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Objective: To introduce a relatively convenient and effective way of conducting Insulin Tolerance Test for diagnosis of Growth Hormone deficiency in children with short stature. Study Design: Cross sectional analytical study. Place and Duration of Study: Conducted at Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from May 2017 to Jul 2018. Methodology: A total of 185 cases were included. Sample selection was done by non-probability consecutive sampling technique. Insulin tolerance test was performed by taking basal sample for serum growth hormone and plasma glucose levels before giving intravenous insulin bolus according to dose of 0.15 IU/kg. Samples for Growth Hormone level were repeated at time of induced hypoglycemia (defined as plasma glucose level of 20 mIU/l) at induction alone, followed by 30 minutes post induction; reflecting the significance of these two samples in diagnosis of growth hormone deficiency. Conclusion: We concluded that there is a simpler ...........

Extending from our first two studies examining the IGF profile (IGF-1, IGFBP-3 and the ratio of IGFBP-3/ IGF-1) in women presenting for assisted reproductive technologies (ART), this study examines its relevance to the testing of human growth hormone (hGH) levels on the same blood sample. These were taken in the morning during the early follicular phase of the woman’s menstrual cycle and included 408 women who were ART-naïve, undertaking the tests as part of an assessment cycle prior to any ART treatment. The growth hormone levels were also tested on a further 945 women classified as ART-interval cases. It was shown that the vast majority of hGH levels (73%) were very low at

It is quite rare that Cushing's disease shows acromegaly, and no pharmacotherapy has yet been discussed. A 21-year-old woman was diagnosed with Cushing's disease and underwent trans-sphenoidal surgery. Five years later, she was diagnosed with recurrent Cushing's disease and biochemical acromegaly because of elevated levels of serum growth hormone (GH), plasma insulin-like growth factor-1, plasma adrenocorticotropic hormone (ACTH), and the 24-hour urinary excretion of free cortisol. After treatment initiation with pasireotide-long-acting release (LAR), both the ACTH and GH declined. Our case is the first to show the efficacy of pasireotide-LAR in controlling both Cushing's disease and acromegaly.

Objective To investigate the changes in serum growth hormone (GH), testosterone, and insulin-like growth factor 1 (IGF-1) during low-intensity resistance exercise under different cuff pressures. Methods We performed a single-blind, cross-over design study. Twenty-five healthy young men performed three exercise protocols as follows: 1) no blood flow restriction exercise (control group), 2) resistance exercise at 40% of arterial occlusion pressure (AOP) (low group), and 3) resistance exercise at 70% of AOP (high group). Blood lactate, GH, testosterone, and IGF-1 levels were measured at four time points. Results There were no differences in the indices before exercise. The blood flow restriction exercise under different pressures had different effects on each index and there was an interactive effect. GH levels were significantly higher in the high group than in the other groups after exercise. Immediately after exercise, IGF-1 and testosterone levels were significantly higher in the high group than in the other groups. At 15 minutes after exercise, testosterone levels were significantly higher in the high group than in the other groups. Conclusions Low-intensity resistance exercise combined with blood flow restriction effectively increases GH, IGF-1, and testosterone levels in young men. Increasing the cuff pressure results in greater levels of hormone secretion.

The objectives of the study were to evaluate the effect of ethanolic extract of P. indica Less leaf (EPI) on serum growth hormone (GH), milk yield, body weight gain of dams, and dam’s organ weight in lactating rats. A total of 25 lactating rats with six pups were randomized and distributed to one of five treatments (control (RO water), standard (domperidone 2,5 mg/kg BW/day), EPI 250 (250 mg/kg BW of EPI), EPI 500 (500 mg/kg BW of EPI), and EPI 750 (750 mg/kg BW of EPI)). The treatment was administered daily starting from the 2nd until the 15th day of lactation. On the 16th day serum growth hormone level, body and organ weight of rats were measured. Serum GH levels in the EPI 750 group (1963.25 ± 360.91 pg/µL) increased significantly compared to the domperidone (409.46 ± 28.80 pg/µL) and the control group (723.40 ± 95.78 pg/µL, p0.05). There was significant body weight gain in the EPI 750 group compared with the domperidone group. There was no significant difference in organ weight gain in each group. The study revealed that ethanolic extract of P. indica Less leaf can increase serum growth hormone in lactating rats.

Growth hormone (GH) and its anabolic mediator, insulin-like growth factor-1 (IGF-1), have a critical role in the central nervous system. However, their detailed roles in the adult human brain are not clear. In this study, structural MRIs of 48 patients with GH-secreting pituitary adenoma (GH-PA), 48 sex- and age-matched clinical Non-Functional pituitary adenoma patients (NonFun-PA) and healthy controls (HCs) were assessed using voxel-based morphometry (VBM) and region-based morphometry (RBM). Correlation analyses helped determine the relationships between serum hormone levels and brain structure. The whole-brain gray matter volume (GMV) and white matter volume (WMV) significantly increased at the expense of cerebrospinal fluid volume (CSFV) in GH-PA (Bonferroni corrected, p

Introduction: The aim of this study was to analyze psychological factors of patients with acromegaly and assessment of their relationship with the quality of life (QoL) in the context of the control of the disease. Materials and methods: A total sample of 50 patients (62% of females; mean age = 51.66 ± 14.5) with acromegaly underwent a comparative, cross-sectional cohort assessment including the QoL (AcroQoL, WHOQoL-BREF), psychiatric morbidity (GHQ-28), the acceptance of illness (AIS) as well as influence of treatment, comorbidities and symptoms in the relation of disease activity. Acromegaly group was divided in two subgroups: patients with uncontrolled acromegaly (UA, n = 28) and patients with controlled acromegaly (CA, n = 22). Results: The acromegaly groups did not differ in health-related QoL measured with AcroQoL and WHOQoL questionnaires. However, obtained results showed QoL impairments in all subscales and the study participants had decreased scores compared to reference values. The interaction of the relationship between the AIS and disease activity as well as the prevalence of all psychopathological symptoms and disease activity were tested and the statistically significantly differences in the context of QoL in AcroQoL questionnaires and its domains were observed in relation to the course of the disease. No difference in acromegaly symptoms as well as in number of comorbidities were found between CA and UA but these two parameters affected the results QoL scores in AcroQol questionnaires and their domains, regardless the disease activity. Similarly, the prevalence of psychopathological symptoms (GHQ-28) contributed the level of acceptance of the disease, regardless the disease activity. The strongest predictors of QoL were related to the level of illness acceptance (p = 0.01) as well as serum growth hormone concentration. Conclusion: Minding people with UA, the control of biochemical factors seemed to be more important for the QoL perception, while among CA, psychological variables such as AIS are observed to play a fundamental role in QoL. Moreover, inclusion of patient's acceptance of the illness into clinical routine would promote holistic, patient-centered care and empower doctor-patient partnership where patients' expectations and perceptions are constantly tracked. Obtaining biochemical control should not be considered as the only measure of treatment success.

1) To compare the retinal, choroidal, Haller’s layer, and Sattler’s/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden. This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller’s layer and Sattler’s/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naive serum GH and IGF-1 levels. Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p

Reductions in dietary protein and the supplementation of diets with feed additives have become two practical strategies in swine production to reduce costs and promote pig growth and health. This study was conducted to evaluate the effects of long-term feeding of Achyranthes japonica Nakai extract (AJE) combined with different dietary protein levels on growth performance, nutrient digestibility, blood parameters, fecal microbiota, fecal noxious gas emissions, meat quality, and carcass grade in growing-fattening pigs. In total, 144 crossbred [Duroc × (Yorkshire × Landrace)] growing pigs with average initial body weight (BW) of 23.77 ± 1.65 kg were used in a 16-week feeding experiment. The pigs were randomly sorted into one of six dietary treatments in a 2 × 3 factorial arrangement with two levels of dietary protein—high crude protein (HCP) vs. low crude protein (LCP), each without (0 g/kg) or with two doses of AJE (0.5 g/kg and 1 g/kg) based on the BW and sex [four pigs per pen (two barrows and two gilts); six pens per treatment]. All samples were taken at the end of the growing (week 6) and fattening (week 16) phases. Growth performance indices were also assessed in the middle of the fattening phase (week 11). The addition of both dosage of AJE improved the average daily gain (ADG) throughout the experimental period. Similarly, the ADG was higher in pigs fed the HCP diet than in those fed the LCP diet during weeks 6 and 11 and throughout the experimental period. At weeks 6 and 16, positive effects on digestibility, blood profiles, fecal microbial population, fecal gas emission concentrations, and the water holding capacity of meat were observed in pigs fed AJE-supplemented diets. The pigs fed the HCP diet had higher nitrogen digestibility, blood total protein, serum growth hormone, and insulin-like growth factor-1 at both weeks 6 and 16. Furthermore, pigs fed the HCP diet had higher blood urea nitrogen concentrations and carcass weights at week 16, and lower fecal Escherichia coli counts at week 6. Additionally, lower concentrations of fecal ammonia and total mercaptans were observed at weeks 6 and 16, respectively. In summary, AJE and high dietary crude protein level improved growth performance, nutrient digestibility, blood parameters, fecal microbiota, fecal noxious gas emission, and meat quality but no interactive effects between protein level and AJE were observed.

Purpose Evaluation of the lacrimal gland volume (LGV) and its correlation with tear film functions, serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels in acromegaly patients compared to a control group was aimed. Methods This prospective case-control study included the eyes of 38 patients with uncontrolled (UA) and 48 patients with controlled acromegaly (CA) and 44 patients with nonfunctioning pituitary adenoma. LGV of the patients was evaluated at the baseline, 3rd, and 6th-month visits with magnetic resonance imaging. Schirmer's test, tear breakup time (TBUT), and ocular surface disease index (OSDI) scores were evaluated at the same visits. Their correlation with serum IGF-1 and GH was investigated. Main outcome measure was the difference in mean LGV. Results The mean LGV of the acromegaly patients at the baseline visit (116.0 ± 33.2 mm3) and the 3rd-month visit (119.5 ± 36.4 mm3) was higher than the control group (65.2 ± 22.3 mm3 and 63.2 ± 22.3 mm3, respectively; p 0.05). Among all patients, IGF-1 and GH levels showed a positive correlation with the LGV (p 0.05). Conclusion Acromegaly patients may have larger lacrimal glands compared to the controls and this increase correlated with the increased IGF-1 and GH levels. Lacrimal gland volume may have no effect on its tear film related functions.

Background: The growth hormone (GH) response to resistance training is altered by many factors including sex steroid concentrations, fitness, intensity of exercise, age, gender, duration of exercise and glycemic state but the exact understanding of the interplay of different exercises to GH levels and its induced physiological adaptations is still obscure. This study aimed to see how resistance exercise affects GH levels and its correlation to plasma glucose levels in healthy non-obese adolescent subjects.Methods: 48 healthy non-obese adolescent subjects, 24 males and 24 females were included in the study. High volume exercise training regimen was used which involved major muscle group of arms, legs and trunk. Pre and post exercise levels of serum GH and random blood sugar were estimated in male and female groups.Results: The mean body mass index (BMI) of male and female groups was 23.22±3.12 kg/m2 and 20.40±4.49 kg/m2, respectively. The post-exercise serum GH levels in male and females increased significantly by 0.54±1.041 ng/ml (p

Introduction Clinically silent somatotroph adenoma is characterized by elevated serum growth hormone but without the clinical symptoms of acromegaly, and it is considered rare. The natural history is not well understood, progress to symptomatic is uncertain, and treatment strategy has not been established. Case presentation The first patient was a 48-year-old-Asian woman who presented with serum growth hormone 6.99 ng/ml and insulin-like growth factor 1 of 476 ng/ml, but no characteristic features of acromegaly. Five years after initial diagnosis, she presented with acromegalic facial appearance. Transsphenoidal surgery achieved gross total removal and endocrinological remission. The second patient was a 40-year-old-Asian woman who presented with serum growth hormone 31.14 ng/ml and insulin-like growth factor 1 of 709.6 ng/ml, but no characteristic features of acromegaly. Three years after initial diagnosis, she presented with acromegalic facial appearance. Transsphenoidal surgery achieved gross total removal and endocrinological remission. The third patient was a 64-year-old-Asian woman who presented with serum growth hormone 6.0 ng/ml and insulin-like growth factor 1 of 341 ng/ml, but no characteristic features of acromegaly. Eight months after initial diagnosis, hand enlargement was detected. Transsphenoidal surgery achieved gross total removal and endocrinological remission. Conclusion Due to its potential for evolving to symptomatic disease, the risks of surgery and observation for patients with somatotroph adenoma should be carefully compared from the viewpoint of better health outcome.

The aim of this study was to investigate the effect of dietary supplementation of nanosize zinc on zinc digestibility, growth performances, immune response and serum parameters of weanling piglets. Ninety-six LYD weanling piglets were assigned to control, zinc oxide (ZnO), organic-Zn (Zn-methionine) and nanosize ZnO (nano-Zn) groups with four replicates. The zinc was at the 120 mg/kg level in the treatment group's diet, while the control group's was 80 mg/kg Zn. The experiment results indicated that the nano-Zn and organic-Zn groups had significantly higher Zn digestibility compared to the ZnO and control groups. For the immune response traits, the IgG level and goat red blood cells (GRBC) antibody titer were nano-Zn and organic-Zn>ZnO>control; in the phytohemagglutinin (PHA) challenge test result, nano-Zn>organic-Zn>ZnO>control; in regard to the γ-globulin level, nano-Zn and organic-Zn>ZnO and control, with significant difference between groups. In the serum parameters aspect, serum Zn concentration in nano-Zn and organic-Zn groups were higher than in the ZnO and control groups, serum growth hormone concentration was increased in the nano-Zn group than in the other groups. In conclusion, nanosize zinc oxide for dietary supplementation can increase zinc digestibility, serum growth hormone levels and carbonic anhydrase activity and enhance the immune response of weanling piglets.

Cysteamine (CS) can increase serum growth hormone concentrations and the growth performance of broiler, sheep, and pigs. However, information of CS supplementation on the milk performance of dairy cows is limited. An experiment was conducted to investigate the effect of dietary cysteamine hydrochloride (CSH) supplementation on lactation performance of dairy cows. Forty-eight multiparous mid-lactation Holsteins were fed a control diet or supplemented with 15, 30, or 45 g/d CSH preparation (cysteamine HCl 20%) for 63 d, including 7 d for adaptation. The base diet was formulated to meet the nutrient requirements of lactating dairy cows according to the Chinese feeding standard (China Standard NY/T 34,Feeding standard of dairy cattle 2004 Issued by Ministry of Agriculture of People's Republic of ChinaBeijing) and the DMI, milk yield, milk composition, and plasma parameters were measured. Milk yield was 7.1% and 6.3% higher for the two higher supplementation amounts (SEM=0.50, P P N were lower for the 30 and 45 g/d CSH groups than for the control. Level of plasma somatostation was reduced and plasma growth hormone was enhanced in CSH groups compared with that of control ( P

Purpose Endocrine-disrupting chemicals interfere with the endocrine system and therefore affect growth and pubertal progression. The study aim was to compare the growth and pubertal progression in wild-type female rats with different bedding types. Methods Twenty 5-week-old female wild-type Sprague Dawley rats were randomly assigned to two groups with different bedding types: one group received wood shaving bedding, while a second group received corncob bedding. We determined crown-rump length and body weight as anthropometric measurements and assessed the serum growth hormone (GH) and estradiol levels. The gh1 mRNA expression levels were compared using quantitative real time transcription polymerase chain reaction. The estrous cycle was evaluated by vaginal smear. Results The anthropometric measurements were not significantly different between the two groups. The mean relative expression of the gh1 gene was lower in the corncob bedding group than that in the wood shaving group (P=0.768). Meanwhile serum GH and estradiol were increased in the wood shaving bedding group; however this difference was not statistically significant. The time to first estrus and the length of the estrous cycle were increased in the corncob bedding group; the proportion of normal estrous cycles was also decreased. These findings indicate irregularities in the estrous cycle. Conclusion Endocrine-disrupting chemicals in corncob bedding might be associated with time to first estrus and length of the estrous cycle. Therefore, the type of bedding should be considered as a factor affecting pubertal progression in rodents.

To evaluate retinal nerve fiber layer (RNFL) thickness in acromegalic patients.A study group of 29 patients with acromegaly and a control group of 38 age-matched healthy individuals were enrolled in a cross-sectional study. The study group was further divided by tumor size into two subgroups, a macroadenoma group and a microadenoma group. Serum growth hormone (GH) and insulin-like growth factor-1 (IGF-I) levels were detected at the time of ophthalmological examination in the study group. In both the study and control group, the RNFL thickness in the four quadrants was measured by optical coherence tomography. The relationship between GH and IGF-I levels and RNLF thickness was also evaluated.The difference in mean RNLF thickness in all quadrants between the study and control groups was not statistically significant. In acromegalic patients with macroadenoma, the mean RNLF thickness of the inferior quadrant decreased significantly compared to both patients with microadenoma and healthy individuals (p = 0,032 and p = 0,046). GH and IGF-1 levels were not significantly correlated with the RNLF thickness in the study group.Excessive GH and IGF-1 levels do not affect the optic nerve or RNLF thickness, whereas the RNLF becomes thinner in the inferior quadrant in acromegalic patients with macroadenoma as a result of the chiasmal compression.

In this study we have determined the effects of 20weeks of endurance running training on the GH-IGF-I axis changes in the context of the skeletal muscle performance and physical capacity level.Before and after the endurance training program a maximal incremental exercise tests, a 1500m race and a muscle strength measurements were performed and the blood samples were taken to determine both resting as well as end-exercise serum growth hormone (GH), insulin-like growth hormone-I (IGF-I), insulin-like growth hormone binding protein-3 (IGFBP-3) and plasma interleukin-6 (IL-6) concentrations.20weeks of endurance running training improved power output generated at the end of the maximal incremental test by 24% (P0.012), 1500m running time by 13% (P0.012) and maximal muscle strength by 9% (P0.02). End-exercise IGF-I/IGFBP-3 ratio was decreased by 22% after the training (P0.04) and the magnitude of IGF-I/IGFBP-3 ratio decrease (ΔIGF-I/IGFBP-3The training-induced changes in the components of the GH-IGF-I axis may have additive effects on skeletal muscle performance and physical capacity improvement.

Due to a scarcity of longitudinal trials directly measuring changes in muscle girth, previous recommendations for inter-set rest intervals in resistance training programs designed to stimulate muscular hypertrophy were primarily based on the post-exercise endocrinological response and other mechanisms theoretically related to muscle growth. New research regarding the effects of inter-set rest interval manipulation on resistance training-induced muscular hypertrophy is reviewed here to evaluate current practices and provide directions for future research. Of the studies measuring long-term muscle hypertrophy in groups employing different rest intervals, none have found superior muscle growth in the shorter compared with the longer rest interval group and one study has found the opposite. Rest intervals less than 1 minute can result in acute increases in serum growth hormone levels and these rest intervals also decrease the serum testosterone to cortisol ratio. Long-term adaptations may abate the post-exercise endocrinological response and the relationship between the transient change in hormonal production and chronic muscular hypertrophy is highly contentious and appears to be weak. The relationship between the rest interval-mediated effect on immune system response, muscle damage, metabolic stress, or energy production capacity and muscle hypertrophy is still ambiguous and largely theoretical. In conclusion, the literature does not support the hypothesis that training for muscle hypertrophy requires shorter rest intervals than training for strength development or that predetermined rest intervals are preferable to auto-regulated rest periods in this regard.

Objective Prior research has indicated that the loss of skeletal muscle mass and bone mineral density observed with aging is related to the prominent age-related decline in the concentration of serum growth hormone (GH). However, there is limited data on the effects of aging on GH responses to acute bouts of heavy resistance exercise (HRE) and aerobic exercise (AE). Design The present investigation examined the effects of a HRE protocol and an AE protocol on immunoreactive GH (IGH) and bioactive GH (BGH) in active young and old women. Results Older women had a diminished serum IGH response to both the HRE and AE protocols compared to the younger women, however a similar response was not observed in serum BGH. Additionally, the HRE protocol elicited a greater BGH response than the AE protocol exclusively in the younger group. Conclusions Regardless of exercise mode, aging induces an increase in growth hormone polymerization that specifically results in a loss of serum growth hormone immunoreactivity without a concurrent loss of serum growth hormone bioactivity. The greater BGH response to the HRE protocol found in the younger group can be attributed to an unknown serum factor of molecular weight between 30 and 55 kD that either potentiated growth hormone bioactivity in response to HRE or inhibited growth hormone bioactivity in response to AE.

The aim of study was to estimate the effect of acute exercise on serum growth hormone (GH) and fatty acid (FFA) levels in elite water polo players. Twelve male water polo players (20.50 ± 2.02 years) and eleven non-athletic male subjects (20.55 ± 1.04 years) participated in this study. In order to determine GH and FFA responses to acute exercise, a treadmill-running test was performed following an incremental protocol. Pre-exercise blood samples for both athletes and non-athletes were taken at 9 AM. Post-exercise samples were taken immediately after and 30 min after the treadmill running test. Water polo players had significantly lower baseline values of serum GH concentration compared to controls, whereas serum FFA concentration was significantly higher in water polo players compared to controls (p

Aims: The aim was to compare the intraocular pressure (IOP), central corneal thickness (CCT), and optic disc topography findings of biochemically controlled acromegalic patients and the control group and to evaluate the effect of the duration of acromegaly and serum growth hormone and insulin-like growth factor-1 (IGF-1) levels on these ocular parameters. Materials and Methods: IOP measurement with Goldmann applanation tonometry, CCT measurement with ultrasonic pachymetry, and topographic analysis with Heidelberg retinal tomograph III were performed on 35 biochemically controlled acromegalic patients and 36 age- and gender-matched controls. Results: Mean IOP and CCT were 14.7 ± 2.9 mmHg and 559.5 ± 44.9 μm in the acromegaly patients and 13.0 ± 1.6 mmHg and 547.1 ± 26.7 μm in controls ( P = 0.006 and P = 0.15, respectively). A significant moderate correlation was found between the duration of acromegaly and CCT ( r = 0.391) and IOP ( r = 0.367). Mean retinal nerve fiber layer (RNFL) thickness was significantly lower in the acromegalic patients (0.25 ± 0.05 mm) as compared to controls (0.31 ± 0.09 mm) ( P = 0.01). A significant moderate correlation was detected between IGF-1 level and disc area ( r = 0.362), cup area ( r = 0.389) and cup volume ( r = 0.491). Conclusion: Biochemically controlled acromegalic patients showed significantly higher CCT and IOP levels and lower RNFL thickness compared to healthy controls and the duration of disease was correlated with CCT and IOP levels.

Determination of serum growth hormone (GH) levels is mandatory for diagnosis of GH deficiency and excess. In the present study, we, the Study Committee for GH and Its Related Factors, The Foundation for Growth Science, Japan measured GH values in serum samples using all the commercially available kits in Japan. Significant discrepancies in the GH values were observed among the kits in spite of using the unified recombinant human GH-based standards. To deal with the discrepancies, we established a formula using a linear structural relationship model and were able to standardize the GH values. We propose to use the formula to diagnose GH deficiency and excess in Japan.

Rationale There are some reports about hypoxemia related to hypopituitarism. However, little is known about the relationship between growth hormone deficiency (GHD) and hypoxemia. Patients concerns A 23-year-old female presented with severe hypoxemia after the operations of craniopharyngioma. Laboratory tests found that serum growth hormone (GH) levels were extremely low. Diagnosis She was diagnosed with growth hormone deficiency-related hypoxemia. Interventions In addition to oxygenation, low doses of GH replacement therapy was conducted for 3-month. Outcomes After 3-month r-hGH replacement therapy, hypoxemia was improved significantly and the level of serum GH was elevated. Lessons We've already known that hypopituitarism may induce hypoxemia owing to multiple possible mechanisms according to previous literature. But little is known about growth hormone deficiency-related hypoxemia. Our case shows that GH replacement therapy is an effective treatment, and it's significant to examination the level of GH in serum for hypoxemia patients especially when the cause of hypoxemia is unknown.