Journal of the Endocrine Society
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Published By The Endocrine Society

Updated Thursday, 29 July 2021

Tasneem Abdel-Karim ◽  
Basma Haris ◽  
Houda Afyouni ◽  
Shayma Mohammed ◽  
Amel Khalifa ◽  

Abstract Background To study the epidemiology, describe the clinical characteristics and report results of genetic studies in pediatric patients with idiopathic type 1 diabetes. Methods Prospective study of type 1 diabetes patients attending Sidra Medicine from 2018-2020. Autoantibodies (GAD65, IAA, IA-2A and ZnT8) measured and genetic testing undertaken in patients negative for autoantibodies to rule out monogenic diabetes. Demographic and clinical data of patients with idiopathic type 1 diabetes compared to patients with autoimmune type 1 diabetes. Results 1157 patients had type 1 diabetes of which 63 were antibody negative. Upon genome sequencing, four had MODY, two had Wolfram syndrome, one had H syndrome and three had variants of uncertain significance in MODY genes. 53 patients had idiopathic type 1 diabetes. The most common age of diagnosis was 10-14 years and C-peptide level was low but detectable in 30 patients (56.6%) and normal in 23 patients (43.4%) The average BMI was in the normal range and 33% of the patients had history of DKA. Conclusions 4% of children have Idiopathic type 1 diabetes. There were statistically significant differences in the C-peptide level and insulin requirement between the two groups. DKA was less common in the idiopathic group. Mutations in MODY genes suggest the importance of autoantibody testing and genetic screening for known causes of monogenic diabetes in idiopathic type 1 diabetes. The mechanism of idiopathic type 1 diabetes is not known but could be due to defects in antibody production or due to autoantibodies that are not yet detectable or discovered.

Alessandro Brancatella ◽  
Nicola Viola ◽  
Grazia Rutigliano ◽  
Daniele Sgrò ◽  
Ferruccio Santini ◽  

Abstract Context Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been related to subacute thyroiditis (SAT). Objectives To compare SAT cases at the time of SARS-CoV-2 pandemic to those observed in the previous years. Methods A cross-sectional, retrospective study was conducted at the Endocrinology Unit of University-Hospital of Pisa, Italy. We included all patients observed from January 2016 to December 2020 because of an untreated SAT, who had developed the disease within 15 days prior to the visit. SAT cases from 2016 to 2019 (N=152) are referred as “pre-SARS-CoV-2”, while 2020 SAT patients are classified as “pos-SARS-CoV-2” (N=18) or “neg-SARS-CoV-2” (N=28), according to positive or negative test for SARS-CoV-2 performed up to 45 days from SAT onset. Results While during the years 2016-2019 most SAT cases were observed in the 3 rd quarter, in 2020 two peaks, superimposable to the outbreaks of SARS-CoV-2 pandemic of the 2 nd and the 4 th quarters, were seen. In the 2 nd and the 4 th quarters of 2020 we observed higher levels of free thyroxine (FT4), C-reactive protein (CRP) and thyroglobulin (Tg) compared to the same quarters of the years 2016-2019. Pos-SARS-CoV-2 had higher FT4 (28.4 vs 24.1 nmol/L), CRP (8.5 vs 3.6 mg/L) and Tg (155 vs 60 μg/L) (P<0.05 for all) and resulted more frequently in hypothyroidism (13/15 vs 30/152 at 3 months) (P<0.001) than to pre-SARS-CoV-2 patients. Neg-SARS-CoV-2 patients showed a clinical picture intermediate between the other two groups. Conclusions SARS-CoV-2 pandemic has caused a shift in the annual timing and severity of SAT cases.

Riley Mickelsen ◽  
Valerie French ◽  
Stephanie Amaya

Abstract Context Molar pregnancies have been associated with hyperthyroidism and hypertensive disorders. Coexisting molar and fetal pregnancies, which are very rare, have an even higher risk of complications. Case Description We describe a case of hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) associated with a molar pregnancy. A 36-year-old patient at 13-weeks gestation with a coexisting molar pregnancy presented with headache, nausea, and vomiting. She was found to have hypertension, hyperthyroidism, and hyponatremia. The hyponatremia was further assessed with an isotonic saline challenge which resulted in a diagnosis of SIADH. The patient underwent dilation and curettage and her hyponatremia resolved. She later developed gestational trophoblastic neoplasia. Conclusions A molar pregnancy can present with unusual associated conditions, such as SIADH. Hyponatremia in a patient with molar pregnancy may be mistakenly attributed to other side effects of trophoblastic tissue (hyperthyroidism, pre-eclampsia, or hyperemesis gravidarum). Hyponatremia in a patient with a molar pregnancy warrants evaluation for SIADH.

Hironobu Sasaki ◽  
Yoshifumi Saisho ◽  
Jun Inaishi ◽  
Hiroshi Itoh

Abstract Type 2 diabetes (T2DM) is characterized by insulin resistance and β-cell dysfunction. Since patients with T2DM have inadequate beta cell mass (BCM), and β-cell dysfunction worsens glycemic control and makes treatment difficult, therapeutic strategies to preserve and restore BCM are needed.In rodent models, obesity increases BCM about 3-fold, but the increase in BCM in humans is limited. Besides, obesity-induced changes in BCM may show racial differences between East Asians and Caucasians. Recently, the Developmental Origins of Health and Disease hypothesis, which states that the risk of developing non-communicable diseases including T2DM is influenced by the fetal environment, has been proposed. It is known in rodents that animals with low birthweight have reduced BCM through epigenetic modifications, making them more susceptible to diabetes in the future. Similarly, in humans, we revealed that individuals born with low birthweight have lower BCM in adulthood. Since β-cell replication is more frequently observed in the five years after birth, and β-cells are found to be more plastic in that period, a history of childhood obesity increases BCM. BCM in patients with T2DM is reduced by 20-65% compared with that in individuals without T2DM. However, since BCM starts to decrease from the stage of borderline diabetes, early intervention is essential for β-cell protection. In this review, we summarize the current knowledge on regulatory factors of human β-cell mass in health and diabetes, and propose the β-cell centric concept of diabetes to enhance a more pathophysiology-based treatment approach for T2DM.

Victoria C Andriessen ◽  
Marissa Lightbourne ◽  
Chelsi Flippo ◽  
Fabio R Faucz ◽  
Angela Delaney ◽  

Abstract Sex hormone-binding globulin (SHBG) in the blood is a major determinant of bioactivity for key sex steroids such as testosterone and estradiol. Low serum levels of SHBG have been associated with obesity, polycystic ovaries and metabolic syndrome, and other states associated with hyperandrogenemia. A 9-year, 6-month-old girl presented with a history of peripheral precocious puberty and aggressive behavior. The patient’s SHBG level was remarkably low for her age, at less than 5 nmol/L [reference range for a girl with a bone age of 10 years, 73 nmol/L (SEM= 10)](1). Upon genetic and protein analysis, the patient was found to have a homozygous missense potentially pathogenic variant in the SHBG gene (c.554 C>T, p.P185L); her parents were asymptomatic heterozygote carriers. Laboratory investigations supported the possible involvement of this genetic alteration in the patient’s phenotype. Various analyses of this variant support its pathogenicity, although the exact mechanism remains unclear. In conclusion, we present a genetic SHBG variant in the homozygote state that may have been associated with gonadotropin-independent precocious puberty in a young girl.

Kazuhisa Akiba ◽  
Yuko Katoh-Fukui ◽  
Kei Yoshida ◽  
Satoshi Narumi ◽  
Mami Miyado ◽  

Abstract Context Recent studies have revealed that every eukaryotic cell contains several membraneless organelles created via liquid-liquid phase separation (LLPS). LLPS is a physical phenomenon that transiently compartmentalizes the subcellular space and thereby facilitates various biological reactions. LLPS is indispensable for cellular functions; however, dysregulated LLPS has the potential to cause irreversible protein aggregation leading to degenerative disorders. To date, there is no systematic review on the role of LLPS in endocrinology. Evidence acquisition We explored previous studies which addressed roles of LLPS in living cells, particularly from the viewpoint of endocrinology. To this end, we screened relevant literature in PubMed published between 2009 and 2021 using LLPS-associated keywords including “membraneless organelle”, “phase transition”, and “intrinsically disordered”, and endocrinological keywords such as “hormone”, “ovary”, “androgen”, and “diabetes”. We also referred to the articles in the reference lists of identified papers. Evidence synthesis Based on 67 articles selected from 449 papers, we provided a concise overview of the current understanding of LLPS in living cells. Then, we summarized recent articles documenting the physiological or pathological roles of LLPS in endocrine cells. Conclusions The discovery of LLPS in cells has resulted in a paradigm shift in molecular biology. Recent studies indicate that LLPS contributes to male sex development by providing a functional platform for SOX9 and CBX2 in testicular cells. In addition, dysregulated LLPS has been implicated in aberrant protein aggregation in pancreatic β-cells, leading to type 2 diabetes. Still, we are just beginning to understand the significance of LLPS in endocrine cells.

Alice L J Carr ◽  
Richard A Oram ◽  
Shannon M Marren ◽  
Timothy J McDonald ◽  
Parth Narendran ◽  

Abstract Context High residual C-peptide in longer duration type 1 diabetes associates with fewer hypoglycemic events and reduced glycemic variability. Little is known about the impact of C-peptide close-to-diagnosis. Objective Using continuous glucose monitoring (CGM) data from a study of newly diagnosed adults with type 1 diabetes, we aimed to explore if variation in C-peptide close-to-diagnosis influenced glycemic variability and risk of hypoglycemia. Design We studied newly diagnosed adults with type 1 diabetes who wore a Dexcom G4 CGM for 7 days as part the EXTOD study. We examined the relationship between peak stimulated C-peptide and glycemic metrics of variability and hypoglycemia for 36 CGM traces from 23 participants. Results For every 100 pmol/l increase in peak C-peptide, percentage time spent range 3.9-10 mmol/l was increased by 2.4% [95% CI: 0.5,4.3], p=0.01) with a reduction in time spent in level 1 hyperglycemia (> 10 mmol/l) and level 2 hyperglycemia (> 13.9 mmol/l) by 2.6% [95% CI: -4.9, -0.4, p=0.02) and 1.3% [95% CI: -2.7, -0.006], p= 0.04) respectively. Glucose levels were on average lower by 0.19 mmol/l ([95 % CI: -0.4,0.02], p=0.06) and standard deviation reduced by 0.14 [95% CI: -0.3, -0.02], p=0.02). Hypoglycemia was not common in this group and no association was observed between time spent in hypoglycemia (p=0.97) or hypoglycemic risk (p=0.72). There was no association between peak C-peptide and insulin dose adjusted HbA1c (IDAA1c, p=0.45). Conclusions C-peptide associates with time spent in normal glucose range and with less hyperglycemia, but not risk of hypoglycemia in newly diagnosed people with type 1 diabetes.

Tae Jung Oh ◽  
Kyuho Kim ◽  
Jae Hoon Moon ◽  
Sung Hee Choi ◽  
Nam H Cho ◽  

Abstract Context Nonalcoholic fatty liver disease (NAFLD) and liver fibrosis, a progressive form of NAFLD, were related to higher mortality. Objective We investigated whether noninvasive indices of NAFLD and liver fibrosis could predict mortality in Korean prospective cohort. Methods We followed 4,163 subjects from the Korean Genome and Epidemiology Study biannually over 16 years. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) of NAFLD or liver fibrosis indices in the total subjects and subgroups according to body mass index (BMI), and glucose metabolism status. Results The mean age of the subjects was 55.7 ± 8.7 years (mean ± SD) and 39.2% were men. During a median follow-up of 15.6 years, 643 subjects (15.4%) died. The Fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS), and aspartate aminotransferase to platelet ratio index were consistently higher in deceased subjects regardless of baseline glucose metabolism status. Among these factors, FIB-4 and NFS displayed acceptable discrimination power for mortality, with area under the receiver operating characteristic curve values of 0.686 and 0.666, respectively. The adjusted HRs for FIB-4 and NFS were 1.41 (95% confidence interval [CI]: 1.18–1.68) and 1.43 (95% CI: 1.21–1.68), respectively. Both FIB-4 and NFS were significantly associated with liver-specific mortality, but not cardiovascular mortality. The association between mortality with fibrosis indices were more prominent in subjects with a lower BMI (< 25 kg/m 2). Conclusions Noninvasive indices of liver fibrosis might be a significant predictor of all-cause and liver-specific mortality in Korean subjects.

Prakash Acharya ◽  
Tarun Dalia ◽  
Sagar Ranka ◽  
Prince Sethi ◽  
Olurinde A Oni ◽  

Abstract Objective Aim of the study was to examine the effects of the vitamin D (Vit-D) treatment and non-treatment on Vit-D-deficient patients without a prior history of myocardial infarction (MI). Materials and Methods This is an retrospective, observational, nested case-control study of patients (N=20,025) with low 25-hydroxyvitamin D [(25-OH)D] levels (<20 ng/ml) who received care at the Veterans Health Administration from 1999-2018. Patients were divided into three groups: Group A (untreated, levels ≤20 ng/ml), Group B (treated, levels 21-29 ng/ml), and Group C (treated, levels ≥30 ng/ml). The risk of MI and all-cause-mortality were compared utilizing propensity score-weighted cox-proportional hazard models. Results Among the cohort of 20,025 patients, the risk of MI was significantly lower in Group C, compared to Group B [hazard ratio (HR) 0.65, 95% CI; 0.49-0.85, P=.002] and Group A (HR 0.73, 95% CI; 0.55-0.96), P=.02). There was no difference in the risk of MI between Group B and Group A (HR 1.14, 95% CI; 0.91-1.42, P=.24]. Compared to Group A, both Group B (HR 0.59, 95% CI; 0.54-0.63, P<.001] and Group C (HR 0.61, 95% CI; 0.56-0.67, P<.001] had significantly lower all-cause-mortality. There was no difference in all-cause-mortality between Group B and Group C (HR 0.99, 95% CI; 0.89-1.09, P=.78). Conclusions In patients with Vit-D-deficiency and no prior history of MI, treatment to the (25-OH)D level of >20 ng/ml and >30 ng/ml was associated with a significantly lower risk of all-cause-mortality. The lower risk of MI was observed only in individuals maintaining the (25-OH)D levels ≥30 ng/ml.

Margaretha L M Prins ◽  
Bartholomeus E P B Ballieux ◽  
Onno C Meijer ◽  
Alberto M Pereira ◽  
Michiel F Nijhoff

Abstract We report on a case of a 50-year-old female patient with primary hyperaldosteronism, in whom adrenal venous sampling was required to differentiate between unilateral and bilateral disease. Because of a history of severe allergy to iodinated contrast media, premedication with glucocorticoids was indicated. Exogenous glucocorticoids, however, can affect measurements of serum cortisol. To avoid this potential confounding effects on the cortisol assay, we decided to use dexamethasone instead of prednisolone or hydrocortisone. A high-dose ACTH stimulation test with the simultaneous use of dexamethasone revealed an adequate adrenal cortisol response. ACTH-stimulated adrenal venous sampling showed reliable results, which provided a solid basis for further clinical decision-making.

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