Multiple Hormone Research Articles

Longitudinal assessment of bone health index as a measure of bone health in short-statured children before and during treatment with recombinant growth hormone.

The aim of our study was the longitudinal assessment of bone health index (BHI) in short-statured children during growth hormone (GH) treatment to estimate changes in their bone health. 256 short-statured children (isolated GH deficiency (IGHD) n=121, multiple pituitary hormone deficiency (MPHD) n=49, intrauterine growth retardation (small for gestational age (SGA)) n=52, SHOX (short stature homeobox gene) deficiency n=9, Ullrich Turner syndrome (UTS) n=25) who started with GH between 2010 and 2018 were included. Annual bone ages (Greulich and Pyle, GP) and BHI were, retrospectively, analysed in consecutive radiographs of the left hand (BoneXpert software) from GH therapy start (T0) up to 10 years (T10) thereafter, with T max indicating the individual time point of the last available radiograph. The results are presented as the median (25 %/75 % interquartile ranges, IQR) and statistical analyses were performed using non-parametric tests as appropriate. The BHI standard deviation scores (SDS) were reduced (-0.97,-1.8/-0.3) as bone ages were retarded (-1.6 years,-2.31/-0.97) in all patients before start of GH and were significantly lower in patients with growth hormone deficiency (GHD) (-1.04,-1.85/-0.56; n=170) compared to non-GHD patients (-0.79,-1.56/-0.01; n=86; p=0.022). BHISDS increased to-0.17 (-1/0.58) after 1 year of GH (T1, 0.5-1.49, p<0.001) and to-0.20 (-1/-0.50, p<0.001) after 5.3 years (T max, 3.45/7.25). BHI SDS are reduced in treatment-naive short-statured children regardless of their GH status, increase initially with GH treatment while plateauing thereafter, suggesting sustained improved bone health.

Complexity of SMAX1 signaling during seedling establishment.

Karrikins (KARs) are small butenolide compounds identified in the smoke of burning vegetation. Along with the stimulating effects on seed germination, KARs also regulate seedling vigor and adaptive behaviors, such as seedling morphogenesis, root hair development, and stress acclimation. The pivotal KAR signaling repressor, SUPPRESSOR OF MAX2 1 (SMAX1), plays central roles in these developmental and morphogenic processes through an extensive signaling network that governs seedling responses to endogenous and environmental cues. Here, we summarize the versatile roles of SMAX1 reported in recent years and discuss how SMAX1 integrates multiple growth hormone signals into optimizing seedling establishment. We also discuss the evolutionary relevance of the SMAX1-mediated signaling pathways during the colonization of aqueous plants to terrestrial environments.

Neonatal screening for primary and central congenital hypothyroidism: is it time to go Dutch?

Thyroid hormone (TH) is indispensable for brain development in utero and during the first two to three years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonatal screening allows early treatment, thereby preventing brain damage. Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroid-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterised by low TH concentrations while TSH is normal, low or slightly elevated. Most newborn screening (NBS) programs for CH are primarily TSH-based thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a unique T4-TSH-thyroxine-binding globulin (TBG) NBS algorithm for CH which enables detection of primary and central CH. Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hypothyroidism instead of mild, and that early detection of central CH by NBS problably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.

Genome-wide identification of the banana GLR gene family and its expression analysis in response to low temperature and abscisic acid/methyl jasmonate

Glutamate receptor-like (GLR) is an important class of Ca2+ channel proteins, playing important roles in plant growth and development as well as in response to biotic and abiotic stresses. In this paper, we performed genome-wide identification of banana GLR gene family based on banana genomic data. Moreover, we analyzed the basic physicochemical properties, gene structure, conserved motifs, promoter cis-acting elements, evolutionary relationships, and used real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) to verify the expression patterns of some GLR family members under low temperature of 4 ℃ and different hormone treatments. The results showed that there were 19 MaGLR family members in Musa acuminata, 16 MbGLR family members in Musa balbisiana and 14 MiGLR family members in Musa itinerans. Most of the members were stable proteins and had signal peptides, all of them had 3-6 transmembrane structures. Prediction of subcellular localization indicated that all of them were localized on the plasma membrane and irregularly distributed on the chromosome. Phylogenetic analysis revealed that banana GLRs could be divided into 3 subclades. The results of promoter cis-acting elements and transcription factor binding site prediction showed that there were multiple hormone- and stress-related response elements and 18 TFBS in banana GLR. RT-qPCR analysis showed that MaGLR1.1 and MaGLR3.5 responded positively to low temperature stress and were significantly expressed in abscisic acid/methyl jasmonate treatments. In conclusion, the results of this study suggest that GLR, a highly conserved family of ion channels, may play an important role in the growth and development process and stress resistance of banana.

Effects of stress-induced ABA on root architecture development: Positive and negative actions

Root architecture development, an agronomic trait that influences crop yield, is regulated by multiple plant hormones. Abscisic acid (ABA) is a stress hormone that responds to multiple stresses, including salt, drought, and cold stress, and modulates various aspects of plant growth and development. In recent years, it has been found that ABA synthesized under mild stress or well-watered conditions can support plant growth and stress resistance by positively regulating root architecture development. In this review, we summarize the molecular, cellular, and organismal basis of ABA homeostasis in the root and how ABA signaling affects root architecture development both as an inhibitor and as an activator. We discuss the implications of these studies and the potential for exploiting the components of ABA signaling in designing crop plants with improved root system development and stress resistance.

Simultaneous monitoring of multiple hormones from human islets of Langerhans using solid-phase extraction-mass spectrometry.

Islets of Langerhans release peptide hormones in controlled amounts and patterns to ensure proper maintenance of blood glucose levels. The overall release of the hormones is shaped by external factors and by autocrine and paracrine interactions occurring within the islets. To better understand what controls the secretion of islet-secreted peptides, and how these processes go awry in diabetes, methods to monitor the release of multiple hormones simultaneously are needed. While antibody-based assays are typically used, they are most often applied to quantification of a single hormone. Mass spectrometry (MS), on the other hand, is well suited for quantifying multiple hormones simultaneously but typically requires time-consuming separation steps with biological samples. In this report, response surface methodology was used to identify a set of optimal solid-phase extraction (SPE) conditions for the islet-secreted peptides, insulin, C-peptide, glucagon, and somatostatin. The optimized SPE method was used with multiple reaction monitoring and isotopically labeled standards to quantify secretion levels. Calibrations were linear from 0.5 to 50 nM with <15% RSD peak area ratios. A microfluidic system was used to perfuse 30 human islets with different glucose conditions, and fractions were collected every 2 min for SPE-MS analysis. Results showed the release dynamics of the individual peptides, as well as patterns, such as positively and negatively correlated release and oscillations. This rapid SPE-MS method is expected to be useful for examining other peptide and small-molecule secretions from islets and could be applied to a number of other biological systems for investigating cellular communication.

TCP Transcription Factors in Pineapple: Genome-Wide Characterization and Expression Profile Analysis during Flower and Fruit Development

TEOSINTE-BRANCHED1/CYCLOIDEA/PCF (TCP) transcription factors contain specific a basic helix–loop–helix structure, which is a significant factor in the regulation of plant growth and development. TCP has been studied in several species, but no pineapple TCP has been reported to date. Whether they are involved in the development of the flower and fruit in the pineapple remains unclear. In this study, nine non-redundant pineapple TCPs (AcTCPs) were identified. Chromosomal localization, phylogenetics, gene structure, motifs, multiple-sequence alignment, and covariance on AcTCP family members were analyzed. Analysis of promoter cis-acting elements illustrated that the AcTCP gene may be mainly co-regulated by light signal and multiple hormone signals. Analysis of expression characteristics showed a significant increase in AcTCP5 expression at 12 h after ethylene treatment, and significantly higher levels of AcTCP8 and AcTCP9 expression in the pistil than in other floral organs. Meanwhile, the AcTCP4, AcTCP5, AcTCP6, AcTCP7, and AcTCP9 expression levels were downregulated at later stages of fruit development. Transcription factors that may interact with TCP protein in the regulation of flower and fruit development are screened by the protein interaction prediction network, AcTCP5 interacts with AcSPL16, and AcTCP8 interacts with AcFT5 and AcFT6 proteins, verified by Y2H experiments. These findings provide a basis for further exploration of the molecular mechanisms and function of the AcTCP gene in flower and fruit development.

The role of walnut bZIP genes in explant browning

BackgroundBasic leucine zipper (bZIP) proteins are important transcription factors in plants. To study the role of bZIP transcription factors in walnut explant browning, this study used bioinformatics software to analyze walnut bZIP gene family members, along with their transcript levels in different walnut tissues, to evaluate the transcriptional expression of this gene family during the primary culture of walnut explants and to reveal the mechanism of action of walnut bZIP genes in walnut explant browning.ResultsThe results identified 65 JrbZIP genes in the walnut genome, which were divided into 8 subfamilies and distributed on 16 chromosomes. The results of transcriptome data analysis showed that there were significant differences in the expression of four genes, namely, JrbZIP55, JrbZIP70, JrbZIP72, and JrbZIP88, under both vermiculite and agar culture conditions. There were multiple hormone (salicylic acid, abscisic acid, auxin, and gibberellin) signaling and regulatory elements that are responsive to stress (low temperature, stress, and defense) located in the promoter regions of JrbZIP55, JrbZIP70, JrbZIP72, and JrbZIP88. The walnut JrbZIP55 protein and Arabidopsis bZIP42 protein are highly homologous, and the proteins interacting with Arabidopsis bZIP42 include the AT2G19940 oxidoreductases, which act on aldehyde or oxygen-containing donors.ConclusionIt is speculated that JrbZIP55 may participate in the regulation of browning in walnut explants.

Endocrinology for the hepatologist.

Endocrinology for the hepatologist.

Pituitary function at presentation and following therapy in patients with non-functional pituitary macroadenomas: a single centre retrospective cohort study

BackgroundNon-functioning pituitary macroadenomas (NFPMs) may present with hypopituitarism. Pituitary surgery and radiotherapy pose an additional risk to pituitary function.ObjectivesTo assess the incidence of hypopituitarism at presentation, the impact of treatment, and the likelihood of endocrine recovery during follow-up.MethodsAll patients treated surgically with and without radiotherapy for NFPMs between 1987 and 2018 who had longer than six months follow-up were identified. Demographics, presentation, investigation, treatment, and outcomes were collected.ResultsIn total, 383 patients were identified. The median age was 57 years, with a median follow-up of 8 years. Preoperatively, 227 patients (227/375; 61%) had evidence of at least one pituitary deficiency. Anterior panhypopituitarism was more common in men (p = 0.001) and older patients (p = 0.005). Multiple hormone deficiencies were associated with large tumours (p = 0.03). Patients treated with surgery and radiotherapy had a higher incidence of all individual pituitary hormone deficiency, anterior panhypopituitarism, and significantly lower GH, ACTH, and TSH deficiencies free survival probability than those treated with surgery alone. Recovery of central hypogonadism, hypothyroidism, and anterior panhypopituitarism was also less likely to be reported in those treated with surgery and radiotherapy. Those with preoperative hypopituitarism had a higher risk of pituitary impairment at latest review than those presented with normal pituitary function (p = 0.001).ConclusionNFPMs are associated with a significant degree of hypopituitarism at time of diagnosis and post-therapy. The combination of surgery and radiotherapy is associated with a higher risk of pituitary dysfunction. Recovery of pituitary hormone deficit may occur after treatment. Patients should have regular ongoing endocrine evaluation post-treatment to assess changes in pituitary function and the need for long-term replacement therapy.

Phenotype-Genotype Correlations of GH1 Gene Variants in Patients with Isolated Growth Hormone Deficiency or Multiple Pituitary Hormone Deficiency

Introduction: Genetic forms of growth hormone deficiency (GHD) may occur as isolated GHD (IGHD) or as a component of multiple pituitary hormone deficiency (MPHD). This study aimed to present the clinical and molecular characteristics of patients with IGHD/MPHD due to the GH1 gene variants. Methods: A gene panel accommodating 25 genes associated with MPHD and short stature was used to search for small sequence variants. Multiplex ligation-dependent probe amplification was performed in patients with normal panel results to investigate gross deletion/duplications. Segregation in the family was performed by Sanger sequencing. Results: The GH1 gene variants were detected in 5 patients from four unrelated families. One patient had IGHD IA due to homozygous whole GH1 gene deletion and one had IGHD IB due to novel homozygous c.162C>G/p.(Tyr54*) variant. Two patients from a family had previously reported heterozygous c.291+1G>A/p.(?) variant in which clinical and genetic characteristics were compatible with IGHD II accompanying MPHD. One patient had clinical and laboratory characteristics of IGHD II with MPHD but the heterozygous c.468 C>T/p.(R160W) variant had conflicting results about the relationship with the phenotype. Conclusion: Expanding our knowledge of the spectrum of GH1 gene variants by apprehending clinical and molecular data of more cases, helps to identify the genotype-phenotype correlation of IGHD/MPHD and the GH1 gene variants. These patients must be regularly followed up for the occurrence of additional pituitary hormone deficiencies.

Management of Neonatal Isolated and Combined Growth Hormone Deficiency: Current Status.

Congenital growth hormone deficiency (GHD) is a rare disease caused by disorders affecting the morphogenesis and function of the pituitary gland. It is sometimes found in isolation but is more frequently associated with multiple pituitary hormone deficiency. In some cases, GHD may have a genetic basis. The many clinical signs and symptoms include hypoglycaemia, neonatal cholestasis and micropenis. Diagnosis should be made by laboratory analyses of the growth hormone and other pituitary hormones, rather than by cranial imaging with magnetic resonance imaging. When diagnosis is confirmed, hormone replacement should be initiated. Early GH replacement therapy leads to more positive outcomes, including reduced hypoglycaemia, growth recovery, metabolic asset, and neurodevelopmental improvements.

Gut hormone co-agonists for the treatment of obesity: from bench to bedside.

The discovery and development of so-called gut hormone co-agonists as a new class of drugs for the treatment of diabetes and obesity is considered a transformative breakthrough in the field. Combining action profiles of multiple gastrointestinal hormones within a single molecule, these novel therapeutics achieve synergistic metabolic benefits. The first such compound, reported in 2009, was based on balanced co-agonism at glucagon and glucagon-like peptide-1 (GLP-1) receptors. Today, several classes of gut hormone co-agonists are in development and advancing through clinical trials, including dual GLP-1-glucose-dependent insulinotropic polypeptide (GIP) co-agonists (first described in 2013), and triple GIP-GLP-1-glucagon co-agonists (initially designed in 2015). The GLP-1-GIP co-agonist tirzepatide was approved in 2022 by the US Food and Drug Administration for the treatment of type 2 diabetes, providing superior HbA1c reductions compared to basal insulin or selective GLP-1 receptor agonists. Tirzepatide also achieved unprecedented weight loss of up to 22.5%-similar to results achieved with some types of bariatric surgery-in non-diabetic individuals with obesity. In this Perspective, we summarize the discovery, development, mechanisms of action and clinical efficacy of the different types of gut hormone co-agonists, and discuss potential challenges, limitations and future developments.

Using skin mucus for the identification of ovulation biomarkers in North American Atlantic salmon (Salmo salar)

In Maine, North American Atlantic salmon production has experienced a 20% decrease in eye-up eggs, the point of embryo development where the black eye spot is visible. The maternal endocrine environment is suggested to be an important factor for ovulation and viable embryos but needs to be further investigated. Combining new sampling matrices (skin mucus) and advanced technologies (liquid chromatography tandem mass spectrometry (LC-MS/MS)) will advance the knowledge of the endocrine status in reproductively mature North American Atlantic salmon. The objectives of this study were to 1) identify mucus as a viable matrix to measure steroid hormones, 2) quantify steroid hormone profile of North American Atlantic salmon during ovulation and 3) compare hormone profiles of salmon with high and low eye-up rates. Mucus and plasma were collected from sexually mature female North American Atlantic salmon (n = 30). A group of females were sampled pre-ovulation (n = 9) and a separate group post-ovulation (n = 21) then analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Fish collected post-ovulation were slotted into groups based on eye-up rate, fish with ≥70% eye-up rate (high eye-up, n = 5) and fish with ≤70% eye up rate (low eye-up, n = 16). In mucus allopregnanolone (p = 0.01), 11-deoxycorticosterone (p = 0.05) and 11-deoxycortisol (p = 0.01) were significantly higher after ovulation. In plasma, allopregnanolone was significantly lower after ovulation (p = 0.01 and 17α, 20β-hydroxyprogesterone was significantly elevated (p = 0.05) after ovulation. Fish with a low eye-up rate had elevated mucus concentrations of corticosterone (p = 0.02). While fish with a high eye-up rate had elevated plasma testosterone concentrations (p = 0.04). Circulating androstenedione (r = 0.46, p = 0.03) and testosterone (r = 0.47, p = 0.03) were significantly correlated with eye-up rate. Mucosal concentrations of steroid hormone correlated with circulating concentrations of related steroids and reflect changes in reproductive physiology. The significant changes in mucosal and circulating steroid concentrations of the 5α reduced pregnane, allopregnanolone suggests a role of 5α-reduced pregnanes during ovulation in North American Atlantic salmon. To our knowledge this is the first time any 5α-reduced pregnane has been reported in teleosts. Mucosal concentrations of precursor glucocorticoids significantly elevated after ovulation combined with significant correlation with hydroxylated pregnanes suggests a dual mechanism needed for ovulation between glucocorticoids and pregnanes. Additionally, glucocorticoids and androgens appear to influence the viability of fertilized eggs highlighting the need for further research into the role's multiple hormones play in both oocyte maturation and embryo viability.

Genome-Wide Identification and Abiotic-Stress-Responsive Expression of CKX Gene Family in Liriodendron chinense.

Liriodendron chinense is a tree species of the Magnoliaceae family, an ancient relict plant mainly used for landscaping and timber production due to its excellent material properties and ornamental value. The cytokinin oxidase/dehydrogenase (CKX) enzyme regulates cytokinin levels and plays an important role in plant growth, development, and resistance. However, too-high or too-low temperatures or soil drought can limit the growth of L. chinense, representing a key issue for research. Here, we identified the CKX gene family in the L. chinense genome and examined its transcriptional responses to cold, drought, and heat stresses. A total of five LcCKX genes, distributed on four chromosomes and divided into three phylogenetic groups, were identified across the whole L. chinense genome. Further analysis showed that multiple hormone- and stress-responsive cis-acting elements are located in the promoter regions of LcCKXs, indicating a potential role of these LcCKXs in plant growth, development, and response to environmental stresses. Based on existing transcriptome data, LcCKXs, especially LcCKX5, were found to transcriptionally respond to cold, heat, and drought stresses. Furthermore, quantitative reverse-transcription PCR (qRT-PCR) showed that LcCKX5 responds to drought stress in an ABA-dependent manner in stems and leaves and in an ABA-independent manner in roots. These results lay a foundation for functional research on LcCKX genes in the resistance breeding of the rare and endangered tree species of L. chinense.

Integrative analysis of exogenous auxin mediated plant height regulation in Moso bamboo (Phyllostachys edulis)

Auxin is important in regulating bamboo growth and development. Morphological and anatomical analyses of naturally growing Moso bamboo treated with auxin revealed that auxin-mediated regulation of bamboo height mainly increased internode length rather than nodes number. For individual internodes, auxin regulated internode elongation mainly by promoting cell elongation. Targeted metabolomic assays of endogenous hormones found that exogenous auxin treatment affected the dynamic balance of endogenous hormones, resulting in increased levels of gibberellin and cytokinin. Transcriptome sequencing indicated that the regulation of internode length by auxin is mainly through phytohormone signaling pathway, amino acid synthesis and protein processing pathway, and energy metabolism pathway. The transcription factors that play major regulatory roles included the ethylene response factor, WRKY and MYB transcription factor, NAC structural domain protein and basic leucine zipper protein. By constructing a gene regulatory network, we found that auxin may crosstalk with multiple plant hormones. Yeast two-hybrid and transgenic experiments demonstrated that the auxin signaling factor PheAUX/IAA34 and the jasmonic acid signaling factor PheTIFY28 do interact and regulate growth in response to phytohormones. Overall we have obtained good quality bamboo internode material for industry through the auxin treatment and have preliminarily investigated the mechanism, which will provide a reference for bamboo plant height regulation.

The role of the NDRG1 in the pathogenesis and treatment of breast cancer.

Breast cancer (BC) is the leading cause of cancer death in women. This disease is heterogeneous, with clinical subtypes being estrogen receptor-α (ER-α) positive, having human epidermal growth factor receptor 2 (HER2) overexpression, or being triple-negative for ER-α, progesterone receptor, and HER2 (TNBC). The ER-α positive and HER2 overexpressing tumors can be treated with agents targeting these proteins, including tamoxifen and pertuzumab, respectively. Despite these treatments, resistance and metastasis are problematic, while TNBC is challenging to treat due to the lack of suitable targets. Many studies examining BC and other tumors indicate a role for N-myc downstream-regulated gene-1 (NDRG1) as a metastasis suppressor. The ability of NDRG1 to inhibit metastasis is due, in part, to the inhibition of the initial step in metastasis, namely the epithelial-to-mesenchymal transition. Paradoxically, there are also reports of NDRG1 playing a pro-oncogenic role in BC pathogenesis. The oncogenic effects of NDRG1 in BC have been reported to relate to lipid metabolism or the mTOR signaling pathway. The molecular mechanism(s) of how NDRG1 regulates the activity of multiple signaling pathways remains unclear. Therapeutic strategies that up-regulate NDRG1 have been developed and include agents of the di-2-pyridylketone thiosemicarbazone class. These compounds target oncogenic drivers in BC cells, suppressing the expression of multiple key hormone receptors including ER-α, progesterone receptor, androgen receptor, and prolactin receptor, and can also overcome tamoxifen resistance. Considering the varying role of NDRG1 in BC pathogenesis, further studies are required to examine what subset of BC patients would benefit from pharmacopeia that up-regulate NDRG1.

Primary adrenocortical carcinoma: a case report.

A 28-year-old man who had no prior history of systemic hypertension or diabetes mellitus presented with bilateral limb swelling for 2 months and facial puffiness for 1 month. He had an episode of hypertensive emergencies. A radiological and hormonal work-up established the diagnosis of primary ACC. One cycle of chemotherapy was given until he lost follow-up and succumbed to death due to financial constraints. Adrenocortical carcinoma is an extremely uncommon tumor of the adrenal gland, and it is even more uncommon when it manifests without any symptoms. If patients exhibit signs of rapid and multiple adrenocortical hormone excess, such as weakness, hypokalaemia, or hypertension, ACC may be suspected. Recently developed gynecomastia in men may be brought on by an ACC producing too much sex hormone. To accurately diagnose the condition and give the patient a fair prognosis, a multidisciplinary approach involving endocrine surgeons, oncologists, radiologists, and internists is advised. Proper genetic counseling is recommended. It is critical to know whether the adrenal mass is malignant or not, and to get this ascertained by a computed tomography finding and biopsy.

Abstract #1397268: A Rare Case of Insulinomatosis in a 58-Year-Old Woman with Recurrent Symptoms of Hypoglycemia

Insulinomatosis is a rare cause of hyperinsulinaemic hypoglycaemia. The ideal management approach is not known. We present a case of recurrent hypoglycemia whose management was complicated by the pandemic. A 58-year-old woman with a family history of a mother who died of a pancreatic tumor and a personal history of congenital bilateral cataract, arterial hypertension, subclinical hypothyroidism, Child A liver cirrhosis, and subtotal pancreatectomy for hyperinsulinemic hypoglycemia in 2019 due to two insulinomas in the head and body of the pancreas. The pathological and immunohistochemical study was consistent with two pancreatic neuroendocrine tumors with Ki67: 1%, we did not have staining for insulin. She was discharged without episodes of hypoglycemia; 10 months after the operation, she presented a recurrence of neuroglycopenic symptoms during periods of fasting, which she controlled with a greater intake of food; furthermore, she recorded fasting capillary glycemia between 40-60mg/dl without symptoms. Due to the pandemic, she could not be evaluated at our center until 2022, when she was hospitalized for study. Hyperinsulinemic hypoglycemia was verified, imaging studies (CT, MRI, PET) did not show lesions in the remaining pancreatic tissue; On its own, endoscopic echocardiography described a 7-mm lesion adjacent to the splenic artery. The patient did not accept new surgery. The genetic study for MEN type 1 was negative. The subcutaneous octreotide test showed a glycemia value greater than 100mg/dL after its administration, so she was discharged with a fractionated diet and subcutaneous octreotide 25-50 ug at night. To date, she has not presented a clinical picture again. and biochemical hypoglycemia with adequate tolerance. Insulinomas are the most frequent pNETs (45%). About 10% are multiple, 10% are malignant, and 16% are associated with MEN1. Insulinomas are usually benign and managed surgically. Insulinomas that appear synchronously or metachronously, but are not associated with MEN1 are termed insulinomatosis. Diagnosis consists of documentation of hyperinsulinemic hypoglycemia, synchronous presence of β-cell micro- or macrotumors, or early recurrence of hyperinsulinemic hypoglycemia with new β-cell lesion in a history of prior insulinoma. Insulinomatosis is distinguished histologically by insulin-expressing monohormonal endocrine cell clusters (IMECCs) and tumor staining only for insulin, whereas MEN-1 associated insulinomas stain for multiple hormones. Regarding management, the first line is surgery, although in some cases total pancreatectomy did not result in a cure for hypoglycemia, so local or systemic treatment can be used (diazoxide, corticosteroids, somatostatin analogues, verapamil, and everolimus).

High-Sucrose Diet Exposure on Larvae Contributes to Adult Fecundity and Insecticide Tolerance in the Oriental Fruit Fly, Bactrocera dorsalis (Hendel)

Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is one of the broad host ranges and economically-important insect pests in tropical and subtropical areas. A wide range of hosts means they have strong adaptation ability to changes in dietary macronutrients (e.g., sucrose and protein). However, the effects of dietary conditions on the phenotypes and genotypes of B. dorsalis are still unclear. In this study, we aimed to investigate the effects of larval dietary sucrose on the life history traits and stress tolerance of B. dorsalis, and its defense response at the molecular level. The results showed that low-sucrose (LS) induced decreased body size, shortened developmental duration, and enhanced sensitivity to beta-cypermethrin. Otherwise, high-sucrose (HS) diet increased developmental duration, adult fecundity, and tolerance to malathion. Based on transcriptome data, 258 and 904 differentially expressed genes (DEGs) were identified in the NS (control) versus LS groups, and NS versus HS groups, respectively. These yielded DEGs were relevant to multiple specific metabolisms, hormone synthesis and signaling, and immune-related pathways. Our study will provide biological and molecular perspective to understand phenotypic adjustments to diets and the strong host adaptability in oriental fruit flies.