Serum GH Research Articles

OSAHS Growth Impairment and Resolution after Adenotonsillectomy in Children.

Introduction:One of the most important complications of OSAHS in children is growth delay. The aim of this study was to investigate changes in clinical body growth, and laboratory growth in children with OSAHS after adeno-tonsillar surgery.Materials and Methods:In our study, among 102 children suffering from sleep-disordered breathing, 70 met the inclusion criteria because they were affected by OSAHS and adenotonsillar hypertrophy. In total, 96 children affected by adeno-tonsillar hypertrophy (55 males and 41 females) underwent nocturnal cardiorespiratory monitoring with Embletta MPR, monitoring for post-operative 24 hours. Patients underwent blood sampling to evaluate preoperative GH and IGF-1 serum levels, “placement” in Cacciari’s growth charts and adenotonsillectomy and saturation monitoring for post-operative 24 hours. According to auxological parameters, 82.86% of the patients were below the fiftieth percentile of BMI Cacciari’s growth charts and IGF-1 preoperative serum levels were below the normal range. All patients underwent adenotonsillectomy. Results:All 70 patients recovered from OSAHS according to the results of nocturnal cardiorespiratory monitoring after six months. IGF-1 serum levels significantly increased after three months and one year after. All the auxological parameters showed a significant increase after surgery. We calculated the average annual growth in height of the patients before and after adenotonsillectomy (AT): the growth rate was impaired by OSAHS (5.4±1.3 cm/year), while in the following year post-surgery we found a significant growth speed acceleration (9.9±1.7 cm/year, P=0.001). Conclusions:In conclusion, growth delay in children can be caused by OSAHS, and when it is due to adenotonsillar hypertrophy, adenotonsillectomy is to be considered as the therapy of choice.

Effects of Different Anesthetic and Analgesic Methods on Cellular Immune Function and Stress Hormone Levels in Patients Undergoing Esophageal Cancer Surgery.

The change of perioperative immune function in patients with esophageal cancer is mainly caused by the joint action of surgical trauma and anesthesia. In our study, we aimed to investigate the effects of different anesthetic methods on the changes of T lymphocyte subsets and cytokines in peripheral blood of patients with esophageal cancer surgery. 50 patients with esophageal cancer were divided into the study group and the control group. Among them, the patients in the control group chose intravenous anesthesia and received self-controlled intravenous analgesia after surgery. Patients in the study group chose thoracic epidural anesthesia combined with general anesthesia, undergoing self-controlled epidural analgesia after surgery; serum interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) were measured by ELISA. Serum stress hormones GH and sIL-8 were measured by radioimmunoassay. Both groups of patients achieved significant postoperative analgesia, but the VAS score in the study group at the T2–T4 time point was lower than that in the control group. The serum GH concentration in the study group increased at T1 and reached its highest peak at T2, then decreased. The serum IL-8 concentration of the two groups showed a downward trend from T1 to T4. Thoracic epidural anesthesia combined with general anesthesia for postoperative epidural analgesia can relieve the degree of cellular immunosuppression during and after surgery. Moreover, the thoracic epidural block combined with general anesthesia for esophageal cancer surgery and epidural analgesia after surgery for patients are anesthetic and analgesic methods with clinically significant effects. Our research results have a positive effect on the promotion of postoperative rehabilitation in patients with malignant cell tumors.

Diagnosis of Chromosome 15q-Terminal Deletion Syndrome through Elevated Fasting Serum Growth Hormone Levels

Chromosome 15q26-qter deletion syndrome is a rare disease that causes prenatal and postnatal growth retardation, microcephaly, developmental delay, and congenital heart diseases, mainly due to haploinsufficiency of IGF1R. In addition, patients with pathogenic variants of the IGF1R show similar symptoms. We report the case of a 5-month-old girl with prenatal and postnatal growth retardation, microcephaly, and congenital heart disease. At 5 months of age, her length was 54.7 cm (−4.3 SD), her weight was 4.4 kg (−3.1 SD), and her head circumference was 37.4 cm (−2.8 SD), thus presenting severe growth retardation. Repeated pre-feeding serum GH levels were abnormally high (26.1–85.5 ng/mL), and IGF-1 levels (+0.16 to +1.2 SD) were relatively high. The 15q sub-telomere fluorescence in situ hybridization analysis revealed a heterozygous deletion in the 15q terminal region. Whole-genome single nucleotide polymorphism microarray analysis showed a terminal deletion of 6.4 Mb on 15q26.2q26.3. This is the first report showing that fasting GH levels are high in early infancy in patients with IGF1R abnormalities. In addition to relatively high IGF-1 levels, elevated fasting GH levels in early infancy may contribute to the diagnosis of IGF1R abnormalities.

Effects of high-dose all-trans retinoic acid on longitudinal bone growth of young rats

ObjectiveThe signaling axis consisting of GH-IGF1-IGFBP3 is the primary signal taht acts prepubertally to influence height development. Growth plate thinning and even premature closure have been reported in children with tumors treated with retinoid chemotherapy, resulting in long bone dysplasia. Growth failure may occur despite received GH treatment, but the reason is unknown. This study investigate the effect of high-dose all-trans retinoic acid (ATRA) on the development of long bones in growing SD rats. MethodsA total of 20 three-week-old male SD rats were randomly divided into a control group and an experimental group (n = 10). Rats were treated by gavage with or without high-dose ATRA for 10 days. The body weights of the rats were recorded daily. At the end of the experiment, we measured the length of nose-tail and tibia, stained the tibia and liver for pathological tissue and RT-PCR reaction, and measured the levels of serum GH, IGF1 and IGFBP3, and so on. ResultsCompared with controls, experimental rats exhibited reduced body weight and shortened nasal-tail and radial tibial length. Cyp26b1 enzyme activity in the liver was elevated, and histopathological staining revealed that the cartilaginous epiphyseal plate was narrowed, the medullary cavity of trabecular bone was sparse, the number of trabecular bones was decreased, trabecular separation was increased, bone marrow mineralization was enhanced, osteoclastic activity was increased, and circulating GH-IGF1-IGFBP3 levels were decreased. However, RT-PCR reaction results of localized proximal tibiae showed upregulation of IGF1 and downregulation of IGFBP3. ConclusionsHigh-dose ATRA intake over a short period of time can reduce GH-IGF1-IGFBP3 levels, affect cartilage and bone homeostasis, and inhibit bone growth in developing animals.

A Case of Persistent Hypoglycemia with Disorder of Sex Development

A Case of Persistent Hypoglycemia with Disorder of Sex Development

Dental arches in inherited severe isolated growth hormone deficiency

ObjectivesThe growth of the dental arches depends on GH and insulin-like growth factor type 1 (IGF1), but the consequences of GH deficiency (GHD) on their growth are still unclear, probably due to the acquired etiology of GHD in most described series, often associated with additional pituitary deficits (thyrotrophic, corticotrophic and gonadotrophic hormones), and imperfections of related replacement therapies, which may affect the dental arch growth. To avoid these limitations, we took advantage of a unique cohort of subjects with isolated GH deficiency (IGHD) due the same mutation in the GH releasing hormone receptor gene, living with very low serum GH and low to undetectable circulating IGF1 levels. Our purpose was to analyze the dimensions of maxillary and mandibular dental arches. Methods22 adult IGHD (15 untreated and 7 previously partially treated with GH) and 33 controls were enrolled in a cross-sectional study using the Ortho Insight 3D and MeshMixer software, ResultsIn untreated IGHD subjects all maxillary arch measures were smaller than controls, while among mandibular arches, only the mandibular canine width and the mandibular arch length were reduced. In partially GH treated subjects only the palate depth, the maxillary canine width, the maxillary and mandibular arch lengths remained smaller than controls. ConclusionsIGHD reduces the growth of maxillary arch to a greater degree than the mandibular arch, suggesting different control of superior and inferior dental arches. GH treatment increases some of these measures.

Dietary excess supplementation of limiting amino acids promotes growth performance in broiler chickens through gh and IGF-I

The aim of this study was to determine the effects of dietary levels of methionine (Met) and lysine (Lys) on growth, carcass traits, breast meat quality, serum parameters and immunity of broiler chickens. A total of 540 one-day-old broiler chicks were distributed to 6 dietary treatments with 6 replicates of 15 birds in each in a 2x3 factorial approach which consisted of two Met and three Lys levels. The body weight gain (BWG) was increased with the main effect of high Met levels during pre-starter, starter and overall period. In Lys effect, BWG had a tendency to increase during the grower (P<0.09) and overall period (P<0.07). Spleen weight was higher (P<0.01) in high levels of Met, and high Met group has more spleen and thymus weight. Breast meat yield and spleen weight was found higher due to high Lys. Significantly higher pH and redness of breast meat was recorded for the sole effect of Lys levels. Serum glucose was found higher in high levels of Lys with no affect in Met added group. Serum GH and IGF-I levels were found higher (P<0.01) as the main effect of high Met levels as well as IGF-I concentration increased (P<0.01) in serum of chickens fed with the interaction of high density Met and Lys diets as compared to those fed with other diets. The current study suggest, that additional Met and Lys in diet of the current practices may improve body weight which may be due to the stimulation of GH and IGF-1growth factor.

Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases.

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

Discordant parameters of insulin-like growth factor 1 and growth hormone in the diagnosis and monitoring of acromegaly

Acromegaly is a rare endocrine disorder associated with multiple complications and increased mortality. Timely diagnosis and adequate treatment can bring the life expectancy of patients with acromegaly closer to the general population level. The tests for the diagnosis of acromegaly are measurement of both serum GH, and GH after oral glucose administration; serum insulin-like growth factor-1 (IGF-1). However, in clinical practice, up to 39% of patients with discordant results are found. The patients with discordant GH and IGF-1levels, are the most difficult to manage. This review discusses the prevalence of discordant GH and IGF-1 outcomes in patients with acromegaly; factors causing this discrepancy; the impact of hormone levels on treatment outcomes. Although endocrinologists are used to dealing with this discrepancy in clinical practice for many years, discordant patients'outcome remains uncertain and undefined The optimal treatment should be individually tailored for each patient, taking into account all clinical parameters.

“Subclinical atherosclerosis in acromegaly: Possible association with cardiovascular risk factors rather than disease activity”

ObjectiveCardiovascular (CV) disease is still a major cause of excessive morbidity and mortality in patients with active acromegaly, which may be attributed to a high prevalence of associated pro-atherosclerotic risk factors. However, a direct effect of GH/IGF-1 excess on the vasculature has been previously suggested, warranting further investigation. The present study was designed to investigate whether chronic GH/IGF-1 excess is associated with an increased prevalence of subclinical atherosclerosis in patients with acromegaly. DesignWe measured carotid intima-media thickness (cIMT) and assessed carotid plaques by ultrasonography along with classical CV risk factors in 54 acromegaly patients (34 females, 50 ± 12 years and compared those with 62 (42 females, 53 ± 13 years) age-, sex- and CV risk factors- matched controls. In order to compare cIMT measurements between patients and controls we analyzed common carotid artery far wall data as well as a combined measurement result, which consisted of the mean value of the six different measurements, three at each side. Resultsmean ± SD serum GH and IGF-1 levels were 2.76 ± 4.65 ng/mL and 1.7 ± 1.25 x ULN, respectively, in all acromegaly patients. Age, body mass index, blood pressure, lipid levels, fasting glucose and Framingham's global cardiovascular risk score classification were similar comparing patients and controls. Combined median [IQR] cIMT measurements were similar in acromegaly patients and matched controls (0.59 [0.52–0.66] mm vs. 0.59 [0.52–0.69] mm; P = 0.872) as well as in acromegaly patients with active and controlled disease (0.59 [0.51–0.68] mm vs. 0.60 [0.54–0.68] mm; P = 0.385). No significant correlations were observed between cIMT measurements and GH (Spearman r = 0.1, P = 0.49) or IGF-1 (Spearman r = 0.13, P = 0.37) levels in patients with acromegaly. Carotid atherosclerotic plaques prevalence was similar in patients and controls (26% vs. 32%; P = 0.54) as well as in patients with active and controlled acromegaly (22% vs. 30%; P = 0.537). ConclusionsOur data suggest that GH/IGF-1 excess itself is not one of the main drivers of subclinical morphological atherosclerosis changes in patients with acromegaly and that optimal control of acromegaly-associated CV risk factors may preserve vasculature structure even when strict biochemical control is not achieved.

Exercise training accelerates UPS- and mTOR-mediated protein turnover of grass carp Ctenopharyngodon idella

The present study is aimed to investigate the effects and mechanism of exercise training on the growth and protein turnover in grass carp Ctenopharyngodon idella. To this end, grass carp were respectively cultured at four water velocities (0 (control), 0.5, 1 and 1.5 body length s−1 (bl s−1)) for 10 weeks. The results showed that exercise training increased weight gain rate (WGR) and specific growth rate (SGR), and significantly decreased feed conversion ratio (FCR). The level of serum GH and the mRNA levels of GH/IGF-1 pathway-related genes (ghr and igf-1) of liver were significantly upregulated in C. idella after exercise training at 0.5 and 1 bl s−1. These indicated that at low and medium water velocities, exercise training was beneficial for fish growth. In addition, histochemical analysis of muscle showed that 0.5 bl s−1 exercise training significantly increased muscle fiber density of C. idella. The mRNA expression levels of UPS-related genes (ub, psmc1, psma2 and murf1) and mTOR-related genes (pi3k, mtor and s6k1) were significantly upregulated by 1 and 1.5 bl s−1 water velocity treatments. The levels of polyubiquitinated protein and 3-methylhistidine (3-MH) were significantly increased by the 1 bl s−1 exercise training treatment. These suggested that exercise training facilitated the protein turnover by motivating UPS and mTOR pathway. Taken together, our study demonstrated mechanism of exercise training increasing the growth rate and protein turnover in water velocity-dependent manner in C. idella, which will help to provide fundamental information for raceway-based and recirculating aquaculture system (RAS) aquaculture.

Promising Role of Growth Hormone-Boosting Peptide in Regulating the Expression of Muscle-Specific Genes and Related MicroRNAs in Broiler Chickens.

Simple SummaryIn chickens, breast muscle is a key contributor to meat yield. Skeletal muscle development is a complex process regulated by many genes, transcription factors, and miRNA through different muscle signaling pathways. The latter are activated by synthetic growth hormone-boosting peptides (GHBP) that mimic the effects of endogenous growth factors, mainly insulin-like growth factor-1 (IGF-1)/mammalian target of rapamycin (mTOR), and modulate myostatin gene expression. The molecular mechanisms underlying chicken breast muscle development in relation to GHBP are still unclear. In the current study, the role of GHBP in a chicken’s growth rate, skeletal muscle development-related genes and myomiRs, serum bio-chemical parameters, and myofiber characteristics post-hatching was evaluated. Using of GHBP at a level of 200 μg/kg positively regulated gene expression related to muscle growth and muscle-specific myomiRs. This was evidenced by upregulation of IGF-1, mTOR, myoD and myogenin genes, and miR-27b and miR-499 and downregulation of myostatin, Pax-3 and -7 genes and miR-1a, miR-133a, miR-133b, and miR-206 compared to the control group. Therefore, administration of GHBP at the level of 200 μg/kg to broiler chicks can accelerate their growth by enhancing skeletal muscle development via controlling the transcription of breast muscle-related genes and associated myomiRs.Appropriate skeletal muscle development in poultry is positively related to increasing its meat production. Synthetic peptides with growth hormone-boosting properties can intensify the effects of endogenous growth hormones. However, their effects on the mRNA and miRNA expression profiles that control muscle development post-hatching in broiler chicks is unclear. Thus, we evaluated the possible effects of synthetic growth hormone-boosting peptide (GHBP) inclusion on a chicken’s growth rate, skeletal muscle development-related genes and myomiRs, serum biochemical parameters, and myofiber characteristics. A total of 400 one-day-old broiler chicks were divided into four groups supplied with GHBP at the levels of 0, 100, 200 and 300 μg/kg for 7 days post-hatching. The results showed that the highest levels of serum IGF-1 and GH at d 20 and d 38 post-hatching were found in the 200 μg/kg GHBP group. Targeted gene expression analysis in skeletal muscle revealed that the GHBP effect was more prominent at d 20 post-hatching. The maximum muscle development in the 200 μg/kg GHBP group was fostered by the upregulation of IGF-1, mTOR, myoD, and myogenin and the downregulation of myostatin and the Pax-3 and -7 genes compared to the control group. In parallel, muscle-specific myomiR analysis described upregulation of miR-27b and miR-499 and down-regulation of miR-1a, miR-133a, miR-133b, and miR-206 in both the 200 and 300 μg/kg GHBP groups. This was reflected in the weight gain of birds, which was increased by 17.3 and 11.2% in the 200 and 300 μg/kg GHBP groups, respectively, when compared with the control group. Moreover, the maximum improvement in the feed conversion ratio was achieved in the 200 μg/kg GHBP group. The myogenic effects of GHBP were also confirmed via studying myofiber characteristics, wherein the largest myofiber sizes and areas were achieved in the 200 μg/kg GHBP group. Overall, our findings indicated that administration of 200 μg/kg GHBP for broiler chicks could accelerate their muscle development by positively regulating muscle-specific mRNA and myomiR expression and reinforcing myofiber growth.

A Comparative Evaluation of Efficacy of Mustadi Yapan Bastiand Baladi Yapan Basti in the Management of Oligozoospermia-Study Protocol

Background: Nowadays most upcoming disease that affecting 8 to 12% of the world population is Infertility.The affected area of this problem have no bar irrespective of metro cities as well as small towns population..Modern treatment with steroids and other medication and interventions shows limited results.Bastichikitsa itself is the best remedies explained in Ayurved text for the treatment of ksheenshukra.Yapan Basti in Ayurveda is known for its action as balya, i.e. giving strength to the sharirdhatu.Incase of Oligozoospermia there is vitiation and loss of formation process of shukradhatu properly as per Ayurveda. Using YapanBasti,the strength of Shukradhatu can be regain and ultimately correction can be seen in oligozoospermia cases. By doingbastikarma,we are trying to establish and confirm the role of yapanbastiexplained in Ayurvedonoligozoospermia.&#x0D; Aims and objectives: To study the efficacy of MustadiYapan Bastion sperm count sperm motility, semen volume.SemenPH,abnormal sperm count along with serum testosterone,GH and FSH level in the management of Oligozoospermia in comparison with BaladiYapanBasti.&#x0D; Methodology: Age ranging between 25 to 50 years will be considered for the study. Secondly Sperm count &lt; 15 million/ml will be consider for the study, also the patients who shows cardinal symptom i.ePratyatmakaLakshana of KshinaShukra, Pathological sample of Semen sample must suggestive of oligozoospermia will be considered for the study.30 Patients in each group will be given Basti for 16 days as explained in classics of Ayurveda .The process of giving basti will be using bastiputak,Basti will be prepared as per the niruhabasti preparation method.Bastigamankal and bastipratyagamankal will be observed properly.Follow-up will be taken after 28thday from starting of treatment.&#x0D; Results: Results will be drawn from the observations of objective parameters.&#x0D; Conclusion: MustadiYapanBasti will be effective in oligozoospermia.

Effects of Dietary Rapeseed Meal on Growth Performance, Carcass Traits, Serum Parameters, and Intestinal Development of Geese.

Simple SummaryThe poultry industry faces challenges such as a shortage of protein feed and increased feed cost. Compared to soybean meal, rapeseed meal (RSM) is a cheaper protein source that can be used in poultry diets. China is both the largest RSM and geese producer in the world. Therefore, the active use of RSM for geese diets can contribute to the development of poultry production. We found that geese had a good adaptation to the diet containing 16% dietary RSM through the investigation.The use of inexpensive nonconventional feed materials, such as rapeseed meal (RSM), could help alleviate the shortage of feed materials in the poultry industry. This study was to investigate the effects of dietary double-low RSM on growth performance, carcass traits, serum parameters, and intestinal development of geese. A total of 270 healthy 35-day-old male Jiangnan White geese were randomly divided into five treatments, with six replicate pens of nine geese each. The geese were fed five isonitrogenous and isocaloric diets containing 0%, 4%, 8%, 12%, and 16% RSM replacing dietary soybean meal for 35 days. At 35, 49, and 70 d, the BW and feed intake were recorded. All Samples were collected at 70 d of age. The results showed that dietary RSM up to 16% did not affect the BW, ADFI, ADG, and feed/gain ratio (F/G) during 35 to 49 d, 49 to 70 d, and 35 to 70 d periods (p > 0.05). At 70 d, no difference was observed in carcass yield or serum biochemical parameters among groups (p > 0.05). Dietary 12% and 16% RSM significantly increased the concentration of serum GH compared with 0%, 4%, 8% groups (p < 0.01), but serum TSH, T3 and T4 were unaffected (p > 0.05). The relative weights of heart, liver, spleen, proventriculus, gizzard, and small intestine were similar among groups (p > 0.05). However, the geese fed dietary 16% RSM had greater bursa of Fabricius than geese in the 8% group (p < 0.05). Intestinal morphology was unaffected by treatments (p > 0.05). According to the findings, dietary RSM up to 16% can be used in geese diets without impact on production performance.

Prevalence of growth hormone deficiency in patients with unexplained chronic fatigue after undergoing bone marrow transplantation in adulthood.

Many patients who undergo bone marrow transplantation (BMT) in adulthood experience unexplained chronic fatigue which can have a major impact on their health-related quality of life (QoL). Pre-BMT treatment regimens increase the risk of developing acquired growth hormone deficiency (GHD), which results in a clinical syndrome with decreased energy and has additionally been linked to metabolic syndrome. Using the gold-standard insulin hypoglycemic test (IHT), we evaluated the prevalence of GHD in 18 post-BMT adult patients with unexplained chronic fatigue, as well as the correlation between peak serum GH response and QoL scores, the metabolic syndrome, and insulin resistance. Peak serum GH cut-point less than 3.0 ug/L was used for the diagnosis of severe GHD. The Fatigue Severity Scale and Quality of Life in Adult GHD Assessment questionnaires were used to quantify fatigue symptoms. The prevalence of severe GHD within this sample of 18 patients was 50%. A trend between lower peak serum GH response and higher fatigue and QoL-AGHDA scores was observed. GHD may represent a remediable contributor to post-BMT chronic fatigue in adults, further studies are needed to evaluate the potential role of screening and GH replacement therapy in this vulnerable patient population. GHD may be a treatable explanation for disabling post-BMT fatigue pending results of intervention studies.

GHRH secretion from a pancreatic neuroendocrine tumor causing gigantism in a patient with MEN1.

SummaryA male patient with a germline mutation in MEN1 presented at the age of 18 with classical features of gigantism. Previously, he had undergone resection of an insulin-secreting pancreatic neuroendocrine tumour (pNET) at the age of 10 years and had subtotal parathyroidectomy due to primary hyperparathyroidism at the age of 15 years. He was found to have significantly elevated serum IGF-1, GH, GHRH and calcitonin levels. Pituitary MRI showed an overall bulky gland with a 3 mm hypoechoic area. Abdominal MRI showed a 27 mm mass in the head of the pancreas and a 6 mm lesion in the tail. Lanreotide-Autogel 120 mg/month reduced GHRH by 45% and IGF-1 by 20%. Following pancreaticoduodenectomy, four NETs were identified with positive GHRH and calcitonin staining and Ki-67 index of 2% in the largest lesion. The pancreas tail lesion was not removed. Post-operatively, GHRH and calcitonin levels were undetectable, IGF-1 levels normalised and GH suppressed normally on glucose challenge. Post-operative fasting glucose and HbA1c levels have remained normal at the last check-up. While adolescent-onset cases of GHRH-secreting pNETs have been described, to the best of our knowledge, this is the first reported case of ectopic GHRH in a paediatric setting leading to gigantism in a patient with MEN1. Our case highlights the importance of distinguishing between pituitary and ectopic causes of gigantism, especially in the setting of MEN1, where paediatric somatotroph adenomas causing gigantism are extremely rare.Learning pointsIt is important to diagnose gigantism and its underlying cause (pituitary vs ectopic) early in order to prevent further growth and avoid unnecessary pituitary surgery. The most common primary tumour sites in ectopic acromegaly include the lung (53%) and the pancreas (34%) (1): 76% of patients with a pNET secreting GHRH showed a MEN1 mutation (1).Plasma GHRH testing is readily available in international laboratories and can be a useful diagnostic tool in distinguishing between pituitary acromegaly mediated by GH and ectopic acromegaly mediated by GHRH. Positive GHRH immunostaining in the NET tissue confirms the diagnosis.Distinguishing between pituitary (somatotroph) hyperplasia secondary to ectopic GHRH and pituitary adenoma is difficult and requires specialist neuroradiology input and consideration, especially in the MEN1 setting. It is important to note that the vast majority of GHRH-secreting tumours (lung, pancreas, phaeochromocytoma) are expected to be visible on cross-sectional imaging (median diameter 55 mm) (1). Therefore, we suggest that a chest X-ray and an abdominal ultrasound checking the adrenal glands and the pancreas should be included in the routine work-up of newly diagnosed acromegaly patients.

Assessment of the Severity of Carpal Tunnel Syndrome in Patients With Acromegaly: A Focus on Clinical, Biochemical and Image Outcomes

This is a descriptive cross-sectional study designed to analyze the prevalence and severity of carpal tunnel syndrome (CTS) in addition to its association with clinical, biochemical, and imaging variables in a cohort of patients with acromegaly. Data collection was performed by entering them in our database and we subsequently analyzed in the SPSS system. Of the 71 patients registered with acromegaly, 68 met the inclusion criteria. Among the results, 97.8% presented CTS evidenced by electroconduction. Of these, 43 (63.1%) showed moderate involvement, followed by 17 severe cases (25%) and 6 mild cases (8.8%). The level of GH in serum, the years of delay in diagnosis, and the size of the adenoma were related to the presence and severity of CTS (p less than 0.05). The multivariate analysis showed that severe grade had a significant association with these variables compared with moderate and mild grade.

Pulse wave velocity is decreased in acromegaly compared to non-acromegaly study participants with similar cardiovascular risk profile

ObjectiveAcromegaly patients were reported to have an increased arterial stiffness that could contribute to the frequent cardiovascular complications in this population. The chronic excess of GH and IGF-1 may lead to arterial stiffening via different mechanisms, including hypertension, impaired glucose tolerance and dyslipidemia, however, it is not known whether the activation of GH/IGF-1 axis might influence arterial stiffening independently of cardiovascular risk factors. The objective of this prospective case-control study was to compare arterial stiffness assessed with pulse-wave velocity (PWV) in acromegaly versus non-acromegaly group with similar cardiovascular risk profile. DesignThis prospective case-control study included 27 patients with active acromegaly, who underwent the assessment of clinical, physiological, biochemical parameters and the evaluation of PWV with applanation tonometry. We used “The epidemiology of cardiovascular disease in different regions of the Russian Federation” study database (n = 522) to establish a non-acromegaly control group with similar cardiovascular risk profile (n = 54). Non-acromegaly control participants underwent the same assessment as acromegaly patients except for the measurement of serum GH and IGF-1 levels. We compared PWV in acromegaly patients to the general non-acromegaly cohort and its subset, matched with acromegaly patients for cardiovascular risk factors. We also investigated the associations of PWV with clinical, physiological and biochemical parameters in acromegaly and non-acromegaly group using correlation and regression analysis with adjustment for age and sex. ResultsAcromegaly patients had lower PWV (6.70 (5.75–7.65) m/s) compared to unmatched non-acromegaly control cohort (7.50 (6.70–8.57) m/s, p = 0.01) and to the non-acromegaly control group matched for cardiovascular risk factors (7.45 (6.73–8.60), p < 0.01). In non-acromegaly control group PWV was associated with BMI (ρ = 0.40, p < 0.01; β = 0.09, p < 0.01), obesity (r = 0.46, p < 0.01; β = 1.36, p < 0.01), systolic blood pressure (ρ = 0.60, p < 0.01; β = 0.05, p < 0.01), diastolic blood pressure (ρ = 0.62, p < 0.01; β = 0.07, p < 0.01), triglycerides (ρ = 0.55, p < 0.01; β = 0.58, p = 0.04), glucose (ρ = 0.54, p < 0.01; β = 0.70, p < 0.01) and diabetes (r = 0.40, p < 0.01; β = 1.10, p = 0.03), while in acromegaly group PWV was associated with IGF-1 expressed in mcg/ml (ρ = −0.49, p ≤0.01; β = −0.002, p ≤0.01) and in percentage of the upper limit of the normal (ρ = −0.47, p = 0.01; β = −0.005, p ≤0.01) as well as with diuretics treatment (β = −1.17, p = 0.03). ConclusionsPWV is decreased in acromegaly patients compared to non-acromegaly control participants with similar cardiovascular risk profile. Future studies need to explore the role of GH/IGF-1 axis in the regulation of arterial wall properties and the reliability of PWV as a prognostic marker of cardiovascular complications in acromegaly.

A CASE OF ACROMEGALY COMPLICATED BY PRIMARY ALDOSTERONISM DIAGNOSED DURING THE COURSE OF HEART FAILURE

Objective: [Case] A 32-year-old male was admitted to the Department of Cardiology of our hospital complaining of weight gain, exertional chest pain, dyspnea, and palpitation. He was pointed out hypertension at the age of 18 and started taking oral antihypertensive drugs at the age of 27. Although his high blood pressure was well-controlled with calcium channel blocker, angiotensin receptor blocker, and alpha-and beta-blocker, he had stopped taking medicines since the age of 30. He was diagnosed as congestive heart failure due to hypertensive heart disease and was transferred to our department for the further examination of suspected secondary hypertension after his heart failure was improved. Design and method: Aldosterone / renin activity ratio (ARR) was &gt;= 200, and primary aldosteronism (PA) was suspected. In consideration of his impaired cardiac function, a captopril challenge test and a rapid ACTH stimulation test were conducted. Since both were positive, the diagnosis of PA was made. Although computed tomography (CT) scans revealed a left adrenal adenoma, adrenal venous sampling showed overproductions of aldosterone from both adrenal glands, and thus he was treated with eplerenone, a mineral corticoid receptor blocker. Results: He was also suspected to have acromegaly because he had protruded chin, thickened lips, enlarged nose, and enlarged hands and feet. Brain magnetic resonance (MR) imaging detected a macroadenoma in the pituitary gland. Endocrinological examinations showed high concentrations of serum GH of 7.78 ng/ml and insulin-like growth factor 1 (IGF-1) of 824 ng/ml (+8.8SD), and 75 g oral glucose tolerance test (OGTT) showed a nadir of GH as 5.22 ng/ml, indicating a failure of suppression of GH. Acromegaly was diagnosed and transsphenoidal sinus pituitary surgery was done after monthly intramuscular injections of octreotide 20 mg four times. Conclusions: [Discussion] We experienced a case of acromegaly complicated by PA diagnosed during the course of heart failure. Both acromegaly and PA may be involved in the development of heart failure, however, the combination of acromegaly and PA is rare. We will discuss Its pathophysiology with a literature review.

Usefulness and Potential Pitfalls of Long-Acting Growth Hormone Analogs.

Daily recombinant human GH (rhGH) is currently approved for use in children and adults with GH deficiency (GHD) in many countries with relatively few side-effects. Nevertheless, daily injections can be painful and distressing for some patients, often resulting in non-adherence and reduction of treatment outcomes. This has prompted the development of numerous long-acting GH (LAGH) analogs that allow for decreased injection frequency, ranging from weekly, bi-weekly to monthly. These LAGH analogs are attractive as they may theoretically offer increased patient acceptance, tolerability, and therapeutic flexibility. Conversely, there may also be pitfalls to these LAGH analogs, including an unphysiological GH profile and differing molecular structures that pose potential clinical issues in terms of dose initiation, therapeutic monitoring, incidence and duration of side-effects, and long-term safety. Furthermore, fluctuations of peak and trough serum GH and IGF-I levels and variations in therapeutic efficacy may depend on the technology used to prolong GH action. Previous studies of some LAGH analogs have demonstrated non-inferiority compared to daily rhGH in terms of increased growth velocity and improved body composition in children and adults with GHD, respectively, with no significant unanticipated adverse events. Currently, two LAGH analogs are marketed in Asia, one recently approved in the United States, another previously approved but not marketed in Europe, and several others proceeding through various stages of clinical development. Nevertheless, several practical questions still remain, including possible differences in dose initiation between naïve and switch-over patients, methodology of dose adjustment/s, timing of measuring serum IGF-I levels, safety, durability of efficacy and cost-effectiveness. Long-term surveillance of safety and efficacy of LAGH analogs are needed to answer these important questions.