Low Growth Hormone Research Articles

Low growth hormone levels predict poor outcome of hepatitis B virus-related acute-on-chronic liver failure

Low growth hormone levels predict poor outcome of hepatitis B virus-related acute-on-chronic liver failure

Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly.

Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.

Ultradian Secretion of Growth Hormone in Mice: Linking Physiology With Changes in Synapse Parameters Using Super-Resolution Microscopy.

Neuroendocrine circuits are orchestrated by the pituitary gland in response to hypothalamic hormone-releasing and inhibiting factors to generate an ultradian and/or circadian rhythm of hormone secretion. However, mechanisms that govern this rhythmicity are not fully understood. It has been shown that synaptic transmission in the rodent hypothalamus undergoes cyclical changes in parallel with rhythmic hormone secretion and a growing body of evidence suggests that rapid rewiring of hypothalamic neurons may be the source of these changes. For decades, structural synaptic studies have been utilizing electron microscopy, which provides the resolution suitable for visualizing synapses. However, the small field of view, limited specificity and manual analysis susceptible to bias fuel the search for a more quantitative approach. Here, we apply the fluorescence super-resolution microscopy approach direct Stochastic Optical Reconstruction Microscopy (dSTORM) to quantify and structurally characterize excitatory and inhibitory synapses that contact growth hormone-releasing-hormone (GHRH) neurons during peak and trough values of growth hormone (GH) concentration in mice. This approach relies on a three-color immunofluorescence staining of GHRH and pre- and post-synaptic markers, and a quantitative analysis with a Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm. With this method we confirm our previous findings, using electron microscopy, of increased excitatory synaptic input to GHRH neurons during peak levels of GH. Additionally, we find a shift in synapse numbers during low GH levels, where more inhibitory synaptic inputs are detected. Lastly, we utilize dSTORM to study novel aspects of synaptic structure. We show that more excitatory (but not inhibitory) pre-synaptic clusters associate with excitatory post-synaptic clusters during peaks of GH secretion and that the numbers of post-synaptic clusters increase during high hormone levels. The results presented here provide an opportunity to highlight dSTORM as a valuable quantitative approach to study synaptic structure in the neuroendocrine circuit. Importantly, our analysis of GH circuitry sheds light on the potential mechanism that drives ultradian changes in synaptic transmission and possibly aids in GH pulse generation in mice.

MON-310 Factors Associated with Remission After Surgery for Acromegaly

Background: Acromegaly is a disorder characterized by excessive growth hormone (GH) secretion, which, in most cases, is caused by a GH secreting adenoma. Surgical removal of the tumor via a transsphenoidal approach is the first choice treatment for most patients. The remission rate after an initial resection is 80 to 90 percent for microadenomas and less than 50 percent for macroadenomas. Objective: To analyze predictive factors of remission in acromegaly patients who underwent transsphenoidal surgery for GH secreting adenoma. Methods: From January 2006 to October 2019, 75 patients with GH secreting pituitary adenoma were evaluated at our center. Patients who had undergone medical treatment or radiotherapy as first treatment were excluded. A total of 60 patients were included in the analysis. Remission was defined as normal serum insulin-like growth factor-1 (IGF-1) age and sex adjusted and a random serum GH less than 1 ng/mL and/or nadir GH during oral glucose tolerance test <0.4 ng/mL. Results: We evaluated 60 patients (41 females and 19 males), with a mean age at diagnosis of 49.6 (ranged from 23 to 77 years). Mean initial IGF-1 was 905.3 ng/mL (range 100-324) and mean initial GH was 25.0 ng/mL (<2.5). Macroadenomas were more common than microadenomas (48 vs 12). The average maximum tumor diameter was 15.6 mm and 21 patients were graded as Knosp 3 or 4, which indicated cavernous sinus invasion. Patients were follow for 11.8 years. Overall, the remission rate was 50.0% after surgery. Mean age of patients in surgical remission (51.6 years) was higher than those patients not in remission (47.5 years) (p=0.439). Remission rates for microadenomas and macroadenomas were 75.0% and 44.9%, respectively (p=0.04). Patients who achieved remission had smaller tumors compared with those who failed to attain remission (mean diameter 11.6mm versus 17.8 mm). Using the Knosp classification system and preoperative magnetic resonance images to determine cavernous sinus invasion, Knosp grade 3 to 4 tumors were found in 5 patients in remission and in 16 patients with persistence of disease (p=0.003). Patients who achieved remission had a significantly lower preoperative IGF-1 level (650.5 ng/mL) compared with those who did not (1211.0 ng/mL) (p=0.04). Preoperative GH levels were lower for the patients who achieved remission (18.7 ng/mL) than for those who did not (32.5 ng/mL, p=0.006). Conclusions: In our study, predictors of biochemical remission after surgery were smaller tumor size, lower Knosp grade, and lower preoperative GH and IGF-1 levels.

SAT-265 An Asynchronous Double Growth Hormone Secreting Pituitary Adenoma as a Cause of Rapid Tumor Regrowth After Initially Successful Surgery

Background. Double pituitary adenomas are a rare entity, which requires clinical attention and a careful follow-up. Case report. A 37-year-old man presented with left-sided painful gynecomastia. He denied typical symptoms of excessive growth hormone (GH) secretion and did not show any acromegalic features. Due to low testosterone and LH levels with mild hyperprolactinaemia, the patient was referred to pituitary MR, which revealed an 11x13 mm right-sided sellar tumor. An increased IGF-1 was noted subsequently (1482 ng/mL; N 109-284 ng/mL), together with the lack of GH suppression in OGTT. Transphenoidal resection of pituitary tumor performed in 2012 led to biochemical (IGF-1 260 ng/mL, GH 0.08 ng/mL) and radiological remission of the disease. A histopathology report revealed a densely granulated somatotropic pituitary adenoma with mild nuclear atypia, expressing somatostatin receptors [sstr2A (+), sstr5 (+/-)]. Due to gradually increasing IGF-1 levels (with low, although rising, GH values ranging from 0.07 to 0.92 ng/mL) in subsequent years, OGTT was repeated in 2015, showing appropriate GH suppression. In 2016, however, acromegaly recurrence was confirmed both biochemically (increasingly high IGF-1 - 664 ng/mL - and unsuppressed post-OGTT growth hormone) and in MR imaging. The patient was reoperated in June 2017. The second histopathology reported an oncocytic somatotropic acidophil stem cell pituitary adenoma with Ki-67 >3% and mitotic figures. Subsequent anterior pituitary lobe insufficiency (adrenal, thyroid and gonadal axis) was found and adequately treated. Complete tumor removal was confirmed by MR performed three months after repeated surgery, as well as a low GH level (0.97 ng/mL), although accompanied by borderline IGF-1 values (277 ng/mL). Eighteen months after surgery, the recurrence of acromegaly was again confirmed, with adenoma regrowth and increased GH (2.31 ng/mL) and IGF-1 (474 ng/mL) levels. Octreotide LAR was started (despite retina wrinkling which was observed when lanreotide was administered before the first surgery), which led to a normalization of GH (0.96 ng/mL) and IGF-1 levels (152 ng/mL), as well as partial pituitary tumor regression after six months therapy. Conclusion. In a case of GH-secreting pituitary adenoma recurrence after apparent successful surgery, a double pituitary tumor with more aggressive histology should be considered.

SAT-287 Mild Perinatal Undernutrition Results in Underweight Pups and a Premature Neonatal Leptin Surge

Malnutrition causes dysregulated pituitary function, which may in part be due to lowered leptin signals. We showed that loss of somatotrope leptin receptors in mice reduces growth hormone (GH) secretion and promotes metabolic dysfunction in adults. More recently, we showed that adult male mice fasted for 12 or 24 hours also had significantly lowered GH secretion, which correlated with a 94% reduction in serum leptin. Malnutrition may result in changes in the leptin surge during neonatal development in rodents or the third trimester in humans. Severe (50% reduction) maternal undernutrition (1) blunted the surge in rodents, however less severe undernutrition (30% reduction) caused a premature leptin surge (2). Both studies reported that pups showed metabolic dysfunction as adults. In our studies of leptin regulation of somatotropes, we tested the more severe calorie restriction model and discovered significant pup and maternal loss. We then elected to develop a milder undernutrition model, which may relate more closely to society’s nutritional challenges with the objective of determining if the timing of the leptin surge had shifted.This maternal undernutrition study consisted of dams fed ad libitum (fed) and pair fed dams receiving 20% reduced caloric intake (undernourished). Undernutrition started at E15 and ended with sacrifice at various times during the leptin surge. While nursing, the undernourished dams did not lose weight, but their weight gain was reduced to 45% of that of fed dams. We have collected data from 177 neonatal pups and 19 fed or undernourished dams. At PND5 and PND10, pups from undernourished moms weighed significantly less (16.3% and 21.8%) than pups from fed dams. Additionally, weanlings (PND 21) from underfed dams exhibited a 28.04% reduction in weight and an 8.43% reduction in nose to anus length (p = 0.0005) compared to pups from control fed dams. The timing of the leptin surge in pups from fed dams was normal in female pups. However, pups from mildly undernourished dams had “premature” leptin surges that peaked 2 days earlier than normal. Ongoing studies are testing metabolic function in these mice, as adults, to determine their sensitivity to a 45% high fat diet and the impact on somatotrope functions. This model demonstrates that even a 20% reduction in nutrition will negatively impact offspring and shift the timing of the leptin surge.1.Delahaye F, Breton C, Risold PY, Enache M, Dutriez-Casteloot I, Laborie C, Lesage J, Vieau D. Maternal perinatal undernutrition drastically reduces postnatal leptin surge and affects the development of arcuate nucleus proopiomelanocortin neurons in neonatal male rat pups. Endocrinology 2008; 149:470-4752.Yura S, Itoh H, Sagawa N, Yamamoto H, Masuzaki H, Nakao K, Kawamura M, Takemura M, Kakui K, Ogawa Y. Role of premature leptin surge in obesity resulting from intrauterine undernutrition. Cell metabolism 2005; 1:371-378

MON-072 A 2 -Year Old Girl with Turner Syndrome and Neurofibromatosis Type 1

Introduction: Turner syndrome (TS) occurs due to loss of either all or part of the X chromosome, in some or all the cells of the body. The most consistent features of TS are short stature and premature ovarian failure. Neurofibromatosis type 1 (NF1) is an inheritable in an autosomal dominant manner tumor predisposition syndrome and is caused by loss-of-function mutations in the tumor suppressor NF1 gene (neurofibromin 1). Literature review indicated rare cases with NF1 and TS (1). We report the sixth girl with mosaic TS and NF1 who presented with optic nerve glioma. Case report: A 2-year-old female presented to us due to short stature. Her height was 2,5 SD lower than the mean parental height curve, and her bone age was delayed only by 3 months. She already had a normal (46XX) peripheral blood karyotype (70 mitoses). She had abnormal body proportions and with short limbs with unremarkable café au lait spots. Additionally, to the short stature laboratory investigation we ordered a gene panel to exclude hypochondroplasia, and a Karyotype in fibroblasts culture from oral cavity sample. The results revealed low IGF-1 and mosaic TS in 14%. We preformed 2 provocative tests which revealed low growth hormone peak < 5 ng/ml. A brain and pituitary MRI to exclude pituitary lesions or structural abnormalities revealed gliomas of the optic chiasma and the right optic nerve with characteristic NF1 “spots” (regions of signal abnormality in T2 sequences) involving the basal ganglia, cerebellum and the right temporal lobe. DNA sequencing targeted to a gene panel related to NF1 and NF2 revealed a novel de novo heterozygous NF1 gene mutation in exon 28 [3764Α>G];[=]p.[Gln1255Arg]. Discussion: NF1- Gliomas are most commonly seen in young children, (mean 4.5 years). Only 1/3 of affected children will require therapeutic intervention. However early diagnosis, of optic gliomas is important. Our patient was completely asymptomatic by the time of diagnosis and no other symptom or sign of NF1 was apparent. Ophthalmologic examination was normal, but visual electrophysiologic testing was abnormal as far the right optic nerve is concerned. The oncology team decided to preform chemotherapy. In TS impaired growth is related to resistance in GH. Some studies suggested that there could be a relationship between GHD and NF1 even in the absence of an organic pituitary damage. In our patient it has been decided not to treat with GH and closely track the patient’s growth. Conclusion: Coexistence of NF1 with TS is rare. Awareness is needed as early identification and treatment of CNS gliomas can prevent visual loss and severe co-morbidities.1.Rare Presentation of Neurofibromatosis and Turner Syndrome in a Pediatric Patient. Pediatr Rep. 2017 Jun 26; 9(2): 6810

Assessment of Levels of Metabolic Hormones and Lipid Profile in Growth Hormone Deficient Patients

Abstract&#x0D; The current study aims to evaluate levels of metabolic hormones and lipid profile in a sample of growth hormone (GH) deficient patients. Seventy five GH deficient patients and twenty healthy subjects used as control group have been participated in this study during their attendance to the National Diabetic Center for Treatment and Research/Al-Mustansiriya University. The studied subjects’ ages were with a range (3-15 years). Blood samples were collected from the studied subjects to determine levels of basal GH, GH2 and GH3 after 1 hr and 1/30 hr provocation with clonidine, respectively; insulin like growth factor (IGF-1); levels of metabolic hormones [thyroid profile: triiodothyronine (T3), thyroxin (T4), and thyroid stimulating hormone (TSH)]; and lipid profile [cholesterol, triglyceride, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL)].&#x0D; The findings of the anthropometric measurements of the studied groups revealed that a non-significant (P&gt;0.05) difference was found in the weight between the patients and the control, while the mean of height in the patients was significantly (P&lt;0.05) lower than its value in the control. Mean of BMI detected a non-significant (P&gt;0.05) difference between the patients and the control. While mean of BMI percentile and mean of BMI Z-score revealed significant (P&lt;0.05) decrease in the patients compared to their values in the control.&#x0D; The results showed that non-significant (P&gt;0.05) difference was found in level of basal GH between the patients and the control, while a high significant (P&lt;0.01) decrease was found in levels of GH2 and GH3 in the patients group compared to the control group. Level of IGF-1 showed a significant (P&lt;0.05) decrease in the patients compared to the control.&#x0D; The results of metabolic hormones revealed a non-significant (P&gt;0.05) difference in serum T3 between the patients and the control, while a high significant (P&lt;0.01) decrease was found in serum T4 in the patients compared to the control. A non-significant (P&gt;0.05) difference was found in serum TSH between the patients and the control. The data of serum cortisol showed a significant (P&lt;0.05) increase in the patients compared to the control.&#x0D; The results of lipid profile showed a non-significant (P&gt;0.05) difference in serum cholesterol between the patients and the control, while triglyceride showed a significant (P&lt;0.05) increase in the patients compared to the control. A non-significant (P&gt;0.05) difference was found in serum HDL between the patients and the control, while a significant (P&lt;0.05) increase was found in levels of LDL and VLDL in the patients compared to the control.&#x0D; It can be concluded from the present study that diagnosis of GHD cannot be done at the basal serum of GH. A high level of GH was detected after 1 hr. provocation with clonidine compared with its value after 1/30 hr. provocation. The IGF-1 is an appropriate parameter to expect GHD in children and adolescences whom GHD was detected by GH stimulation testing. Low GH secretion is associated with high level of cortisol resulting in GHD. Patients with GHD displayed a tendency towards lipids disturbances.

Altered metabolic and hormonal responses to moderate exercise in overweight/obesity

BackgroundAn adequate metabolic and hormonal response to the switch from rest to exercise is critical for the health benefits of exercise interventions. Previous work suggests that this response is impaired with overweight/obesity but the specific differences between overweight/obese and lean individuals remain unclear. MethodsWe compared glucose and non-esterified fatty acid (NEFA) regulation and the changes of key homeostatic hormones during 45 min of moderate exercise between 17 overweight/obese and 28 lean premenopausal women. For this comparison, we implemented an exercise protocol at 60% of individual peak oxygen uptake, with frequent blood sampling and under fasting conditions. ResultsWe found that at the same exercise intensity in the overweight/obese and the lean group of women, the metabolic and hormonal response differed. In contrast to the lean group, the overweight/obese group portrayed an activation in the stress axis (adrenocorticotropic hormone (ACTH)/cortisol) and a lower growth hormone (hGH) response and exercise-increase of plasma NEFA. Both groups, however, displayed increased insulin sensitivity during exercise that was accompanied by a normalization of the elevated fasting glucose in the overweight/obese group after 15–20 min. ConclusionWe conclude that the response to exercise in overweight/obese subjects indeed differs from that in lean individuals. Additionally, we demonstrate that exercise can elicit beneficial (improved glucose regulation) and unwanted effects (stress axis activation) in overweight/obese subjects at the same time. This second finding suggests that exercise interventions for overweight/obese subjects need careful consideration of intensity and dose in order to achieve the intended results and avoid acute, undesired reactions.

Effect of One-Year Growth Hormone Therapy on Cardiometabolic Risk Factors in Boys with Obesity.

It has been recognized that people with obesity are more likely to have low growth hormone secretion. Recent studies have also confirmed that the abnormalities of the growth hormone/insulin-like growth factor 1 axis were associated with cardiovascular complications in people with obesity. However, little is known about whether recombinant human growth hormone therapy could improve cardiovascular and metabolic risks in obese children. This study aims to evaluate the effect of one-year growth hormone therapy on obesity-related comorbidities and to assess the safety in Chinese boys with obesity. Eighteen boys with obesity were treated with recombinant human growth hormone for one year. Anthropometric measurements, endocrine testing, and cardiovascular risk markers were performed in all obese boys in baseline, and follow-up visits were performed at 3 months, 6 months, 9 months, and one year, respectively. After one year of recombinant human growth hormone treatment, the body mass index standard deviation scores decreased (P < 0.001) and insulin-like growth factor 1 levels increased (P < 0.001). GH treatment also reduced low density lipoprotein cholesterol (P < 0.001), total cholesterol (P < 0.001), triglycerides (P=0.042), and alanine aminotransferase (P=0.027) when compared with the baseline. One-year of recombinant human growth hormone treatment could improve cardiometabolic risk markers, without adverse effects on glucose homeostasis in boys with obesity.

Preoperative growth hormone (GH) peak values during a GH releasing peptide-2 test reflect the severity of hypopituitarism and the postoperative recovery of GH secretion in patients with non-functioning pituitary adenomas.

Non-functioning pituitary adenoma (NFPA) is one common cause of adult growth hormone deficiency (AGHD). In Japan, a GH-releasing peptide (GHRP)-2 test is used to evaluate GH secretion. Although the cut-off for peak GH during a GHRP-2 test for severe AGHD is ≤9 ng/mL, severe AGHD may further diminish responses (range, nearly no-response to ≤9 ng/mL). We studied whether the peak GH responses during a GHRP-2 test could be predicted based on clinical characteristics of patients with NFPA. We compared patients with almost no-response during a GHRP-2 test with other patients considered as severe AGHD. Among the 76 patients with NFPA who were admitted to our institution, 36 patients (mean age, 61 years; male/female, n = 23/n = 13) were diagnosed with severe AGHD based on a preoperative GHRP-2 test. Based on the preoperative median peak GH concentration (2.83 ng/mL), patients were divided into two groups (<median = low or group L, n = 18; ≥median = moderate or group M, n = 18). Clinical manifestations, body mass index, severity of hypopituitarism and tumor size, volume, and extension were analyzed retrospectively. Compared with group M, group L patients were significantly older and more gonadotropin and ACTH deficient. A lower peak GH release during a GHRP-2 test was associated with a higher number of anterior pituitary hormone deficiencies across all 76 patients. Postoperatively, seven in group M and no patient in group L were assessed as having no longer severe AGHD, respectively. Preoperative peak GH concentrations assessed during a GHRP-2 test reflected the severity of hypopituitarism and the recovery of postoperative GH secretion.

A case of Dubowitz syndrome with growth hormone deficiency

Background: Dubowitz syndrome is a rare multiple congenital syndrome with unknown etiology, characterized primarily by growth retardation, distinctive facial dysmorphism, cutaneous eczema, microcephaly, intellectual deficit, skeletal and genital abnormalities, abnormal hematological and endocrinal findings, and other systemic affections. Case presentation: We report the case of a 3-year-old male patient presenting with repeated chest infections, failure to thrive, history of low birth weight, and seasonal skin allergies. Examination revealed abnormal facial features and skeletal and genital abnormalities along with delays in social development. Cardiac echocardiography showed atrial septal defect and ventricular septal defect. Blood tests revealed low growth hormone levels, and a clonidine stimulation test confirmed growth hormone deficiency. Conclusion: Careful examination of the patient leads to the diagnosis of Dubowitz syndrome and growth hormone deficiency. The combination of these two findings has rarely been reported before, but patients may get the benefit of testing for growth hormone deficiency to receive proper treatment.

Low Dose Growth Hormone Adjuvant Treatment With Ultra-Long Ovarian Stimulation Protocol in Poor Responders Showed Non-inferior Pregnancy Outcome Compared With Normal Responders.

Background: Growth hormone (GH) has long been used as adjuvant treatment in ovarian stimulation for in vitro fertilization (IVF), especially in poor responder (PR) patients. However, its clinical efficacy remains unclear, and most studies are underpowered owing to their small sample size with different regimens.Methods: Our study was divided into two parts. The first part was a parallel randomized, observational study in which 184 patients who fulfilled the criteria of poor ovarian response (POR) were enrolled and received ultra-long ovarian stimulation protocol with or without GH adjuvant therapy. For the second part, clinical data were retrospectively extracted from 163 patients classified as PRs who received 10 IU GH adjuvant therapy and 157 patients classified as normal responders (NRs) who received the same IVF protocol treatment without GH adjuvant therapy.Results: For the first part of the study, the ovarian response, the number of oocytes retrieved, and the number of available embryos transferred were all significantly higher in the GH (+) group than in the GH (–) group. The clinical pregnancy rate was significantly higher in the GH (+) group (31.9 vs. 16.7%, p = 0.0168). The miscarriage rate did not differ significantly between the groups. The ongoing pregnancy rate was also significantly higher in the GH (+) group than in the GH (–) group (26.6 vs. 14.4%, p = 0.0418). Logistic regression revealed that the chance of clinical pregnancy in the GH (+) group significant increased 2.34-fold in comparison with the GH (–) group (p = 0.018). Subgroup analysis showed that the chance of clinical pregnancy in the GH (+) group significantly increased 2.38-fold (p = 0.034). The second part of the study showed no statistical difference between the PR with GH and the NR without GH groups regarding the implantation rate (15.6 vs. 19.8%, p = 0.3254) and the clinical pregnancy rate (31.9 vs. 39.5%, p = 0.1565). The NR without GH group showed insignificantly higher chance of clinical pregnancy (OR = 1.39, p = 0.157) compared with the PR with GH group.Conclusion: Our results suggested that low-dose GH supplementation may improve ovarian response and pregnancy outcome in POR patients, particularly in patients younger than 40 years old. Moreover, the low-dose GH effect in POR patients resulted in non-inferior clinical pregnancy outcome compared with NRs.

Impact of BMI on peak growth hormone responses to provocative tests and therapeutic outcome in children with growth hormone deficiency

This study investigated the relationship between peak stimulated growth hormone (GH) and body mass index (BMI), as well as the impact of BMI on therapeutic response in patients with GH deficiency (GHD). A total of 460 patients were enrolled in the study. The patients were divided into four groups as per the etiology and peak GH values: idiopathic (n = 439), organic (n = 21), complete (n = 114), and partial (n = 325) GHD groups. Subsequently, they were classified as normal, overweight, or obese based on their BMI. There was no difference in BMI between complete and partial GHD. A significant negative relationship between peak GH and BMI were found. Moreover, obese GHD children had a considerably better therapeutic response in height increase and BMI decrease during 2 years of GH treatment compared to non-obese children with GHD. There was no difference between peak GH and type of GH stimulation test (GHST), except the clonidine test, which showed a much lower peak GH in obese GHD children. In conclusion, BMI had a negative impact on peak GH response, and therapeutic outcome was more favorable in the obese group. Despite no difference in GH response by type of GHST, the degree of obesity differentially affected the results.

Effect of growth hormone and somatomedin-C axis on fracture healing

Aim: Many studies have examined the effects of different calciotropic hormones on fracture healing, whereas few studies focus on growth factors. Local detection of somatomedin C (IGF-1) in fracture callus, application of growth hormone (GH) and IGF-1 as non-union treatment, and low GH and IGF-1 levels in osteoporotic fractures indicate that these hormones are effective in fracture healing. However, most of these studies are based on post fracture GH and IGF-1 levels. GH and IGF-1 are also involved in acute phase response and can change due to trauma. The aim of this study is to investigate the change in GH and IGF-1 levels in patients treated with osteotomy, in which an iatrogenic fracture is created, and to evaluate the effect of these hormones on fracture healing by comparing the results before and after the fractures. Methods: Patients who were diagnosed with developmental dysplasia of the hip and underwent surgery between 2014-2015 were prospectively followed for this cohort study. Forty-one patients were included, and two groups were formed. Patients who underwent open reduction and soft tissue release without osteotomy (n=20) were included in the first group. Patients who underwent pelvic osteotomy (n=21), in which iatrogenic fractures were created, were included in the second group. Blood samples were obtained from all patients pre-operatively and on the 1st and 28th postoperative days. Friedman and Mann-Whitney U tests were used for statistical analysis. Results: Mean age of the first group, comprising 19 females (95%) and 1 male (5%), was 11.25 months (Range: 6-25 months). Mean age of the second group, including 17 females (85.7%) and 4 males (14.3%), was 74.4 months (Range: 24-120 months). While there was no significant difference between pre- and postoperative GH values in the first group (P=0.05), postoperative GH levels were significantly higher than preoperative GH levels in the second group (P&lt;0.001). Postoperative IGF-1 levels were significantly lower than preoperative IGF-1 levels in both groups (P&lt;0.001). When the difference of preoperative and postoperative 1st day GH and IGF-1 values were compared between two groups, GH changes were found significantly higher in the second group (P&lt;0.001) whereas serum IGF-1 changes were significantly lower in the second group (P=0.043). Conclusion: IGF-1 is inadequate in the investigation of fracture healing due to its short half-life and local production. On the other hand, GH plays an active role in fracture healing and increases significantly in comparison to pre-fracture values. Considering the GH increase during fracture healing, it may be beneficial to support patients with pathological fracture healing with growth hormone.

Majewski osteodysplastic primordial dwarfism type II (MOPD-II): A rare case report

Majewski osteodysplastic primordial dwarfism type II (MOPD-II) is a rare syndrome characterized by the presence of intrauterine growth restriction, post-natal growth deficiency and microcephaly. Individuals affected by this disease present at an adult height of less than 100 cm, a post-pubertal head circumference of 40 cm or less, mild mental retardation, an outgoing personality and skeletal dysplasia, renal, hematopoietic abnormalities, cerebral vascular anomalies (aneurysm and Moyamoya disease). It is an autosomal recessive syndrome with equal gender occurrence involving the DNA damage-response PCNT gene. Here is an interesting case report of a 15-year-old boy, who presented with growth failure since age of one year, noticed by his parents with history of low birth weight (1.5 kg), delayed developmental milestones, microcephaly, low IQ and difficulty in walking due to short left leg. He had bird like head with beaked nose, crowding of teeth and malocclusion. Complete blood picture and hormonal analysis are within normal range except low growth hormone, typical radiographic features including severe scoliosis and dislocation of hip correlated with MOPD-II. Growth hormone therapy was thought to be ineffective. Genetic counselling is important to prevent the occurrence of MOPD-II.&#x0D; Birdem Med J 2019; 9(3): 254-256

Timing of GH Peak in Both Glucagon and Clonidine Tests is of Major Clinical Importance

Objective: To detect a possible correlation between timing of the peak value of growth hormone (GH) during stimulatory tests (STs) and the effectiveness of treatment with recombinant human growth hormone (rhGH) in children with idiopathic GH deficiency (iGHD). Methods: We retrospectively studied 92 patients with iGHD (57 boys; mean age at diagnosis: 9.93 years). Diagnosis was confirmed by 2 different STs, glucagon stimulation test (GST), and clonidine stimulation test (CST). Auxologic parameters were recorded, while observed and predicted (according to KIGS Prediction Model) height velocity during the first year of treatment and the index of responsiveness (IoR) were calculated for the prepubertal children (n = 65). Results: Atypical GST was defined as that with peak GH value at time 0 minutes, 30 minutes, 60 minutes, or 180 minutes, whereas atypical CST was defined as that with peak timing at 0 minutes, 30 minutes, or 120 minutes. Atypical GST was detected in 18 patients (19.57%). IoR was lower in the prepubertal children with atypical GST (-1.81 ± 0.67 versus -1.34 ± 0.85; P = .051). In the CST, the 18 children who had atypical timing, had significantly lower IoR (-1.86 ± 0.66 versus -1.35 ± 0.84; P = .047). When the patients were categorized according to the number of atypical tests, significant differences in the IoR were detected (-2.09 ± 0.68 with 2 atypical STs [n = 6], -1.64 ± 0.61 with 1 atypical ST [n = 16], and -1.29 ± 0.87 with no atypical ST [n = 43], P = .045). Conclusion: The presence of atypical peak GH timing during ST may be a factor that predicts lower growth hormone velocity during the first year of rhGH treatment in prepubertal children with iGHD. Abbreviations: CST = clonidine stimulation test; GH = growth hormone; GHD = growth hormone deficiency; GST = glucagon stimulation test; iGHD = idiopathic growth hormone deficiency; IoR = index of responsiveness; rhGH = recombinant human growth hormone; SDS = standard deviation scores; ST = stimulatory test.

P1.03: Intravenous glucose nocturnal infusion reduces growth hormone secretion in children on total parenteral nutrition

Introduction: Most children with intestinal failure (IF) benefit from home parenteral nutrition (HPN). It allows a familial life with normal children activities such as going to school, sports, and being at home. In order to do so, PN is provided with cyclic infusion at night. Children with IF on HPN should have normal growth. However, some children grow under their genetic target height and present with decreased height velocity. Methods: We report the case of two children on HPN who presented with decreased height velocity while their weight gain was normal. After ruling out usual etiology (insufficient protein intake, acidosis, sodium deficiency, IFALD…), growth hormone (GH) deficiency was considered. Extensive testings were performed such as IgF1 levels, GH secretion stimulation test and nocturnal GH secretion. PN dependency was assessed using the PN/REE index (parenteral nutrition non-protein energy intake divided by resting energy expenditure calculated using Schofield equation, expressed in percentage). Results: These two children needed extremely high PN caloric intake to achieve a normal weight gain with a PN dependency index of 163% and 150%. Table 1 shows their clinical characteristics. Table 2 shows the results of the biological testings. These two children showed a normal GH peak under stimulation, but a low nocturnal GH secretion meaning they were able to produce GH under stimulation, but their nocturnal physiological secretion was inhibited. Their mean glycemia during PN perfusion was high compared to fasting glycemia which should normally be observed at night in children. Hyperglycemia is a well known inhibitor of GH secretion. Conclusion: Children with very high PN dependency are at risk of developing reduced height. In some children, GH secretion seems to be inhibited by nocturnal high glucose infusion. A longer PN infusion time can be proposed and/or a decrease in glucose intake with an increase in lipid intake. Also, growth hormone supplementation might be discussed and should be evaluated in this setting.

Effects of somatotropic axis on cognitive dysfunction of obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with a variety of neuroendocrine disorders and may lead to many complications, including cognitive dysfunction. The aim of this study was to assess the change of somatotropic axis and to detect the relation between somatotropic axis hormone and cognitive dysfunction. Sixty-six patients with OSA and 16 healthy controls were enrolled in this cross-sectional study. Cognitive function assessment using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) and polysomnography were performed on all individuals. Blood samples were taken the next morning following the polysomnography and the level of serum growth hormone-releasing hormone (GHRH) and growth hormone (GH) were analyzed by enzyme-linked immunosorbent assay. Compared with the control group, OSA patients showed significantly lower serum GH level (p < 0.05), whereas no statistical significance of GHRH level was found. In addition, lower MMSE and MoCA scores were found only in the severe OSA patients when compared with the controls. Furthermore, in severe OSA patients with cognitive dysfunction (MMSE score < 27 and MoCA score < 26), serum GHRH and GH levels were significantly lower than those without cognitive dysfunction. Logistic analysis revealed that cognitive dysfunction in severe OSA patients was associated with micro-arousal index and the level of serum GHRH and GH. Decreased serum GH and GHRH levels were found among severe OSA patients with cognitive dysfunction who were overweight, which might promote the occurrence of cognitive dysfunction.

Trans-omics analyses revealed differences in hormonal and nutritional status between wild and cultured female Japanese eel (Anguilla japonica)

Long-term stock decline in the Japanese eel (Anguilla japonica) is a serious issue. To reduce natural resource utilization in Japan, artificial hormonal induction of maturation and fertilization in the Japanese eel has been intensively studied. Recent experiment on feminized (by feeding a commercial diet containing estradiol-17β for first half year) cultured female eels have shown ovulation problems, which is seldom observed in captured wild female eels. Therefore, the aim of this study is to try to investigate causes of ovulation problem frequently seen in cultured female eels by comparative trans-omics analyses. The omics data showed low growth hormone and luteinizing hormone transcription levels in the brain and low sex hormone–binding globulin transcription levels in the liver of the cultured female eels. In addition, it was found that high accumulation of glucose-6-phosphate and, maltose in the liver of the cultured female eel. It was also found that docosahexaenoic (DHA) acid, eicosapentaenoic acid (EPA) and arachidonic acid (ARA) ratios in cultured female eels were quite different from wild female eels. The data suggested that ovulation problem in cultured female eels was possibly resulted from prolonged intake of a high-carbohydrate diet and/or suboptimal DHA/EPA/ARA ratios in a diet.