Low Insulin-like Growth Factor-1 Research Articles

Associations between insulin-like growth factor-1 standard deviation score and overall nutritional parameters in patients with maintenance hemodialysis: a cross-sectional study.

This study investigated the association between insulin-like growth factor-1 and nutritional status indicators in patients undergoing maintenance hemodialysis (MHD). Patients undergoing MHD for > 3months were included in this single-center cross-sectional study in March 2021. Clinical, demographic, and body mass data and blood samples were collected before the hemodialysis sessions. Serum insulin-like growth factor-1 (IGF-1) levels were measured using a radioimmunoassay, and serum IGF-1 standard deviation score (SDS) was calculated for MHD patients according to age and sex. The nutritional status of patients was assessed using serum albumin, serum prealbumin, handgrip strength, pinching strength, upper arm muscle circumference, lean body mass, phase angle, seven-point subjective global assessment (SGA) score, and geriatric nutritional risk index (GNRI). The patients were divided into groups according to tertiles of serum IGF-1 SDS levels. Spearman correlation analyses and univariate and multivariate binary logistic regression analyses were used to determine the association between serum IGF-1 SDS and nutritional status parameters. A total of 155 MHD patients (male: female = 90:65) were enrolled in the study, witha median dialysis vintage of 28.0 (11.0, 55.0)months, and an average age of66 (65.5 ± 13.0)years. The median of IGF-1 SDS was - 0.1 (- 0.6 to 0.6). Compared to patients with higher IGF-1 SDSs, patients with lower IGF-1 SDSs had lower levels of serum ceruloplasmin (341.0 [287.5, 416.0] vs 395.0 [327.0, 451.0] vs 409.0 [349.5, 507.5], p = 0.002), serum albumin (34.7 ± 3.0 vs 37.0 ± 3.1 vs 37.8 ± 2.6, p < 0.001), serum prealbumin (270.3 [233.7, 327.8] vs 326.0 [279.3, 355.6] vs 363.0 [324.2, 398.2], p < 0.001), handgrip strength (13.8 [10.0, 20.7] vs 17.7 [10.7, 22.5] vs 23.3 [16.6, 27.8], p < 0.001), pinch strength (4.6 [3.9, 6.0] vs 4.9 (3.9, 6.9) vs 6.5 [4.7, 8.7], p = 0.002), phase angle (3.3 [3.0, 3.8] vs 3.9 [3.4, 4.7] vs 4.3 [3.6, 5.2, p < 0.001), modified Creatinine Index (83.1 ± 19.7 vs 93.1 ± 23.4 vs 113.9 ± 24.3, p < 0.001), intracellular water (14.5 ± 4.4 vs 16.1 ± 4.9 vs 16.9 ± 4.4, p = 0.031), higher extracellular water (26.9 ± 5.8 vs 25.7 ± 5.5 vs 25.1 ± 3.1, p = 0.042), and higher malnutrition risk as defined by GNRI (49.0% vs 15.7% vs 11.5%, p < 0.001) and SGA (53.9% vs 23.5% vs 7.7%, p < 0.001). Lower IGF-1 SDSs are independently associated with higher malnutrition risk in patients with MHD.

CTCF variant begets to short stature by down-regulation of IGF1.

Pathogenic variants in the transcription factor CCCTC-binding factor (CTCF) are associated with mental retardation, autosomal dominant 21 (MRD21, MIM#615502). Current studies supported the strong relationship between CTCF variants and growth, yet the mechanism of CTCF mutation leading to short stature is not known. Clinical information, treatment regimens, and follow-up outcomes of a patient with MRD21 were collected. The possible pathogenic mechanisms of CTCF variants leading to short stature were investigated using immortalized lymphocyte cell lines (LCLs), HEK-293T, and immortalized normal human liver cell lines (LO2). This patient received long-term treatment with recombinant human growth hormone (rhGH) which resulted in an increased height of 1.0 SDS. She had low serum insulin-like growth factor 1 (IGF1) before the treatment and the IGF1 level was not significantly increased during the treatment (-1.38 ± 0.61 SDS). The finding suggested that the CTCF R567W variant could have impaired IGF1 production pathway. We further demonstrated that the mutant CTCF had a reduced ability to bind to the promoter region of IGF1, consequently significantly reducing the transcriptional activation and expression of IGF1. Our novel results demonstrated a direct positive regulation of CTCF on the transcription of the IGF1 promoter. The impaired IGF1 expression due to CTCF mutation may explain the substandard effect of rhGH treatment on MRD21 patients. This study provided novel insights into the molecular basis of CTCF-associated disorder.

Insulin-like growth factor type 2 is a better survival marker than insulin-like growth factor type 1 in patients after acute decompensated heart failure.

A decreased insulin-like growth factor 1 (IGF-1) level has been found in heart failure (HF). There are no reports assessing IGF-2 in HF, although in vitro research has shown that IGF-2 stimulates cardiomyocyte proliferation more than IGF-1. The study aim was to compare the IGF-1 and IGF-2 concentrations depending on HF exacerbation and annual survival. Among 75 patients hospitalized due to newly diagnosed or exacerbated HF, the following evaluations were performed: anthropometric measurements, basic laboratory tests, heart echocardiography, and IGF-1 and IGF-2 concentrations. The annual survival was assessed. The participants were divided into NYHA II and NYHA III/IV groups. They did not differ in age, gender, body mass index (BMI), waist-hip ratio, glycated hemoglobin (HbA1c), high-density lipoprotein cholesterol, or triglycerides, but differed in echocardiographic parameters, BNP, total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol levels. Nine (12%) patients died during the 12-month follow-up. There were no differences in IGF-1 between NYHA groups and depending on the BMI, carbohydrate metabolism disorders and annual survival. A significantly lower IGF-2 concentration was found in NYHA III/IV vs. NYHA II: 583.71 (162.35) vs. 676.08 (172.09), p = 0.02, and in those who died: 501.47 (172.89) vs. 645.31 (166.17) nmol/l, p = 0.04. There was a positive correlation between IGF-2 and TC: r = 0.28, p = 0.015 and LDL: r = 0.29, p = 0.011 in the whole group and among patients with BMI ≥ 25 kg/m2: respectively for TC (r = 0.31, p = 0.014) and LDL (r = 0.28, p = 0.028). No IGF-1 correlation was found. Reduced IGF-2 concentration is a better marker of patients with more advanced HF and a higher 1-year death risk than low IGF-1. Its secretion may depend on the cholesterol concentration.

The Role of Insulin-Like Growth Factor 1 in Delirium: A Systematic Review and Meta-Analysis

Background: The relationship between delirium and low levels of insulin-like growth factor 1 (IGF-1) is contradictory and uncertain. We hypothesised that low levels of IGF-1 are a predisposing factor for delirium in medical and abdominal surgical cohorts, in contrast to other surgical cohorts. Aims: Systematic review and meta-analysis investigating the association between peripheral levels of IGF-1 and delirium in medical and surgical patients to explore if there are distinct patterns of associations by using subgroup meta-analysis. Methods: PubMed, Scopus, CINAHL, Cochrane, and Embase databases were searched. Inclusion criteria were prospective studies in medical and surgical populations and available data. The following were collected: the setting (surgical/medical), the type (orthopaedic surgery, abdominal, cardiovascular, or medical), the number of participants, mean age, the number of delirious patients, scale/criteria for delirium, IGF-1 levels, and MMSE. Results: Thirteen studies were included and analysed. Low levels of IGF-1 are significantly associated with delirium in abdominal surgical samples and medical samples but not in the other surgical samples. Age, cognition, and the setting (medical vs. surgical) do not have any significant effect on the differences in IGF-1 levels between those with and without delirium. Discussion: Delirium in acute medical and abdominal surgery is triggered by low IGF-1 which may reflect chronic conditions like frailty/cachexia/sarcopenia, while in other surgeries perhaps from an inflammatory process. Conclusions: Low peripheral levels of IGF-1 are a predisposing factor for delirium only in acute medical and abdominal surgery. More studies are needed to confirm and to explore further this finding.

Sex Differences in Long-Term Safety and Tolerability of GH Replacement Therapy in GH Deficient Adults.

Previous studies report that outcomes of growth hormone (GH) replacement therapy (GHRT) might be less beneficial in growth hormone deficient (GHD) women compared with men. This study investigated possible contributing factors regarding this previously found sex difference. This retrospective cohort study, conducted at a nationwide outpatient clinic (the Dutch National Registry of GH Treatment in Adults), included Dutch adult GHD men (n = 1335) and women (n = 1251) treated with GHRT. The patients' baseline characteristics, details of GHRT, and the tolerability and long-term safety of GHRT were measured. During treatment, sensitivity analysis showed that insulin-like growth factor-1 (IGF-1) SD scores remained subnormal more often in women (P < 0.001), while scores above normal were more frequent in men (P < 0.001). Women reported more adverse events (P < 0.001), especially symptoms related to fluid retention, and more often needed a dose reduction or temporary stop of GHRT (P = 0.001). In percentages, both sexes equally discontinued GHRT, as was also true for the risk in developing type 2 diabetes mellitus, benign neoplasms, and tumor recurrence. The risk of developing malignant neoplasms was higher in men (P = 0.012). Data obtained from the Dutch National Registry of GH Treatment in Adults indicate that GHD women might be treated suboptimally, reflected as lower IGF-1 status and lower GHRT tolerability, leading to more frequent changes in treatment regimen but not discontinuation of GHRT. Regarding long-term safety, we found a higher risk for development of malignancies in GHD men.

Spectrum of Growth Hormone Disorders in Children: A Case Series of 5 Cases

Growth Hormone Deficiency (GHD) is one of the most important treatable endocrine causes of short stature. A problem anywhere in the Growth Hormone (GH) - Insulin-Like Growth Factor-1 (IGF-1) axis can lead to short stature. Childhood GH deficiency can be congenital, acquired, or idiopathic. Hereby, the authors present a case series consisting of five cases of short stature, aimed to provide an overview of the spectrum of GH-related disorders. All five patients presented to the Paediatric Endocrinology Outpatient Department of a tertiary care Institute with complaints of not gaining height. The patients in present case series had significant short stature (Z score for height &lt;-3 SD (Standard Deviation) in each case). These patients were suspected of having GH deficiency based on clinical presentation and investigations. After a proper diagnostic work-up and GH stimulation tests, cases 1 to 4 were found to have GH deficiency. The 5th case was suspected of having Laron Syndrome based on high GH levels and low IGF-1. There were subtle differences in the spectrum of GH deficiency. The 1st case had Multiple Pituitary Hormone Deficiency (MPHD). Cases 2 to 4 had Isolated Growth Hormone Deficiency (IGHD). Case 2 had findings of pituitary stalk interruption on brain imaging. We found a genetic association in the 3rd case, while the 4th case had almost normal brain imaging. Cases 1 to 4 received GH therapy, and all showed appreciable height gain. These subtle differences can sometimes make the diagnosis difficult, and often a different approach to treatment is required.

Effects of Perinatally Acquired Cytomegalovirus Infection on Growth Hormone Axis

Cytomegalovirus (CMV) is one of the most common causes of perinatally acquired infection worldwide. It affects almost every organ system with varied type of clinical manifestation. In this case series, effect of perinatally acquired cytomegalovirus infection was studied on relatively unexplored area i.e, on growth hormone axis. Effect of standard antiviral treatment was also studied in these children. Five children were diagnosed to have perinatally acquired cytomegalovirus infection and it was found that all of these children were suffering from growth hormone deficiency (as evidenced by low insulin-like growth factor 1 and insulin-like growth factor binding protein 3 level as well). Some of the children were also found to have other endocrine manifestations like hypothyroidism and hypoglycaemia. They were treated with intravenous Ganciclovir followed by oral Valganciclovir and most of them responded well.

Влияние полиморфизма rs9939609 гена FTO на прибавку массы тела при беременности, уровни лептина и ИПФР-1 в грудном молоке и рост младенцев на грудном вскармливании

The search for possible ways of early prevention of obesity is an urgent task. Previous studies have provided evidence of the association of breast milk (BM) hormones with growth in young children. However, information on the influence of the mother’s genetic predisposition to obesity and her weight gain during pregnancy on their level is limited. Objective. To assess the effect of the rs9939609 polymorphism in the maternal FTO gene on body weight gain during pregnancy, the levels of leptin and insulin-like growth factor-1 (IGF-1) in BM, as well as the dynamics of the physical development of exclusively breastfed children. Patients and methods. The study involved 103 healthy women aged (M ± m) 32.2 ± 0.5 years, with a BMI of 19.8 ± 2.8 kg/m2 and their children living in Smolensk. Mothers gave informed consent to participate in the study. BM was taken on days 10–14, at 1 and 3 months of lactation. Levels of leptin and IGF-1 were determined in the morning midstream portion of BM serum by ELISA. Anthropometric data of children were assessed at birth, at 1 and 3 months of life using the WHO Anthro software (2009) by calculating the Z-scores of “weight-for-age” (WAZ) and “length-for-age” (LAZ). The women were genotyped for rs9939609 by real-time PCR. Results. Mothers with the TT genotype (frequency of occurrence – 62%) had higher body weight gain during pregnancy than carriers of the AT (22%) and AA (16%) genotypes, as well as significantly higher leptin and lower IGF-1 levels in BM during the entire observation period. Their infants had significantly lower WAZ at birth and at 1 month and LAZ at 3 months of life than children born to mothers with the AA and AT genotypes. Conclusion. Lower parameters of the physical development of infants born to mothers with the TT genotype of the rs9939609 polymorphism in the FTO gene can be explained by their low genetic predisposition to obesity. However, we cannot exclude the existence of an additional mechanism of growth restriction due to the influence of BM hormones on it, i.e., a reduced level of IGF-1 and the anorexigenic effect of an increased level of leptin, probably associated with a higher BMI and weight gain in mothers with the TT genotype over the period of pregnancy. Key words: anthropometry, breast milk, insulin-like growth factor-1, leptin, rs9939609 polymorphism, pregnancy weight gain

Insulin-Like Growth Factor -1 (IGF-1) and Glucose Dysregulation in Young Adult Patients with β-Thalassemia Major: Causality or Potential Link?

Insulin-like growth factor-1 (IGF-1) has been shown to lower blood glucose through stimulating glucose transport to fat and muscle and inhibiting hepatic glucose output. Although previous cross-sectional reports reported an association between low circulating concentrations of IGF-1 and glucose dysregulation (GD), its role is still debated. The present retrospective study was designed to assess the circulating IGF-1 levels in β-thalassemia major (β -TM) patients with normal oral glucose tolerance test (NGT-OGTT) and (GD) referred for an endocrine evaluation to explore the potential link between low IGF-1 and GD. Our study included 34 young adult patients with β-TM; 12 patients with NGT after OGTT, 7 with impaired glucose tolerance (IGT), 9 with impaired fasting glucose (IFG) plus IGT, and 6 patients with β-TM-related diabetes mellitus (β-TM- DM). Twenty-two β-TM patients with GD or β-TM- DM and 1 patient with NGT had IGF-1 levels below the 2.5th percentile. Correlation of IGF-1 with fasting plasma glucose, HOMA-IR (homeostatic model assessment for insulin resistance) and OGIS (oral glucose insulin sensitivity) was found. Moreover, a negative correlation was documented between ALT and the Insulinogenic Index (IGI) and a positive correlation between serum ferritin and PG 2-h after OGTT. This study reports for the first time an association between low levels of IGF-1 and GD in β-TM patients. Despite some limitations, our study can serve to generate proposals for more convenient and efficient methods to identify and treat early GD in patients with β-TM, and to conduct more extensive studies. www.actabiomedica.it).

Efficient generation of epigenetic disease model mice by epigenome editing using the piggyBac transposon system

BackgroundEpigenome-edited animal models enable direct demonstration of disease causing epigenetic mutations. Transgenic (TG) mice stably expressing epigenome-editing factors exhibit dramatic and stable changes in target epigenome modifications. Successful germline transmission of a transgene from founder mice to offspring will yield a sufficient number of epigenome-edited mice for phenotypic analysis; however, if the epigenetic mutation has a detrimental phenotypic effect, it can become difficult to obtain the next generation of animals. In this case, the phenotype of founder mice must be analyzed directly. Unfortunately, current TG mouse production efficiency (TG founders per pups born) is relatively low, and improvements would increase the versatility of this technology.ResultsIn the current study, we describe an approach to generate epigenome-edited TG mice using a combination of both the dCas9–SunTag and piggyBac (PB) transposon systems. Using this system, we successfully generated mice with demethylation of the differential methylated region of the H19 gene (H19-DMR), as a model for Silver–Russell syndrome (SRS). SRS is a disorder leading to growth retardation, resulting from low insulin-like growth factor 2 (IGF2) gene expression, often caused by epimutations at the H19-IGF2 locus. Under optimized conditions, the efficiency of TG mice production using the PB system was approximately threefold higher than that using the conventional method. TG mice generated by this system showed demethylation of the targeted DNA region and associated changes in gene expression. In addition, these mice exhibited some features of SRS, including intrauterine and postnatal growth retardation, due to demethylation of H19-DMR.ConclusionsThe dCas9–SunTag and PB systems serve as a simple and reliable platform for conducting direct experiments using epigenome-edited founder mice.

Association Between Insulin-Like Growth Factor-1 and Social Cognition in Huntington's Disease.

Insulin-like growth factor 1 (IGF-1) seems to be involved in the neural circuits associated with social cognition and brain structure. To investigate the association of IGF-1 levels with social cognition and brain structure in Huntington's disease (HD). We evaluated social cognition using the Ekman test in 22 HD patients and 19 matched controls. Brain structure was assessed using standard volume-based voxel-based morphometry and surface-based cortical thickness pipeline. We analyzed the association of IGF-1 levels with social cognition and brain structure using adjusted regression analysis. Social cognition was worse in HD patients (P < 0.001), on antidopaminergic drugs (P=0.02), and with lower IGF-1 levels (P=0.04). In neuroimaging analyses, lower IGF-1 levels were associated with social cognition impairment and atrophy mainly in frontotemporal regions (P < 0.05 corrected). In HD, abnormal IGF-1 function seems to be associated with brain atrophy leading to clinical deficits in social cognition.

Neurotrophic and growth factor response to acute exercise across the lifespan

AbstractBackgroundThere is evidence that aerobic exercise is beneficial to the brain and may reduce risk for cognitive decline and dementia. However, clinical trials have shown the benefits of exercise programs vary amongst individuals. This variability may occur in part due to differences in the physiological biomarker response to acute exercise. Characteristics such as age, sex, and apolipoprotein E4 (APOE4) genotype may affect these responses, but differences in blood processing protocols may introduce additional variability into the measures.MethodWe characterized the blood biomarker response to acute exercise in 80 individuals, including older adults (n=62, mean age 73y) and 18 young controls (n=18, mean age 37). Participants engaged in an acute, 15 minute bout of moderate intensity exercise (45‐55% HRR) following a 5 minute warm‐up. Blood was collected immediately prior to exercise, immediately post exercise, and 40 minutes post exercise. After collection, each timepoint sample was immediately processed for plasma and platelet poor plasma and frozen; this was done to limit release of growth factors from activated platelets post‐blood draw. Time course responses of brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin like growth factor 1 (IGF1) were measured using ELISA in platelet poor plasma. Lactate was measured in plasma (YSI 2500).ResultLinear mixed modeling performed with age, sex, and APOE4 genotype as covariates revealed a significant change in BDNF (p&lt;0.001) and lactate (p&lt;0.001) over time, with the highest levels of lactate observed immediately post‐exercise, while BDNF was elevated at 40 minutes post‐exercise in both young and older adults. There was no significant change with either VEGF or IGF1 over time in response to exercise, although older adults had significantly higher VEGF (p=0.01) and lower IGF1 (p&lt;0.001) compared to young controls across all timepoints.ConclusionWe report here that analysis of the acute exercise response reveals a significant increase in circulating BDNF and lactate, but not VEGF or IGF1, following aerobic exercise in both young controls and older adults. Further investigation into the mechanisms that contribute to these changes and the relevance to additional fluid and imaging brain health biomarkers in this cohort is ongoing.

Bone loss is ameliorated by fecal microbiota transplantation through SCFA/GPR41/ IGF1 pathway in sickle cell disease mice

Bone loss is common in sickle cell disease (SCD), but the molecular mechanisms is unclear. Serum insulin-like growth factor 1 (IGF1) was low in SCD subjects and SCD mice. To determine if decreased IGF1 associated with low bone mass in SCD is due to reduced SCFA production by gut microbiota, we performed reciprocal fecal microbiota transplantation (FMT) between healthy control (Ctrl) and SCD mice. uCT and histomorphometry analysis of femur showed decreased bone volume/total volume (BV/TV), trabecular number (Tb.N), osteoblast surface/bone surface (Ob.S/BS), mineralizing surface/ bone surface (MS/BS), inter-label thickness (Ir.L.Th) in SCD mice were significantly improved after receiving Ctrl feces. Bone formation genes Alp, Col1, Runx2, and Dmp1 from SCD mice were significantly decreased and were rescued after FMT from Ctrl feces. Transplantation of Ctrl feces increased the butyrate, valerate, and propionate levels in cecal content of SCD mice. Decreased G-coupled protein receptors 41 and 43 (GPR41 and GPR43) mRNA in tibia and lower IGF1 in bone and serum of SCD mice were partially restored after FMT from Ctrl feces. These data indicate that the healthy gut microbiota of Ctrl mice is protective for SCD bone loss through regulating IGF1 in response to impaired bacterial metabolites SCFAs.

Insulin-like growth factor-1 levels are associated with high comorbidity of metabolic disorders in obese subjects; a Japanese single-center, retrospective-study

Insulin like growth factor-1 (IGF-1) plays important roles in metabolic functions, especially in adulthood. Additionally, obese subjects are reportedly predisposed to having low absolute IGF-1 levels. However, the prevalence and clinical characteristics of obese subjects with low IGF-1 levels are unknown. We examined 64 obese subjects with a body mass index (BMI) ≥ 35 kg/m2, with no history of endocrinological disorders, receiving inpatient care. IGF-1 levels were interpreted based on the IGF-1 standard deviation score (SDS) clinically used and standardized by age and sex (low IGF-1 group; ≤ − 2.0 SDS and standard IGF-1 group; − 2.0 < and < + 2.0 SDS). Notably, 26.6% of the subjects had low IGF-1. Body fat mass and percentage, but not BMI, were significantly higher in the low than in the standard IGF-1 group. Furthermore, natural log-transformed high-sensitivity C-reactive protein, and the frequencies of dyslipidemia and hyperuricemia were higher in the low IGF-1 group. Moreover, among the subjects without diabetes, fasting glucose levels were significantly higher in the low IGF-1 group. Stepwise variable selection procedure revealed body fat percentage to be a parameter most strongly associated with low IGF-1. Thus, low IGF-1 levels may be an important marker of adiposity-associated metabolic disorders in obese patients.

Insulin-like growth factor 1 and the hormonal mediation of sibling rivalry

In altricial animals, young are completely dependent on parents for provisioning. The ability to outcompete siblings to receive parental provisioning has clear fitness benefits, and may be mediated by hormones that influence growth. We analyzed the effects of insulin-like growth factor 1 (IGF-1) on body size, growth, and sibling rivalry in eastern bluebirds (Sialia sialis). To determine whether IGF-1 is upregulated in response to the competitive environment, we manipulated brood sizes and examined the effect on IGF-1 levels, nestling body size, growth rate, and behavior. In a separate experiment, we injected nestlings with exogenous IGF-1 to study its impacts on body size, growth rate, and sibling competition. Brood size manipulation did not influence endogenous IGF-1 levels, but male nestlings with higher IGF-1 levels early in the nestling period tended to have greater mass gain than males with lower IGF-1 levels. Nestlings with higher IGF-1 levels also tended to be fed more frequently by parents. In the injection experiment, IGF-1 injected individuals tended to be heavier than vehicle injected young by the end of the nestling period, which suggests that IGF-1 can influence mass gain in bluebirds. IGF-1 has been proposed to be a mediator of life-history strategies and post-hatching behavior. Our results suggest that although bluebird nestlings do not adaptively elevate IGF-1 in response to the presence or number of siblings, IGF-1 may influence growth during the nestling period. These findings shed light on sibling competition, life history strategies, and the hormones that underlie them.

PSUN314 Severe Insulin Resistance Impacts the Growth Hormone-Insulin-Like Growth Factor-I Axis and Linear Growth

Abstract Diabetes and insulin resistance (IR) may impact growth hormone (GH), insulin-like growth factor 1 (IGF-1), and linear growth. Poorly controlled diabetes impairs growth, while high insulin may increase growth. To understand relationships between diabetes, IR, and growth, we examine height, body mass index (BMI), glucose, GH, and IGF- in patient populations with IR, including (in order of increasing IR): congenital generalized lipodystrophy (CGL), heterozygous pathogenic variants of the insulin receptor INSR (+/-), homozygous INSR variants (INSR-/-), and autoantibodies to the insulin receptor (Type B IR). Patients with CGL and INSR +/- have less IR, lower glucose, higher BMI, and higher IGF-1 vs patients with INSR -/- and Type B INSR. Patients with INSR -/- have short stature, while those with CGL have tall stature. GH is comparable in all groups. After remission of Type B IR, patients had normalization of insulin resistance, glucose, and IGF-1, supporting the idea that IR or elevated glucose caused low IGF-1. Our findings suggest that severe IR causes elevated blood glucose with inadequate glucose reaching cells mimicking a starvation state and causing low IGF-1. If this occurs during childhood growth (as in INSR -/-, but not in Type B IR), it leads to short stature. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSAT253 Differentiation of Pituitary Hyperplasia From Adenoma in the Setting of Severe Hypothyroidism

Abstract Introduction Pituitary hyperplasia due to long-standing or profound primary hypothyroidism is a rare finding in children. It occurs because of constant stimulation of thyrotrope cells by a thyrotropin-releasing hormone secreted from the hypothalamus due to a lack of negative feedback from thyroid hormones. The clinical presentation and imaging can mimic a pituitary mass. Patients can present with features of hypothyroidism, hyperprolactinemia, and even visual field defects if the hyperplastic pituitary gland compresses the optic chiasm. This case highlights this uncommon finding and discusses subtle clinical signs of hypothyroidism in children. Case Presentation A 10-year-old boy was incidentally found to have a pituitary lesion (15 mm×14 mm) when an MRI of the brain was performed as a healthy volunteer screening procedure. History and physical exam revealed cold intolerance, lack of height growth for 2 years (crossing down from 75th to 25th percentile), and dry skin with the barely palpable thyroid gland. There was no family history of thyroid or auto-immune disease. Evaluation of pituitary hormones showed remarkably high thyroid-stimulating hormone (&amp;gt;500 mcIU/ml) in the setting of undetectable free thyroxine, positive thyroid peroxidase antibody, low insulin-like growth factor-1, mildly elevated prolactin (67.4 mcg/L), and mild macrocytic anemia. Conclusions Differentiation of pituitary hyperplasia from pituitary hormone-secreting or non-secreting adenomas is crucial, as the primary modality of treatment of pituitary hyperplasia secondary to primary hypothyroidism is thyroid hormone replacement and not surgery unless the patient has visual field defects necessitating of decompression of the optic chasm to avoid permanent vision loss. In general, pituitary hyperplasia is described as homogeneously enhancing with the "nipple sign," which is when the pituitary gland has smooth contours, but a central protrusion of a pituitary mass is present. Elevated TRH can also lead to lactotroph hyperplasia, causing increased prolactin. Growth hormone secretion may be reduced by hypothyroidism and/or by damaged somatotroph cells due to space-occupying pituitary hyperplasia. Macrocytic anemia has been reported in patients with hypothyroidism and is thought to be an adaptation to a decreased basal metabolism. Early recognition and treatment of hypothyroidism during childhood is essential for normal growth and development. In children with the prolonged disease, final height may be compromised, and academic performance and psychosocial well-being may decline. Gradual replacement of thyroid hormone to therapeutic doses by slowly escalating doses of levothyroxine may be beneficial to prevent complications of therapy such as pseudotumor cerebri or empty sella due to rapid shrinkage of lactotroph and thyrotrope cells. Previous studies have shown approximately 85% of those with pituitary hyperplasia due to primary hypothyroidism demonstrate decreased pituitary gland size after starting thyroxine replacement and recommend repeating pituitary MRI after 2-4 months. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PMON219 Disparities in Musculoskeletal Health Profiles Across Race and Ethnicity in United States-Based Women with Polycystic Ovary Syndrome per the 2018 International Guideline

Abstract The magnitude and direction to which alterations in non-fat components of musculoskeletal composition (bone, muscle) may disproportionately impact diverse populations of women with polycystic ovary syndrome (PCOS) are unknown, despite clinical relevance. The uncertainty stems, partly, from heterogeneity in PCOS diagnostic criteria used and technical barriers in the reliable assessment of PCOS. We evaluated whether musculoskeletal (total and regional lean body mass [LBM] and bone mineral density [BMD]) outcomes were different in PCOS (n=126) across 4 prospectively recruited groups matched for age, body mass index, waist to hip ratio, and lack of recent (&amp;lt;3 mos) hormonal contraceptive and metformin use: self-identified (1) White (n=86); (2) Black (n=17); (3) Asian (n=12); and, (4) Hispanic (n=11) women in 3 academic medical centers in NY. PCOS was defined by the Rotterdam criteria using the recommended thresholds of the most recent (2018) PCOS Guideline. Fat and lean tissue mass and BMD were evaluated by dual-energy X-ray absorptiometry. Within the PCOS group, percentages of total body, trunk fat, and appendicular lean mass were comparable across races and ethnicities (All: P≥0.40); in contrast, total LBM and total and regional BMD were different across the groups (All: P&amp;lt;0.002). Post hoc pairwise comparisons revealed Asian women (mean±standard deviation; 39.64±6.42) exhibited lower total LBM vs. Black (53.93±10.60) and White (49.47±8.87; All: P&amp;lt;0.01) but not vs. their Hispanic (46.30±8.77 kg; P=0.29) counterparts. Total, upper, and lower limb BMD were higher in Black women (1.28±1.13; 0.82±0.09; 1.28±0.12) vs. all other counterparts: (White [1.12±0.9; 0.75±0.09; 1.18±0.10;]; Asian [1.09±0.09; 0.67±0.03; 1.08±0.05]; and, Hispanic [1.09±0.09; 0.72±0.15; 1.07±0.10] g/cm2; All: P&amp;lt;0.04), respectively. Similarly, lower limb BMD was compromised in Asian and Hispanic vs. White women (All: P≤0.03). Groups exhibited comparable glucoregulatory status (insulin and glucose responses to a standard 75-g oral glucose tolerance test), blood pressure, androgen status (Ferriman-Gallwey scores, total, free, and bioavailable testosterone), and intermenstrual interval length (All: P≥0.14). Conversely, groups differed by insulin-like-growth-factor-1 (IGF-1) and IGF-2 levels (All: P≤0.05). Post hoc pairwise comparisons showed lower IGF-1 in Black (255.92±145.12) and White (325.42±140.25) vs. Hispanic (549.21±266.26 ng/mL) women (All: P≤0.04). Also, Black women (426.74±82.66) had lower IGF-2 vs. White women (553.07±111.10 ng/mL; P≤0.4). Collectively, Asian women with PCOS show the lowest LBM and BMD, whereas their Black counterparts exhibit higher BMD after matching for age, body mass index, waist to hip ratio, lack of hormonal contraceptive and metformin use, and percentages of total body and trunk fat. Future research should delineate the true effects of PCOS-specific endocrine milieu (e.g., IGF axis) and relevance of genetic variants and/or environmental determinants of musculoskeletal health in this understudied clinical population. If confirmed by larger studies, our observations support the need for population-specific preventative and management considerations in future Guideline recommendations (e.g., PCOS-specific physical activity) to improve musculoskeletal health and associated reproductive and metabolic comorbidities. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

S1291 Low Insulin-Like Growth Factor 1 as a Predictor of Poor Prognosis in Liver Cirrhosis

S1291 Low Insulin-Like Growth Factor 1 as a Predictor of Poor Prognosis in Liver Cirrhosis

Acute effects of low load resistance training with blood flow restriction on serum growth hormone, insulin-like growth factor-1, and testosterone in patients with mild to moderate unilateral knee osteoarthritis

ObjectiveTo investigate the acute effects of blood flow restriction (BFR) with single-leg low load resistance exercise and high load resistance exercise on serum insulin-like growth factor-1 (IGF-1), growth hormone (GH), and testosterone in patients with unilateral knee osteoarthritis (OA). MethodsThis study recruited 18 postmenopausal female patients with mild to moderate unilateral knee OA, which was then followed by randomly conducting three resistance exercise protocols by drawing lots: 1. A 30% 1-repetition maximum (1-RM) resistance exercise with BFR of 70% arterial occlusive pressure (AOP) (BFR group); 2. A 70% 1-RM resistance exercise without BFR (RES group); 3. A 30% 1-RM resistance exercise without BFR (CON group). Blood lactate (BLA) and muscle growth related hormone levels were tested at 4-time points: before exercise, immediately after exercise, 15 min after exercise, and 30 min after exercise. ResultsThere was no statistical difference between the indexes in each group before exercise, but the different exercise had different effects on each index and also an interactive effect (P < 0.05). The increase of rating of perceived exertion in the BFR and RES groups, which were of similar magnitude, was greater compared to the levels in the CON group (P < 0.05). Post-exercise BLA levels were lower in the CON group in comparison to the BFR and RES groups (P < 0.05). Rather than the RES group, GH levels of the BFR group were also significantly higher than the CON group (P < 0.05) at 15 min post-exercise. At post- and 15 min after exercise, the CON group recorded significantly lower IGF-1 levels compared to the BFR and RES groups (P < 0.05). At post- and 15 min after exercise, the CON group (P < 0.05) reflected the lowest testosterone levels, followed by the RES group (P < 0.05), and the highest in the BFR group (P < 0.05). ConclusionsMyogenesis-related hormones in women with unilateral knee OA could be increased by high load resistance exercise and low load resistance exercise with BFR on unaffected limb.