.3%), PPV 63.6% (39.3%; 82.5%), NPV 88.9% (75.4%; 95.4%). Rates of short-term and long-term remission after endoscopic transsphenoidal adenomectomy in our cohort is 79,5% и 61,4%, respectively, and is comparable with literature data for expert pituitary centers. Preoperative GH shows potential value in predicting the long-term remission of acromegaly, but further studies in a larger sample are needed to obtain more accurate cut-off values.

Frequency of hyperostosis frontalis interna in patients with active acromegaly: is there a possible role of GH excess or hyperprolactinemia in its etiopathogenesis?

Acromegaly is characterized by bone changes due to excessive growth hormone (GH) secretion. Hyperostosis frontalis interna (HFI) is described as an overgrowth in the inner plate of the frontal bone. An increased incidence of HFI has been reported in patients with acromegaly. Since the etiology of HFI is poorly understood, we have analyzed whether there is a relationship between the hormonal and metabolic status of patients with acromegaly (with or without hyperprolactinemia) and the pathogenesis of HFI. Forty-five patients with acromegaly and two control groups consisting of 25 patients with prolactinoma (group 1) and 47 healthy subjects (group 2) were included in this retrospective study. Baseline hormonal data and cranial imaging were obtained from medical records and analyzed. Mean frontal bone thickness was 6.75mm in acromegaly, 4.85mm in group 1, and 5.1mm in group 2 of controls (p < 0.001). The frequency of HFI was higher in acromegalic patients than in the controls (22%, 0%, and 2.2%, respectively). There was no difference between the HFI positive and negative acromegalic patients in basal GH, IGF-1, and PRL levels, IGF-1 index, diagnosis lag time, and insulin resistance. There was no difference between groups regarding parietal and occipital bone thickness. Although the frequency of HFI is 22% in patients with acromegaly, neither excess GH nor hyperprolactinemia plays a role in its etiopathogenesis. Various genetic or epigenetic factors may contribute to its etiology.

Sex and age differences among patients with acromegaly.

Acromegaly is a chronic, slowly progressive disorder caused mostly by growth hormone (GH)-producing pituitary neuroendocrine tumors (PitNETs). Recently, the associations between sex and age at the time of diagnosis and the course of acromegaly have been a focus of debate. The aim of our study was to evaluate the association between sex and age at the time of diagnosis of acromegaly and the clinical features, biochemical status, severity of the disease, and comorbidities. This was a single‑center study conducted in a group of consecutive patients with acromegaly and no family history of PitNETs. The participants were divded into 2 subgroups according to sex (male, female) and 3 subgroups according to age at the time of diagnosis: i) younger (≤40 years), ii) middle‑aged (41-59 years), and iii) elderly patients (≥60 years). Our study included 101 patients (41 men, 60 women) who met the eligibility criteria. The mean (SD) age at the time of diagnosis was 47.3 (14.1) years and the median diagnostic delay was 5 years (interquartile range, 3-10). Age at the time of diagnosis and diagnostic delay were not statistically different in men and women. Levels of insulin‑like growth factor 1 (IGF‑1) above the upper limit of age‑adjusted normal range (%ULN IGF‑1) were greater in men than in women (mean [SD], 174.8% [98.9%] vs 109.4% [66.6%]; P = 0.002), while there was no significant difference in terms of %ULN IGF‑1 between the age groups. Median basal and nadir GH levels did not differ between the sexes. Men presented with hypogonadism more frequently than women (54% vs 26%; P = 0.005). Hyperprolactinemia, hypogonadism, and macroadenoma were more frequently observed in the younger patients than in the middle‑aged and elderly individuals (all P <0.05). According to our results, hypogonadism and greater IGF‑1 values were more frequently observed in men with acromegaly. Hyperprolactinemia, hypogonadism, and macroadenoma were more frequent in patients with acromegaly aged 40 years or younger.

Impact of chronic variable stress on neuroendocrine hypothalamus and pituitary in male and female C57BL/6J mice.

Chronic stress exerts multiple negative effects on the physiology and health of an individual. In the present study, we examined hypothalamic, pituitary and endocrine responses to 14days of chronic variable stress (CVS) in male and female C57BL/6J mice. In both sexes, CVS induced a significant decrease in body weight and enhanced the acute corticosterone stress response, which was accompanied by a reduction in thymus weight only in females. However, single-point blood measurements of basal prolactin, thyroid-stimulating hormone, luteinising hormone, growth hormone and corticosterone levels taken at the end of the CVS were not different from those of controls. Similarly, pituitary mRNA expression of Fshb, Lhb, Prl and Gh was unchanged by CVS, although Pomc and Tsh were significantly elevated. Within the adrenal medulla, mRNA for Th, Vip and Gal were elevated following CVS. Avp transcript levels within the paraventricular nucleus of the hypothalamus were increased by CVS; however, levels of Gnrh1, Crh, Oxt, Sst, Trh, Ghrh, Th and Kiss1 remained unchanged. Oestrous cycles were lengthened slightly by CVS and ovarian histology revealed a reduction in the number of preovulatory follicles and corpora lutea. Taken together, these observations indicate that 14days of CVS induces an up-regulation of the neuroendocrine stress axis and creates a mild disruption of female reproductive function. However, the lack of changes in other neuroendocrine axes controlling anterior and posterior pituitary secretion suggest that most neuroendocrine axes are relatively resilient to CVS.

Associations of GNAS Mutations with Surgical Outcomes in Patients with Growth Hormone-Secreting Pituitary Adenoma.

BackgroundThe guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics.MethodsWe studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor.ResultsGNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively).ConclusionGNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

The Prevalence of Cancer and Its Relation to Disease Activity in Patients With Acromegaly: Two Centers' Experience

ObjectiveAcromegaly is characterized by increased serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Although animal studies have demonstrated a relationship between these hormones and cancer risk, the results of human studies evaluating cancer prevalence in acromegaly are inconsistent. We aimed to investigate the prevalence of malignant neoplasms in patients with acromegaly. MethodsCancer risk was evaluated in a cohort of 280 patients (male/female: 120/160; mean age: 50.93 ± 12.07 years) with acromegaly. Patients were categorized into 2 groups according to the presence or absence of cancer. Standard incidence ratios were calculated as compared to the general population. ResultsFrom 280 patients, cancer was diagnosed in 19 (6.8%) patients; 9 (47%) of them had thyroid cancer, which was the most common cancer type. Standard incidence ratios of all cancers were 0.8 (95% CI, 0.5-1.1) and 1.0 (95% CI, 0.8-1.3) in men and women, respectively. Compared to patients without cancer, the current age was higher in patients with cancer (59 [49-65] to 51 [42-59], P = .027). In contrast, the age at diagnosis was similar in both groups. Not only was the time to diagnosis and disease duration similar in both groups but also the basal and current GH and IGF-1 levels. The prevalence of active disease was also similar between the groups (32% to 23%, P = .394). ConclusionOur findings were not consistent with the studies suggesting that patients with acromegaly encounter an increased cancer risk. Furthermore, there were similar basal and current GH and IGF-1 levels in patients with acromegaly, both with and without cancer.

Early postoperative measurement of growth hormone level for prognosis of surgical outcomes in acromegaly

To investigate the value of 24 hours post-surgery measurement of growth hormone (GH) level for prognosis of surgical outcomes in acromegaly. A prospective cohort study included 45 patients with newly diagnosed acromegaly. The degree of parasellar extension was measured on the preoperative sellar magnetic resonance imaging according to the Knosps classification. All patients underwent a transsphenoid adenomectomy performed by one neurosurgeon. Basal GH level was measured at 24 hours after surgery. The efficacy of transsphenoidal adenomectomy evaluated at 12 months after surgery. Acromegaly remission was achieved in 19 (42%) of 45 patients at 12 months after surgery. Pituitary microadenomas and the absence of paracellular invasion, corresponding to Knosp Grade 02, had low prognostic value for long-term remission due to low sensitivity (31.6%) and low specificity (38.5%), respectively. The highest prognostic value for acromegaly remission was showed for 24 hours post-surgery GH level with cut-off 1.30 ng/ml with sensitivity of 96.2% (95% confidence interval 81.199.8%) and specificity of 84.2% (95% confidence interval 62.494.4%). The study demonstrated the possibility of using GH level at 24 after surgery as a predictor for acromegaly remission. GH level 1.30 ng/ml at 24 hours after surgery showed better predictive value for long-term remission compared with the presence of microadenomas and Knosp Grade 02. The absence of decrease of GH level on the first day after surgery may serve as a reason for more close monitoring of patients in the postoperative period. Further studies in a larger number of observers are required to confirm our findings.

Early basal growth hormone level and nadir growth hormone level in oral glucose tolerance test as predictors for surgical cure in acromegaly

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

Pretreatment serum GH levels and cardio-metabolic comorbidities in acromegaly; analysis of data from Iran Pituitary Tumor Registry.

Acromegaly is a rare chronic disabling disorder, in which growth hormone (GH) excess is associated with a range of clinical features and systemic complications. The present study aims to evaluate the association between pretreatment basal GH levels as well as GH levels after oral glucose tolerance test (OGTT) and cardio-metabolic comorbidities, including diabetes mellitus (DM), left ventricular hypertrophy (LVH) and hypertension (HTN) in patients with active acromegaly. A retrospective study of the medical records regarding 113 patients with acromegaly registered at two main centers of Iran Pituitary Tumor Registry during 2011-2018. The mean age of the patients was 42.76 ± 11.6 (range: 21-72) years. Mean GH level at baseline was 21 ng/ml while nadir GH levels at 60 and 120 min after glucose were 6.95 and 9.05 ng/ml, respectively. There was a negative correlation between age and basal serum GH level (r= -0.196, p = 0.038). Hypertension and diabetes mellitus were detected in 26.8% and 19.7% of the patients. A positive correlation was detected between serum GH values and systolic blood pressure. There was not any significant difference in basal GH and GH post OGTT regarding DM, Diastolic blood pressure and LVH. Our findings suggest that pretreatment basal GH levels are higher in younger patients with acromegaly. Furthermore, higher GH values (0, 60 and 120 min) during OGTT are associated with higher systolic blood pressure. A comprehensive evaluation of this population regarding comorbidities should be performed.

Pretreatment with somatostatin analogs does not affect the anesthesiologic management of patients with acromegaly.

Acromegaly may be associated with an increased risk of complex intraoperative management and anesthetic complications. No study addressed whether pretreatment with somatostatin receptor ligands (SRLs) affects anesthesiologic management. We studied 211 consecutive acromegalic patients who had a recorded intraoperative computerized anesthetic record (ICAR) available for analysis. Ninety-six (45.5%) patients were SRL-pretreated while 115 patients were treatment naïve. Treatment with SRLs reduced mean basal growth hormone level from 23.8 ± 4.2 to 5.9 ± 1.3µg/L. Normalization of insulin-like growth factor-1 was achieved in 26 patients (27.1%). The frequency of comorbidities at surgery was similar in the two groups. Five patients with difficult intubation were naïve (4.3%) as compared with 5 SRL-pretreated patients (5.2%; P = 1.0). ICAR registration did not show any significant change of intraoperative vital parameters in the two groups of patients as well as in the intraoperative utilization of drugs. Total duration of anesthesia and surgery were similar in the two groups. Four patients with an intraoperative adverse event were naïve (3.5%) as compared with 4 SRL-pretreated patients (4.2%; P = 1.00). Remission of disease occurred in 83 of 114 naïve patients (72.8%) and in 57 of 93 SRL-pretreated patients (61.3%; P = 0.11). SRL-pretreatment of patients with acromegaly had no significant impact on intraoperative anesthesiologic management. Despite a better Cormack-Lehane score in SRL-pretreated than in naïve patients, the rate of difficult intubation was similar in both groups. SRL-pretreatment did not affect the rate of surgical remission or complications as well.

Hormonal response to a non-exercise stress test in athletes with overtraining syndrome: results from the Endocrine and metabolic Responses on Overtraining Syndrome (EROS) — EROS-STRESS

ObjectivesOvertraining syndrome (OTS) leads to worsened sports performance and fatigue. The pathophysiology of OTS has not been entirely elucidated, and there is a lack of accurate markers for its diagnosis. Changes in hormonal responses implicated in OTS were stimulated by exercise, which has limited their interpretation. Hence, we aimed to evaluate growth hormone (GH) and prolactin responses to a gold-standard and exercise-independent stimulation test, the insulin tolerance test (ITT). DesignVolunteers were recruited and divided into OTS-affected athletes (OTS), healthy athletes (ATL), and healthy non-active subjects (NCS) groups, after general and specific inclusion and exclusion criteria. MethodsWe evaluated the responses of growth hormone (GH) and prolactin to the ITT, and compared between groups. ResultsA total of 51 subjects were included (OTS, n=14, ATL, n=25, and NCS, n=12). OTS disclosed significantly lower basal levels of GH (p=0.003) and prolactin (p=0.048), and GH (p=0.001) and prolactin (p<0.001) responses to ITT (p=0.001), compared to ATL, but similar to NCS. OTS showed a later rise in GH levels in response to hypoglycemia, compared to ATL, but not to NCS. We suggest cutoffs for GH and prolactin levels to aid in the diagnosis of OTS. ConclusionsOTS-affected athletes show reduced GH and prolactin basal levels and responses to a non-exercise stress test compared to healthy athletes, but not to sedentary subjects.

The effect of short-term hypothyroidism on growth hormone secretory responses to growth hormone-releasing hormone (1-29) and insulin-induced hypoglycemia

Introduction: Hypothyroidism is frequently associated with growth failure. In long-standing hypothyroidism the growth hormone (GH) secretory responses to growth hormone-releasing hormone (GRH) and insulin-induced hypoglycemia are decreased. Methods: To investigate whether hypothyroidism of short duration affects pituitary GH release, we measured the serum GH response to synthetic GRH (1-29), 1g/kg body weight, given IV to six athyreotic patients during thyroxine (T4) treatment and one month after stopping T4 (short-term hypothyroid state). This served as a direct measure of pituitary somatotroph function .We also assessed the serum GH response to insulin-induced hypoglycemia in three patients as an indirect assessment of hypothalamic function. Results: We found that basal GH levels remained the same both during (euthyroid state) and after stopping T4 therapy (hypothyroid state). Peak serum GH response to GRH was significantly greater in patients while they were hypothyroid than during T4 therapy when they were euthyroid (p

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.