Elevated Growth Research Articles

Deep Venous Thrombosis as the Clinical Expression of POEMS Syndrome

This case suggests that POEMS syndrome does present with a constellation of signs and symptoms that may lead a clinician to a multitude of other possible diagnoses. Diagnosis is often difficult and delayed. A good history and physical examination as well as a careful review of all workups are paramount in establishing this particular diagnosis. The major criteria of diagnostic for the syndrome are polyradiculoneuropathy, clonal plasma disorder, sclerotic bone lesions, the presence of Castleman disease, and elevated vascular endothelial growth factor. Minor features include organomegaly, extravascular volume overload, endocrinopathy, characteristic skin changes, papilledema, and thrombocytosis. The diagnosis is made with three of the major criteria, two of which must include polyradiculoneuropathy and clonal plasma cell disorder, and at least one of the minor criteria. In this article, we discuss the differential diagnosis and outline the clinical evaluation indicated.

Momordica charantia saponins administration in low-protein-high-carbohydrate diet improves growth, blood biochemical, intestinal health and microflora composition of juvenile common carp (Cyprinus carpio).

An 8-week feeding trial was conducted to explore the feasibility of Momordica charantia saponins (MCS) administration to facilitate the protein-sparing action of high carbohydrate in diets for juvenile common carp (Cyprinus carpio) with initial mass of 5.41±0.02g. Based on our previous study, four diets with different the ratio of protein and carbohydrate (P/C ratio) were designed: 32%P/40%C, 30%P/43%C, 28%P/46%C, 28%P/46%C supplemented with 0.16% MCS (28%P/46%C+MCS). Each diet treatment was divided into 3 replicates. Results revealed that 30%P/43%C group increased growth performance and intestinal digestion, decreased intestinal inflammation, and optimized the intestinal microbiota compared to 32%P/40%C group, which presented the stronger protein-sparing action of high carbohydrate. But if the P/C ratio reduced to 28%P/46%C or less, the saving action would be restrained. However, compared to the 30%P/43%C and 28%P/46%C groups, 28%P/46%C+MCS group significantly elevated growth performance and activities of digestive enzymes and antioxidative enzymes, whilst the opposite trend occurred in the contents of glucose, triglyceride, total cholesterol, low density lipoprotein cholesterol, blood urea nitrogen, glutamic oxalacetic transaminase, glutamic-pyruvic transaminase and malondialdehyde. In addition, 28%P/46%C+MCS group markedly upregulated the expressions of GH/IGF axis genes, genes involved in protein synthesis, antioxidant genes and anti-inflammatory cytokine, whilst the opposite trend occurred in the expressions of pro-inflammatory cytokines. Moreover, 28%P/46%C+MCS group obtained the remarkably higher Enterococcus proportion and lower Lactococcus proportion compared to the 30%P/43%C and 28%P/46%C groups, whereas the opposite occurred in 30%P/43%C group, which indicated that there existed differences in the improvement mechanism on intestinal microflora composition between MCS and appropriate P/C ratio. Combined with the above mentioned changes in our research, we concluded that 0.16% MCS administration in a 28%P/46%C diet could facilitate the protein-sparing action of high carbohydrate in diets for common carp, which could decrease the 5% dosage of soybean meal and synchronously reduce the 4% crude protein of diets without affecting the growth and immune ability for common carp.

Plant Growth-Promoting Rhizobacteria (PGPR) Reduce Adverse Effects of Salinity and Drought Stresses by Regulating Nutritional Profile of Barley

With the growing emphasis on sustainable agriculture, food security, and environmental protection, the use of beneficial soil microbes is imperative, as the use of chemicals such as fertilizers, pesticides, and herbicides has resulted in food contamination, disease, weed resistance, and negative environmental consequences, which ultimately impacted human health. Climate change is a major factor and is of great concern for crop production. Abiotic stresses, including salt and drought stress, restrain the crop yield. The aim of this particular study is to understand what role do plant growth-promoting rhizobacteria (PGPR) play in combating the salinity and drought stresses through modification of nutritional profile. In the current study, inoculated barley (Hordeum vulgare L.) plants were subjected to various stresses such as 200 mM and 1000 mM salinity stress as well as drought stress, and then their various parameters such as seed germination as well as shoot and root biomasses and photosynthetic activity were compared with non-treated stressed barley plants. Our data depicted an improvement or significant enhancement of these parameters in PGPR (Pseudomonas fluorescens SBW25 and Pseudomonas putida KT2440) applied barley plants. Furthermore, the particle-induced X-ray emission (PIXE) technique was used for the elemental analysis of PGPR-inoculated and non-inoculated plants under stress vs. no stress conditions. Our PIXE analysis of various macro- and micronutrients revealed an enhancement of Ca, Mg, K, P, S, Al, and Si uptake in PGPR-treated plants. PGPR applications depicted reduced Cl− contents in 200 mM salt-stressed barley roots (KT2440 = 7.7 mg/kg and SBW25 = 6.3 mg/kg) and stems (KT2440 = 406.4 mg/kg and SBW25 = 365.5 mg/kg) as compared to controls (roots = 8.9 and stems = 469.5), while they displayed a significant increase in the barley leaves (KT2440 = 405 mg/kg and SBW25 = 416.4 mg/kg) when compared to control (110.6 mg/kg) under the same stress condition. In 1000 mM salt stress, a significant reduction in the Cl− content was observed in PGPR-applied barley roots (KT2440 = 7.6 mg/kg), stems (KT2440 = 1205.8 mg/kg and SBW25 = 1008.3 mg/kg), and leaves (KT2440 = 967.8 mg/kg and SBW25 = 530.8 mg/kg) when compared to controls (roots = 15.2 mg/kg, stems = 1605.2 mg/kg, and leaves = 1165.2 mg/kg). On the other hand, a significant increase in the Cl− content was noticed in PGPR-applied barley roots (KT2440 = 29.5 mg/kg and SBW25 = 25.8 mg/kg), stems (KT2440 = 1023.8 mg/kg and SBW25 = 894.9 mg/kg), and leaves (KT2440 = 369.2 mg/kg and SBW25 = 409.8 mg/kg) when compared to controls (roots = 13.5 mg/kg, stems = 505.3 mg/kg, and leaves = 219.9 mg/kg) under drought stress condition. PGPR application was also found to be effective for enhancing the uptake of micronutrients (Mn, Fe, Co, Ni, Cu, and Zn) in barley plant parts under control and also under stressed conditions. Overall, our findings revealed an improvement in the uptake of macro- and micronutrients for the enhancement of salinity and drought stress tolerance. Conclusively, these PGPR species are an effective source of plant stress tolerance and elevated growth of barley and related plants under stress conditions.

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.

De Novo Large Deletions in the PHEX Gene Caused X-Linked Hypophosphataemic Rickets in Two Italian Female Infants Successfully Treated with Burosumab.

Pathogenic variants in the PHEX gene cause rare and severe X-linked dominant hypophosphataemia (XLH), a form of heritable hypophosphatemic rickets (HR) characterized by renal phosphate wasting and elevated fibroblast growth factor 23 (FGF23) levels. Burosumab, the approved human monoclonal anti-FGF23 antibody, is the treatment of choice for XLH. The genetic and phenotypic heterogeneity of HR often delays XLH diagnoses, with critical effects on disease course and therapy. We herein report the clinical and genetic features of two Italian female infants with sporadic HR who successfully responded to burosumab. Their diagnoses were based on clinical and laboratory findings and physical examinations. Next-generation sequencing (NGS) of the genes associated with inherited HR and multiple ligation probe amplification (MLPA) analysis of the PHEX and FGF23 genes were performed. While a conventional analysis of the NGS data did not reveal pathogenic or likely pathogenic small nucleotide variants (SNVs) in the known HR-related genes, a quantitative analysis identified two different heterozygous de novo large intragenic deletions in PHEX, and this was confirmed by MLPA. Our molecular data indicated that deletions in the PHEX gene can be the cause of a significant fraction of XLH; hence, their presence should be evaluated in SNV-negative female patients. Our patients successfully responded to burosumab, demonstrating the efficacy of this drug in the treatment of XLH. In conclusion, the execution of a phenotype-oriented genetic test, guided by known types of variants, including the rarest ones, was crucial to reach the definitive diagnoses and ensure our patients of long-term therapy administration.

Rare manifestation of familial vitreous amyloidosis caused by Gly103Arg transthyretin.

To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis (FVA) in a Chinese Han family. Pars plana vitrectomy (PPV) surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment, without evidence of cardiac, renal, gastrointestinal, central nervous system or peripheral nervous system dysfunction. During the surgery, the patient presented with a gray-white dense and thick cotton wool-like change in the vitreous body, accompanied by complete retinal detachment. Additionally, hard, free and movable yellow-white deposits were observed in the posterior pole and surrounding retina, the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination, and whole exome sequencing was performed on blood samples from the patient and her cousin. During the operation, it was discovered that there was a complete detachment of the retina and a significant amount of hard, free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina. This is an exceedingly rare ocular manifestation. Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining, as well as elevated vascular endothelial growth factor (VEGF) expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination. The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin (TTR) gene, resulting in a substitution of glycine (Gly) at position 103 with arginine (Arg). FVA may present with various ocular manifestations, but panretinal detachment is a rare occurrence. In cases where retinal detachment persists for an extended period of time, amyloid deposits may form under the retina through retinal tears, leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis. Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state, necessitating careful postoperative follow-up. The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.

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.

Elevated Opioid Growth Factor Alters the Limbus in Type 1 Diabetic Rats.

Ocular surface complications occur in more than 50% of individuals diagnosed with diabetes. The financial and health-related burden of diabetes is increasing annually. Several major ocular complications associated with diabetes involve the limbus. The vascular limbus, adjacent to the avascular cornea, is the source of circulating growth factors, elevated glucose, and cytokines for the cornea. The Opioid Growth Factor (OGF) - Opioid OGF Receptor (OGFr) axis is comprised of its effector peptide, OGF, [Met5]-enkephalin and the nuclear-associated receptor, OGFr, and has been demonstrated to be dysfunctional in diabetes with elevated serum and tissue levels of the inhibitory growth factor OGF recorded in corneal tissue. Little is known regarding the impact of OGF-OGFr axis dysregulation in diabetes on the functioning of the limbus constituents in support of corneal homeostasis. Adult male and female Sprague-Dawley rats were rendered hyperglycemic through intraperitoneal injections of streptozotocin (T1D); a subset of T1D rats received topical naltrexone (NTX) applied to the cornea and limbus daily for 8 weeks. At 4 and/or 8 weeks of hyperglycemia, different cohorts of animals were euthanized, eyes removed and processed for assessment of limbal morphology, expression of OGF, OGFr, cytokeratin 15, a marker for limbal cells, and Ki-67, a marker of proliferation. Limbal epithelial morphology (cell diameter, packing density) was altered in T1D male and female rats. OGF and OGFr were overexpressed in the limbus and CK15 expression was decreased, relative to normal control rats of the same sex. Blockade of the OGF- OGFr axis with NTX reversed limbal epithelial cell defects, and reduced OGF limbal tissue levels to those recorded in non-diabetic rats. In summary, OGF-OGFr axis dysregulation was observed in the limbus of T1D rats, contributing to the altered limbal morphology and delayed corneal surface healing observed in diabetic animals.

Identified root signals unlocking the relationship between elevated CO2 shoot growth and shoot nutrient deficiencies.

This article is a Commentary on Cassan et al. (2023), 239: 992–1004.

Supplemental Clostridium butyricum modulates skeletal muscle development and meat quality by shaping the gut microbiota of lambs

This study evaluated the contributions of Clostridium butyricum on skeletal muscle development, gastrointestinal flora and meat quality of lambs. Eighteen Dorper (♂) × Small Tailed Han sheep (♀) crossed ewe lambs of similar weight (27.43 ± 1.94 kg; age, 88 ± 5 days) were divided into two dietary treatments. The control group was fed the basal diet (C group), and the probiotic group was supplemented with C. butyricum on the basis of the C group (2.5 × 108 cfu/g, 5 g/day/lamb; P group) for 90 d. The results showed that dietary C. butyricum elevated growth performance, muscle mass, muscle fiber diameter and cross-sectional area, and decreased the shear force value of meat (P < 0.05). Moreover, C. butyricum supplementation accelerated protein synthesis by regulating the gene expression of IGF-1/Akt/mTOR pathway. We identified 54 differentially expressed proteins that regulated skeletal muscle development through different mechanisms by quantitative proteomics. These proteins were associated with ubiquitin-protease, apoptosis, muscle structure, energy metabolism, heat shock, and oxidative stress. The metagenomics sequencing results showed that Petrimonas at the genus level and Prevotella brevis at the species level in the rumen, while Lachnoclostridium, Alloprevotella and Prevotella at the genus level in the feces, were significantly enriched in the P group. Also, butyric acid and valeric acid levels were elevated in both rumen and feces of the P group. Overall, our results support the idea that C. butyricum could change gastrointestinal flora, and affect skeletal muscle development and meat quality of lambs by modulating gut-muscle axis.

Astragalus polysaccharide improves the growth, meat quality, antioxidant capacity and bacterial resistance of Furong crucian carp (Furong carp♀ × red crucian carp♂)

To evaluate the functional effects of APS (Astragalus polysaccharide) on Furong crucian carp, APS-supplemented diets (0.00 %, 0.05 %, 0.10 % and 0.15 %) were prepared and utilized in feeding experiment. The results showed that the 0.05 % APS group has the highest weight gain rate and specific growth rate, and the lowest feed coefficient rate. In addition, 0.05 % APS supplement could improve muscle elasticity, adhesiveness and chewiness. Moreover, the 0.15 % APS group had the highest spleen-somatic index and the 0.05 % group had the maximum intestinal villus length. 0.05 % and 0.10 % APS addition significantly increased T-AOC and CAT activities while MDA contents decreased in all APS groups. The plasma TNF-α levels in all APS groups significantly increased (P<0.05), and the 0.05 % group showed the highest TNF-α level in spleen. In APS addition groups, the tlr8, lgp2 and mda5 gene expressions were significantly elevated, while xbp1, caspase-2 and caspase-9 expressions decreased in uninfected and A. hydrophila-infected fish. Finally, higher survival rate and slower disease outbreak rate were observed in APS-supplemented groups after being infected by A. hydrophila. In conclusion, Furong crucian carp fed by APS-supplemented diets possesses elevated weight gain rate and specific growth rate, and improved meat quality, immunity and disease resistance.

Mast Cell Tryptase Promotes Airway Remodeling by Inducing Anti-Apoptotic and Cell Growth Properties in Human Alveolar and Bronchial Epithelial Cells

Bronchial and alveolar remodeling and impaired epithelial function are characteristics of chronic respiratory diseases. In these patients, an increased number of mast cells (MCs) positive for serine proteases, tryptase and chymase, infiltrate the epithelium and alveolar parenchyma. However, little is known regarding the implication of intraepithelial MCs on the local environment, such as epithelial cell function and properties. In this study, we investigated whether MC tryptase is involved in bronchial and alveolar remodeling and the mechanisms of regulation during inflammation. Using novel holographic live cell imaging, we found that MC tryptase enhanced human bronchial and alveolar epithelial cell growth and shortened the cell division intervals. The elevated cell growth induced by tryptase remained in a pro-inflammatory state. Tryptase also increased the expression of the anti-apoptotic protein BIRC3, as well as growth factor release in epithelial cells. Thus, our data imply that the intraepithelial and alveolar MC release of tryptase may play a critical role in disturbing bronchial epithelial and alveolar homeostasis by altering cell growth–death regulation.

The energy-water limitation threshold explains divergent drought responses in tree growth, needle length, and stable isotope ratios.

Predicted increases in extreme droughts will likely cause major shifts in carbon sequestration and forest composition. Although growth declines during drought are widely documented, an increasing number of studies have reported both positive and negative responses to the same drought. These divergent growth patterns may reflect thresholds (i.e., nonlinear responses) promoted by changes in the dominant climatic constraints on tree growth. Here we tested whether stemwood growth exhibited linear or nonlinear responses to temperature and precipitation and whether stemwood growth thresholds co-occurred with multiple thresholds in source and sink processes that limit tree growth. We extracted 772 tree cores, 1398 needle length records, and 1075 stable isotope samples from 27 sites across whitebark pine's (Pinus albicaulis Engelm.) climatic niche in the Sierra Nevada. Our results indicated that a temperature threshold in stemwood growth occurred at 8.4°C (7.12-9.51°C; estimated using fall-spring maximum temperature). This threshold was significantly correlated with thresholds in foliar growth, as well as carbon (δ13 C) and nitrogen (δ15 N) stable isotope ratios, that emerged during drought. These co-occurring thresholds reflected the transition between energy- and water-limited tree growth (i.e., the E-W limitation threshold). This transition likely mediated carbon and nutrient cycling, as well as important differences in growth-defense trade-offs and drought adaptations. Furthermore, whitebark pine growing in energy-limited regions may continue to experience elevated growth in response to climate change. The positive effect of warming, however, may be offset by growth declines in water-limited regions, threatening the long-term sustainability of the recently listed whitebark pine species in the Sierra Nevada.

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.

Elevated fetal growth during the antenatal period is associated with maternal obesity class

Obesity is characterized as a body mass index (BMI) &gt;30.0 kg/m2. Obesity is further classified into Obesity Class 1 (BMI 30-34.9 kg/m2), Obesity Class 2 (BMI 35-39.9 kg/m2), and Obesity Class 3 (BMI ≥ to 40 kg/m2). In Mississippi, over 43% of women of childbearing age (18-44 years old) are obese. Numerous studies support the concept that in-utero exposure to a maternal obesogenic environment promotes fetal macrosomia (fetal growth above average per gestational age) and program offspring to metabolic complications throughout their lifespan. Yet, the association of obesity class on fetal growth and development is not well defined. Thus, we tested the hypothesis that increases in maternal obesity class promote excess fetal growth in offspring from obese mothers during the antenatal period. This study evaluated ultrasounds of pregnant women (n= 568) at the University of Mississippi Medical Center (UMMC) from 2019-2020. Women were evenly divided by BMI class (Normal, Obesity Class 1, Obesity Class 2, and Obesity Class 3). Obesity Class 3 was limited to a BMI of 40-44.9 kg/m2. Women were of reproductive age (18-44 years old). Maternal and fetal measurements were assessed at 1 time point at a routine ultrasound visit between 18-38 weeks gestation. Average maternal age was 28.27±6.15 years. Average gestational age of offspring was 23.91±5.41 weeks. Estimated fetal weight did not differ between Normal, Obesity Class 1, and Obesity Class 2. Estimated fetal weight was significantly increased in Obesity Class 3 (854.50±677.00 g) ( p&lt;0.05) vs. Normal (401.10±159.60 g) ( p&lt;0.05), Obesity Class 1 (445.9±202.3 g) ( p&lt;0.05), and Obesity Class 2 (532.5±348.3 g) ( p&lt;0.05). Estimated fetal weight by offspring gender per BMI Class did not differ. Abdominal circumference, a predictor of fetal growth, was only significantly increased in Obesity Class 2 (47.85±28.58 mm) vs Normal (37.15±24.85 mm) ( p&lt;0.05). We also evaluated abdominal circumference by offspring gender per BMI class. Abdominal circumference was significantly reduced in Normal females (25.90±20.79 mm) vs. Normal males (44.67±24.60 mm) ( p&lt;0.05), Obesity Class 1 females (48.25±27.79 mm) ( p&lt;0.05), Obesity Class 2 males (45.26±27.74 mm) ( p&lt;0.05) and females (48.31±30.03 mm) ( p&lt;0.05), and Obesity Class 3 males (52.18±33.29 mm) ( p&lt;0.05). These data indicate that severe obesity (BMI ≥ to 40 kg/m2) increases risk for fetal macrosomia, placing offspring at risk for metabolic disorders throughout their lifespan. Females exhibit greater increases in abdominal circumference by obesity class which suggests that female offspring are at greater risk of excess gestational growth in obesogenic environments compared to male counterparts. Yet, these data do not represent offspring weight or abdominal circumference at birth. Further studies are warranted to determine the influence of obesity on fetal growth after 38 weeks gestation and the placental mechanisms associated with fetal growth and development in maternal obesity. UMMC Department of Obstetrics and Gynecology This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

POEMS syndrome associated with vitiligo (P13-8.007)

<h3>Objective:</h3> To report a case of POEMS syndrome with vitiligo. This is the second case to be reported and the first in an Afro-American patient. <h3>Background:</h3> POEMS syndrome is a rare plasma-cell disorder with multisystem involvement, characterized by the acronym composing its name: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein (M-protein), and Skin changes. Major criteria include mandatory polyneuropathy and monoclonal plasma cell proliferative disorder in addition to Castleman’s disease, sclerotic bone lesions, or elevated vascular endothelial growth factor (VEGF). Minor criteria, still helpful for diagnosis, include organomegaly, endocrinopathy, papilledema, thrombosis, and skin changes, the most common being hyperpigmentation. <h3>Design/Methods:</h3> Case Presentation <h3>Results:</h3> A 50-year-old Afro-American male presented with 3 years of ascending stocking-glove pattern numbness and skin discoloration in his feet. Other positive history included anhidrosis, heat intolerance and erectile dysfunction suggestive of dysautonomia. Medical history included hypoparathyroidism and idiopathic cirrhosis. He did not have history of alcohol overuse, diabetes, or glucose intolerance. Examination revealed confluent hypopigmented macules in feet, vibratory sensation impairments up to knees, absent temperature sensation in feet, and abnormal Romberg test and tandem gait. Remainder of the neurological examination was normal. Laboratory tests were significant for elevated free kappa and lambda light chains, plasma VEGF levels twice over normal range, and an IgA monoclonal band on serum protein electrophoresis. Other relevant laboratory findings included PTH-independent hypercalcemia and alkaline phosphatase elevation. Radiographs of hands, elbows, shoulders, and knees disclosed non-sclerotic lytic lesions. Nerve conduction studies were consistent with a sensorimotor axonal polyneuropathy. The patient met diagnostic criteria for POEMS syndrome. Autologous stem cell transplantation was recommended but the patient declined. His vitiligo, neuropathy, and monoclonal gammopathy remain stable under surveillance at 4 years without pharmacotherapy. <h3>Conclusions:</h3> POEMS syndrome should be suspected in any patient with new onset of vitiligo in the presence of an underlying polyneuropathy and a monoclonal plasma cell proliferative disorder. <b>Disclosure:</b> Dr. Landman has nothing to disclose. Dr. Escobar-Montealegre has nothing to disclose. Dr. Singh has nothing to disclose. Dr. Morales has nothing to disclose. Dr. Rossi has nothing to disclose.

Elevated Preoperative Serum Vascular Endothelial Growth Factor Does Not Predict Poor Outcomes in Curatively Resected Non-metastatic Colorectal Cancer Treated Without Neoadjuvant Therapy.

Vascular endothelial growth factor (VEGF) influences colorectal cancer (CRC) progression and is a key target in the treatment for metastatic CRC. However, the oncological impact of preoperative circulating VEGF in non-metastatic CRC (non-mCRC) has not been clearly elucidated. Herein, we have investigated the prognostic significance of elevated preoperative serum VEGF concentration in curatively resected non-mCRC without neoadjuvant therapy. A total of 474 patients with pStage I-III CRC who underwent curative resection without neoadjuvant therapy were included. The relationship between preoperative serum VEGF concentration and clinicopathologic characteristics, overall survival (OS), and recurrence-free survival (RFS) were investigated. The median follow-up duration was 47.4 months. No significant relationship between preoperative VEGF and clinicopathologic characteristics including tumor markers, pStage, and lymphovascular invasion was identified; however, VEGF values were wide-ranged in every pStage. Patients were categorized into four groups as follows: VEGF < median, median to 75th percentile, 75th percentile to 90th percentile, and ≥90th percentile. A tendency for a difference in 5-year OS (p=0.064) and RFS (p=0.089) was observed among the groups; however, OS and RFS were not correlated with VEGF elevation. In multivariate analyses, VEGF ≥90th percentile was paradoxically associated with better RFS. Preoperative elevated serum VEGF concentration was associated with neither worse clinicopathological characteristics nor worse long-term outcomes in curatively resected non-mCRC. The prognostic value of preoperative circulating VEGF in initially resectable non-mCRC remains limited.

Severe painful neuropathy as the presenting feature of POEMS syndrome (P13-8.012)

<h3>Objective:</h3> POEMS is a rare and disabling paraneoplastic syndrome, with a plasma cell disorder background and a multisystem dysfunction. The acronym, first coined in 1980 by Bardwick, refers to polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. Not all of the features in this acronym are required to establish the diagnosis and other ones, not included in the name, are of utmost importance, such as elevated vascular endothelial growth factor (VEGF) levels, sclerotic bone lesions, extravascular volume overload, thrombocytosis and papilledema¹. The diagnosis of POEMS syndrome is based upon the presence of the two mandatory major criteria (polyneuropathy and monoclonal gammopathy), at least 1 other major criteria (Castleman disease, sclerotic bone lesions and VEGF elevation) and at least 1 minor criteria (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema and thrombocytosis/polycythemia)². <h3>Background:</h3> A 60-year-old man presented with a two-year history of severe neuropathic pain in limbs, distal weakness and hypoesthesia for pain and light touch. Due to a suspicion of a myeloradiculopathy, the patient underwent a cervical arthrodesis. On neurological examination there was distal muscular atrophy, a steppage gait, hyporeflexia in the lower limbs and allodynia in the feet. Complementary etiological investigation of neuropathy showed IgG lambda monoclonal gammopathy. MRI showed sclerotic bone lesion in the lumbosacral spine, and a mielography was compatible with plasma cell neoplasms. The patient began cyclophosphamide chemotherapy with significant improvement, and now waits for hematopoietic stem cell transplantation. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> The neuropathy is commonly the first clinical finding in POEMS and is usually demyelinating, sensory-motor, length-dependent and may be painful (65%). In this case report we reinforce not only the importance of a throughout clinical evaluation, but also an extensive etiologic investigation when facing neuropathies, as they can be the unique early manifestation of a serious treatable disorder, as POEMS syndrome. <b>Disclosure:</b> Rodrigo Queiroz has nothing to disclose. Dr. Pinheiro has nothing to disclose. Dr. Marques has nothing to disclose. Dr. Silva has nothing to disclose. Dr. Braune has nothing to disclose.

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.