Peak Growth Hormone Concentrations Research Articles

6743 Decline in IGF-1 after surgery of the nonfunctioning pituitary neuroendocrine tumor

Abstract Disclosure: J. Sugata: None. S. Fujio: None. R. Makino: None. T. Hanada: None. R. Hanaya: None. Background: Patients undergoing surgical treatment for nonfunctioning pituitary neuroendocrine tumors (PitNET) may experience impaired secretion of growth hormone (GH). The optimal timing for assessing GH secretory function postoperatively remains unclear. In our department, we typically conduct hormone-loading tests three months after surgery. However, even in some cases without a diagnosis of growth hormone deficiency (GHD) at that point, there might be a gradual decline in Insulin-like growth factor-1 (IGF-1). Methods: We studied patients who exhibited peak GH levels > 1.8ng/ml in an insulin tolerance test (ITT) three months after undergoing surgery for nonfunctioning PitNET. We evaluated the levels of IGF-1 during the last observation, excluding cases where reoperation or radiosurgery was performed. Results: We identified 67 cases (29 males, 38 females) meeting the study criteria, with a median age of 54 years. The median follow-up time spanned 6 years (range 1-13 years). The median standard deviation (SD) scores of IGF-1 three months after surgery were -0.96, with 14 cases (21%) below -2.0 SD. At the end of the follow-up period, the median SD scores of IGF-1 were -1.31. This was significantly lower than the three-month time point (p<0.01), and 21 cases (31%) recorded were below -2.0 SD. In 6 cases suspected of severe GHD due to subjective symptoms or decreased IGF-1, ITT, or GH-releasing peptide-2 were retested. Among these, 2 cases were diagnosed with severe GHD, while the remaining demonstrated normal secretion of GH despite the low concentration of IGF-1. The IGF-1 SD scores at the end of follow-up and the three-month time-point exhibited a significant correlation (R2=0.74, p<0.01). However, no correlation was found between IGF-1 scores and peak GH concentration, age, tumor size, pituitary apoplexy, or preoperative IGF-1 SD scores. Conclusions: IGF-1 exhibited a progressive decrease in the majority of cases without severe GHD, with some cases showing reductions greater than -2.0 SD. Our findings emphasize the importance of cases with long-term clinical follow-up low IGF-1 after PitNET surgery, even when GH secretion appears normal. Presentation: 6/1/2024

The somatotroph pituitary gland function in high-aged multimorbid hospitalized patients with IGF-I deficiency

PurposeIt is unclear whether the age-related decline in the somatotropic axis stems from a reduced growth hormone (GH) production in the pituitary gland, or from a peripheral origin akin to an acquired GH resistance. With the help of a GHRH/arginine test, high-aged multimorbid hospitalized patients with IGF-I deficiency are to be tested to determine whether there is primarily a pituitary GH deficiency in the sense of a somatopause.MethodsSeventeen multimorbid patients (eleven men and six women) with a mean age of 82 years, with IGF-I concentrations below two standard deviations of 30-year-old men and women were identified. Patients suffered from a variety of common age-related stable diseases including coronary artery disease, chronic liver or kidney disease, chronic heart failure as well as acute conditions e.g., urosepsis or endocarditis. To assess the somatotropic axis they underwent a GHRH/arginine test. Results were evaluated using descriptive statistics.ResultsIn average, the peak concentration of GH after stimulation was 14.8 µg/L with a range from 2.76 to 47.4 µg/L. Taking into account both, gender and BMI (with a mean of 26.5 kg/m²) for each participant, the pituitary gland was adequately stimulated in 16 out of the 17 patients. No patient reported common side effects related to the GHRH/arginine test.ConclusionThe somatotroph pituitary gland retains its secretory capacity in the advanced aged. Therefore, age does not seem to be the driving pacemaker for the functional decline of the somatotropic axis within the aged population.

Isolated growth hormone deficiency in children with vertically transmitted short stature: What do the genes tell us?

The growth hormone deficiency (GHD) diagnosis is controversial especially due to low specificity of growth hormone (GH) stimulation tests. It is therefore believed that children diagnosed with GHD form a heterogeneous group with growth disorder frequently independent on GH function. No study evaluating the complex etiology of growth failure in children with diagnosed GHD has been performed thus far. To discover genetic etiology of short stature in children with diagnosed GHD from families with short stature. Fifty-two children diagnosed with primary GHD and vertically transmitted short stature (height SDS in the child and his/her shorter parent <-2 SD) were included to our study. The GHD diagnosis was based on growth data suggestive of GHD, absence of substantial disproportionality (sitting height to total height ratio <-2 SD or >+2 SD), IGF-1 levels <0 for age and sex specific SD and peak GH concentration <10 ug/L in two stimulation tests. All children were examined using next-generation sequencing methods, and the genetic variants were subsequently evaluated by American College of Medical Genetics standards and guidelines. The age of children at enrollment into the study was 11 years (median, IQR 9-14 years), their height prior to GH treatment was -3.0 SD (-3.6 to -2.8 SD), IGF-1 concentration -1.4 SD (-2.0 to -1.1 SD), and maximal stimulated GH 6.3 ug/L (4.8-7.6 ug/L). No child had multiple pituitary hormone deficiency or a midbrain region pathology. Causative variant in a gene that affects growth was discovered in 15/52 (29%) children. Of them, only 2 (13%) had a genetic variant affecting GH secretion or function (GHSR and OTX2). Interestingly, in 10 (67%) children we discovered a primary growth plate disorder (ACAN, COL1A2, COL11A1, COL2A1, EXT2, FGFR3, NF1, NPR2, PTPN11 [2x]), in one (7%) a genetic variant impairing IGF-1 action (IGFALS) and in two (12%) a variant in miscellaneous genes (SALL4, MBTPS2). In children with vertically transmitted short stature, genetic results frequently did not correspond with the clinical diagnosis of GH deficiency. These results underline the doubtful reliability of methods standardly used to diagnose GH deficiency.

ODP379 Brain MRIs may be value in children with isolated growth hormone deficiency whose peak GH level below 5 ng/mL in two growth hormone provocation test

Abstract Brain MRIs are considered essential in the evaluation of children diagnosed with growth hormonedeficiency (GHD), but there is uncertainty about the appropriate cut-off for diagnosis of GHD and little data about the yield of significant abnormal findings in patients with peak growth hormone (GH) of 7–10 ng/mL. We aimed to assess the frequency of pathogenic MRIs and associated risk factors in relation to peak GH concentrations. In this retrospective multicenter study, charts of patients diagnosed with GHD who subsequently had a brain MRI were reviewed. MRIs findings were categorized as normal, incidental, of uncertain significance, or pathogenic pituitary hypoplasia, small stalk and/or ectopic posterior pituitary and tumors. Of the 379 patients with GHD, 60.4% had normal MRIs. 22.4% had incidental findings, 3.2% had pathogenic findings including ectopic pituitary gland, pituitary hypoplasia, and pituitary stalk interruption syndrome. Patient with peak GH level &amp;lt;5 ng/mL had a significantly higher prevalence of pathogenic findings. Presentation: No date and time listed

Growth Hormone Stimulation Testing Patterns Contribute to Gender Disparities in Growth Hormone Treatment

Introduction: Growth hormone (GH) registries demonstrate that males outnumber females 2:1 for all indications combined and 3:1 for the idiopathic short stature indication. The aim of this study was to determine if gender disparities in GH treatment are due to differences in rates of stimulation testing and/or GH prescribing. Methods: Retrospective chart review was performed including children aged 2-16 years seen for short stature or poor growth in 2012-2019 at a large tertiary referral center. Children previously diagnosed with GHD were excluded. Continuous variables, reported as medians [IQR], were compared by Wilcoxon rank sum test and categorical variables by Chi-squared test. A two-tailed p-value <0.05 defined statistical significance. Results: Of 10,125 children seen for evaluation of short stature or poor growth (35% [3542] females [F], 65% [6583] males [M]), 1,245 underwent GH stimulation testing (30% [379] F, 70% [866] M). A larger proportion of males than females were tested (M 13.2%, F 10.7%; p <0.001). Amongst the entire study population, females had lower height Z-scores than males (F -1.98 [-2.46, -1.44], M -1.80 [-2.24, -1.31]; p<0.001). This difference persisted in those who proceeded to GH stimulation testing (F -2.52 [-3.00, -2.04], M -2.18 [-2.6, -1.81]; p<0.001) and GH treatment (F -2.62 [-3.11, -2.07], M -2.19 [-2.60, -1.81; p<0.001). Mean difference between height Z-score and mid-parental height (MPH) Z-score for the entire population did not differ by sex (F -1.52 [-2.17, -0.87], M -1.52 [-2.04, -0.97]; p=0.76), but the difference was greater in females among those who underwent GH stimulation testing (F -1.95 [-2.57, -1.40], M -1.79 [-2.32, -1.32]; p=0.009) and started GH treatment (F -1.93 [-2.58, -1.48], M -1.80 [-2.30, -1.32]; p=0.016). Peak stimulated GH levels were similar for males and females (F 9.6 [6.0, 13.6] ng/mL, M 9.4 [6.1, 13.2] ng/mL, p=0.62). The proportion of children prescribed GH after stimulation testing did not differ by gender (F 55% [208], M 56% [488]; p=0.63). This finding did not change upon sub-analysis by peak stimulated GH concentration groups (peak GH concentrations <7 ng/mL, 7-10 ng/mL, and >10 ng/mL). Conclusion: The male predominance among children seen for subspecialist evaluation of short stature was compounded by a greater proportion of those males subsequently undergoing GH stimulation testing despite less severe short stature. Although females who underwent GH stimulation testing had greater height deficit from their genetic potential than tested males, peak stimulated GH concentrations and GH prescription rates were similar by sex. Thus, gender disparities in GH treatment occur at the subspecialist referral and stimulation testing, but not GH prescription, steps. Further, GH stimulation test results failed to account for the more severe shortness among tested females, yet another limitation identified with such testing.

Impact of IGF-1 Normative Datasets on Indication and Outcome of Growth Hormone Stimulation Testing

In the Netherlands, the diagnosis of growth hormone deficiency in children follows the Dutch national guidelines for Triage and Diagnosis of Growth Disorders in Children. Initial biochemical evaluation includes an IGF-1 measurement as screening parameter for growth hormone deficiency. Based on the clinical probability of growth hormone deficiency and the IGF-1 Z-score, a growth hormone stimulation test is performed if serum IGF-1 Z-score is < 0 SD in case of a high probability and if serum IGF-1 Z-score is < -1 SD in case of low probability. An IGF-1 Z-score > 0 SD virtually excludes a growth hormone deficiency disorder. The interpretation of growth hormone stimulation testing is dependent on both the peak growth hormone concentration, but also on the baseline IGF-1 Z-score, particularly in cases of partial deficiency. Although, nation wide, Dutch laboratories have harmonized their measurement for IGF-1 (as was previously done for growth hormone), a Dutch harmonized normative data set has not been widely adopted. Moreover a clinical evaluation of the implementation of this dataset based on dynamic testing has not been published. To assess the impact of choice of a particular normative dataset on the diagnosis of growth hormone deficiency we recalculated Z-scores of IGF-1 measurements between 2016 and 2019, using our home reference values based on de normative dataset by Elmlinger (E)1, and using the normative datasets defined by Bidlingmaier (B)2 and by the Dutch IGF-1 harmonization program (NL). Based on these three Z-scores, the outcomes of growth hormone stimulation tests performed in this period (n=86) were reassessed according to the interpretation described in the Dutch guideline. Using all three normative datasets the same 4 patients were identified as likely to have a growth hormone deficiency, whereas 10(E), 10(B), or 8(NL) patients were identified as possible partial growth hormone deficiency. In 70(E), 66(B) or 72(NL) patients the growth hormone stimulation test was unaffected. Using normative dataset B, 6 patients displayed a pattern associated with a possible growth hormone resistance, or of bio-inactive growth hormone syndromes, which based on its incidence would be unlikely for a secondary care setting. A striking observation was however, that of all patients with a normal stimulation test 9 (E)/16 (B) or 30 (NL) had a IGF-1 Z-score of > 0 SD. This implies that, for the diagnosis of growth hormone deficiency, it is safe to implement the Dutch harmonized dataset, which in addition could result in a reduction in the number of growth hormone stimulation tests that have to be performed.

Racial/Ethnic Disparities in the Investigation and Treatment of Pediatric Growth Hormone Deficiency

Introduction: In the United States, non-Hispanic white (NHW) children are disproportionately over-represented relative to children of racial and ethnic minorities in pediatric growth hormone (GH) treatment registries. This study sought to determine if this racial inequity is due to differences in GH stimulation testing and/or GH prescribing patterns in children referred for endocrine evaluation of short stature. Methods: Retrospective chart review was performed including children aged 2-16 years, with height z-score ≤ -1.5, and of NHW, non-Hispanic black (NHB) or Hispanic race/ethnicity, referred for endocrine growth evaluation between January 1, 2012 and December 31, 2019. Age, sex, anthropometry, GH stimulation test results and GH treatment data were extracted. Comparisons between NHB, NHW and Hispanic children were performed using analysis of variance, chi-squared tests, Mann Whitney U and logistic regression tests. Results: This study included 7,425 patients (5,905 NHW, 800 NHB, and 720 Hispanic). GH stimulation testing was performed in 992, and 576 were prescribed GH. NHW children were 1.4 (95% CI 1.04 - 1.8) times more likely than NHB children and 1.7 (95% CI 1.2 - 2.2) times more likely than Hispanic children to undergo GH stimulation testing. NHB children treated with GH had: 1) lower median peak GH concentration when compared with NHW (p=0.02) and Hispanic (p=0.08) children (NHB 4.7 [1.2, 8.3] ng/ml, NHW 7.2 [4.9, 9.7] ng/ml, Hispanic 7.1 [4.3, 11.9] ng/ml); 2) lower median height z-scores than NHW (p=0.01) but not Hispanic children (p=0.5); and 3) a greater height deficit from mid-parental height when compared with NHW (p=0.01) and Hispanic (p=0.002) children Discussion: Racial and ethnic disparities are present in the evaluation and treatment of children with disordered growth. This likely results from both over-investigation of NHW children as well as under-investigation and under-treatment of children from minority communities. The evaluation and treatment of children with short stature should be determined by clinical concern alone, but this is unfortunately not current practice.

Racial and Ethnic Disparities in the Investigation and Treatment of Growth Hormone Deficiency

To determine if the racial/ethnic inequity in growth hormone (GH) use is due to differences in GH stimulation testing and/or prescribing patterns in children referred for endocrine evaluation of short stature. Retrospective chart review was performed including children aged 2-16years, height z-score of ≤-1.5, and of non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic race/ethnicity, referred for endocrine growth evaluation between January 2012 and December2019. This study included 7425 children (5905 NHW, 800 NHB, and 720 Hispanic). GH stimulation testing was performed in 992, and 576 were prescribed GH. NHW children were 1.4 (95% CI, 1.04-1.8) times more likely than NHB children and 1.7 (95% CI, 1.2-2.2) times more likely than Hispanic children to undergo GH stimulation testing. GH-treated NHB children had (1) a lower median peak GH concentration when compared with NHW (P=.02) and Hispanic (P=.08) children (NHB 4.7ng/mL [95% CI, 1.2-8.3ng/mL] ng/mL, NHW 7.2ng/mL [95% CI, 4.9-9.7ng/mL], Hispanic 7.1ng/mL [95% CI, 4.3-11.9ng/mL]); (2) lower median height z-scores than NHW (P=.01) but not Hispanic children (P=.5); and (3) a greater height deficit from midparental height when compared with NHW (P=.01) and Hispanic (P = .002) children. Racial and ethnic disparities exist in the evaluation and treatment of children with disordered growth. This likely results from both overinvestigation of NHW children as well as underinvestigation and undertreatment of children from minority communities. The evaluation and treatment of children with short stature should be determined by clinical concern alone, but this is not current practice.

Brain MRIs may be of low value in most children diagnosed with isolated growth hormone deficiency.

Brain MRIs are considered essential in the evaluation of children diagnosed with growth hormone deficiency (GHD), but there is uncertainty about the appropriate cut-off for diagnosis of GHD and little data about the yield of significant abnormal findings in patients with peak growth hormone (GH) of 7-10ng/mL. We aimed to assess the frequency of pathogenic MRIs and associated risk factors in relation to peak GH concentrations. In this retrospective multicenter study, charts of patients diagnosed with GHD who subsequently had a brain MRI were reviewed. MRIs findings were categorized as normal, incidental, of uncertain significance, or pathogenic (pituitary hypoplasia, small stalk and/or ectopic posterior pituitary and tumors). Charges for brain MRIs and sedation were collected. In 499 patients, 68.1% had normal MRIs, 18.2% had incidental findings, 6.6% had uncertain findings, and 7.0% had pathogenic MRIs. Those with peak GH<3ng/mL had the highest frequency of pathogenic MRIs (23%). Only three of 194 patients (1.5%) with peak GH 7-10ng/mL had pathogenic MRIs, none of which altered management. Two patients (0.4%) with central hypothyroidism and peak GH<4ng/mL had craniopharyngioma. Pathogenic MRIs were uncommon in patients diagnosed with GHD except in the group with peak GH<3ng/mL. There was a high frequency of incidental findings which often resulted in referrals to neurosurgery and repeat MRIs. Given the high cost of brain MRIs, their routine use in patients diagnosed with isolated GHD, especially patients with peak GH of 7-10ng/mL, should be reconsidered.

A Correlation between Serum Level of Alkaline Phosphatase and Acne Severity in Children and Adolescents: A Retrospective Cross-Sectional Study.

BackgroundAcne is a chronic inflammatory disease of the pilosebaceous unit and usually affects adolescents when the peak concentrations of growth hormone, insulin-like growth factor 1, and androgen are demonstrated. The activity of alkaline phosphatase (ALP), which increases physiologically in growing children and adolescents, in the pilosebaceous unit has been reported. However, the correlation between the serum level of ALP and the number of acne lesions has not been studied.ObjectiveThe present cross-sectional study was designed to evaluate the correlation between serum level of ALP and the numbers of non-inflammatory and inflammatory acne lesions in children and adolescents.MethodsFor this study, 202 pediatric and adolescent patients clinically diagnosed with acne vulgaris were included. Age, sex, serum level of ALP, number of non-inflammatory acne lesions, number of inflammatory acne lesions, and number of total acne lesions were evaluated. Additionally, the serum level of dehydroepiandrosterone sulfate was evaluated in 117 patients. Multiple regression analysis was performed. Multicollinearity was quantified using the variance inflation factor.ResultsIn the 202 patients, serum level of ALP was the only independent factor that significantly affected both the number of non-inflammatory acne lesions and of total acne lesions (regression coefficient=0.089 and 0.086, respectively, p<0.001).ConclusionThere was a significant correlation between serum level of ALP and the extent of acne (non-inflammatory acne lesions and total acne lesions).

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.

Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats.

PurposeGrowth hormone secretagogues (GHSs) possess the ability to release growth hormone (GH) in the body. This study aimed to investigate the effects of MK-677, an orally active GHS, on somatic growth in rats.Materials and MethodsThe serum levels of GH were measured after oral administration of MK-677 to confirm GH stimulatory effects. Body weight, body length, tibia length, epiphyseal plate width, and serum levels of insulin-like growth factor (IGF)-I were measured after oral administration of 4 mg/kg of MK-677 for 6 weeks to investigate growth-promoting effects.ResultsOral administration of MK-677 at 4 mg/kg increased peak GH concentrations by 1.8-fold, compared to baseline. However, oral administration of MK-677 for 6 weeks did not increase body growth or serum levels of IGF-I. At 6 weeks after treatment, the GH response to MK-677 was abolished. Pituitary GH mRNA and hypothalamic GH-releasing hormone mRNA, and GH secretagogue receptor (GHSR) mRNA expression in the pituitary and hypothalamus did not differ between the control and treatment group. Somatostatin (SST) mRNA expression in the hypothalamus was markedly increased in the treatment group, whereas SST receptor (SSTR)-2 mRNA expression in the pituitary gland was decreased. Protein expression of hypothalamic GHSR, SST, and pituitary SSTR-2 showed patterns similar to those for mRNA expression.ConclusionOur results suggest that prolonged administration of MK-677 in rats does not promote growth despite the GH stimulatory effect of MK-677, which may be related to increased expression of SST in the hypothalamus. Further studies are needed to overcome the observed desensitization to GHS.

Increases in Serum Growth Hormone Concentrations Associated with GHB Administration.

The administration of gamma-hydroxybutyrate (GHB) has been reported to augment the increase in growth hormone (GH) secretion associated with the onset of sleep. The ability of GHB to stimulate GH production in the absence of sleep in both male and female volunteers was investigated as part of a GHB administration study. Twelve healthy volunteers (six men and six women) were given a small oral dose (25 mg/kg) of GHB (as Xyrem®) at 10:00 h. Basal blood samples (as serum) were taken 10 min prior to GHB administration, with additional samples taken at 10, 15, 20, 25, 30, 45, 60, 90, 120, 150, 180, 240, 360 and 480 min post-administration. The serum concentrations of GHB were measured by GC-MS and GH by immunometric assay. Following GHB administration, volunteers exhibited effects consistent with mild sedation, i.e., relaxed with normal responses to verbal stimuli. Despite none being asleep, an increase in serum GH concentration occurred in 11 out of the 12 volunteers (5 women and 6 men). In these volunteers, peak GH concentrations occurred 45-60 min post-administration compared with a mean serum tmax for GHB of 23 min (SD = 5.4 min). The absolute increase in GH was similar formen and women, averaging 3.4 and 3.7 ng/mL, respectively. The mean intra-individual increase in GH was much greater in males (29 times) compared with females (2 times), as males had (as expected) smaller basal GH concentrations (mean = 0.26 ng/mL) compared with females (mean = 5.4 ng/mL). After maximizing, the GH concentration decreased rapidly (in agreement with GHB concentrations), returning to basal concentrations at ~90-120 min post-administration. GHB administration at a small therapeutic dose results in increases in serum GH concentrations in healthy male and female volunteers in the absence of sleep onset.

Circadian variations in peripheral levels of growth hormone and testosterone in male Murrah buffaloes

The aim of this study was to investigate the endocrine profiles of growth hormone (GH), testosterone and their interrelationship in prepubertal, pubertal and orchiectomised male Murrah buffaloes under starving conditions. The prepubertal and pubertal buffaloes were subjected to frequent blood sampling over 24 h at an interval of 1 h, whereas in orchiectomised buffaloes, the blood samples were collected over 18 h. Irrespective of group, the GH concentrations fluctuated in an episodic manner over 24 h and the fluctuations did not exhibit a consistent pattern between the animals of each group. The mean basal and peak concentrations of GH did not differ significantly (p > 0.05) among the groups. A significant (p > 0.0001) difference in testosterone concentrations was observed between prepubertal and pubertal groups. The differences in mean basal and peak testosterone concentrations between the prepubertal and pubertal groups were also significant (p < 0.01). The associations between testosterone and GH levels in both prepubertal (r = 0.15; p > 0.05) and pubertal (r = −0.37; p > 0.05) buffaloes were non-significant. The possible reasons for erratic episodic pattern of GH secretion will be discussed.

Endocrine Responses to Exercise in the Developing Child and Adolescent.

The impact of exercise training on the neuroendocrine control of the pituitary in the developing child is complex and the exact mechanisms are not fully understood. Multiple determinants influence adaptive hypothalamic-pituitary secretory responses to physical stress, namely, training intensity and duration, nutrition and energy balance, gender, age, sex, and sexual maturation status. The increase in growth hormone (GH) in response to acute exercise is dependent on pubertal status; children in more advanced pubertal stages respond with larger peak GH concentrations compared to those in earlier stages. The adolescent female athlete is more prone to menstrual disorders than the more mature athlete, and recent data suggest that athletes may be able to reverse menstrual disorders by increasing their dietary energy intake without decreasing their exercise levels. The thyroid changes observed are of minor impact, practically reflecting the relative negative energy balance during strenuous exercise. Studies that evaluated changes in cortisol secretion during aerobic exercise in children and adolescents show either an increase or no change in response to the exercise bout. Recent research showed that physical activity is an important contributor to bone strength prior to adolescence and increasing levels of physical activity during childhood likely enhance optimal bone strength.

Analysis of the clinical and molecular characteristics of a child with achondroplasia: A case report.

Achondroplasia (ACH) is a hereditary dwarfism caused by the disturbed proliferation and differentiation of growth plate chondrocytes, followed by impaired endochondral bone growth. ACH is caused by mutations in the gene encoding the transmembrane receptor, fibroblast growth factor receptor 3 (FGFR3). In total, >90% of patients with ACH have a G1138A mutation in the transmembrane domain of the FGFR3 gene. Patients with ACH usually have no growth hormone (GH) deficiency. The current study presents the case of a four-year-old male with clinical manifestations suggestive of ACH, including a large head, prominent forehead, short upper arms and legs, and short hands with fingers assuming a trident position. The patient showed normal responses to GH provocation tests with L-dopa (peak GH concentration, 42.38 ng/ml) and insulin (peak GH concentration, 23.29 ng/ml during hypoglycemia), but a blunted response to a GH provocation test with arginine (peak GH concentration, 7.31 ng/ml). Furthermore, the GH concentration during exercise was low (4.8 ng/ml). Magnetic resonance imaging revealed a decreased pituitary volume. Thyroid function tests and the levels of sex hormones (follicle stimulating hormone, luteinizing hormone, estradiol, prolactin and progesterone), cortisol and adrenocorticotropic hormone were normal. A heterozygous G1138A mutation within the FGFR3 gene was detected, confirming the diagnosis of ACH. Thus, recombinant human GH therapy (0.1 IU/kg/day) was initiated. At the six-month follow-up, the height, arm span-to-height ratio and lower limb length-to-height ratio of the patient had increased, while the head circumference had decreased. The present results corroborate the finding that the G1138A mutation within FGFR3 is the most common ACH-causing mutation in different populations. GH may be beneficial in the treatment of short stature in ACH patients with subnormal GH secretion.

Exercise-Induced growth hormone during acute sleep deprivation.

The effect of acute (24‐h) sleep deprivation on exercise‐induced growth hormone (GH) and insulin‐like growth factor‐1 (IGF‐1) was examined. Ten men (20.6 ± 1.4 years) completed two randomized 24‐h sessions including a brief, high‐intensity exercise bout following either a night of sleep (SLEEP) or (24‐h) sleep deprivation (SLD). Anaerobic performance (mean power [MP], peak power [PP], minimum power [MinP], time to peak power [TTPP], fatigue index, [FI]) and total work per sprint [TWPS]) was determined from four maximal 30‐sec Wingate sprints on a cycle ergometer. Self‐reported sleep 7 days prior to each session was similar between SLEEP and SLD sessions (7.92 ± 0.33 vs. 7.98 ± 0.39 h, P =0.656, respectively) and during the actual SLEEP session in the lab, the total amount of sleep was similar to the 7 days leading up to the lab session (7.72 ± 0.14 h vs. 7.92 ± 0.33 h, respectively) (P =0.166). No differences existed in MP, PP, MinP, TTPP, FI, TWPS, resting GH concentrations, time to reach exercise‐induced peak GH concentration (TTP), or free IGF‐1 between sessions. GH area under the curve (AUC) (825.0 ± 199.8 vs. 2212.9 ± 441.9 μg/L*min, P <0.01), exercise‐induced peak GH concentration (17.8 ± 3.7 vs. 39.6 ± 7.1 μg/L, P <0.01) and ΔGH (peak GH – resting GH) (17.2 ± 3.7 vs. 38.2 ± 7.3 μg/L, P <0.01) were significantly lower during the SLEEP versus SLD session. Our results indicate that the exercise‐induced GH response was significantly augmented in sleep‐deprived individuals.

Adult Growth Hormone Deficiency: Current Concepts

The clinical syndrome of adult growth hormone deficiency (AGHD) was widely recognized in the 1980s. In this review, we first describe the clinical features and diagnosis of AGHD and then state the effects of growth hormone (GH) therapy for these patients. The main characteristics of AGHD are abnormal body composition, dyslipidemia, insulin resistance, and an impaired quality of life (QoL) due to decreased psychological well-being. For diagnosing AGHD, the international consensus guidelines have suggested that an insulin tolerance test (ITT) is the gold standard, but in Japan, the growth hormone releasing peptide-2 (GHRP-2) test is available and is recommended as a convenient and safe GH stimulating test. The cut-off for diagnosing severe AGHD is a peak GH concentration of 9 g/L during the GHRP-2 test. Since 2006, GH therapy has been approved for Japanese patients with severe AGHD. For adults, GH replacement therapy should be initiated at a low dose (3 g/kg body weight/day), followed by individualized dose titration while monitoring patients' clinical status and serum insulin-like growth factor-I (IGF-I) concentrations. A variety of favorable effects of GH replacement have been indicated; however, it has not yet been established fully whether there is a direct effect of GH treatment on reducing mortality.

Urinary growth hormone level and insulin-like growth factor-1 standard deviation score (IGF-SDS) can discriminate adult patients with severe growth hormone deficiency

Adult growth hormone (GH) deficiency (AGHD) in Japan is diagnosed based on peak GH concentrations during GH provocative tests such as GHRP-2 stimulation test. In this study, we aimed to evaluate the ability of serum insulin-like growth factor-1 (sIGF-1) and urinary GH (uGH) at the time of awakening to diagnose AGHD. Fifty-nine patients with pituitary disease (32 men and 27 women; age 20-85 y (57.5 ± 15.5, mean ± SD) underwent GHRP-2 stimulation and sIGF-1 testing. Thirty-six and 23 patients were diagnosed with and without severe AGHD, respectively based on a peak GH response of <9 ng/mL to GHRP-2 stimulation. Serum IGF-1 was evaluated as a standard deviation score (IGF-1 SDS) based on age and sex. We determined whether uGH levels in urine samples from 42 of the 59 patients at awakening were above or below the sensitivity limit. We evaluated IGF-1 SDS and uGH levels in a control group of 15 healthy volunteers. Values for IGF-1 SDS were significantly lower in patients with, than without (-2.07 ± 1.77 vs.-0.03 ± 0.92, mean ± SD; p < 0.001) AGHD whereas the range of IGF-1 SDS substantially overlapped at > -1.4. IGF-1 SDS discriminated AGHD more effectively in patients aged ≤60 years. The χ2 test revealed a statistical relationship between uGH and AGHD (test statistic: 7.0104 ≥ χ2 (1; 0.01) = 6.6349). When IGF-1 SDS is < -1.4 or uGH is below the sensitivity limit, AGHD can be detected with high sensitivity.

Resistance exercise‐induced hormonal response under the influence of delayed onset muscle soreness in men and boys

It was hypothesized that exercise-induced muscle damage (EIMD)-related alterations in hormonal responses could be observed if a second exercise bout is performed soon after an identical unaccustomed bout leading to delayed onset muscle soreness (DOMS). Eight men (31 ± 7 years) and eight boys (14 ± 0 years) performed two exercise bouts (E1 and E2, with 48 h rest in between) consisting of three sets of bilateral knee extensions until exhaustion with 40% load. No differences between the groups or bouts were observed in the number of repetitions performed and maximal isometric force decline, or between groups in serum creatine kinase activity and DOMS. Decreased peak epinephrine (EPI) (-38%), growth hormone (GH) (-45%) and cortisol (COR) (-31%) concentrations were found in E2 in men (P<0.05). In men, the peak GH concentration was also lower in E2 and COR was higher in both bouts than in boys. No changes in norepinephrine and testosterone responses were found in either group. The results suggest that in men, the responses of EPI, GH and COR are attenuated when the second bout is performed under the influence of DOMS. In boys, the lack of this attenuation may not be explained by less severe EIMD.