Low IGF-1 Levels Research Articles

Effect of Iron Deficiency Anemia on Insulin Like- Growth Factor-1 Level Among Children: A Cross-Sectional Study

Objective: To assess the effect of iron deficiency anemia on the serum level of IGF-1 by comparison between low ferritin and low hemoglobin group and healthy control. Study Design: Comparative case control study. Place and Duration: Study The study was conducted at department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from Jul to Dec 2022. Methodology: The case control study was done in 110 children, aged between 2-14 years. Children with short stature and iron deficiency anemia (cases) were compared to a group of age and gender matched healthy children (controls). The sample size of 110 children was calculated using WHO sample size calculator. After brief history and examination, 3ml venous blood was drawn by standard technique. Complete blood picture estimation and the estimation of IGF-1 and ferritin levels was done. Parameters of complete blood picture included were Hemoglobin in (Hb), Red blood cells (RBC), Packed cell volume (PCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular volume (MCV). Data was analyzed using SPSS. Results: Comparison of the serum levels of IGF-1, analyzed by chemiluminescent immunoassay between two groups showed lower IGF-1 levels among iron deficiency anemia group (8.60 µmol/L) as compared to control group (38.80 µmol/L) which is statistically significant (p-value<0.001). Results showed a positive correlation of Hemoglobin and serum ferritin with Serum IGF-1 levels with a r value of 0.78 and 0.81 (p-value 0.001) respectively. Conclusion: There is a strong correlation between Iron Deficiency anemia and IGF-1 levels. Children with Iron deficiency anemia have

8524 Pituitary Hormone Dysregulation In Symptomatic Long COVID: A Multi-Center Observational Study

Abstract Disclosure: S.L. Sims: None. A. Labadzhyan: None. Z. Chen: None. S. Kim: None. J. Brathwaite: None. L. Cullen: None. M. Koga: None. U. Cheliadinova: None. V. Hwe: None. D. Gomez: None. C. Andriakos: None. T. Melnik: None. E. Puig-Wong: None. S. Whelan: None. S. Cheng: None. S. Joung: None. Z. Abelev: None. C. Le: None. R. Zabner: None. Y. Kawakami: None. T. Araki: Consulting Fee; Self; Chiesi. Objective: Pituitary hormone dysregulation has been reported in symptomatic long COVID, but it has not been rigorously studied. We conducted a multicenter observational cross-sectional study to assess pituitary hormone levels in long COVID patients and a longitudinal study to follow patients with abnormal results. Methods: Male and female adults with confirmed symptomatic long COVID were recruited from post COVID clinics at Mount Sinai in New York, Cedars-Sinai in Los Angeles, and the University of Minnesota, as well as nationwide physician referrals. Pituitary hormone levels were measured, and because fatigue is common in long COVID, patients completed the QoL-AGHDA survey. Those who exceeded pre-determined survey cutoffs or demonstrated any hormone abnormality were invited to the longitudinal study to repeat surveys and blood work every 3 months. A separate cohort with banked serum samples from before and 3, 6, and 9 months after subacute COVID was used as a comparator. Correlation analysis examined associations between QoL-AGHDA scores and pituitary hormone levels. Results: 246 patients were enrolled in the cross-sectional study after a median of 17.0 months (range, 1-39) since the most recent SARS-CoV2 infection prior to the onset of long COVID symptoms. 56% were enrolled in the longitudinal study due to a high questionnaire score and/or pituitary hormone abnormalities. Current mean follow-up period is 7.95 ± 3.2 months. Mildly elevated prolactin levels were most frequent, observed in 12.7% of patients (males 14.0%, females 12.2%). These patients presented post-COVID with galactorrhea, irregular menses, erectile dysfunction, and nonspecific symptoms of hyperprolactinemia. On follow-up, mild hyperprolactinemia tended to persist. Mildly low IGF1 levels (Z-score <-1.0) were observed in 9.0% of patients (males 6.3%, females 10.0%); on follow-up, IGF1 levels recovered in only 15% of these patients. 2.0% of the entire cohort showed transiently elevated IGF1 levels (Z-score >2.0). Low morning cortisol (<5.0 µg/dL) was observed in 3.3% of patients, but response to cosyntropin stimulation was normal. Mild secondary hypothyroidism was observed in 3.7% of all patients, and mild hypogonadism was observed in 7.8% of males. There was no correlation between QoL-AGHDA score and level of each pituitary hormone. After excluding pre-COVID hormone abnormalities in the post subacute COVID cohort, the rate of hyperprolactinemia was lower than that seen in the long COVID cohort (1% vs 12.7%). The rate of low IGF1 levels was higher in the subacute COVID cohort (22% vs 9.0), but unlike with long COVID, low IGF1 levels after subacute COVID recovered in 3-6 months. Conclusion: Abnormalities in pituitary hormone levels in symptomatic long COVID are frequent, with persistent hyperprolactinemia in >10%. Pituitary hormone screening may be important in patients with prolonged symptomatic long COVID. Presentation: 6/3/2024

6367 Growth gone Awry: A Rare Case of Acromegaly in a 16-Year-Old Female with Panhypopituitarism Secondary to Craniopharyngioma on Low Doses of Growth Hormone with Low IGF-1 levels

Abstract Disclosure: L.M. Ayala Castro: None. J. Ye Tay: None. A. Diaz: None. This report highlights a rare case of a 16-year-old female with panhypopituitarism due to craniopharyngioma, where GH replacement therapy triggered acromegaly features despite having low IGF-1 levels. Background: Craniopharyngiomas are the most common tumors causing acquired pituitary deficiencies in children. Various mechanisms contribute to acromegaly, and hypersensitivity to hormonal treatment in this benign tumor emerges as a plausible avenue for investigation. Case Presentation: A 16-year-old female diagnosed with craniopharyngioma at age 5 developed secondary panhypopituitarism. Baseline hormonal profiles indicated markedly reduced levels of IGF-1 and insulin growth factor–binding protein 3 (IGF-BP3). Despite the established condition, GH treatment was initiated at age 8 for potential growth and development benefits. Before commencing GH therapy, a bone age assessment revealed normal skeletal development. However, GH replacement therapy led to an unexpectedly robust response, resulting in physical changes consistent with acromegaly. Paradoxically, laboratory evaluations showed low IGF-1 levels. Imaging studies, including pituitary MRI, ruled out new abnormalities or tumors. As the patient approached peak adult height at 16, having been on adult GH therapy since age 13, a decision was made to discontinue GH replacement therapy and address acromegaly symptoms. Frequent follow-up visits were planned to assess growth velocity, monitor hormonal levels, and evaluate potential adverse effects. Discussion: This case demonstrates an unusual sensitivity to exogenous GH, resulting in an exaggerated response contrary to expected IGF-1 elevation. Atypical IGF-1 levels may suggest alterations in liver physiology, GH receptor signaling pathways (e.g., Laron Syndrome), or downstream defects in IGF-1 synthesis. Further research is crucial to elucidate the underlying mechanisms. Conclusion: Only 3 cases of acromegaly as a side effect of GH replacement therapy have been reported in the literature. We report a further case that underscores the complexity of managing hormonal imbalances, especially in unique patient populations with panhypopituitarism secondary to craniopharyngioma. The unexpected response to GH treatment emphasizes the need for individualized approaches and vigilant monitoring.

Clinical characteristics and management status of Turner syndrome in 1 089 children

Objective: To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China. Methods: As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed. Results: Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years. Conclusions: The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Sembra un deficit di GH, e invece non lo è!

A 2.5-year-old girl was evaluated for poor growth. Despite low IGF-1 levels, GH deficiency was excluded. Further investigation revealed celiac disease, diagnosed via EGDS. After starting a gluten-free diet, catch-up growth was observed. The patient remained under follow-up to monitor her growth progress.

Insulin-like Growth Factor-1 Levels Reflect Muscle and Bone Health and Determine Complications and Mortality in Decompensated Cirrhosis

The growth hormone-insulin-like growth factor (GH-IGF-1) axis and its impairment with sarcopenia, frailty, bone health, complications, and prognosis are not well characterized in cirrhosis. We investigated the adult decompensated cirrhosis out-patients at a tertiary care institute between 2021 and 2023 for serum GH and IGF-1 levels, and associated them with sarcopenia (CT-SMI in cm2/m2), liver frailty index (LFI), osteodystrophy (DEXA), clinical decompensations (overall, ascites, encephalopathy, infection, and bleed), and survival up to 180 days. One-hundred-seventy-two patients, 95% males, aged 46.5 years (median). logIGF-1 levels were negatively associated with sarcopenia, osteodystrophy, LFI, CTP, and MELD-Na score (P<0.05 each). Patients with low IGF-1 levels had a higher incidence of complications (overall, ascites and encephalopathy) than those with intermediate, and high IGF-1 levels (P<0.05 each). Both logIGF-1 (AUC: 0.686) and MELD (AUC: 0.690) could predict 180-day mortality (P<0.05, each). Adding logIGF-1 with MELDNa further improved discriminative accuracy of MELDNa (AUC: 0.729) P<0.001. The increase in IGF-1 on follow-up was associated with better survival and fewer complications. Reduced IGF-1 levels reflect sarcopenia, frailty, and osteodystrophy in cirrhosis. Low IGF-1 are associated with severity, development of decompensations, and mortality.

Neuroendocrine challenges and clinical outcomes in men with chronic traumatic brain injury: a cross-sectional study.

Marked changes in the hypothalamic-pituitary axis have been documented in patients with traumatic brain injury (TBI). These enduring endocrine challenges could significantly influence the physical and psychological outcomes thereby impacting overall recovery. This study aimed to determine the prevalence and types of endocrine dysfunction in men with chronic TBI and to determine the association of endocrine dysfunction with clinical outcomes. A cross-sectional study that included male participants of 25-45 years (N = 66) with moderate to severe TBI within 6-24 months of injury. Serum Cortisol, Free T4, TSH, Luteinizing hormone, Testosterone, ACTH, Prolactin and IGF-1 were assessed. Glasgow Outcome Scale Extended (GOS-E) and Modified Barthel Index (MBI) scores were also assessed in them. The study cohort comprised male patients with a mean ± age of 32.8 ± 5.7 years. Low IGF-1 levels were most commonly encountered, followed by hypogonadism. Hypopituitarism was present in 56.1%. The proportion of hypogonadism was significantly higher in the group with moderate-total dependence (13/26) as compared to the functionally independent (8/40) group (50% vs. 20%; P = 0.011). Univariate and multivariate logistic regression analysis was used to determine the factors associated with hypopituitarism, revealing that severity of injury (OR = 2.6;) and GOS-E (OR = 3.1) were significant (P < 0.10) on univariate analysis. This study emphasizes the need to screen TBI patients for neuroendocrine dysfunction during the chronic phases and to establish screening criteria.

Moderate aerobic training enhances the effectiveness of insulin therapy through hypothalamic IGF1 signaling in rat model of Alzheimer's disease

Alzheimer's disease (AD) is a neurological condition that is connected with a decline in a person's memory as well as their cognitive ability. One of the key topics of AD research has been the exploration of metabolic causes. We investigated the effects of treadmill exercise and intranasal insulin on learning and memory impairment and the expression of IGF1, BDNF, and GLUT4 in hypothalamus. The animals were put into 9 groups at random. In this study, we examined the impact of insulin on spatial memory in male Wistar rats and analyzed the effects of a 4-week pretreatment of moderate treadmill exercise and insulin on the mechanisms of improved hypothalamic glucose metabolism through changes in gene and protein expression of IGF1, BDNF, and GLUT4. We discovered that rat given Aβ25–35 had impaired spatial learning and memory, which was accompanied by higher levels of Aβ plaque burden in the hippocampus and lower levels of IGF1, BDNF, and GLUT4 mRNA and protein expression in the hypothalamus. Additionally, the administration of exercise training and intranasal insulin results in the enhancement of spatial learning and memory impairments, the reduction of plaque burden in the hippocampus, and the enhancement of the expression of IGF1, BDNF, and GLUT4 in the hypothalamus of rats that were treated with Aβ25–35. Our results show that the improvement of learning and spatial memory due to the improvement of metabolism and upregulation of the IGF1, BDNF, and GLUT4 pathways can be affected by pretreatment exercise and intranasal insulin.

Study of the Relationship between Diabetic Retinopathy, Basal Insulin Therapy (Glargine or NPH) and Insulin-Like Growth Factor 1 Serum Level

Abstract Background Diabetic retinopathy (DR) is the major cause of preventable blindness worldwide. DR is a microvascular complication of diabetes mellitus that is more prevalent in patients with type 1 diabetes. Type 1 diabetes mellitus is an autoimmune disease that leads to insulin deficiency so patients require long term therapy with basal insulin for optimum glycemic control. Insulin- like growth factor 1 (IGF-1) is an important growth factor that is involved in cell proliferation and angiogenesis. There is a lot of evidence that IGF-1 is tightly related to DR development. Insulin Glargine is a long-acting insulin analogue which is peak-free and less hypoglycemic as compared to the intermediate-acting NPH insulin. Glargine has an increased affinity to IGF-1 receptor and this raised concern about its role in development of DR. The relationship between diabetic retinopathy, basal insulin therapy and IGF-1 serum level is still in debate. Aim we aimed to compare the incidence and severity of diabetic retinopathy in type 1 diabetic patients on basal insulin therapy (Glargine or NPH) and its relation to serum IGF-1 level. Methods The current study included 88 subjects with type 1 diabetes divided into 44 on basal insulin therapy with Glargine and actrapid ( Group A) and 44 on NPH and actrapid ( Group B). Hemoglobin A1c, Total cholesterol, Triglycerides, High density lipoproteins, Low density lipoproteins and serum IGF-1 levels were assessed. Full clinical examination including (weight, height, BMI), vital signs (pulse, blood pressure) was done and Fundus examination by Optomed Aurora® IQ handheld fundus camera. Results On comparing the 2 studied groups, There was no statistical significant difference as regarding fundus examination findings between studied groups (P value = 0.429). There was no statistically significant relation between diabetic retinopathy and serum IGF-1 (P value = .080 with Mean ± SD of serum IGF-1 level in patients with Normal fundus 14.8 ± 11 vs. Patients with Diabetic retinopathy 21.3 ± 16.9). There was statistically significant association between diabetic retinopathy and duration of diabetes (P value&amp;lt; 0.05 with Mean ± SD of diabetes duration in patients with Diabetic retinopathy 17.7 ± 6.9 vs. Patients with Normal fundus 14.6 ± 5.6). There was a statistical significant difference as regarding age (P value&amp;lt; 0.05 with Mean ± SD of age in Group B regimen 28.4 ± 6.7 vs. Group A 25.5 ± 4.9). Conclusion Serum IGF-1 levels showed no statistically significant difference in patients either on Glargine or NPH and also in patients either with normal fundus or with diabetic retinopathy. The incidence and severity of diabetic retinopathy in patients with type 1 diabetes mellitus is directly proportionate to duration of disease. No noted difference concerning diabetic retinopathy changes between patients on basal insulin therapy either Glargine or NPH.

Prevalence and risk factors predisposing low bone mineral density in patients with thalassemia.

A common complication of thalassemia is secondary osteoporosis. This study aimed to assess the prevalence and factors associated with low BMD in thalassemic patients. This is a cross-sectional study. Eligible patients were males aged within 18-49 years or premenopausal women diagnosed with thalassemia in Chiang Mai University Hospital between July 2021 and July 2022. The diagnosis of low BMD by dual-energy x-ray absorptiometry (DXA) was defined as a Z-score of -2.0 SD or lower in either the lumbar spine or femoral neck. Clinical factors associated with low BMD were analyzed using a logistic regression model. Prevalence of low BMD was 62.4% from 210 patients with a mean age of 29.7 ± 7.6 years. The predominant clinical characteristics of low BMD thalassemia patients were being female, transfusion-dependent (TDT) and a history of splenectomy. From multivariable analysis, the independent variables associated with low BMD were transfusion dependency (odds ratio, OR 2.36; 95%CI 1.28 to 4.38; p=0.006) and body mass index (BMI) (OR 0.71; 95%CI 0.61 to 0.82; p<0.001). Among patients with low BMD, we observed a correlation between a Z-score with low IGF-1 levels (β=-0.42; 95% CI -0.83 to -0.01; p=0.040), serum phosphate levels (β=0.40; 95% CI 0.07 to 0.73; p=0.016) and hypogonadism (β=-0.48, 95% CI -0.91 to -0.04, p=0.031). This study found a prevalence of low BMD in 62.4% of subjects. Factors associated with low BMD were TDT and BMI. Within the low BMD subgroup, hypogonadism, serum phosphate and low serum IGF-1 levels were associated with a lower Z-score.

Linear growth and response to GH therapy in short children with normal vs low IGF1 level and normal BMI at presentation

Linear growth and response to GH therapy in short children with normal vs low IGF1 level and normal BMI at presentation

Hormonal Dysfunction in Paediatric Patients Admitted to Rehabilitation for Severe Traumatic Brain Injury: Analysis of the Associations with Rehabilitation Outcomes.

Traumatic brain injury is often accompanied by defects in hormone levels, caused by either peripheral gland dysfunctions or by an insufficient central stimulation of hormone production. The epidemiology of endocrinological defects after traumatic brain injury is quite well described, but the consequences of hormone defects are largely unknown, especially in paediatric patients undergoing neurological rehabilitation. Only one previous study reported on a cohort of 20 children with traumatic brain injury and found a low incidence of hormone defects and a correlation between some hormone levels and neurological recovery. In this study, we performed a retrospective chart review on patients affected by severe subacute traumatic brain injury. Their levels of cortisol, ACTH, IGF-1, TSH, free T4, free T3, and prolactin were collected and compared with reference ranges; we then used regression models to highlight any correlation among them and with clinical variables; last, we probed with regression models whether hormone levels could have any correlation with clinical and rehabilitation outcomes. We found eligible data from the records of 52 paediatric patients with markedly severe traumatic brain injury, as shown by an average GCS of 4.7; their age was 10.3 years, on average. The key results of our study are that 32% patients had low IGF-1 levels and in multiple regression models, IGF-1 levels were correlated with neurological recovery, indicating a possible role as a biomarker. Moreover, 69% of patients had high prolactin levels, possibly due to physical pain and high stress levels. This study is limited by the variable timing of the IGF-1 sampling, between 1 and 2 months after injury. Further studies are required to confirm our exploratory findings.

Mendelian randomization analysis demonstrates the causal effects of IGF family members in diabetes.

Observational studies have consistently shown significant associations between the IGF family and metabolic diseases, including diabetes. However, these associations can be influenced by confounding factors and reverse causation. This study aimed to assess the causal relationship between the IGF family and diabetes using Mendelian randomization (MR). We conducted a two-sample MR analysis to investigate the causal effects of the IGF family on diabetes. Instrumental variables for the IGF family and diabetes were derived from summary-level statistics obtained from genome-wide association studies. Horizontal pleiotropy was assessed using MR-Egger regression and the weighted median method. We applied the inverse-variance weighted method as part of the conventional MR analysis to evaluate the causal impact of the IGF family on diabetes risk. To test the robustness of the results, we also employed MR-Egger regression, the weighted median method, and a leave-one-out analysis. Our study revealed that IGF-1 causally increases the risk of Type 2 Diabetes (T2D), while IGFBP-6, adiponectin and INSR decreases the risk (IGF-1, OR 1.02 [95% CI 1-1.03], p = 0.01; IGFBP-6, OR 0.92 [95% CI 0.87-0.98], p = 0.01; Adiponectin, OR 0.837 [95% CI 0.721-0.970], p = 0.018; INSR, OR 0.910 [95% CI 0.872-0.950], p = 1.52 × 10-5). Additionally, genetically lower levels of IGF-1 and IGFBP-5, along with higher levels of IGFBP-7, were associated with an increased risk of Type 1 Diabetes (T1D) (IGF-1, OR 0.981 [95% CI 0.963-0.999], p = 0.037; IGFBP-5, OR 0.882 [95% CI 0.778-0.999], p = 0.049; IGFBP-7, OR 1.103 [95% CI 1.008-1.206], p = 0.033). In summary, our investigation has unveiled causal relationships between specific IGF family members and T1D and T2D through MR analysis. Generally, the IGF family appears to reduce the risk of T1D, but it presents a more complex and controversial role in the context of T2D. These findings provide compelling evidence that T2D is intricately linked with developmental impairment. Our study results offer fresh insights into the pathogenesis and the significance of serum IGF family member concentrations in assessing diabetes risk.

P-02 A case of solitary fibrous tumor originating from the adrenal gland presenting with hypoglycemia

Abstract Introduction Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm usually located in the pleura and associated with NAB2-STAT6 gene fusion. According to the World Health Organization (WHO) classification, although most SFTs are considered well benign, some SFTs have cytological atypia, hypercellularity, tumor necrosis, Ki-67 greater than 5%, high mitotic rate (&amp;gt;4 per high-power field (HPF)) and/or the presence of infiltrative surgical margins are considered malignant. SFT with severe hypoglycemia is called Doege-Potter syndrome which occurs with ectopic secretion of a prohormone of insulin-like growth factor 2 (IGF-2) from tumor tissue. We present a case who applied with severe hypoglycemia and was diagnosed with a solitary fibrous tumor thought to originate from the adrenal gland located in the right retroperitoneal region. Clinical Case A 61-year-old female patient was admitted to the hospital after hypoglycemia was detected in her application due to clouding of consciousness. While the patient's glucose level was 23 mg/dL, insulin:0.4 µIU/mL, C-peptide:&amp;lt;0.01 ng/mL, serum cortisole: 24,20 (µg/mL), growth hormone (GH): 13,20 ng/ mL and insulin-like growth factor I (IGF-1) 38 ng/mL were measured. Insulinoma was excluded and because of IGF-2 level could not be measured in our hospital, low serum insulin and IGF-1 levels suggested high serum IGF-2 levels. HbA1c, adrenal gland, and pituitary function tests were normal (Table 1). A mass lesion of approximately 145×133 mm in size, with heterogeneous contrast, containing cystic areas, was seen, which was thought to originate from the right adrenal gland in the upper abdomen tomography taken due to the presence of a palpable abdominal mass on physical examination (Figure 1). Urine catecholamines were found to be normal, and the plasma aldosterone concentration (PAC)/plasma renin activity (PRA) ratio was 2.56. The patient was operated under intravenous infusion of 10% dextrose due to persistent hypoglycemia. The immunohistochemical evaluation showed CD34, SOX-1 and STAT6 positivity and negativity for S-100, HMB45, straight muscle actin, desmin, caldesmon and melan A, thus confirming the diagnosis of a solitary fibrous tumor. After the operation, the patient's hypoglycemia disappeared. Since there are cases in the literature in which Doege-Potter syndrome was diagnosed without measuring IGF-2, we think that our patient had IGF-2-related hypoglycemia. Conclusion The development of hypoglycemia in Doege-Potter syndrome has been associated with the secretion of large amounts of IGF-2 by tumor tissue, resulting in decreased IGF-1 and Insulin-like growth factor-binding protein 3 (IGFBP-3) concentrations. In these patients, the tumor originates from mesenchymal tumors of low malignant potential. In our case, the Ki-67 proliferation index was around 2%, it was considered benign, and the patient's symptoms completely regressed after resection.Figure 1.CT images of the patientA mass in the right retroperitoneal area, associated with the adrenal gland and containing areas of necrosis, is seen on non-contrast (a) and contrast-enhanced (b) CT scans. Table 1.Laboratory workup

Postoperative Craniopharyngioma in a 10-Year-Old Girl Presenting with Central Precocious Puberty, Central Diabetes Insipidus, and Growth Hormone Deficiency

Background: Hypopituitarism is the most common endocrinology complication of postoperative craniopharyngioma. However, we found a 10-year-old girl with a history of postoperative craniopharyngioma presenting with central precocious puberty (CPP), central diabetes insipidus (CDI), and growth hormone deficiency (GHD).&#x0D; Case presentation: A 5-year-old girl experienced breast growth followed by menstruation six months later. The patient's weight was 19 kg (weight-for-age: P25-P50), height was 109 cm (height-for-age: P10-P25), and good nutritional status (Waterlow 90%). The stage of pubertal development was M2P2. There was a history of craniopharyngioma, and it was resected at the age of 2 years. After surgery, the patient developed CDI and has received desmopressin. No new tumour growth was found from evaluation with periodic MRIs every three years. After CPP was established, with increased serum levels of LH, FSH, and estradiol, GnRH agonist therapy was given at 100 mcg/kg BW every month. During five years of follow-up, the patient experienced clinical and laboratory improvement. However, the growth is only 3-4 cm/year (&lt;P3) with short stature (height-for-age: &lt;P3) and overweight. Low levels of IGF1 and GH were found in the stimulation test results, so the diagnosis of GHD was confirmed. The patient will receive growth hormone therapy and is expected to reach her potential genetic height (148.5 - 165.5 cm).&#x0D; Conclusion: Even though the craniopharyngioma tumour has been resected and no recurrence has occurred, it is crucial to evaluate the hormones produced by the pituitary thoroughly.

The Potential of Lifestyle Medicine: Strategies to Optimize Health and Well-Being in Oncology Care with Dr. Amy Comander.

The field of lifestyle medicine in cancer care and survivorship is undergoing significant transformation, presenting both challenges and opportunities. This collection of insights and reflections by an esteemed speaker aims to address critical facets of this evolving landscape and the intersection of healthcare, lifestyle, and cancer. With a focus on optimizing the health of cancer survivors, the speaker emphasizes the correlation between general population health and strategies for mitigating cancer risk. Evidence-based resources have a key role in their comprehensive insights into lifestyle changes' role in cancer prevention and survivorship. Lifestyle interventions also have a promising role in mitigating the late effects in the pediatric context. Therefore, encouraging the early adoption of healthy practices in childhood cancer survivors emerges as a pivotal strategy. Furthermore, challenges in enhancing education and access to lifestyle medicine are addressed. This highlights the importance of patient-centered communication, motivational interviewing, and personalized guidance in facilitating lifestyle changes with patients. Finally, the role of nutritionists in advising breast cancer patients to consider calorie restriction to lower IGF-1 levels is explored. This collection underscores the multifaceted nature of lifestyle medicine in cancer care, highlighting challenges, opportunities, and the transformative power of passion and curiosity in shaping healthcare careers.

SAT033 Disruption Of GHR In “Middle Aged” Mice Enhances Insulin Sensitivity And Extends Male Lifespan

Abstract Disclosure: S. Duran-Ortiz: None. E.O. List: None. J.A. Young: None. S.C. Mathes: None. R. Basu: None. Y.B. Slama: None. D.E. Berryman: None. Reduced growth hormone (GH) action has been shown to extend healthspan and lifespan in several organisms. In fact, mice and humans with a congenital disruption in the GH receptor (R) gene (GHRKO mice and patients with Laron Syndrome, respectively) have improved insulin sensitivity and are resistant to diabetes, cancer and age-associated cognitive decline. Importantly, the GHRKO mice hold the record for the longest-lived laboratory mice, with a lifespan one week shy of five years of age. GHRKO mice also show reduced markers of aging such as adipose tissue senescence and mTORC1 signaling in liver, kidney, heart and muscle. However, as GH action is required for normal growth and development, we and others have hypothesized that targeted inhibition of GH action at an adult age could be a potent method to extend healthy lifespan. To test this hypothesis and to elucidate how far in development would disruption of GHR extend healthy lifespan, our laboratory recently reported on two mouse lines with post-natal ablation of the GHR at a pubertal age (1.5 months - 1.5mGHRKO mice) and at mature-adult age (6 months - 6mGHRKO mice). We found that ablation of the GHR gene at both 1.5- and 6-months of age extends maximal and mean lifespan preferentially in females. Furthermore, 6mGHRKO mice showed improved oxidative stress resistance while males had improved insulin sensitivity and reduced cancer incidence. With these promising results, we believe that interventions to extend aging should be effective when administered later in life. In the current study, we disrupted the GHR in middle aged mice (12 months - 12mGHRKO mice) using the Cre-Lox system. We found that 12mGHRKO mice exhibit GH insensitivity (high serum GH and low IGF-1 levels), increased adipose tissue mass, reduced lean mass, minimal impact on body weight and length, improved insulin sensitivity and reduced glucose levels in males as well as decreased adipose tissue fibrosis in females compared to males. Moreover, despite the increased fat mass, motor coordination and strength as measured by rotarod and grip strength tests show no deficit in 12mGHRKO mice compared to the controls. Importantly, the male 12mGHRKO mice showed a preferential and significant lifespan extension compared to control mice. Collectively, our results indicate that not only does post-natal GHR disruption does not affect growth and development, but it also confers several crucial healthspan and lifespan advantages. Acknowledgements: This work is supported by the State of Ohio's Eminent Scholar Program, by NIH grant AG059779, by the American Federation for Aging Research (AFAR) and by the Diabetes Institute and by the AMVETS. Presentation: Saturday, June 17, 2023

SAT150 "Sawtooth" Hypoglycemia: Rare Case Of IGF-2 Mediated Hypoglycemia With Elevated Proinsulin Level And "Sawtooth" Pattern On CGMS

Abstract Disclosure: P. Goparaju: None. M. Zena: None. Background: IGF-2 mediated hypoglycemia is usually associated with low Insulin, C-peptide and Proinsulin levels. We present an extremely rare case of IGF-2 mediated hypoglycemia with elevated Proinsulin level and an unusual “saw tooth” pattern on Continuous glucose monitoring system(CGMS). Clinical Case: 53-year-old male with history of metastatic Liposarcoma was admitted to the hospital with severe hypoglycemia. Whipple’s triad was positive on presentation, patient had symptoms of altered sensorium, blood glucose of 24 mg/dl, and symptoms improved upon correction of hypoglycemia. The patient was admitted to the ICU and IV dextrose was initiated.As Liposarcomas are known to be associated with Non-islet cell tumor hypoglycemia (NICTH), treatment with Prednisone was started. Prior to this, initial hypoglycemia workup was sent when blood sample was drawn during a hypoglycemia episode. Patient has no personal or family history of Diabetes. Adrenal insufficiency was ruled out with morning cortisol of 17.8 ug/dl. Serum glucose was low at 40mg/dl, Insulin&amp;lt;1(0-17 pmol/L), C-peptide level low at 0.4 (0.8-3.9 ng/ml), IGF-1 level was low at 68 (74-225 ng/ml), normal IGF-2 at 626 (333-967 ng/ml) and increased IGF-2/IGF-1 ratio of 9.2(Normally around 3:1). All the lab work above is consistent with IGF-2 mediated hypoglycemia with low Insulin, C-peptide and IGF-1 levels and increased IGF-2/IGF-1 ratio. Interestingly, he has an elevated Proinsulin level of 36.9 (0.0-10.0 pmol/L) which is very unusual.Prednisone was started at 20mg daily to which there was reasonable response, dose was eventually increased to 60mg daily before he was safely sent home. He was discharged on a CGMS and the data was downloaded 2 weeks later. He had an interesting “Saw tooth” pattern of glycemia on the daily glucose graphs. As the patient had access to live data, he was trying to correct the falling blood glucose which briefly improved the readings but was quickly followed by another drop and this sequence carried on leading to a unique blood glucose pattern on the CGMS. Conclusion: Proinsulin level is usually suppressed in IGF-2 mediated hypoglycemia. Our case is unusually associated with high Proinsulin level. One hypothesis is the possible structural similarities leading to lab assay interactions between Proinsulin and “Pro-IGF-2”, which is thought to be one of the main molecules responsible for hypoglycemia in this condition. More studies in future will be helpful to study this possible association. Our case also had a remarkable “Saw tooth” pattern on CGMS glucose graphs which is very rarely seen in clinical practice.

Biomarkers of delirium and relation to dementia among the elderly in the intensive care unit: A narrative review

Delirium is a neuropsychiatric disorder highly prevalent in the intensive care unit (ICU), especially among elderly patients. Symptoms develop suddenly over a short period of time in the form of a fluctuating mental state marked by severe inattention and disturbance in cognition. Dementia, on the other hand, develops over a long period of time as a result of a neurodegenerative disorder. In this review, we aim to identify overlapping biomarkers between delirium and dementia to have a better understanding of the underlying pathophysiological mechanisms relating these two disorders. Overlapping biomarkers included low levels of albumin and IGF-1, a presence of the APOE ε4 allele (APOE ε4 +), as well as higher levels of of AβN-40, S100β, procalcitonin, IL-1β, NfL, prolactin, creatinine, MMP-9, and homocysteine. We put forward several hypotheses on the convergence of the pathophysiology of these two disorders. It is plausible that ICU-acquired delirium arises as a sign of prodromal dementia or as a result of chronic systemic inflammation and concomitant neuroinflammation due to an increase in S100β proteins in the brain as a byproduct of chronic glial activation. Simultaneously, accumulation of creatinine may render the functioning of the kidneys sub-optimal, which can have deleterious effects on cognitive functioning, while lower serum albumin can increase the risk of Aβ accumulation in the brain and therefore increase the likelihood of delirium and future dementia. Moreover, homozygosity in the APOE ε4 allele coupled with elevated plasma CRP might increase the risk of delirium and trigger the onset of Alzheimer’s disease (AD). Therapeutic approaches targeting the above biomarkers need to be the subject of further investigation, especially among those exhibiting persistent delirium.

Effects of acromegaly treatment on left ventricular systolic function assessed by speckle tracking echocardiography in relation to sex differences: results from a prospective single center study.

Despite the preserved LVEF, patients with acromegaly are characterized by subclinical systolic dysfunction i.e., abnormal global longitudinal strain (GLS) assessed by speckle tracking echocardiography (STE). The effect of acromegaly treatment on LV systolic function assessed by STE, has not been evaluated so far. Thirty-two naïve acromegalic patients without detectable heart disease were enrolled in a prospective, single-center study. 2D-Echocardiography and STE were performed at diagnosis, 3&6 months on preoperative somatostatin receptor ligand (SRL) treatment and 3 months after transsphenoidal surgery (TSS). Treatment with SRL resulted in reduction in median (IQR) GH&IGF-1 levels after 3 months, from 9.1(3.2-21.9) to 1.8(0.9-5.2) ng/mL (p<0.001) and from 3.2(2.3-4.3) to 1.5(1.1-2.5) xULN (p<0.001), respectively. Biochemical control on SRL was achieved in 25.8% of patients after 6 months and complete surgical remission was achieved in 41.7% of patients. TSS resulted in decrease in median (IQR) IGF-1 compared to IGF-1 levels on SRL treatment: from 1.5(1.2-2.5) to 1.3(1.0-1.6) xULN (p=0.003). Females had lower IGF-1 levels at baseline, on SRL and after TSS compared to males. The median end diastolic and end systolic left ventricle volumes were normal. Almost half of the patients (46.9%) had increased LVMi, however the median value of LVMi was normal in both sex groups: 99g/m2 in males and 94g/m2 in females. Most patients (78.1%) had increased LAVi and the median value was 41.8mL/m2. At baseline 50% of patients, mostly men (62.5% vs. 37.5%) had GLS values higher than -20%. There was a positive correlation between baseline GLS and BMI r=0.446 (p=0.011) and BSA r=0.411 (p=0.019). The median GLS significantly improved after 3 months of SRL treatment compared to baseline: -20.4% vs. -20.0% (p=0.045). The median GLS was lower in patients with surgical remission compared to patients with elevated GH&IGF-1 levels: -22.5% vs. -19.8% (p=0.029). There was a positive correlation between GLS and IGF-1 levels after TSS r=0.570 (p=0.007). The greatest beneficial effect of acromegaly treatment on LV systolic function is visible already after 3 months of preoperative SRL treatment, especially in women. Patients with surgical remission have better GLS compared to patients with persistent acromegaly.