Severe Growth Hormone Deficiency Research Articles

Exploring the sex difference in cardiovascular risk during Growth Hormone Therapy in adults.

Given the previously identified sex differences in cardiovascular morbidity and mortality in patients with growth hormone deficiency (GHD) receiving GH replacement therapy (GHRT), our aim is to investigate sex specific differences in the efficacy of (long-term) GHRT on cardiovascular (CV) risk profile and disease in subjects with GHD. Our hypothesis is that women will experience less beneficial effects than men. Retrospective nationwide cohort study. We compared all men (n = 1335) and women (n = 1251) with severe GHD registered in the Dutch National Registry of GH Treatment in Adults database with respect to cardiovascular risk profile and morbidity at baseline and during follow-up. Men had a more unfavourable CV risk profile at baseline. During the first years of GHRT, the reduction in waist circumference, waist-to-hip ratio, total cholesterol and triglyceride levels was greater in men than in women (all p < 0.05). Between-sex differences in effects during later follow-up were less clear. No sex differences were found in the risk of developing non-fatal cardio- or cerebrovascular disease during GHRT. Our results suggest that men with GHD did indeed experience more beneficial effects of GHRT on body composition and lipoprotein metabolism than women, at least in the early years of treatment. Also, the more unfavourable CV risk profile at baseline in men did not translate into a sex difference in the risk of developing cardiovascular and cerebrovascular morbidity during GHRT.

Auxological, Clinical, and MRI Abnormalities in Pediatric Patients With Isolated Growth Hormone Deficiency.

This study aimed to assess the auxological, clinical, and MRI features of pediatric patients with isolated growth hormone deficiency (GHD) by analyzing the demographic and clinical characteristics of the study cohort. A cohort of 115 pediatric patients diagnosed with isolatedGHD was included. The patients were evaluated at a tertiary center in Jeddah, Saudi Arabia. Collected data included demographic information and auxological evaluations, such as height standard deviation (SD), height centile, weight SD, weight centile, and bone age SD. Neuroradiological assessments, particularly magnetic resonance imaging (MRI) of the hypothalamic-pituitary region, were collectedto identify any structural abnormalities contributing to GHD. A total of 67 (SD 58.3) were males. The mean age was 9.55 years (SD 3.45). The mean bone age was 7.37 years (SD 3.24), indicating delayed bone development. Height measurements reflected a significant growth impairment, with a mean height SD of -2.45 (SD 1.12). Out of the 115 pediatric patients in the study cohort, 84 (73%) underwent neuroradiological assessments using brain MRI. Among these, 12% were found to have MRI abnormalities. The prevalence of MRI abnormality in the subgroup with severe growth hormone deficiency was higher, reaching 21%. The peak growth hormone (GH) in the growth hormone stimulation test was 6.38 ng/mL (SD 3.24). There was a significant difference in the peak GH levels between the subgroup of patients with normal MRI findings (mean 6.02 ng/mL, SD 2.47) and those with abnormal MRI findings (mean 3.2 ng/mL, SD 2.8) (p=0.01). Children with isolated GHD exhibited significant growth impairment and clinical characteristics consistent with thedisorder. Neuroradiological abnormalities are common among patients with severe growth hormone deficiency; therefore, radiological assessment including MRI of the pituitary gland is recommended in patients with severe isolated growth hormone deficiency.

The influence of pituitary volume on the growth response in growth hormone-treated children with growth hormone deficiency or idiopathic short stature.

Magnetic resonance imaging (MRI) can be used for assessing the morphology of the pituitary gland in children with short stature. The purposes of this study were: (1) to determine if pituitary volume (PV) can distinguish patients with growth hormone (GH) deficiency from those with idiopathic short stature (ISS), (2) to validate an association between PV and severity of GH deficiency, and (3) to compare PV between good and poor response groups in children with GH deficiency or ISS after 1 year of treatment. Data were collected from the medical records of 152 children with GH deficiency or ISS who underwent GH stimulation test, sella MRI, and GH treatment for at least 1 year. Estimated PVs were calculated using the formula of an ellipsoid. We compared the PVs in patients with GH deficiency with those of patients with ISS. In addition, we assessed the association between PV and severity of GH deficiency, and we assessed growth response after treatment. No difference was observed in PV between patients with GH deficiency and those with ISS. The severity of the GH deficiency seemed to be associated with PV (P=0.082), and the height of the pituitary gland was associated with severity of GH deficiency (P<0.005). The PV in the good response group was less than that of the poor response group in patients with GH deficiency (P<0.005), and PV showed no association with responsiveness to GH treatment in patients with ISS (P=0.073). The measurement of PV cannot be used for differential diagnosis between GH deficiency and ISS. In patients with GH deficiency, PV tended to be smaller as the severity of GH deficiency increased, but the difference was not significant. PV may be a good response predictor for GH treatment. Further studies, including a radiomics-based approach, will be helpful in elucidating the clinical implications of pituitary morphology in patients with short stature.

Effect of GH Deficiency Caused by Nonfunctioning Pituitary Masses on Serum C-reactive Protein Levels.

GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear. We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels. We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst. Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without (P < .001) and significantly correlated with the peak GH (r = -0.50, P < .001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (β = -0.345; 95% CI, -0.533 to -0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [β] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (β = -0.391; 95% CI, -0.675 to -0.108), independent of alterations in other anterior hormones and metabolic parameters. The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP.

THU069 Growth Hormone Secretion And Serum High-sensitivity C-reactive Protein Levels In Adult Patients With Non-functioning Pituitary Tumors

Abstract Disclosure: Y. Seki: None. S. Morimoto: None. K. Bokuda: None. D. Watanabe: None. S. Watanabe: None. K. Yamashita: None. N. Takano: None. A. Ichihara: None. Background: Growth hormone (GH) deficiency, which causes visceral obesity and non-alcohol fatty liver disease, increases cardiovascular event risks. Serum high-sensitivity C-reactive protein (hs-CRP) levels has been reported to estimate those risks. GH supplementation therapy was reported to decrease the serum hs-CRP levels in GH deficient patients, however, the association between GH secretion and serum hs-CRP levels have been unclear. Patients and Methods: We retrospectively reviewed charts of the patients with non-functioning pituitary adenoma and Rathke’s cysts who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests to assess GH secretion, and investigated the association between GH secretion and background characteristics. Patients who had a history of pituitary surgery, severe renal insufficiency or active inflammatory diseases, or received GH supplementation therapy were excluded. Results: Among 171 patients (100 NFPA and 71 Rathke’s cysts), 55 (32%) presented severe GH deficiency, as diagnosed using GHRP-2 tests. Serum hs-CRP levels were significantly higher in the patients with severe GH deficiency than in those without severe GH deficiency (754 [393—1330] vs 249 [113—537] ng/mL, P &amp;lt; 0.001). Serum hs-CRP levels were significantly correlated with logarithm of peak GH response to GHRP-2 (r = -0.50, P &amp;lt; 0.001), but not with IGF-1 SD score (r = -0.10, P = 0.21). In the multiple regression analysis, peak GH response to GHRP-2 was a significant variable for determining serum hs-CRP levels (β = -0.340, P = 0.001) after adjustment with age, sex, BMI, smoking habit, alcohol consumption, hypertension, diabetes mellitus, dyslipidemia, abnormal liver function, and other pituitary hormone deficiencies. Severe GH deficiency were significantly associated with for serum hs-CRP levels higher than 1000 ng/mL (Odds ratio, 2.58 ;95% Confidence interval 1.15-5.78) when adjusted for obesity and abnormal liver function. Conclusion: GH secretion was significantly and negatively associated with serum hs-CRP levels independent of atherosclerotic risk factors, metabolic complications of GH deficiency, and other anterior pituitary hormone secretions. Presentation: Thursday, June 15, 2023

THU172 Accuracy Of The Glucagon Testing In The Diagnosis Of Growth Hormone Deficiency During Transition

Abstract Disclosure: N. Di Iorgi: None. D. Guglielmi: None. N. Flavia: None. A. Allegri: None. D. Fava: None. E. Casalini: None. G. Patti: None. M. Maghnie: None. Objectives: To evaluate the accuracy of the Glucagon test (GST) compared with the Insulin Tolerance test (ITT) as the gold standard in the diagnosis of Growth Hormone deficiency (GHD) in young adults with childhood-onset GHD (COGHD). Methods: Eighty-six subjects with COGHD (33F, 55M) were evaluated by ITT and GST stimulation tests and IGF-1 SDS at adult height achievement (median age of 17.5; IQR 13.9-18.4 years). Subjects were recruited from a single Center and based on the AACE 2019 Guidelines [1] classified as 1. idiopathic isolated GHD (I-GHD n=40 with normal brain MRI); 2. organic moderate GHD (omGHD with less than 3 pituitary deficiencies-PD and IGF-1&amp;lt;0 SDS, total n=40; n=12 midline defects, n=2 ALL, n=26 CNS tumors); 3. congenital/genetic defects/organic severe GHD (osGHD ≥3 PD and IGF-1 &amp;lt;-2 SDS, total n=6; n=1 midline defect, n=5 CNS tumors). ROC analyses were performed in order to analyze the Sensitivity (Se) and Specificity (Sp) of the GH peak after GST and of IGF-1 SDS compared to ITT. A peak GH value &amp;lt;6μg/L after ITT was suggestive of permanent GHD [2]. Results: Median GH peak to ITT (0.2; IQR 0.01-0.7 μg/L) and GST (0.1; IQR 0.01-1.4μg/L) were lower in osGHD compared to I-GHD subjects (15.0; IQR 8.6-21.9 to ITT and 12.6; IQR 10.5-18.8 μg/L to GST, P’s &amp;lt;0.0001); similarly, GH peak to ITT (2.1; IQR 1.1-6.8 μg/L) and GL (2.7; IQR 1.2-5.8) were lower in omGHD compared to I-GHD subjects (P’s &amp;lt;0.0001). Mean IGF-1 were also lower in osGHD (-3.2 SDS; IQR -7.4- -2.9, P&amp;lt;0.0001) and in omGHD (-2.0 SDS; IQR -2.8 - -0.7; P&amp;lt;0.0001) compared to I-GHD subjects (0,1; IQR -0.6-1.1SDS). A GH peak value to GST of 7.59 mcg/L (Se 92.3%, Sp of 87.2%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 89.5% of the entire cohort while an IGF-1 cut-off of -1.45 SDS (Se 73%; Sp 93.5%; AUC=0.84; 95% CI, 0.75 - 0.94) correctly classified 83,1%. A GH peak value to GST of 5.81 mcg/L (Se 96.6%, Sp of 81.8%; AUC=0.95; 95% CI, 0.88-1.02) correctly classified 92.5% of omGHD patients while an IGF-1 cut-off of -1.64 SDS (Se 72.3%, Sp of 90.9%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 77.5% omGHD patients. Median BMI SDS was higher in patients with osGHD (1.8; IQR 1,6- 2.2, P&amp;lt;0.001) and omGHD (0.6; IQR 0.1- 1.8, P&amp;lt;0.001) compared to I-GHD (0.2; IQR -0.7- 1.1). GH peak to GST correlated with BMI SDS only in the total cohort (r -0.313, P=0.0031). Conclusions: Our results suggest that a peak value &amp;lt;6 μg/L after GST is accurate in detecting permanent GHD during transition in a cohort of patients with organic GHD with less than 3 pituitary defects and IGF-1 values &amp;lt;0 SDS; the GH response to GST could be affected by BMI SDS, but further studies are needed. [1] Yuen KCJ et al. Endocr Pract 2019; 25 (11):1191-1232. [2] Maghnie M et al, EJE 2005; 152:589-596. Presentation: Thursday, June 15, 2023

Discontinuation of long-term growth hormone treatment in adults with severe growth hormone deficiency: A United Kingdom web-based survey of endocrine practice

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

Severe Growth Hormone Deficiency in an Indian Boy Caused By a Novel 6 kb Homozygous Deletion Spanning the GH1 Gene.

Growth disorders resulting in extreme short stature are often a result of deficiency in growth hormone released from the pituitary gland or defective growth hormone releasing receptor. Genetic defects in the GH1 and GHRHR genes account for around 11.1-20% of extreme short stature cases, resulting in a rare condition called Isolated Growth Hormone Deficiency. We describe the characterization of a GH1 genetic defect discovered in a 3-year-old male patient with extreme short stature, developmental failure and undetectable serum levels of growth hormone. There is a familial history of short stature with both parents being short. Whole genome sequencing of the patient DNA revealed a large novel 6 kb homozygous deletion spanning the entire GH1 gene in the patient. While the deletion was homozygous in the subjects, it was found in a heterozygous state in the parents. Thus we report a novel homozygous deletion including the GH1 gene leading to Isolated Growth Hormone Deficiency- Type 1A associated with extreme short stature.

Sheehan syndrome: Cardiovascular and metabolic comorbidities.

Sheehan syndrome (SS) caused by postpartum hemorrhage leads to partial or complete pituitary hormone deficiency. In addition to lipid and glucose abnormalities, patients with SS have increased body fat, insulin resistance (IR), coagulation abnormalities, increased leptin concentration, low-grade inflammation, and endothelial dysfunction that predispose them to cardiovascular diseases. Untreated growth hormone (GH) deficiency, hypogonadism, and excess glucocorticoid use are considered risk factors for these abnormalities. Compared to other hypopituitary subjects, patients with SS are younger and have a longer duration of disease and severe GH deficiency. Replacement with GH in addition to standard hormone replacement improves their cardiometabolic profile.

ODP323 Increased Serum High-Sensitivity C-Reactive Protein Levels in Adult Growth Hormone Deficient Patients with Non-Functioning Pituitary Tumors

Abstract Background Growth hormone (GH) deficiency, a common endocrine deficit in non-functioning pituitary tumors, causes visceral obesity and fatty liver and increases cardiovascular event risks. High-sensitivity C-reactive protein (hs-CRP) has been used as a useful marker to estimate cardiovascular event risks. Because GH supplementation therapy was reported to decrease serum hs-CRP levels in GH deficient patients, inflammatory processes might be activated in GH deficient state, however, the underlying mechanism has been still unknown. Patients and Methods We retrospectively reviewed charts of 134 patients with non-functioning pituitary adenoma and Rathke's cysts who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests and investigated the association between serum hs-CRP levels and background characteristics. Patients who had a history of pituitary surgery, severe renal insufficiency or active inflammatory diseases or received GH supplementation therapy were excluded. GH secretion was determined by GHRP-2 tests. Results Among 134 patients (94 NFPA and 40 Rathke's cysts), 46 (34%) presented severe GH deficiency, as diagnosed using GHRP-2 tests. Serum hs-CRP levels were significantly higher in the patients with severe GH deficiency than in those without severe GH deficiency (723 [299-1285] vs 278 [124-561] ng/mL, P &amp;lt; 0. 001). Serum hs-CRP levels were significantly higher in men (P = 0. 003) and in patients with diabetes mellitus (P = 0. 040) and were significantly correlated with age (r s = 0.19, P = 0. 039), body mass index (r s = 0.37, P &amp;lt; 0. 001), serum levels ofgamma-glutamyl transpeptidase(r s = 0.28, P = 0. 001), creatinine (r s = 0.30, P &amp;lt; 0. 001), low-density lipoprotein cholesterol (r s = 0.21, P = 0. 013), triglyceride (r s = 0.38, P &amp;lt; 0. 001) and free thyroxine (r s = -0.30, P= 0. 001), blood hemoglobin A1c levels (r s = 0.20, P = 0. 018), peak GH response to GHRP-2 (r s = -0.47, P &amp;lt; 0. 001) and IGF-1 SD score (r s = -0.18, P = 0. 040). In the multiple regression analysis, peak GH response to GHRP-2 was a significant variable for determining serum hs-CRP levels (β = -0.340, P = 0. 003) after adjustment with age, sex, BMI, smoking, alcohol consumption, hypertension, diabetes mellitus, serum levels ofgamma-glutamyl transpeptidase, creatinine,triglyceride and free thyroxine and adrenal function. Conclusion We observed a significant association between GH deficiency and increased serum hs-CRP levels independent to BMI and liver dysfunction. GH deficient state might cause inflammation independent to development of visceral obesity and fatty liver. Presentation: No date and time listed

LBODP006 Clinical Usefulness Of The Growth Hormone-releasing Peptide-2 Test For Hypothalamic-pituitary Disorder

Abstract Purpose Growth hormone deficiency (GHD) develops early in patients with hypothalamic-pituitary disorder and is frequently accompanied by other anterior pituitary hormone deficiencies including secondary adrenal insufficiency (AI). A growth hormone-releasing peptide-2 (GHRP2), which is wildly used for the diagnosis of patients with GHD, has been considered to induce not only growth hormone (GH) release but also ACTH release. However, its clinical usefulness in hypothalamic-pituitary disorder is unclear. Methods The GHRP2 test, a cosyntropin stimulation test, corticotropin-releasing hormone (CRH) tests and/or insulin tolerance tests (ITTs) were performed on 36 patients having hypothalamic-pituitary disorder. Results Twenty-two (61%) had severe GHD, and 3 (8%) had moderate GHD by GHRP2. There was no difference in baseline ACTH and cortisol between non-GHD, moderate GHD and severe GHD participants. However, a cosyntropin stimulation test and subsequent CRH tests and/or ITTs revealed that 17 (47%) had secondary AI and 16/17 (94%) cases of secondary AI were concomitant with severe GHD. ROC curve analysis demonstrated that the ACTH response in the GHRP2 test was useful for screening pituitary-AI, with a cut-off value of 1.55-fold (83% sensitivity and 88% specificity). Notably, the combination of ACTH response and the peak cortisol level in the GHRP2 test using each cut-off value (1.55-fold and 10 µg/dl, respectively) showed high specificity (100%) with high accuracy (0.94) for diagnosis of pituitary-AI. Conclusion We recommend measuring ACTH as well as GH during the GHRP2 test to avoid overlooking and delays in diagnosis of secondary AI that frequently accompanies GHD. Presentation: No date and time listed

ODP399 Growth Hormone Peak did not predict presence of Pituitary Stalk Interruption Syndrome

Abstract Background Pituitary stalk interruption syndrome (PSIS) is a congenital abnormality of the pituitary gland characterized by a triad of the thin or interrupted pituitary stalk, aplasia, or hypoplasia of the anterior pituitary and absent or ectopic posterior pituitary. This can be associated with midline defects and pituitary endocrine deficiencies, ranging from isolated growth hormone deficiency to combined pituitary hormone deficiency. PSIS is a rare entity with an estimated incidence rate of 0.5/1,000,000 births. Clinical case: A 3-year-old neurodevelopmentally appropriate male was initially seen at the PCP office for growth failure. After birth, the patient appeared to have normal growth parameters, as he was in the 61st percentile for length and at the 19th percentile for weight. His growth velocity trended downwards, as he dropped to the 34th percentile at nine weeks old and the 2nd percentile by nine months old. PCP records showed that the patient was at the 10th percentile for height at one year old, but by 18-months, he had fallen below the 1st percentile. His mid-parental height was 175cm, between 25th and 50th percentile. Initial workup showed elevated TSH 9.12 mIU/ml (0.5-4.3 mIU/mL) with negative thyroid antibodies, thus started on 25 mcg of levothyroxine. The screen for systemic disease and inflammatory markers was negative. Insulin-like growth factor 1 (IGF-1) was low at &amp;lt;16 ng/mL (24-148 ng/mL) and insulin-like growth factor binding protein-3 (IGFBP-3) was normal at 1.2mcg/ml (0.7-3.6)A growth hormone (GH) stimulation test was obtained due to suboptimal growth, short stature, and undetectable IGF-1 level. The patient failed his GH stimulation study with a GH peak of 5.1 ng/mL (&amp;gt;10) after clonidine and 2ng/ml (&amp;gt;10) after arginine. A clinical and biochemical diagnosis of GHD was made, an MRI was ordered to evaluate for anatomic cause. Brain MRI showed an ectopic posterior pituitary gland with an absent infundibulum, suggesting PSIS. The patient was started on GH therapy with excellent response. He is currently growing well on a low dose of somatropin, around 0.234mg/kg/week. Conclusion PSIS is a congenital pituitary anatomical defect with a heterogeneous presentation. It is typically encountered in infancy and childhood, possibly progressing to panhypopituitarism by adulthood. Diagnosis can be delayed, as brain MRI imaging is not always obtained based on growth hormone peaks. As seen in our patient, the severity of GHD based on peak levels did not adequately predict the presence of brain anomalies. Historically, severe GHD (&amp;lt;5 ng/mL) is strongly associated with brain MRI abnormalities, but GH levels may not suffice to determine the severity of the disease. Based on our findings, we recommend obtaining brain MRI in all patients diagnosed with GHD to identify critical anatomical abnormalities, like PSIS, that require long-term close monitoring of pituitary function. Presentation: No date and time listed

RF26 | PSAT150 Growth Outcomes From the Phase 2 and Phase 3 Studies of Once Weekly Somatrogon vs Daily Genotropin in Pediatric Patients With Growth Hormone Deficiency: Comparisons With Published Literature and an International Growth Study Database

Abstract Background Somatrogon is a long-acting recombinant human growth hormone (hGH) currently in development as a once-weekly injectable treatment for children with growth hormone deficiency (GHD). In a phase 2 (NCT01592500) and a phase 3 (NCT02968004) study, patients received either once-weekly somatrogon or once-daily Genotropin. Aims Compare the phase 2 and 3 study results with growth data from published literature and a database of children treated with once-daily Genotropin. Methods In the 12-month main portion of the phase 2 study (004), patients were randomized to 1 of 3 once-weekly somatrogon doses (0.25, 0.48, and 0.66 mg/kg/week) or once-daily Genotropin (0.24 mg/kg/week). After the main portion of 004, patients continued into the open-label extension (OLE), consisting of an additional 12 months at the original somatrogon dose (Genotropin recipients were randomized to 1 of the 3 somatrogon dose regimens), after which all patients received somatrogon at 0.66 mg/kg/week. In the 12-month main portion of the phase 3 study (006), patients were randomized to once-weekly somatrogon (0.66 mg/kg/week) or once-daily Genotropin (0.24 mg/kg/week). After the main portion of 006, all patients received somatrogon (0.66 mg/kg/week) in an OLE. Four year growth data from 004 and 006 were pooled and analyzed, then compared with growth data from matched subsets of hGH-treated patients as reported by Ranke and Lindberg1 (Genotropin dose: 0.22-0.31 mg/kg/week) and Bakker et al,2 (hGH dose: most patients received 0.3 mg/kg/week) and with data from a matched cohort from the Pfizer International Growth Study Database (KIGS), in which patients received once-daily Genotropin (0.20-0.28 mg/kg/week). Results The combined mean height velocity (HV) at the end of the 12-month main portions of study 004 and 006 was 10.37 cm/year for somatrogon-treated patients. The Year 1 mean HV reported by Ranke and Lindberg for children with a chronological average-centered age of 7.5 years was 9.4 cm/year and 8.3 cm/year for children with severe and moderate GHD, respectively. The Year 1 mean HV reported by Bakker et al for children with idiopathic GHD aged 7.5 years at the beginning of hGH therapy was ∼10 cm/year (for males and females). The mean annual HVs during the OLE period were 9.37, 8.97, and 9.03 cm/year at OLE Year 1, 2 and 3 in somatrogon-treated patients, which were numerically greater than HVs of 7.09, 6.35, and 6.08 cm/year at the corresponding annual visit in the matched KIGS cohort (Genotropin dose: 0.20–0.28 mg/kg/week). Conclusions Comparisons with published literature and the KIGS database indicate that children treated with once-weekly somatrogon (0.66 mg/kg/week) showed good growth, compared with children treated with once-daily hGH, strengthening the expectation that somatrogon-treated children are likely to achieve a satisfactory final adult height.

Clinical Usefulness of the Growth Hormone-Releasing Peptide-2 Test for Hypothalamic-Pituitary Disorder.

ContextGrowth hormone deficiency (GHD) develops early in patients with hypothalamic-pituitary disorder and is frequently accompanied by other anterior pituitary hormone deficiencies, including secondary adrenal insufficiency (AI). A growth hormone–releasing peptide-2 (GHRP2) test, which is widely used for the diagnosis of patients with GHD, is thought to induce release of not only growth hormone (GH) but also ACTH. However, its clinical usefulness in hypothalamic-pituitary disorder is unclear.ObjectiveWe aimed to determine the clinical utility of the GHRP2 test in patients with hypothalamic-pituitary disorders, particularly for AI concomitant with GHD.MethodsThe GHRP2 test, a cosyntropin stimulation test, corticotropin-releasing hormone (CRH) tests, and/or insulin tolerance tests (ITTs) were performed on 36 patients with hypothalamic-pituitary disorder.ResultsTwenty-two (61%) had severe GHD, and 3 (8%) had moderate GHD by GHRP2. There was no difference in baseline ACTH and cortisol between non-GHD, moderate GHD, and severe GHD participants. However, a cosyntropin stimulation test and subsequent CRH tests and/or ITTs revealed that 17 (47%) had secondary AI and 16/17 (94%) cases of secondary AI were concomitant with severe GHD. ROC curve analysis demonstrated that the ACTH response in the GHRP2 test was useful for screening pituitary-AI, with a cutoff value of 1.55-fold (83% sensitivity and 88% specificity). Notably, the combination of ACTH response and the peak cortisol level in the GHRP2 test using each cutoff value (1.55-fold and 10 µg/dL, respectively) showed high specificity (100%) with high accuracy (0.94) for diagnosis of pituitary-AI.ConclusionWe recommend measuring ACTH as well as GH during the GHRP2 test to avoid overlooking or delaying diagnosis of secondary AI that frequently accompanies GHD.

Abstract #1184265: Endothelial Dysfunction and Increased Carotid Intima-Media Thickness in the cardiovascularly asymptomatic Growth hormone naive Patients of Sheehan’s Syndrome

Inflammation plays an important role in the atherosclerotic process of the arterial wall, and peripheral markers of inflammatory activity such as C - reactive protein, TNF-α and IL-6 have been shown to correlate with the risk of atherosclerosis in patients with Growth hormone deficiency(GHD). While severe GHD is a well-established feature of Sheehan's syndrome (SS) and is associated with clustering of adverse CV risk factors. There is evidence linking adverse CV events with elevated circulating levels of inflammatory markers in the general population undermining the importance of determination of such markers in patients with SS.We aim to determine the proinflammatory markers of endothelial dysfunction and carotid artery IMT in GH naive patients of SS.

Association between overweight and growth hormone secretion in patients with non-functioning pituitary tumors.

IntroductionGrowth hormone (GH) deficiency (GHD) is often complicated by non-functioning pituitary tumors (NFPTs); however, its prevalence remains unclear because preoperative screening for GHD with provocative tests is not recommended. Accordingly, we attempted to clarify the characteristics of GHD in unoperated patients with NFPT.Materials and methodsWe retrospectively reviewed adult patients with non-functioning pituitary adenoma (NFPA) and Rathke’s cyst who underwent preoperative GH-releasing peptide-2 (GHRP-2) tests from January 2013 to December 2016. We investigated the association between peak GH response to GHRP-2 and background characteristics.ResultsAmong 104 patients (85 NFPA and 19 Rathke’s cysts), 45 (43%) presented severe GHD, as diagnosed using GHRP-2 tests. Body mass index (β = -0.210, P = 0.007), free thyroxine (β = 0.440, P < 0.001), and tumor height (β = -0.254, P < 0.001) were significant variables for determining the peak GH response to GHRP-2 in multiple regression analyses. Overweight (odds ratio, 3.86; 95% confidence interval, 1.02–14.66) was significantly associated with severe GHD after adjustment for age, sex, creatinine, free thyroxine, tumor height and clinical diagnosis. The regression slopes between tumor height and peak GH response to GHRP-2 significantly differed between overweight patients and non-overweight individuals, as determined by analysis of covariance (P = 0.040). In the 48 patients who underwent postoperative GHRP-2 tests, severe postoperative GHD was significantly more common in overweight patients than non-overweight individuals (100% vs. 48%, P < 0.001).ConclusionWe observed a negative synergistic effect between overweight and tumor size on GH secretion in patients with NFPTs, indicating that GH provocation tests for diagnosing underestimated GHD could be considered in overweight unoperated patients with large NFPTs.

Changes, limitations, and prospects of adult height in GH treatment for Japanese GHD patients.

For the treatment of pituitary dwarfism (called pituitary short stature in 1987 and renamed as growth hormone deficiency [GHD] in 1993), pituitary-derived human growth hormone (phGH) was approved in 1975, and recombinant hGH (rhGH) was approved in 1988. Adult height in patients with isolated GH deficiency (IGHD) improved by 2000. However, this improvement was mainly due to the increase in height SDS at treatment initiation. Although the mean adult height in patients with idiopathic GHD has been reported to be approximately -1.0 SD or higher in Europe and the United States, the mean adult height of patients with idiopathic GHD in Japan has not improved as much as that in Europe and the United States after 2000. The possible reasons were: low therapeutic doses than those in Europe and the United States; changes in background factors, such as reduction in severe GHD; differences in response to GH between Caucasians and Japanese; and, no increase in height at puberty onset because delayed puberty was normalized by GH treatment. In the future, long-acting GH is expected to improve adult height in GHD patients in Japan.

Increased glycated albumin levels in patients with acromegaly related to glucose fluctuation caused by growth hormone excess but not albumin metabolism.

Acromegaly is often complicated by impaired glucose tolerance. The accuracy of glycated hemoglobin (HbA1c) and glycated albumin (GA) levels in representing glycemic profiles in patients with endocrine disorders, such as acromegaly, is unclear. This retrospective study reviewed data from patients whose GA levels had been recorded. 14 patients with acromegaly without diabetes mellitus (DM) (the acromegaly group), 15 patients with severe adult GH deficiency without DM (the growth hormone deficiency (GHD) group), and 55 nondiabetic patients (the control group) were included in this study. GA levels were significantly increased in the acromegaly group compared with the control and GHD groups, but no significant differences were observed between the control and GHD groups. The three groups were matched using propensity score matching (13 patients with acromegaly, 13 with GHD, and 13 control patients). Nonetheless, the results after matching were the same as those before matching. GA levels in the acromegaly group were significantly associated with plasma glucose (PG) levels at 0, 30, and 120 min after a 75-g oral glucose tolerance test (OGTT). Further, GH levels at 120 min after a 75-g OGTT in the acromegaly group were significantly correlated with GA levels and the difference in PG levels at baseline and 30 min. Our findings suggest that increases in PG levels attributable to excess GH after glucose loading are related to increases in GA levels in patients with acromegaly without DM. Hence, both HbA1c and GA should be checked to accurately assess impaired glucose tolerance in patients with acromegaly.

Demographic characteristics of children with growth hormone deficiency from 1996 to 2015 in Japan: 20 years of data from the foundation for growth science in Japan.

Growth hormone (GH) deficiency (GHD) in children is a heterogeneous condition that includes several entities of various severities. GH treatment has been affected by various factors. Because comprehensive analyses for Japanese children with GHD over time are scarce, we investigated the baseline characteristics of patients with GHD at the start of GH treatment between 1996 and 2015 using data from the Foundation for Growth Science in Japan. During the registration period, 19,717 subjects were determined to be eligible for GH treatment as GHD. Overall analyses revealed that there were twice the number of male patients as female patients, and the etiology was idiopathic in 91.1%, central nervous system (CNS) tumor at the hypothalamus-pituitary area in 1.7%, CNS tumor distant from the hypothalamus-pituitary area in 0.68%, other tumors in 0.91%, congenital CNS malformations in 0.83%, and other diseases in 1.1% with their specific characteristics. The latest average age, height standard deviation score (SDS), insulin-like growth factor-1 SDS, and proportion of severe GHD at GH treatment initiation were 8.8 years, -2.76, -1.42, and 19.5%, respectively. The proportions of breech delivery and asphyxia gradually decreased, whereas that of caesarean section gradually increased during the registration period with the latest values of 2.2%, 4.9%, and 14.0%, respectively (all analyses: p < 0.0001). In contrast, the proportion of idiopathic GHD with breech delivery seemed to reach the lowest level among those with a birth year before 2000. This study identified the characteristics and changes of patients with GHD over 20 years.

Cardiovascular risk profile in growth hormone-treated adults with craniopharyngioma compared to non-functioning pituitary adenoma: a national cohort study

Cardiovascular (CV) risk profile might differ between growth hormone-treated patients with craniopharyngioma and non-functioning pituitary adenoma (NFPA), since patients with craniopharyngioma more frequently suffer from hypothalamic metabolic disruption. The aim of this study is to investigate the CV risk profile in adult patients with craniopharyngioma compared to NFPA before and after treatment with growth hormone (GH) replacement therapy due to severe GH deficiency. A sub-analysis of the Dutch National Registry of Growth Hormone Treatment in Adults was performed, in which we compared 291 patients with craniopharyngioma to 778 patients with NFPA. CV risk profile and morbidity were evaluated at baseline and during long-term follow-up within and between both groups. At baseline, patients with craniopharyngioma demonstrated higher BMI than patients with NFPA, and men with craniopharyngioma showed greater waist circumference and lower HDL compared to men with NFPA. During follow-up, BMI, as well as diastolic blood pressure among patients using antihypertensive drugs, deteriorated in the craniopharyngioma group compared to the NFPA group. Lipid profile improved similarly in both groups over time. No differences were found between groups in the occurrence of diabetes mellitus, cerebrovascular accidents, CV disease, or overall mortality. This study suggests that overall CV risk profile is worse in craniopharyngioma patients with GH deficiency compared to patients with NFPA. During GH replacement therapy, patients with craniopharyngioma demonstrated an increase in BMI over time, where BMI remained stable in patients with NFPA. Also, diastolic blood pressure did not improve with antihypertensive drugs in craniopharyngioma patients as seen in patients with NFPA.