Glucagon Stimulation Test Research Articles

Elucidating the relationship between blood glucose dynamics and growth hormone responses in glucagon stimulation tests among children with short stature

Introduction: The use of glucagon as a provocative agent for growth hormone (GH) assessment is a cornerstone in pediatric endocrinology. Glucagon's role as a GH secretagogue is integral to growth hormone stimulation tests (GHSTs), which diagnose suspected GH deficiency (GHD) in children. These tests are crucial for assessing the hypothalamic-pituitary-adrenal (HPA) axis's integrity. Despite its prevalent use, the exact mechanisms by which glucagon prompts GH release and the impact of ensuing blood glucose (BG) fluctuations are not fully understood. Objectives: This study aims to explore the relationship between GH and BG levels in children with short stature following glucagon administration. Patients and Methods: A retrospective cohort study involved 42 pediatric patients, aged 6 to 11, with short stature. We analyzed GH and BG levels before and after intramuscular glucagon Simulation test (GST). Blood samples were taken at baseline and multiple intervals post-injection. Results: The results revealed that the mean glucose peaked at 60 minutes and declined to a nadir at 120 minutes, which corresponded with a significant rise in GH levels. GH concentrations peaked at 120 minutes post-injection, with 31% of children showing peak GH levels of less than 7 μg/L. Notably, the study found an inverse correlation between BG and GH at peak glucose times, suggesting a complex interplay between glucose dynamics and GH response. Discussion: Our findings indicate a dynamic interrelation between BG and GH post-glucagon injection, challenging traditional interpretations of GST results. The study reinforces the notion that GHST results should be interpreted with consideration of patient-specific factors such as BMI to ensure accurate evaluation of GH reserve and subsequent clinical decision-making. Conclusion: The study corroborates the dynamic nature of GH and glucose responses following glucagon administration and highlights the need for personalized approaches in interpreting GHSTs. Further investigation is warranted to elucidate the mechanisms influencing this complex relationship, which is crucial for accurate diagnosis and management of GHD in children.

6369 Weiss-Kruszka Syndrome and Growth Hormone Deficiency, Adrenal Insufficiency, and Morbid Obesity

Abstract Disclosure: T. Falcon-Rodriguez: None. N. Solano: None. A. Diaz: None. Background: Weiss-Kruszka syndrome (WKSA) is a rare autosomal dominant genetic disorder caused by heterozygous loss-of-function variants in the ZNF462 gene. Individuals affected by this condition exhibit distinctive craniofacial features, ptosis, dysgenesis of the corpus callosum, hearing loss, intellectual disability, and hypotonia. There is one other case report that described a boy with empty sella syndrome with growth hormone deficiency and delayed puberty. Case Presentation: We present the case of a 15-year-old boy who initially came under the care of endocrinology at age 9 due to severe obesity and short stature. Past medical history included ADHD (for which he was on stimulants since age 5), microcephaly, VUR, asthma, and developmental delay. He grew along the 2nd percentile for height from the ages of 6 and 13, after which his growth velocity notably decelerated. His initial bone age at 9 years old was advanced by 3 years. His BMI had exceeded the 99th percentile since age 3. His family history was relevant for maternal type 1 diabetes mellitus, paternal height of 165 cm, and maternal height of 160 cm. Upon physical examination, notable findings included short stature, severe obesity, a low anterior hairline, arched eyebrows, upslanted palpebral fissures, low-set ears, a tubular and short nasal bridge, and an exaggerated cupid's bow. At age 9, the patient was diagnosed with growth hormone (GH) deficiency following a clonidine and glucagon stimulation test, with a GH peak of 1.9 ng/mL (normal >7 ng/mL). Additionally, he was diagnosed with adrenal insufficiency (cortisol peak of 5 ug/dL, after 250 mcg of cosyntropin). A brain/sella MRI revealed a hypoplastic pituitary gland. Subsequently, hydrocortisone replacement was initiated at a dose of 6 mg/m2/day, and GH treatment at a weekly dose of 0.3 mg/kg. Despite treatment with growth hormone and IGF-1 levels on the upper side of the normal range, his growth velocity did not improve significantly. He reached his peak adult height of 150 cm at age 15. His BMI had consistently been at the 99th percentile. According to his mother, he did not have issues with satiety, and his portion sizes were considered normal. He did not consume fast foods or sugary drinks, and his level of physical activity was suboptimal. Whole Exome Sequencing identified a heterozygous de novo pathogenic variant in the ZNF462 gene, specificallyc.2664 C>A, p.(C888*) (NM_021224.4), consistent with the diagnosis of Weiss-Kruszka syndrome (OMIM # 618619). Conclusion: We present, to our knowledge, the first report of morbid obesity and central adrenal insufficiency in a child with WSKA. GH deficiency had been previously reported in 1 patient with WSKA. The finding of a hypoplastic pituitary gland supports the diagnosis of GH deficiency and central adrenal insufficiency. Presentation: 6/3/2024

Anterior pituitary hormone dysfunction among individuals with complete heart block requiring pacemaker.

Background & objectives Neuronal hypoxia associated with conditions like traumatic brain injury and cardiac tachyarrhythmia has been implicated in causing hypopituitarism. Individuals with complete heart block (CHB) may be predisposed to develop anterior pituitary hormone dysfunction in the long term. The objective of this study was to investigate anterior pituitary hormone functions in individuals after CHB. Methods This prospective cohort study included 30 individuals (21 men and 9 women) with CHB requiring pacemaker implantation, who were evaluated at admission and then at a mean follow up of 12.4 ± 2.2 months to look for development of any degree of hypopituitarism. In addition to the measurement of hormones like follicle-stimulating hormone (FSH), luteinising hormone (LH), thyroid stimulating hormone (TSH), total tetra iodothyronines (TT4), free tetraiodothyronines (FT4), cortisol, insulin-like growth factor-1 (IGF-1), testosterone and estradiol, a fixed-dose glucagon stimulation test (GST) was performed to assess growth hormone (GH) and adrenocorticotrophic hormone (ACTH) axis. Results The mean age of the participants was 64.9 ± 11.3 yr. At follow up evaluation, 17 (56.7%) had low serum IGF-1, and among them, seven (23%) had growth hormone deficiency (GHD) (peak GH <1.0 ng/ml after GST). Six participants (20%) had ACTH deficiency (peak cortisol <9 ug/dl after GST) and one had TSH deficiency. None had prolactin (PRL) or gonadotropin deficiency. Overall, hormone deficiencies were observed in nine patients (30%). Interpretation & conclusions This pilot study detected loss of anterior pituitary hormones in a significant number of individuals of CHB at 12 months follow up. Unrecognised hypopituitarism may have resulted in significant morbidity and mortality in these individuals.

Glucagon Stimulation Test and Insulin Secretory Capacity in Clinical Assessment of Incretin-Based Therapy for Diabetes.

Evaluation of insulin secretory capacity is essential to understand the pathophysiological condition of individuals with diabetes and to assess the efficacy of drugs used in treatment of the disease. The 1 mg intravenous glucagon stimulation test (GST) is widely used to evaluate residual β cell function; we previously reported that GST assessment of insulin secretory capacity is useful in assessing the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs). However, recent reports indicate that pharmacological concentrations of glucagon stimulate insulin secretion through GLP-1 receptors, confounding the issue. The present studies were undertaken to reassess the reliability of the GST for evaluation of insulin secretory capacity under GLP-1RAs and dipeptidyl peptidase-4 inhibitors (DPP-4is). Our first study comprised individuals initiated with the treatment of GLP-1RAs evaluated by GSTs before and after treatment. Although the fasting C-peptide levels (CPR) were elevated after treatment, the induction of insulin secretion by glucagon was significantly reduced. Our second study compared glucagon-induced insulin secretion between DPP-4i users and non-users, assessed by GST after propensity score matching. While the fasting CPR were similar in the two investigations, glucagon-induced insulin secretion was significantly lower with DPP-4i use. These results suggest that GST might underestimate insulin secretory capacity under incretin-based therapy.

Determination of glucose cut-off points for optimal performance of glucagon stimulation test.

The glucagon stimulation test (GST) is widely used to assess growth hormone (GH) and cortisol secretion, nevertheless the precise mechanisms underpinning these hormonal responses remain unclear. We have endeavoured to explore the relationship between glucose and insulin fluctuations during GST and their impact on GH and cortisol secretion. We retrospectively studied 139 subjects (mean age 35.5 ± 15.1 years, BMI 26.6 ± 6.61 kg/m²), including 62 individuals with a history of pituitary disease (27 with an intact adrenal axis) and 77 healthy controls. Standard dose intramuscular GST was performed in all subjects. Once BMI and age were excluded from multivariate model, the nadir of glucose concentration during GST was the sole variable associated with maximal GH secretion (ΔGH, p<0.0003), while neither glucose/insulin peak, nor Δglucose/Δinsulin concentrations contributed to ΔGH. 100% pass rate for GH secretion above 3 ng/ml or 1.07 ng/ml cut-offs was observed for glucose concentrations at, or below 60 mg/dl (3.33 mmol/l) (for Controls), or 62 mg/dl (3.44 mmol/l) (for Controls and patients with an intact adrenocortical axis). Such low glucose concentrations were obtained, however, only in about 30% of studied individuals. Conversely, cortisol secretion did not correlate with glucose or insulin fluctuations, suggesting alternative regulatory mechanisms. This study reveals that glucose nadir below 3.33 mmol/l is the only biochemical biovariable linked with optimal GH secretion during GST, whereas mechanisms responsible for cortisol secretion remain unclear. We emphasize the importance of glucose monitoring during GST to validate GH stimulation and support clinical decisions in GH deficiency management.

Elimination of fall in glucose during glucagon stimulation test does not completely abolish an increase in growth hormone and cortisol concentrations

Elimination of fall in glucose during glucagon stimulation test does not completely abolish an increase in growth hormone and cortisol concentrations

Evaluation of pituitary function and metabolic parameters in patients with traumatic maxillofacial fractures

PurposeThis study was designed to assess the pituitary functions of patients with traumatic maxillofacial fractures and compare the results with healthy controls.MethodsThirty patients (mean age, 38.14 ± 14.15 years; twenty-six male, four female) with a traumatic maxillofacial fracture at least 12 months ago (mean 27.5 ± 6.5 months) and thirty healthy controls (mean age, 42.77 ± 11.36 years; twenty-five male, five female) were included. None of the patients were unconscious following head trauma, and none required hospitalization in intensive care. Basal pituitary hormone levels of the patients were evaluated. All patients and controls had a glucagon stimulation test and an ACTH stimulation test to evaluate the hypothalamic–pituitary–adrenal axis and the GH–IGF-1 axis.ResultsFive of thirty patients (16.6%) had isolated growth hormone (GH) deficiency based on a glucagon stimulation test (GST). The mean peak GH level after GST in patients with hypopituitarism (0.54 ng/ml) was significantly lower than those without hypopituitarism (7.01 ng/ml) and healthy controls (11.70 ng/ml) (P < 0.001). No anterior pituitary hormone deficiency was found in the patients, except for GH.ConclusionOur study is the first to evaluate the presence of hypopituitarism in patients with traumatic maxillofacial fractures. Preliminary findings suggest that hypopituitarism and GH deficiency pose significant risks to these patients, particularly during the chronic phase of their trauma. However, these findings need to be validated in larger scale prospective studies with more patients.

Once upon a time: the glucagon stimulation test in diagnosing adult GH deficiency.

The clinical features of adult GH deficiency (GHD) are nonspecific, and its diagnosis is established through GH stimulation testing, which is often complex, expensive, time-consuming and may be associated with adverse side effects. Moreover, diagnosing adult GHD can be challenging due to the influence of age, gender, and body mass index on GH peak at each test. The insulin tolerance test (ITT), GHRH + arginine test, glucagon stimulation test (GST), and, more recently, testing with macimorelin are all recognized as useful in diagnosing adult GHD. To date GST is still little used, but due to the unavailability of the GHRH all over the world and the high cost of macimorelin, in the next future it will probably become the most widely used test when ITT is contraindicated. The aim of the present review is to describe the current knowledge on GST. Narrative review. In the last years several studies have suggested some changes in the original GST protocol and have questioned its diagnostic accuracy when the classic GH cut-point of 3 μg/L is used, suggesting to use a lower GH cut-point to improve its sensitivity and specificity in overweight/obese patients and in those with lower pretest GHD probability. This document provides an update on the utility of GST, summarizes how to perform the test, shows which cut-points should be used in interpreting the results, and discusses its drawbacks and caveats referring to the most recent studies.

Pragmatic Evaluation of Growth Hormone Stimulation Tests in Short Stature.

To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature. It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency. A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%). Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR).

Evaluation of growth hormone deficiency in women with unexplained infertility

PurposeGrowth hormone (GH) has been recognized to play a regulatory role in female reproduction. It has been reported that infertile GH deficient patients regained fertility after GH replacement. The frequency of GH deficiency is not established in patients diagnosed with unexplained infertility. Here, we aim to present the prevalence of GH deficieny in this patient group. MethodsWe included patients diagnosed with unexplained infertility throughout 18 months. Insulin tolerance test (ITT) and glucagon stimulation tests (GST) were performed and insufficient response to both tests was required for the diagnosis of GH deficiency. ResultsTwenty-five patients were included in the study, the mean age was 27.4 ± 4.5 years and the median duration of infertility was 60 months (min:14, max:120). Two patients were GH deficient according to GST and 14 to ITT. Two patients (8%) showed lack of response on both tests and were diagnosed with GH deficiency. ConclusionThe rate of GH deficiency among women with unexplained infertility was 8% in this preliminary study. There is need for further studies with larger patient groups to verify the results.

Influencing factors for treatment escalation from metformin monotherapy in youth-onset type 2 diabetes in Northern Taiwan

With the increasing prevalence of obesity, childhood type 2 diabetes (T2D) is a growing concern in Taiwan. Unlike its adult counterpart, T2D in children exhibits a more aggressive nature and earlier onset of complications. Metformin represents the first line of drug, but if blood sugar levels do not improve, other drugs are used. This retrospective cohort study endeavors to scrutinize and assess the pattern of treatment modification and associate factors among 79 young people with T2D in Taiwan.The study categorized participants into three distinct groups based on their treatment trajectory and outcomes: (1) those maintaining metformin (n = 34); (2) cases achieving remission (n = 7); and (3) individuals experiencing escalation through oral drugs or insulin (n = 38). The average follow-up period spanned 3.48 years. Findings from univariate analysis using a Cox proportional hazards model and propensity score weighting revealed that HbA1c and weight gain correlated with elevated risk of treatment escalation. Conversely, factors such as hypertension, high weight or body mass index (BMI) SDS, leptin levels, c-peptide concentrations, peak c-peptide values during glucagon stimulation test and LDL-cholesterol levels were associated with reduced risk of escalation. However, in multivariate analyses employing stepwise selection, the sole predictive factor for treatment escalation emerged as weight gain one year post-therapy (HR: 1.06, p < 0.001).This study underscores the interconnectedness between weight management and the trajectory toward either treatment escalation or disease remission. Furthermore, it highlights the cost-effective potential of intervening in younger populations. Ultimately, these insights accentuate the considerable opportunity for enhancing health care management strategies concerning pediatric T2D in Taiwan.

Should we routinely assess hypothalamic-pituitary-adrenal axis in pediatric patients with Prader-Willi syndrome?

It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH). To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature. A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve. Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%). We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone.

Homeostasis Model Assessment of β-Cell Function for Diagnosis of Insulinoma.

Diagnosis of insulinoma is based on different criteria from the 72-hour fasting test according to current guidelines (Endocrine Society [ES], European [ENETS], and North American [NANETS] Neuroendocrine Tumor Societies), including assessment of β-cell function by glucagon stimulation test. This study tested whether the homeostasis model assessment of insulin secretion, including assessment of β-cell function, (HOMA-B) at the end of the fasting test provides comparable efficacy for insulinoma diagnosis. In 104 patients with suspected insulinoma, 72-hour fasting tests were performed with frequent assessment of glucose, insulin, and C-peptide in venous blood. HOMA-B values using insulin and C-peptide were calculated at the end of the fasting test, as defined by the lowest glucose concentration from each participant. HOMA-B was more than 6.5-fold higher in patients with (n = 23) than in those without (n = 81) insulinoma (insulin and C-peptide; both P < .001). HOMA-B (cutoff using insulin >253 a.u. and C-peptide >270 a.u.) had a sensitivity of 0.96, 0.78 to 1.00, and a specificity of 0.96 or greater (≥0.89-0.99) for insulinoma diagnosis. ES and ENETS/NANETS criteria reached a diagnostic sensitivity of less than or equal to 0.96 (≤0.78-1.00) and ≤0.83 (≤0.61-0.95) as well as specificity of ≤0.85 (≤0.76-0.92) and less than or equal to 1.00 (≤0.96-1.00) for insulin, and C-peptide, respectively. Using insulin for HOMA-B, sensitivity tended to be higher compared to ENETS/NANETS criteria (P = .063) and specificity was higher compared to ES criteria using insulin and C-peptide (both P < .005). HOMA-B, as calculated at the end of the fasting test employing defined cutoffs for insulin and C-peptide, provides excellent diagnostic efficacy, suggesting that it might represent an alternative and precise tool to diagnose insulinoma.

FRI340 Growth Hormone Deficiency Post Carbon Monoxide Poisoning

Abstract Disclosure: A.Y. Ghamlouche: None. O. Alzohaili: None. A.H. Elkadry: None. Carbon monoxide (CO) is the poisonous byproduct of combustion of fossil fuels, that is odorless and tasteless. In toxic levels CO leads to the impaired functioning of red blood cell’s ability to transport oxygen to tissues.1 Following CO toxicity, white matter demyelination and necrosis of the Globus pallidus that further results in other neurologic disorders, is common.2 A novel and underrecognized consequence of CO poisoning is growth hormone deficiency (GHD). GHD is the most common pituitary hormone deficiency following a traumatic brain injury.3 Four cases of GHD were described following an event of CO poisoning. Recommended GHD diagnosis criteria of less than 5.0 ng/mL was used with these patients. The Insulin Tolerance Test (ITT) and Glucagon stimulation test (GST) were administered. All patients had no causes of GHD in their medical history prior to their encounters with CO poisoning. A 44-year-old male with exposure in 2020, came for an evaluation in January of 2022 complaining of memory impairment, brain fog, mental fatigue, cognitive decline, anxiety, poor libido, and neuropathy. showed a GH peak of 1.1 ng/mL during the ITT a peak of 1.0 ng/mL during the GST. A 51-year-old male with exposure in 2016, came for an evaluation in December of 2020 complaining of memory impairment, blurry vision, fatigue, physical weakness, mood changes, and stuttered speech. Results showed a GH peak of 4.4 ng/mL during ITT and a GH peak of 0.157 ng/mL during the GST.A 43-year-old female with exposure in 2017, came for an evaluation in January of 2022 complaining of memory loss, attention issues, anxiety, depression, fatigue, weight gain and neuropathy. Results showed a GH peak of 1.7 ng/mL during ITT and a GH peak of 2.6 ng/mL during the GST. A 42-year-old male with exposure in 2018, came for an evaluation in November of 2019 complaining of memory impairment, headaches, tremors, fatigue, anxiety, depression, declining cognition, insomnia, poor libido, lack of concentration, and poor vision. Results showed a GH peak of 3.6 ng/mL during ITT and a GH peak of 0.109 ng/mL during the GST. All 4 patients were started on GH replacement therapy following their tests. All patients responded well, and showed significant improvements in quality of life. A possible connection can be drawn between pituitary gland damage and hypoxia from CO poisoning.

Reliability of Agreement between Insulin, Clonidine, and Glucagon Stimulation Tests for the Diagnosis of Growth Hormone Deficiency in Children: A Retrospective Cohort Study.

Growth hormone (GH) deficiency (GHD) is a rare disorder. The diagnosis of GHD requires a combination of two provocative GH tests. This study aimed to find agreement between commonly used medications to determine which combined tests have high reliability of agreement. This retrospective cohort included 201 children who underwent GH provocation testing from January 2012 to December 2022. The insulin tolerance test (ITT) with the clonidine stimulation test (CST) or glucagon stimulation test (GST) with the CST were performed. We calculated Cohen's kappa to determine the agreement between the test medications by considering the post-stimulation peak GH level with a cut-off value of 10 ng/mL as the primary outcome. A total of 151 patients underwent the two provocative tests and were included in the analysis. Of these patients, 119 underwent the ITT and CST and 54 (45.3%) were diagnosed with GHD. However, 32 patients underwent the GST and CST and 18 (56.2%) were diagnosed with GHD. The kappa value for ITT and CST was 0.258 (25.8%), indicating fair agreement between clonidine and insulin (p = 0.005). However, the kappa value for CST and GST was 0.178 (17.8%), representing slight agreement. The correlation coefficient revealed a very strong relationship between ITT and CST. Clonidine has fair agreement and a very strong correlation coefficient with ITT when used to diagnose GHD in children. Among the commonly used pharmacological tests for GH provocation in our unit, the CST was considered the best pharmacological test in terms of safety and reduced parental anxiety.

Combined growth hormone stimulation testing: Could the tests be shortened?

IntroductionGrowth hormone stimulation tests (GHST) remain the cornerstone for diagnosing growth hormone deficiency (GHD), yet they can be lengthy and costly. We aimed to examine whether the combined clonidine and glucagon stimulation test (CGST) and l-dopa and glucagon stimulation test (LDGST) can be shortened without compromising the test's specificity. Material and methodsWe retrospectively analyzed the baseline characteristics, auxological and laboratory data of children with short stature who had undergone a CGST and an LDGST for GHD. We compared the diagnostic accuracy for the standard test and shortened test, eliminating time points of 0 and 210 min. ResultsWe reviewed 830 charts (8.17 ± 2.92 years old; 56.27% males), with 431 (57.0%) children in the CGST group, and 38 (51.35%) in the LDGST group who tested negative for GHD. The peak and maximum GH levels occurred at the 60-min time point for both the CGST and LDGST. Eliminating the 0-min time point was the only time that did not affect the specificity of the CGST, with a false-positive rate of 2 (2.99%), specificity of 0.99 (0.99–0.99), and p value of 0.25. Eliminating the 0- and 210-min time points did not affect the specificity of the LDGST, with a false-positive rate of 2 (5.26%), specificity of 0.95 (0.95–0.95), and p value of 0.24. ConclusionsWe concluded that 0-min time point could be eliminated without compromising the combined GHST diagnostic value, thus resulting in cost reduction. Larger studies are needed for the combined LDGST to explore whether the 30- and 210-min time points could be eliminated, thus resulting in cost and time savings.

Hormonal changes in veterans with Gulf War Illness

AimsGulf War Illness (GWI) is a multi-system condition of complex etiology and pathophysiology without specific treatment. There is an overlap between the symptoms of GWI and endocrinopathies. This study aimed to identify hormonal alterations in 1990–91 Gulf War (GW) veterans and the relationship between GWI and hormonal dysregulation. Main methodsData from 81 GW veterans (54 with GWI and 27 controls without GWI) was analyzed in a cross-sectional, case-control observational study. Participants completed multiple questionnaires, neuropsychiatric assessments, and a comprehensive set of hormone assays including a glucagon stimulation test (GST) for adult growth hormone deficiency (AGHD) and a high-dose adrenocorticotropic hormone (ACTH) stimulation test for adrenal insufficiency. Key findingsThe GWI group had lower quality of life and greater severity of all symptoms compared to controls. Pain intensity and pain-related interference with general activity were also higher in the GWI group. AGHD was observed in 18 of 51 veterans with GWI (35.3 %) and 2 of 26 veterans without GWI (7.7 %) (p = 0.012 for interaction). Veterans with GWI also exhibited reduced insulin-like growth factor 1 (IGF-1) levels and IGF-1 Z-scores compared to controls. One participant with GWI met the criteria for adrenal insufficiency. No significant changes were observed in other hormonal axes. SignificanceThe frequency of AGHD was significantly higher in veterans with GWI compared to controls. Recombinant human growth hormone replacement therapy (GHRT) may become a breakthrough therapeutic option for this subgroup. A large clinical trial is needed to evaluate the efficacy of GHRT in patients with GWI and AGHD.

1301-P: Glucagon Stimulation Test—Is It Time for an Easy Interpretation Proposal?

Background and Aims. Guidelines suggest the use of c-peptide in case of ambiguous diabetes. Glucagon stimulation test (GST), with the intravenous administration of glucagon 1 mg, is a 10-minutes test and it is suitable in clinical practice. It can describe residual beta-cell function although an easy way to identify from this test the type of diabetes or need for insulin in the short term is not available. The aims of this pilot study were to describe c-peptide response during GST and to identify classes of subjects corresponding to different types of diabetes or need of insulin. Methods: We retrospectively recorded c-peptide levels of adults with ambiguous diabetes who underwent to GST. We divided subjects in 4 classes according to basal c-peptide (BCP) and to mean stimulated c-peptide increase (SCPi): class 1 (BCP &amp;lt;0.5 and SCPi &amp;lt;0.7 mmol/L from basal levels); class 2 (BCP &amp;lt;0.5 mmol/L and SCPi ≥0.7 mmol/L), class 3 (BCP ≥0.5 mmol/L and SCPi &amp;lt;0.7 mmol/L); class 4 (BCP ≥0.5 mmol/L and SCPi ≥0.7 mmol/L). Data about antibody positivity for anti-GAD and I.C.A. (Ab+) and need for insulin within two months were recorded. Results: We enrolled 61 subjects, age 48.4 (14.6) years [mean (standard deviation)]. 7 subjects (11%) were included in class 1. Mean basal c-peptide was 0.3 mmol/L. 5 subjects (71%) were Ab+ and all required insulin. None of the participants were included in class 2. 18 subjects (29.5%) were included in class 3. Mean basal c-peptide was 1.0 mmo/L. 11 (61%) of class 3 subjects were Ab+ and required insulin within 2 months. 36 subjects (59.5%) were included in class 4. Mean basal c-peptide was 1.8 mmol/L. 5 (13%) of them required insulin therapy within 2 months and 4 (11%) were Ab+. Class 1 and 3 presented with lower BMI than class 4 (p&amp;lt;0.001). Conclusions: In those preliminary data subjects in class 1 are more likely type 1 diabetes, while subjects in class 3 are more likely T1DM or LADA requiring insulin in the short term. Those preliminary data suggest an easy interpretation for GST to include it more frequently in clinical practice. Disclosure A.Rizzi: None. L.Tartaglione: None. S.Gugliandolo: None. E.Di stasio: None. A.Barberio: None. D.Pitocco: None.

1553-P: Postprandial C-Peptide–to–Glucose Ratio Is Valuable in Assessing Beta-Cell Function in Japanese Patients with Type 2 Diabetes

Onset of type 2 diabetes (T2D) is based on the insulin secretion (loss of β-cell function) and resistance. Residual β-cell function is a key factor in achieving optimal glycemic control in T2D patients. Glucagon stimulates insulin, therefore glucagon stimulation test (GST) is a reliable marker for β-cell function. Fasting C-peptide (CPR) to glucose ratio (CPR[ng/ml] to glucose[mg/dl] x100; F-CPR-index) is used as a marker of insulin secretion. We evaluated the efficacy of postprandial CPR to glucose ratio (P-CPR-index) for evaluating β-cell function in T2D. Japanese T2D patients with inadequate glycemic control (HbA1c&amp;gt;7.0) were enrolled in the study (n=500, insulin therapy=283). HbA1c, fasting CPR and glucose, postprandial (120 min after breakfast) CPR and glucose were measured, and F-CPR-index and P-CPR-index were calculated. GST was performed as follows: 1mg of glucagon was injected intravenously, CPR was determined before and 6 min after injection, GSTΔCPR (CPR[6 min] - CPR[0 min]) was calculated. Factors correlated with GSTΔCPR were analyzed using simple and multiple stepwise regression analysis. P value&amp;lt;0.05 was defined as statistically different. F-CPR-index, P-CPR-index and GSTΔCPR were 1.60±0.95, 2.67±1.92 and 1.93±1.21, respectively. Simple regression analysis showed that GSTΔCPR was significantly correlated with age, height, body weight (BW), BMI, waist circumference, duration of diabetes, retinopathy, insulin therapy, urinary CPR, F-CPR-index and P-CPR-index. Multiple stepwise regression analysis revealed that independent factors contributing to GSTΔCPR were BW (β=0.336), duration of diabetes (β= −0.107), presence of retinopathy (β= −0.121), use of DPP-4i (β= −0.099), metformin (β= −0.109), SGLT2i (β= −0.108, p=0.002) and P-CPR-index (β=0.432)(R2=0.453). Our date demonstrated that P-CPR-index was valuable and simple method in assessing residual β-cell function with/without insulin therapy in daily clinical practice. Disclosure Y.Matsuhashi: None. T.Abe: None. T.Fujita: None. S.Mizushiri: None. S.Chikazawa: None. M.Daimon: None.

Outcomes of Pancreas Transplantation for Lower-Ranked Candidates

To perform more pancreas transplantation (PTx), our center sometimes performs pancreas transplantation for candidates ranked sixth place or lower. In this study, we analyzed the outcomes of PTx performed in our center to compare the outcomes of higher- and lower-ranked candidates. Seventy-two cases in which PTx was performed at our center were divided into 2 groups according to the candidate's rank. Cases in which PTx was performed for candidates up to fifth place were classified into the higher rank candidate group (HRC group; n=48), whereas PTx for candidates who were ranked sixth place or lower were classified into the lower rank candidate group (LRC group; n=24). The outcomes of PTx were retrospectively compared. Although the LRC group included a greater number of older donors (age ≥60 years), a greater number of donors with deteriorated renal function, and a greater number of HLA mismatches, the 1- and 5-year patient survival rates in the HRC group were 91.6% and 91.6%, respectively, compared with 95.8% and 87.0%, respectively, in the LRC group (P=.755). In terms of both pancreas and kidney graft survival, there were no significant differences between the 2 groups. Additionally, there were no significant differences between the 2 groups regarding the glucagon stimulation test and 75 g OGTT results, insulin independence rate, HbA1c, or serum creatinine level after transplantation. In Japan, where there is a severe donor shortage, the performance of transplantation for lower-ranked candidates would increase the number of opportunities for patients to receive PTx.