Elevated Insulin-like Growth Factor Research Articles

IGF-1 induces sex-specific oxidative damage and mortality in a songbird.

The insulin-like growth factor1 (IGF-1) is a pleiotropic hormone that regulates essential life-history traits and is known for its major contribution to determining individual ageing processes. High levels of IGF-1 have been linked to increased mortality and are hypothesised to cause oxidative stress. This effect has been observed in laboratory animals, but whether it pertains to wild vertebrates has not been tested. This is surprising because studying the mechanisms that shape individual differences in lifespan is important to understanding mortality patterns in populations of free-living animals. We tested this hypothesis under semi-natural conditions by simulating elevated IGF-1 levels in captive bearded reedlings, a songbird species with an exceptionally fast pace of life. We subcutaneously injected slow-release biodegradable microspheres loaded with IGF-1 and achieved a systemic 3.7-fold increase of the hormone within the natural range for at least 24h. Oxidative damage to lipids showed marked sexual differences: it significantly increased the day after the manipulation in treated males and returned to baseline levels four days post-treatment, while no treatment effect was apparent in females. Although there was no overall difference in survival between the treatment groups, high initial (pre-treatment) IGF-1 and low post-treatment plasma malondialdehyde levels were associated with enhanced survival prospects in males. These results suggest that males may be more susceptible to IGF-1-induced oxidative stress than females and quickly restoring oxidative balance may be related to fitness. IGF-1 levels evolve under opposing selection forces, and natural variation in this hormone's level may reflect the outcome of individual optimization.

Successful medical management of a pituitary macroadenoma with features of resistant acromegaly and hyperprolactinemia using pasireotide.

The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment. A 48-year-old male reported that during a workup for obesity in his home country, hyperprolactinemia was diagnosed and a 3.5 × 3.5 cm pituitary macroadenoma was identified on pituitary MRI. He received cabergoline for 6 months; then he was lost to follow-up. He presented at our Endocrine clinic 2 years later for treatment of obesity (BMI 49.5 kg/m2). Biochemical workup revealed that in addition to hyperprolactinemia (7,237 [normal: 85-323 mIU/L), he had acromegaly, evident by elevated insulin-like growth factor 1 (IGF-1) level (450 [normal: 88-210 µg/L]), and a positive growth hormone suppression test, secondary hypothyroidism, and secondary hypogonadism. Pituitary MRI showed that the adenoma encased parts of the left and right internal carotid arteries and encroached on the optic chiasm. Surgical excision was therefore not feasible. He was treated with cabergoline and later, long-acting release (LAR) octreotide. Prolactin levels were reduced with cabergoline, but IGF-1 levels did not respond to octreotide, and it was discontinued. The patient abandoned radiotherapy after two sessions. He was started on LAR pasireotide 40 mg every 4 weeks and continued on cabergoline 0.5 mg per week. His biochemical response was dramatic, with a near normalization of IGF-1 levels in 3 months. After 6 months from starting pasireotide, we increased cabergoline dose from 0.5 mg/week to 3 mg/week. Three months later, IGF-1 level was normalized. The patient developed type 2 diabetes as a side effect of pasireotide; however, this was well-controlled with medications. The case suggests that pasireotide can provide marked biochemical improvement in acromegaly after the failure of both cabergoline monotherapy and cabergoline plus octreotide. This further confirms a potentially efficacious treatment regimen in treatment-resistant acromegaly with hyperprolactinemia.

Polymorphisms in insulin pathway genes and cancer risk

Background: Insulin is a big hormone (5808 Da) generally produced with the aid of the pancreas. Insulin receptors (IR) are found in neurons and glial cells. Insulin resistance has been related to increased plasma insulin levels, glucose intolerance, elevated insulin-like growth factor-1 (IGF-I), glucose and free fatty acids, body mass index, and an elevated risk for colorectal cancers. Proinflammatory cytokines, boom components, and hormones secreted by adipocytes play a key role in colorectal cancer etiology. Acetyl-CoA acetyltransferase (ACAT1) mediates insulin-precipitated cell proliferation and metastatic outcomes in colorectal cancer cells. Therefore, miRNAs might serve as a biological connection between metabolic changes linked to obesity and the beginning and progression of Colorectal Cancer Cancer (CRC). Furthermore, these findings shed new light on weight problems as a CRC danger component in which miRNA dysregulation may be involved. The function of IGFs in CRC is investigated by examining the association of two genetic polymorphisms in IGFBP-3 (a G → C single nucleotide polymorphism) and IGF-1 (a cytosine-adenosine dinucleotide repeat) with CRC risk in addition to the possibility of the other interventions, including physical activity, body mass index (BMI), and the use of postmenopausal hormones. These factors can exert their effects by modifying IGF-1 and the related binding proteins (IGFBP). Furthermore, the IGFBP-3 genotype can lead to a substantial effect modifier in the association between CRC and risk factors. It has been found that functional polymorphisms in the pathway of insulin genes, including IGFBPI, INSR, INS, and insulin receptor substrates 1 and 2 (IRS1 and IRS2), can be related to CRC.

Cerebral blood flow and cerebrovascular reactivity are modified by maturational stage and exercise training status during youth.

What is the central question of this study? Gonadal hormones modulate cerebrovascular function while insulin-like growth factor 1 (IGF-1) facilitates exercise-mediated cerebral angiogenesis; puberty is a critical period of neurodevelopment alongside elevated gonadal hormone and IGF-1 activity: but whether exercise training across puberty enhances cerebrovascular function is unkown. What is the main finding and its importance? Cerebral blood flow is elevated in endurance trained adolescent males when compared to untrained counterparts. However, cerebrovascular reactivity to hypercapnia is faster in trained vs. untrained children, but not adolescents. Exercise-induced improvements in cerebrovascular function are attainable as early as the first decade of life. Global cerebral blood flow (gCBF) and cerebrovascular reactivity to hypercapnia ( ) are modulated by gonadal hormone activity, while insulin-like growth factor 1 facilitates exercise-mediated cerebral angiogenesis in adults. Whether critical periods of heightened hormonal and neural development during puberty represent an opportunity to further enhance gCBF and is currently unknown. Therefore, we used duplex ultrasound to assess gCBF and in n=128 adolescents characterised as endurance-exercise trained (males: n=30, females: n=36) or untrained (males: n=29, females: n=33). Participants were further categorised as pre- (males: n=35, females: n=33) or post- (males: n=24, females: n=36) peak height velocity (PHV) to determine pubertal or 'maturity' status. Three-factor ANOVA was used to identify main and interaction effects of maturity status, biological sex and training status on gCBF and . Data are reported as group means (SD). Pre-PHV youth demonstrated elevated gCBF and slower mean response times than post-PHV counterparts (both: P≤0.001). gCBF was only elevated in post-PHV trained males when compared to untrained counterparts (634(43) vs. 578(46)mlmin-1 ; P=0.007). However, mean response time was faster in pre- (72(20) vs. 95(29)s; P≤0.001), but not post-PHV (P=0.721) trained youth when compared to untrained counterparts. Cardiorespiratory fitness was associated with gCBF in post-PHV youth (r2 =0.19; P≤0.001) and mean response time in pre-PHV youth (r2 =0.13; P=0.014). Higher cardiorespiratory fitness during adolescence can elevate gCBF while exercise training during childhood primes the development of cerebrovascular function, highlighting the importance of exercise training during the early stages of life in shaping the cerebrovascular phenotype.

Acromegaly with initial negative oral glucose tolerance test: a case report

BackgroundAcromegaly can be diagnosed by a growth hormone value ≥ 1 µg/L following an oral glucose tolerance test. However, normal growth hormone suppression following oral glucose tolerance test may not exclude acromegaly.Case presentationWe present a case of a 55-year-old Chinese man with pituitary macroadenoma incidentally noted after a traffic accident. He reported feet enlargement in the past few years. At the beginning, elevated insulin-like growth factor-1 was noted with growth hormone value < 1 µg/L after oral glucose tolerance test. Fracture-related high insulin-like growth factor-1 was suspected. Insulin-like growth factor-1 decreased gradually but was still above the upper limit of normal . However, he suffered from dizziness 1 year later and insulin-like growth factor-1 increased again. Besides, secondary hypocortisolism developed. The size of the pituitary macroadenoma was stationary. Follow-up oral glucose tolerance test showed a growth hormone value > 1 µg/L. Endoscopic endonasal approach to the remove pituitary macroadenoma was performed subsequently. After the resection of the pituitary macroadenoma, pathology showed positive staining of growth hormone and prolactin. Insulin-like growth factor-1 normalized as well.ConclusionsSuppressed growth hormone after oral glucose tolerance test cannot exclude acromegaly, and some patients may have only mild or no clinical presentation of acromegaly. Patients with pituitary microadenoma or macroadenoma and elevated insulin-like growth factor-1 should be closely monitored for signs/symptoms of acromegaly and hypopituitarism.

Elevated IGF-1 concentrations in children with low grade glioma: A descriptive analysis in a retrospective national cohort.

Children with low grade glioma (LGG) may present with, or develop, elevated concentrations of insulin-like growth factor 1 (IGF-1). The prevalence, pathophysiology, or its possible clinical effects are poorly understood. Our aim was to evaluate the prevalence of such elevated IGF-1 concentrations and to describe its association with linear growth, body mass index (BMI), pituitary outcome, and tumor behavior in a large retrospective national cohort. From a nationwide retrospective cohort of pediatric brain tumor survivors diagnosed between 2002 and 2012, tumor, treatment, endocrine, and auxological data of children with LGG were collected (n = 358). Prevalence and risk factors for elevated IGF-1 concentrations, as well as the association between having elevated IGF-1 concentrations and receiving tumor treatment, were explored. IGF-1 concentrations had only been measured in 45.5% of cases (n = 163/358). In 18.4% of 163 children with available IGF-1 measurements, IGF-1 concentrations were found elevated. No association was described between having an elevated IGF-1 concentration and tumor behavior or height SDS at last moment of follow-up. Multivariate logistic regression identified posterior pituitary disorder (OR 6.14 95% CI: 2.21-17.09) and BMI SDS at follow-up (OR 1.56 95% CI: 1.09-2.20) to be significantly associated with elevated IGF-1 concentrations. In this retrospective cohort of children with LGG, IGF-1 was found elevated in 18.4% of children with available IGF-1 measurements. Elevated IGF-1 seems to be related to hypothalamic dysfunction worsening over time. Larger prospective cohort studies are needed.

Non-islet cell tumour hypoglycaemia: A rare cause of persistent hypoglycaemia.

Non-islet cell tumour hypoglycaemia (NICTH) is a rare cause of hypoglycaemia. There is no single pathogenic mechanism that can explain all cases of NITCH. With this case, we wish to highlight the complexity in diagnosis and management of this condition.

Machine learning analysis of the UK Biobank reveals IGF-1 and inflammatory biomarkers predict Parkinson's disease risk.

Parkinson's disease (PD) is the most common movement disorder, and its prevalence is increasing rapidly worldwide with an ageing population. The UK Biobank is the world's largest and most comprehensive longitudinal study of ageing community volunteers. The cause of the common form of PD is multifactorial, but the degree of causal heterogeneity among patients or the relative importance of one risk factor over another is unclear. This is a major impediment to the discovery of disease-modifying therapies. We used an integrated machine learning algorithm (IDEARS) to explore the relative effects of 1,753 measured non-genetic variables in 334,062 eligible UK Biobank participants, including 2,719 who had developed PD since their recruitment into the study. Male gender was the highest-ranked risk factor, followed by elevated serum insulin-like growth factor 1 (IGF-1), lymphocyte count, and neutrophil/lymphocyte ratio. A group of factors aligned with the symptoms of frailty also ranked highly. IGF-1 and neutrophil/lymphocyte ratio were also elevated in both sexes before PD diagnosis and at the point of diagnosis. The use of machine learning with the UK Biobank provides the best opportunity to explore the multidimensional nature of PD. Our results suggest that novel risk biomarkers, including elevated IGF-1 and NLR, may play a role in, or are indicative of PD pathomechanisms. In particular, our results are consistent with PD being a central manifestation of a systemic inflammatory disease. These biomarkers may be used clinically to predict future PD risk, improve early diagnosis and provide new therapeutic avenues.

Abstract #1398813: A Rare Case of Acromegaly with Negative Immunohistochemical Staining for Growth Hormone

We are presenting a case of mixed prolactin and growth hormone (GH)-pituitary tumor with negative immunostaining for GH. 81-year-old male with history of type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and colon polyps was found to have a pituitary macroadenoma during evaluation of his visual disturbances. Years before the presentation, he noticed his shoe size had increased and his wife observed his jaw becoming more prominent. Physical exam was notable for enlarged nose, mandibular prognathism, and enlarged hands. Pre-operative laboratory results were remarkable for significantly elevated levels of insulin-like growth factor-1 (IGF-1), GH, and prolactin. He underwent transsphenoidal resection (TSPR) of the mass and pathology demonstrated a lactotroph adenoma, negative for GH immunostaining. After surgery he was started on cabergoline 0.5mg PO twice weekly. Three months afterwards his IGF-1 level remained elevated at 415 ng/mL. Acromegaly was confirmed by an elevated GH level of 13.8 ng/mL 2-hours after oral glucose challenge, then a long-acting somatostatin analogue depot was initiated for treatment. In the first year of therapy, he had weight loss and hypoglycemia that required discontinuation of insulin therapy. His IGF-1 and GH levels decreased to within age-appropriate ranges. His prolactin level returned to normal and cabergoline was stopped after a successful discontinuation trial. Clinical suspicion for acromegaly is confirmed by elevated IGF-1 and GH levels. When a GH-secreting pituitary adenoma is resected, immunocytochemistry with GH staining typically supports the diagnosis. It is not common for these tumors to stain negative for GH in the presence of clinical and biochemical acromegaly. The opposite—termed silent somatotroph— is more common and may represent an early stage in the development of a somatotroph adenoma. Failure to provide adequate diagnostic tissue, histopathology misread, or loss of antigenicity during fixation or embedding may be reasons for false negatives. However, it has been suggested that sparse cytoplasmic stores of GH do not parallel the hypersecretion of GH and may reduce staining capacity. Thus, a diagnosis of acromegaly should be made in patients with clinical and biochemical findings, even in the absence of GH immunostaining.

Association between metabolic syndrome, insulin resistance, and IGF-1 in breast cancer survivors of DIANA-5 study

PurposeCirculating insulin-like growth factor-1 (IGF-1) is positively associated with the risk of BC recurrence, and is more frequently dysregulated in older people, especially in those with metabolic syndrome (MetS) and obesity. This study aimed to analyze the association between IGF-1 levels and indices of MetS and insulin resistance in BC survivors.MethodsBaseline data of 563 BC survivors enrolled in the DIet and ANdrogen-5 (DIANA-5; NCT05019989) study were analyzed.ResultsLower circulating IGF-1 levels in subjects with MetS than in those without MetS were found. After stratification of the patients according to the diagnosis of MetS, we highlighted that the insulin was the main predictor of elevated IGF-1 levels only in subjects without MetS. Moreover, we found an interaction between high-density lipoprotein cholesterol (HDL-C), glycemia, and IGF-1 levels, showing a positive correlation between HDL-C and IGF-1, especially in subjects with higher values of glycemia and without a diagnosis of MetS.ConclusionsWhile IGF-1 levels appear to be much more impaired in subjects diagnosed with MetS, in non-MetS subjects, IGF-1 levels may respond better to metabolic parameters and lifestyle changes. Further studies are needed to analyze the role of physical activity and/or dietary intervention in modulating IGF-1 concentrations in BC survivors.Implications for cancer survivorsThese results could have important clinical implications for planning customized strategies aimed at modulating IGF-1 levels in BC survivors. In fact, while the IGF-1 system seems to be much more compromised in subjects with a diagnosis of MetS, in noMetS subjects, IGF-1 levels could better respond to lifestyle changes.

Elevated insulin-like growth factor-1 in patients without clinical evidence of acromegaly.

To 1) identify the frequency of IGF-1 elevation in a cohort of patients without clinically suspected GH excess, in a state-based reference laboratory over a 24-month period, and 2) to examine potential differences in comorbidities and relevant medications between people with an elevated IGF-1 compared to a matched control group. All IGF-1 measurements at Pathology Queensland between 1/12/2018 - 1/12/2020 were identified. The medical records of those with IGF-1 ≥1.1x the upper limit of the reference range were appraised to determine: 1) documentation of acromegalic features, 2) relevant comorbidities and medication use, and 3) further investigations to exclude pathological GH excess. There were 2759 IGF-1 samples measured in 1963 people ≥18 years, over the specified period. Of these, 204 had IGF-1 ≥1.1x the upper limit of the age-matched reference range; 102 cases (61M, 41F) met inclusion criteria, and were matched to 102 controls with a normal IGF-1 based on age, sex, gonadal status and pituitary anatomy on MRI. There were significant differences in the frequency of dopamine agonist use (19/102 cases vs 6/102 controls, OR=3.66, 95%CI: 1.45-9.29, P=0.009) and chronic kidney disease (CKD) (14/102 cases vs 4/102 controls, OR = 3.90, 95%CI: 1.28-11.14, P=0.024). Out of 1963 patients having IGF-1 measured, 102 (5.2%) had an elevated IGF-1 where there was no known acromegaly, GH replacement or endogenous glucocorticoid excess. Intra-individual biological variability, assay imprecision and physiological factors are known contributors to falsely elevated IGF-1, dopamine agonist therapy and CKD should also be considered. This article is protected by copyright. All rights reserved.

Laron syndrome in South Indian children – A descriptive study

Objectives: The objectives of this study were to describe the clinical and biochemical features of five children with Laron syndrome (LS) from South India. Material and Methods: This is a prospective descriptive case series of five children with clinical and biochemical features of LS managed over 5 years. Results: Five children (two girls and three boys) with LS with the mean age group of 5.9 ± 1.7 years and the mean age at diagnosis of 2.7 ± 0.8 years are described. All children were born out of consanguinity and all had typical phenotypic facies of LS. The mean Z-scores of height, weight, and body mass index on follow-up for the cohort were −7.0 ± 1.6, −5.9 ± 2.8, and −0.1 ± 0.7, respectively, and they were within ± 2 SD of the mean for children in LS chart. The median basal growth hormone level for age was 13 ng/mL and the median growth hormone levels at 30 min, 60 min, 90 min, and 120 min post-stimulation test were 35 ng/mL, 35 ng/mL, 44 ng/mL, and 50 ng/mL, respectively. All of them had insulin-like growth factor-1 (IGF-1) levels less than the 3rd percentile and no increment during the IGF-1 generation test. The prevalence of micropenis was 100% and one child had symptomatic hypoglycemic episodes. Genetic analysis was performed in two boys and both harbored variants in the growth hormone receptor gene. Conclusion: LS should be suspected in children with clinical features of growth hormone deficiency along with elevated growth hormone levels and low IGF-1 levels with no increment of IGF-1 in the IGF-1 generation test.

SerpinA3N deficiency attenuates steatosis and enhances insulin signaling in male mice.

Aberrant hepatic lipid metabolism is the major cause of non-alcoholic fatty liver disease (NAFLD) and is associated with insulin resistance and type 2 diabetes. Serine (or cysteine) peptidase inhibitor, clade A, member 3N (SerpinA3N) is highly expressed in the liver; however, its functional role in regulating NAFLD and associated metabolic disorders are not known. Male wildtype and hepatocyte Serpina3N knockout (HKO) mice were fed a control diet, methionine- and choline-deficient diet or high-fat high-sucrose diet to induce NAFLD and markers of lipid metabolism and glucose homeostasis were assessed. SerpinA3N protein was markedly induced in mice with fatty livers. Hepatic deletion of SerpinA3N attenuated steatosis which correlated with altered lipid metabolism genes, increased fatty acid oxidation activity and enhanced insulin signaling in mice with NAFLD. Additionally, SerpinA3N HKO mice had reduced epididymal white adipose tissue mass, leptin, and insulin levels, improved glucose tolerance, and enhanced insulin sensitivity which was associated with elevated insulin-like growth factor binding protein-1 (IGFBP1) and activation of the leptin receptor (LEPR)-STAT3 signaling pathway. Our findings provide a novel insight into the functional role of SerpinA3N in regulating NAFLD and glucose homeostasis.

PMON117 IGF-1 Testing: Diagnostic Pitfalls

Abstract Introduction Acromegaly is a rare endocrine disorder, with an incidence of 5.3/million/year, that results from persistent hypersecretion of growth hormone (GH), which stimulates hepatic secretion of insulin-like growth factor-1 (IGF-1). The best single test for the diagnosis of acromegaly is measurement of serum IGF-1; however, the result must be interpreted with caution, with understanding of potential pitfalls. Here we present a case of falsely elevated IGF-1 levels. Case Description A 43-year-old female with medical history of prediabetes, sleep apnea, and headaches was referred to endocrine clinic for evaluation of possible acromegaly. Patient had been evaluated by her primary care physician for frequent headaches, unintentional weight gain, and bilateral leg and hand swelling. Patient endorsed being unable to wear her wedding ring for a few years. Initial laboratory evaluation by primary care physician 3 months prior revealed normal thyroid function, prolactin, FSH, LH, random cortisol, but elevated IGF-1 of 310 ng/mL (normal 71-258 ng/mL), with negative pregnancy test. Brain MRI at that time revealed a pineal gland cyst but no pituitary abnormality. During her initial endocrine visit, IGF-1 was repeated, which was again elevated but improved to 283 ng/mL (normal 71-258 ng/mL). Other pertinent labs included a normal random ACTH of 18 pg/mL (normal &amp;lt;47 pg/mL), and pm cortisol of 2.4 mcg/dL (normal 2.9-17.3 mcg/dL). Physical examination was notable for a few light purple striae on abdomen, acanthosis nigricans, and mild limb edema, but no macrognathia, enlarged hands or feet. Given patient's lack of typical features of acromegaly, normal pituitary imaging, and spontaneous IGF-1 improvement, it was decided to postpone GH measurements with oral glucose tolerance test but repeat IGF-1 in 6 months. Patient was able to follow up 11 months after initial visit at which patient denied any worsening symptoms. At that time, repeat laboratory study showed normal IGF-1 of 231. Given spontaneous normalization of IGF-1 levels, no further laboratory testing or imaging studies were recommended, and patient was instructed to follow up in 11-12 months. Discussion Prompt diagnosis of acromegaly is crucial. However, it is important to note IGF-1 could be falsely elevated. A retrospective review by Erickson et. al of 2747 unique patients with IGF-1 elevation, 117 (4%) were found to have false-positive results following a review of the clinical data. In addition to acromegaly, other causes of elevated IGF-1 levels include high protein and high glycemic-index diet, pregnancy, hyperthyroidism, IGF-1 assay problems, and some rare tumors (carcinoids) secreting IGF-1. Discovery of "falsely" elevated IGF-1 may lead to unnecessary testing and physician visits. Therefore, clinicians should consider retesting patients after some time interval if spurious IGF-1 is suspected, before aggressively pursuing more extensive investigations. Presentation: No date and time listed

ODP187 Doedge-Potter syndrome and papillary thyroid carcinoma: An unusual association

Abstract Hypoglycemia can occur in non-diabetic individuals. Doege-Potter is a rare paraneoplastic syndrome presented as a hypoinsulinemic hypoglycemia caused by ectopic secretion of insulin-like growth factor-2 (IGF-2) from a solitary fibrous tumor. There is recent evidence of the involvement of the IGF system in different malignancies as papillary thyroid carcinoma, being exceptional. A 69-year-old female was brought to Emergency after a routine analysis uncovered severe hypoglycemia. She mentioned a history of morning sickness, dizziness, and confusion for the last week that reverted after breakfast, and dry cough for three months. She had a 25-pack-year history of smoking, no history of alcohol use, no other antecedent of interest, no history ofdiabetes mellitus or weight loss surgery, nor chronic treatments. Physical examinations revealed diminished breath sounds in the left middle lung. A thorax radiography showed a submassive left pleural effusion and toracocentesis revealed a hemorrhagic exudate. Laboratory data showed normal GH, and cortisol levels. Despite marked hypoglycemia, insulin level was 0.4 μIU/mL (2,6-24,9), C-peptide 0.11ng/ml (1,1-4,4) and hydroxy butyrate &amp;lt;0.1 mg/dl. The serum IGF-2 level was 428μg/dL (350-1000), and the IGF-1 level was 55.4 μg/L(161-384). Anti-insulin antibodies and sulfonylureas concentration were negative. CT showed a solid mass concerning parietal pleura with areas of necrosis and calcifications, measuring 14.6×15.4×20cm. Low blood glucose with suppressed insulin, C-peptide and IGF-1 levels, elevated IGF-2/IGF-1 ratio (7,7, normal&amp;lt;3) and CT findings suggested the possibility of non-islet cell tumor hypoglycemia (NICTH). Corticoid treatment was initiated to manage the hypoglycemia. Biopsy of the mass showed a malignant solitary fibrous tumor, positive for CD34 and BCL2. After surgery, glucose and IGF-2 levels returned to normal, the patient didn't experience further episodes of hypoglycemia, and corticoid treatment was gradually suspended. A FDG-PET scan, part of extension study, found a PET-positive thyroid nodule. A thyroid ultrasound confirmed a solid, taller than wide thyroid nodule, measuring 6.7×6.4×9,5mm and fine-needle aspiration biopsy was suggestive of papillary thyroid carcinoma. Hemithyroidectomy was performed. The patient is with no evidence of disease. Doege-Potter syndrome is a rare cause of hypoglycemia, resulting from a tumor producing elevated levels of IGF-2. Diagnosis is suggested by low insulin, C-peptide and IGF-1 levels, normal or elevated IGF-2, and elevated IGF2/IGF1 ratio. High levels of ''big-IGF-2'' are associated with high risk papillary thyroid carcinoma, suggesting the relation between the IGF-system and tumor growth, nevertheless there are few cases reported describing this association. Surgical resection of the tumor is the treatment of choice. Presentation: No date and time listed

Elevated IGF-1 and GH Levels Are Correlated With a Thicker Iris and Wider Anterior Chamber Angle in Treatment-Naïve Acromegaly Patients.

To compare the difference in anterior segment biometrics derived from anterior segment optical coherence tomography (AS-OCT) between treatment-naïve acromegaly patients and normal controls and evaluate the correlations between above biometrics and insulin-like growth factor 1 (IGF-1) and growth hormone (GH) levels. Sixty eyes of 30 acromegaly patients and 60 eyes of 30 normal controls were included in this case-control study. Central corneal thickness, pupil diameter, iris thickness (IT), iris curvature (IC), anterior chamber depth (ACD), anterior chamber width, lens vault (LV), angle open distance (AOD) 500, AOD750, and trabecular iris space area (TISA) 500 and TISA750 were measured by AS-OCT. General linear regression models were constructed to evaluate the independent endocrine factors affecting iris morphology and anterior chamber angle (ACA) width. The acromegaly patients had an evenly thicker iris (P &lt; 0.001), a smaller IC (P &lt; 0.05), a smaller LV (P = 0.040) and significantly larger AOD500, AOD750, TISA500 and TISA750 (P &lt; 0.001). There was a positive correlation between the serum GH level and ACD in the acromegaly patients (P = 0.031). Linear regression models showed the lower LV and smaller IC were independent influencing factors of the increase in the AOD500, AOD750, and TISA750 and nasal TISA500. Serum IGF-1 was an independent factor for the increase in pupil diameter (β = 0.002, P = 0.031) and both the average nasal (β = 6.781*10-5, P = 0.049) and temporal (β = 7.736*10-5, P = 0.045) IT values and for the decrease in temporal IC (β &lt; 0.001, P = 0.037). GH was an independent factor for the increase in temporal AOD750 (β = 0.001, P = 0.030) and temporal TISA750 (β = 0.002, P = 0.016). Patients with acromegaly have a thicker IT, smaller IC, and lower LV with a wider ACA than normal controls. Serum GH is independently correlated with the temporal ACA width, whereas serum IGF-1 is independently correlated with IT, pupil diameter, and IC.

Lipid Peroxidation Linking Diabetes and Cancer: The Importance of 4-Hydroxynonenal.

Significance: It is commonly believed that diabetes mellitus may be associated with cancer. Hence, diabetic patients are at higher risk for hepatocellular carcinoma, pancreatic cancer, colorectal cancer, and breast cancer, but the mechanisms that may link these two severe diseases are not well understood. Recent Advances: A number of factors have been suggested to promote tumorigenesis in diabetic patients, including insulin resistance, hyperglycemia, dyslipidemia, inflammation, and elevated insulin-like growth factor-1 (IGF-1), which may also promote pro-oxidants, and thereby alter redox homeostasis. The consequent oxidative stress associated with lipid peroxidation appears to be a possible pathogenic link between cancer and diabetes. Critical Issues: Having summarized the above aspects of diabetes and cancer pathology, we propose that the major bioactive product of oxidative degradation of polyunsaturated fatty acids (PUFAs), the reactive aldehyde 4-hydroxynonenal (4-HNE), which is also considered a second messenger of free radicals, may be the key pathogenic factor linking diabetes and cancer. Future Directions: Because the bioactivities of 4-HNE are cell-type and concentration-dependent, are often associated with inflammation, and are involved in signaling processes that regulate antioxidant activities, proliferation, differentiation, and apoptosis, we believe that further research in this direction could reveal options for better control of diabetes and cancer. Controlling the production of 4-HNE to avoid its cytotoxicity to normal but not cancer cells while preventing its diabetogenic activities could be an important aspect of modern integrative biomedicine. Antioxid. Redox Signal. 37, 1222-1233.

A Rare Cause of Severe Hypoglycemia in Intracranial Hemangiopericytoma Associated With Non-Islet Cell Tumor Hypoglycemia

A 60-year-old man with a history of metastatic intracranial hemangiopericytoma and type 2 diabetes mellitus presented with acute episodes of confusion and dizziness. A magnetic resonance imaging scan of the brain showed progressing calvarial metastasis without intracranial abnormality. He was found to have severe persistent hypoglycemia. The initial hypoglycemia work-up revealed low serum insulin and C-peptide level and negative panel for oral hypoglycemic agents. Further laboratory testing revealed an elevated insulin-like growth factor II (IGF II):IGF-I ratio and low β-hydroxybutyrate, consistent with nonislet cell tumor hypoglycemia. The patient received prednisone and his hypoglycemia improved.

Elevated insulin-like growth factor 2 mRNA binding protein 1 levels predict a poor prognosis in patients with breast carcinoma using an integrated multi-omics data analysis.

Background: Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) controls the cytoplasmic fate of certain mRNAs and is hypothesized to predict a poor patient prognosis in several malignant tumors. However, the prognostic relevance of IGF2BP1 in breast cancer remains debatable. Methods: We interrogated large publicly available datasets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and cBioportal databases to analyze the genetic alterations in the expression levels of IGF2BP1 in patients with invasive breast carcinoma (BRCA), and to discern the prognostic value of IGF2BP1 in BRCA. We applied Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genome (KEGG), and gene set enrichment analysis (GSEA) to uncover a functional association between IGF2BP1 and BRCA using differentially expressed genes (DEGs), and we screened genes and proteins related to BRCA. Results: We determined that both genetic alterations in IGF2BP1 (approximately 10%) and an increase in IGF2BP1 mRNA levels were related to certain cancer subtypes and an unfavorable prognosis in BRCA patients, and we then established an OS nomogram upon our multivariate regression model. The DEGs and IGF2BP1-correlated genes/proteins that implied the involvement of cornification, keratinization, drug/xenobiotic metabolism by cytochrome P450, chemical carcinogenesis, cell interactions, and cell adhesion to the extracellular matrix (ECM) pathways with respect to the prognostic relevance of IGF2BP1. Conclusion: In summary, our results indicated that both genetic alterations in IGF2BP1 and increased levels of IGF2BP1 mRNA and protein predict a poor patient prognosis in BRCA patients.

Paraneoplastic Hypoglycemia: A Case Report

Introduction: Paraneoplastic hypoglycemia unrelated to insulinoma is a rare cause of hypoglycemia and is due to paraneoplastic secretion of either IGFI, IGFII, or more rarely insulin Observation: We report a case of paraneoplastic hypoglycemia in a patient with metastases of an unknown primary. This is a 60-year-old patient admitted to the ward for recurrent hypoglycemia, the first of which was discovered following an apyretic coma. He has a history of hepatic and gluteal metastases from an undifferentiated carcinoma, the primary of which is unknown, followed in the oncology department and treated by chemotherapy. The biological assessment shows microcytic hypochromic anemia, hypoinsulinism &lt;0.1mIU / l associated with a collapsed C peptide &lt;0.15ng / ml (RV: 1.1- 4.4) with a concomitant glycemia of 21 mg/l. In view of the clinical context and the paraclinical explorations, the diagnosis of paraneoplastic hypoglycemia was retained after the elimination of the factitious origin and the insulinoma. The patient was put on diet, infusion of 5% glucose serum from which he was weaned after the introduction of prednisolone corticosteroid therapy: 60 mg per day with good tolerance and disappearance of hypoglycemia. Discussion/Conclusion: Paraneoplastic hypoglycemia is hypoglycemia most commonly caused by the overproduction of insulin-like growth factor 2 (IGF-2) and its precursors which can activate the insulin receptor. In general, large mesenchymal and epithelial tumors may be the cause. The diagnosis is confirmed by the discovery of an elevated IGF-2 / IGF-1 ratio. The basic treatment is surgical excision. Glucocorticoids are among the drugs that can be used in cases where surgery is not possible as a first line followed by other alternatives in case of failure.