Endocrine Abstracts

Introduction: Altered intrauterine endocrine environments can ‘programme’ adverse health outcomes. Linkage between altered androgen exposure in utero and adverse offspring health is robust. For example, increased maternal androgen concentrations and PCOS in female offspring and dyslipidaemia in male offspring. We hypothesised that the liver was a major target for androgenic programming in utero and hepatic dysfunction would be present in offspring. ...

Introduction: Known to be ‘male Turner syndrome’, Noonan syndrome (NS) classically associates short stature, facial dysmorphism, and congenital heart disease. It is an autosomal dominant disease with an incidence of 1: 1,000 to 1: 2,500. We report 3 observations of NS.Observations: Case 1: A 7-year-old female patient was admitted for a growth delay. On examination, she had a dysmorphic syndrome suggestive of NS: facial dysmorphism with triangul...

Objective: Patients who receive ≥5 mg prednisolone per day, for more than 2–3 weeks, are at risk of developing glucocorticoid (GC) induced adrenal insufficiency (tertiary adrenal insufficiency, 3° AI). The aim of this study was to a) determine the prevalence of GC use in doses that are associated with development of 3° AI, b) assess prescription pattern of short and long-term GC treatment in adults and children, and c) investigate the indication for the GC...

Background: Retinol-binding protein 4 (RBP4) is known as an acute phase inflammatory reactant, associated with insulin resistance. Increased levels of this novel adipokine is observed in obesity, type 2 diabetes mellitus, metabolic syndrome (MetS) and cardiovascular diseases, as well as in nonalcoholic fatty liver disease (NAFLD), but some of these data remain controversial. The aim of this study was to evaluate the relationship between RBP4 and prediabetes in...

Background: Hyponatremia is the most prevalent electrolyte disorder in hospitalized adult medical patients and is associated with a significant healthcare resource burden. However, evidence remains scarce whether hyponatremia is a marker of disease severity or whether it has an independent effect on clinical outcomes.Methods: In this nationwide cohort study, we analyzed medical inpatients with hyponatremia diagnosed between January 2009 through December ...

Angiotensin II (AngII) mainly acts through type 1 angiotensin II receptor (AT1R) to promote a broad variety of biological effects. The vascular smooth muscle cells are one of the main target of AngII and its stimulation activates numerous signaling pathways which could result in gene expression changes in these cells. We carried out Affymetrix GeneChip experiments to analyze the effects of AngII stimulation on gene expression. More than 200 genes were upregulated in response t...

Cardiovascular (CV) diseases significantly contribute to the mortality excess observed in survivors of pediatric acute lymphoblastic leukemia (ALL) who received hematopoietic stem cell transplantation (HSCT). The study explores advanced glycation end-products (AGEs) levels, inflammatory status and lipid profile in a cohort of ALL survivors, in order to investigate their potential role in the pathogenesis of CV late effects. Inclusion criteria were: a) previous diagnosis of ALL...

Introduction: Women with a high breast density have an increased risk of breast cancer, which prevalence increases after menopause in obese subjects. Breast density can be calculated on mammograms as the proportion of dense tissue (percent mammographic density-PMD). Several factors may influence the PMD, including age, menopausal status, body mass index (BMI), and bone mineral density (BMD) taken as an index of overall estrogen exposure. However, conflicting data have been rep...

Context: Diagnosis announcement of a chronic disease is a crucial moment for patients as well as for their families and an important step of the management of severe conditions like rare endocrine diseases. It is considered as an ‘eternal minute’, marking the end of a time of life when the disease was absent. Little is known on how diagnosis is communicated to patients and families. FIRENDO as defined by the National Plan for Rare Diseases aims at promoting education...

The Mineralocorticoid Receptor (MR), a hormone-activated transcription factor that mediates sodium-retaining action of aldosterone, is highly expressed in the distal nephron in which large variations in extracellular fluid tonicity are generated by the cortico-papillary gradient. However, mechanisms regulating MR expression remain sparse. We recently showed that extracellular tonicity modulates renal MR expression through posttranscriptional mechanisms (Viengchareun, Mol Endoc...

Background: Turner Syndrome (TS) is a sex chromosome aneuploidy (45,X) associated with social skill difficulties. The 2016 Cincinnati clinical care guidelines recommend that the Program for the Education and Enrichment of Relational Skills (PEERS) social skills intervention is piloted. PEERS has previously been used in face to face interventions with male adolescents with autism spectrum conditions. This pilot project will be the first to examine the feasibility and acceptabil...

Cushing’s Syndrome (CS) is associated with a severe myopathy mainly affecting type 2 muscle fibres, with a higher prevalence in male subjects. The excess of glucocorticoids (GC) levels represents the most common cause of myopathy due to an alteration of protein metabolism. The non-coding post-transcriptional gene regulators muscle-specific microRNAs (miRNA) control muscle development and differentiation but when dysregulated lead to skeletal muscle (SM) disorder. The aim ...

Introduction: 46 XY sex development disorders are a group of rare congenital conditions in which chromosomal, gonadal or anatomic sex is atypical. Less than 20% of cases have a precise genetic diagnosis. We report here the case of a patient suffering from a 46 XY sexual development disorder secondary to the MAMLD 1 gene mutation.Observation: The patient is a nine month infant who was admitted for abnormalities of the external genital organs. The physical...

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disease that is manifested by progressive loss of cognitive function. Neuroactive steroids and their metabolites have an important regulatory role in the nervous system, affect neuronal plasticity, response to stress, learning and memory and have a neuroprotective effect. One of the not fully elucidated risk factors for AD is impaired glucose tolerance/type 2 diabetes (T2D). It is well known that lower androgen...

The Miller-McKusick-Malvaux (3M) syndrome is a primordial growth disorder characterized by low birth weight, reduced birth length, severe postnatal growth restriction, a spectrum of skeletal anomalies, facial dysmorphism and normal intelligence. Mutations in the CUL7 gene (6p21.1) are most often responsible for 3M syndrome (67% of cases). Other causal mutations include those in the OBSL1 gene (2q35), in 28% of cases, or the CCDC8 gene (19q13.33), in ...

Background: Immune function and responses are tightly regulated by the circadian clock system and hypothalamic-pituitary-adrenal (HPA) axis. Accumulating evidence supports that there is a strong mutual relationship between these two regulatory systems at multiple levels. Recent publications suggest that the clock system may also regulate glucocorticoid release from adrenal glands by altering the sensitivity of the adrenal cortex to adrenocorticotropic hormone (ACTH).<p cla...

Introduction: Malnutrition in neonates and children has been associated with adult-onset diseases such as obesity and atherosclerosis. Infants breastfeeding exhibit a different pattern of orexin-α secretion compared to formula-fed or infants on parenteral feeding. Given the protective role of maternal milk in the onset of metabolic syndrome and atherosclerosis in later life, we hypothesized that orexin-α may be involved in this process. We studied in vitro t...

Purpose: HPA axis activation resulting in increased cortisol production by the adrenals is a crucial part of the response to critical illness. The action of cortisol may also be modulated at the tissue level, through changes in the availability of the free fraction and modifications of the glucocorticoid receptor activity. It has been proposed that tissue resistance to glucocorticoids may occur, at least in some patients, and relate to insufficient anti-inflammatory activity a...

Background: Immune checkpoint inhibitors (ICIs) are approved for the treatment of non-small cell lung cancer (NSCLC) and are associated with specific immune-related adverse events (iRAEs) including endocrine toxicities. However, data concerning the type, occurrence, and dynamics of iRAEs and their predictive value on treatment outcome are lacking. In this study, we evaluated the relation of iRAEs to anti-PD/L1 (programmed cell death protein/ligand-1) ICIs focusing particularly...

The European Working Group on Sarcopenia in Older People (EWGSOP2) defined in 2018 ‘sarcopenia as muscle disease (muscle failure), with low muscle strength overtaking the role of low muscle mass as a principal determinant’; sarcopenia increases risk of falls and fractures, impairs ability to perform activities of daily living, leads to mobility disorders and low quality of life and death. The diagnosis is confirmed by low muscle quantity or quality. The muscle quanti...

Introduction: Animals have long been considered the best friends of man, but as it turns out, the degree of empathy towards them is ontogenic variable. So far there have been studies showing the influence of mutations in the oxytocin gene on our level of empathy.Method: It was decided to check if hormonal factors have the influence on our relations with animals. For this purpose, patients treated in our department of endocrinology were examined. The stud...

Objectives: Adenosine is a purinergic mediator involved in the regulation of many physiological and pathological processes. It acts as neurotransmitter in the central and autonomic nervous system, where it counterbalanaces sympathetic activity. Adenosine is produced by majority of human cellsexerting autocrine, paracrine as well as systemic effects. Due toits vasodilatatory and negative inotropic effects it seems to play a role in ethiopathogenesis of orthostatic intolerance, ...

Background: Acid Sphingomyelinase Deficiency (ASMD) is a rare lysosomal storage disease caused by mutations in the SMPD1 gene. Typically, the p.Arg610del homozygotes had normal linear growth.Case report: We reported the cases of 2 Tunisian brothers aged 23 and 13 years respectively, who have been admitted for splenomegaly and polyadenopathies. Physical examination showed pubertal and growth delay for both cases. Biological evaluation showed mode...

Objectives: To evaluate the efficacy of growth hormone (GH) treatment in children with Turner syndrome (TS) and to analyze the factors affecting the success of treatment.Methods: Retrospective observational study was conducted for 62 patients with TS. 3 groups of patients were identified: group 1 with karyotype 45, X (n=32), group 2 with mosaic variant 45,X/46,XX (n=8), group 3 with structural anomalies of X chromosome (n=22). ...

Adipose tissue performs an important endocrine role, mediated by hormones (adipocytokines) which are specifically secreted by the adipocytes. Epidemiological data consistently show an association between weight gain and the risk of colorectal cancer in adults.This observation led to the evaluation of a possible linking role of adipocytokines with cancer pathogenesis. There are several studies that associate adipocytokines with colorectal malignancy, but few data about patients...

Background: LC-MS/MS is replacing immunoassays for serum steroid measurement in clinical labs worldwide. The intrinsic high specificity of LC-MS/MS is supposed to guarantee accurate quantitation, however, differences in pre-analytical and analytical procedures, and overall performance may influence the result. A few studies so far investigated the reproducibility among different LC-MS/MS assays for sex steroids. No data are available for adrenal steroids.<p class="abstext"...

Reproductive timing strongly influences the fitness of the individual. While most vertebrates rely on photoperiodic changes to induce seasonal reproduction, the arctic ground squirrel (AGS) naturally undergoes reproductive maturation in a photoperiod-independent manner. In addition, males spontaneously activate their reproductive axis during hibernation, but the timing of reproduction is sensitive to external cues. We are using electron microscopy to examine, define, and measu...

Introduction: When hypoglycemia is deep and repeated, it can induce various neurological disorders, including epileptic seizures. The link between hypoglycemia and epileptic phenomena is complex and poorly explained. We report 3 cases of epilepsy induced by repeated episodes of deep hypoglycemia.Cases report: Mr D.M, 48 years old, with a history of 3 episodes of hypoglycemic coma, admitted for status epilepticus with a blood glucose level of 0.4 g/l; cer...

Introduction: Beta-thalassemia major is a genetic syndrome accompanied by a defect in hemoglobin synthesis leading to severe anemia. Conventional treatment of this hemoglobinopathy involves repeated blood transfusions exposing the patient to iron overload, which represents the main morbidity due to visceral and endocrine complications. We report the case of a patient treated for beta-thalassemia with endocrine complications associated with post transfusion hemochromatosis....

Background: Among chronic hypoparathyroidism (HypoPT) patients, the baseline prevalence of type 2 diabetes (T2D) appeared to be higher than the general population in previous studies. Since little is known about the potential assocation between HypoPT and T2D, this study evaluated whether HypoPT is associated with increased risk of T2D.Methods: A retrospective cohort study, based on a US commercial claims database (Q1 2007 – Q2 2017), was conducted ...

Introduction: Increased insulin-like growth factor 1 (IGF-1) levels in patients with acromegaly are associated with clinical and radiological osteoarthritis (OA). We aimed to elucidate whether serum IGF-1 levels differ in patients with primary OA as compared to healthy controls and whether genetic variants known to affect serum IGF-1 levels are also associated with primary OA.Methods: Patients from the GARP study with familial generalized OA (n=...

Monoclonal antibodies against the Programmed cell death-1 protein (PD-1) are a new treatment for advanced cancer. Endocrine and metabolic diseases are known to be frequently associated with this class of drugs. We describe two cases of Nivolumab-induced diabetes mellitus.Case 1: A 73-year-old man with a mutated BRAF-V600K advanced stage melanoma was treated with Nivolumab (240 mg IV every 2 weeks). He had normal-weight (BMI: 21.6 Kg/mq), and no previous ...

Introduction: Immunotherapy has become standard treatment for an increasingly wide range of cancers. Checkpoint inhibitors (ICT; CTLA4, PD1 & PD-L-1) can cause endocrine toxicity, principally affecting the pituitary and thyroid glands. We have studied the clinical management and outcome of patients with endocrine adverse effects over 5 years at our cancer centre.Methods: All patients treated with ICT agents between 1 Jan 2014 to 31 Jan 2019 were incl...

Introduction: Immune checkpoint therapies are novel cancer agents, which have been associated with the development of endocrine toxicities. ESMO and SfE endorsed management guidelines have been helpful for the early recognition of these toxicities, but in clinical practice, having early access to specialist endocrine advice improves the decision making and effective use of these agents when toxicities occur. In response to need we developed an easily accessible interdisciplina...

Objective: To evaluate changes in gut microbiota induced by treatment in patients with gestational diabetes mellitus (GDM) treated with insulin in comparison to those treated with metformin.Material and methods: Thirty-one patients with GDM not controlled by diet, included in MeDiGes study (‘Efficacy of metformin in gestational diabetes not controlled by diet in comparison to insulin’), were aleatorized to receive insulin (n=14) or met...

Introduction: Turner syndrome (TS) is characterized by the complete or partial loss of one X chromosome and associated with a wide range of clinical manifestations. The clinical appearance depends on the specific karyotype, which may include different mosaic forms. Main features of almost all the karyotypes are short stature and delayed or absent puberty. Adult women in particular are at high risk of developing cardiac complications, metabolic syndrome, increased liver enzyme ...

Background: Immune related adverse events (iRAEs) of the endocrine system are commonly recognised in Checkpoint Inhibitor Therapy treatment with current research suggesting clinically significant endocrinopathies occur in 10%. As the use of these drugs continues to rise, so too does the importance of routine endocrine monitoring in order to avoid potentially life-threatening adverse-events.Aims: To establish the frequency, severity, management and outcom...