Primary adrenal insufficiency is rare in childhood. Hypotension and hyponatremia are usually present at diagnosis, but only half of patients have hyperkalemia.
Context:
Primary adrenal insufficiency ...is usually diagnosed in infancy or adulthood, and cases presenting in childhood have not been systematically reviewed.
Objective:
Our objective was to determine etiologies, signs, and symptoms of primary adrenal insufficiency presenting in childhood.
Design and Setting:
We conducted a retrospective chart review at a tertiary-care pediatric hospital.
Patients:
Patients were children with corticoadrenal insufficiency, glucocorticoid deficiency, or mineralocorticoid deficiency.
Results:
Seventy-seven cases were identified in 1999–2010. Thirty-five had congenital adrenal hyperplasia (CAH) and were not reviewed further. Forty-two patients (20 diagnosed at our institution) had primary adrenal insufficiency. These had etiologies as follows: autoimmune (18), autoimmune polyendocrinopathy syndrome (an additional five), ACTH resistance (four), adrenoleukodystrophy (three), adrenal hypoplasia congenita (two), adrenal hemorrhage (two), IMAGe syndrome (one), and idiopathic (two). Of 20 patients diagnosed at our institution, two were being monitored when adrenal insufficiency developed and were not included in the analysis of presenting signs and symptoms: 13 of 18 patients were hypotensive; 12 of 18 had documented hyperpigmentation. Hyponatremia (<135 mEq/liter) occurred in 16 of 18. However, hyperkalemia (>5.0 mEq/liter) was noted in only nine. Hypoglycemia and ketosis were documented in four of 15 and four of six patients in whom it was sought, respectively. Fifteen patients underwent cosyntropin stimulation testing with median baseline and stimulated cortisol of 1.1 and 1.2 μg/dl, respectively. ACTH and renin were markedly elevated in all patients.
Conclusions:
Hyperkalemia is not a consistent presenting sign of primary adrenal insufficiency in childhood, and its absence cannot rule out this condition. A combination of chronic or subacute clinical symptoms, hypotension, and hyponatremia should raise suspicion of adrenal insufficiency.
Lumped hydrological models are catchment-scale representations of the transformation of precipitation into discharge. They are widely-used tools for real-time flow forecasting, flood design and ...climate change impact assessment, and they are often used for training and educational purposes. This article presents an R-package, airGR, to facilitate the implementation of the GR lumped hydrological models (including GR4J) and a snow-accumulation and melt model. The package allows users to calibrate and run hourly to annual models on catchment sets and to analyse their outputs. While the core of the models is implemented in Fortran, the user can manage the input/output data within R. A number of options and plotting functions are proposed to ease automate tests and analyses of the results. The codes are flexible enough to include external models, other calibration routines or efficiency criteria. To illustrate the features of airGR, we present one application example for a French mountainous catchment.
Abstract
The adrenal is a small, anatomically unimposing structure that escaped scientific notice until 1564 and whose existence was doubted by many until the 18th century. Adrenal functions were ...inferred from the adrenal insufficiency syndrome described by Addison and from the obesity and virilization that accompanied many adrenal malignancies, but early physiologists sometimes confused the roles of the cortex and medulla. Medullary epinephrine was the first hormone to be isolated (in 1901), and numerous cortical steroids were isolated between 1930 and 1949. The treatment of arthritis, Addison’s disease, and congenital adrenal hyperplasia (CAH) with cortisone in the 1950s revolutionized clinical endocrinology and steroid research. Cases of CAH had been reported in the 19th century, but a defect in 21-hydroxylation in CAH was not identified until 1957. Other forms of CAH, including deficiencies of 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, and 17α-hydroxylase were defined hormonally in the 1960s. Cytochrome P450 enzymes were described in 1962-1964, and steroid 21-hydroxylation was the first biosynthetic activity associated with a P450. Understanding of the genetic and biochemical bases of these disorders advanced rapidly from 1984 to 2004. The cloning of genes for steroidogenic enzymes and related factors revealed many mutations causing known diseases and facilitated the discovery of new disorders. Genetics and cell biology have replaced steroid chemistry as the key disciplines for understanding and teaching steroidogenesis and its disorders.
Graphical Abstract
Graphical Abstract
The coronavirus disease-2019 (COVID-19) pandemic had widespread impacts on the lives of parents and children. We determined how the pandemic affected Type 1 diabetes patients at a large urban ...pediatric teaching hospital.
We compared patient characteristics, glycemic control, PHQ-9 depression screen, in person and virtual outpatient encounters, hospitalizations and continuous glucose monitor (CGM) utilization in approximately 1600 patients in 1 year periods preceding and following the local imposition of COVID-related restrictions on 3/15/2020 ("2019" and "2020" groups, respectively).
In a generalized linear model, increasing age, non-commercial insurance, Black and Hispanic race/ethnicity, and non-utilization of CGMs were all associated with higher hemoglobin A1c (HbA1c), but there was no difference between the 2019 and 2020 groups. The time in range in CGM users was lower with non-commercial insurance and in Black and Hispanic patients; it improved slightly from 2019 to 2020. CGM utilization by patients with non-commercial insurance (93% of such patients were in government programs, 7% uninsured or "other") increased markedly. In 2020, patients with commercial insurance (i.e., private-pay or provided by an employer) had fewer office visits, but insurance status did not influence utilization of the virtual visit platform. There was no change in hospitalization frequency from 2019 to 2020 in either commercially or non-commercially insured patients, but patients with non-commercial insurance were hospitalized at markedly higher frequencies in both years. PHQ-9 scores were unchanged.
Hospitalization frequency, glycemic control and depression screening were unchanged in our large urban pediatric teaching hospital during the COVID pandemic. Increased utilization of CGM and rapid adoption of telemedicine may have ameliorated the impact of the pandemic on disease management.
La survenue d’une acidose lactique dans l’asthme aigu grave (AAG) est classique chez l’adulte mais peu décrite chez l’enfant. Sa reconnaissance peut avoir des conséquences sur la prise en charge ...thérapeutique de la crise d’asthme. Une petite fille de 2 ans a été hospitalisée en réanimation pédiatrique pour un AAG, traité par oxygénothérapie à haut débit, méthylprednisolone et salbutamol par voie intraveineuse. Elle a présenté une acidose métabolique (pH=7,29) avec hypocapnie (26 mmHg), chute des bicarbonates (12 mmol/L), trou anionique (20 mmol/L) et augmentation des lactates (8 mmol/L). La recherche d’une maladie métabolique sous-jacente a été négative. L’évolution a été favorable avec amélioration spontanée de l’acidose lactique permettant la sortie de l’unité de réanimation après 72 heures. L’origine d’une acidose lactique au cours de l’AAG est multifactorielle. Bien que sa résolution soit spontanée, il est essentiel de la reconnaître car elle peut modifier la symptomatologie respiratoire et conduire à une escalade thérapeutique inappropriée.
Lactic acidosis is a recognized event in adult patients with acute severe asthma (ASA). Only a few cases have been reported in children. Hereinafter is reported the case of a 2-year-old girl hospitalized in the pediatric intensive care unit for ASA, which was treated with high-flow oxygen therapy and intravenous methylprednisolone and salbutamol. During hospitalization, she had metabolic acidosis with a 7.29 pH, a 26mmHg hypocapnia, and a decrease in bicarbonates to 12 mmol/L. The anion gap was increased to 20 mmol/L and lactates to 8 mmol/L. The work-up for a congenital metabolic disease was normal. Progression was propitious with spontaneous improvement of lactic acidosis, and the child was discharged from the intensive care unit after 72 h. The origin of lactic acidosis during ASA seems to be multifactorial. Although its recovery can be spontaneous, it is important to know how to identify it because it can worsen respiratory symptoms and can lead to incongruous therapeutic escalation.
Objective: We developed clinical practice guidelines for congenital adrenal hyperplasia (CAH).
Participants: The Task Force included a chair, selected by The Endocrine Society Clinical Guidelines ...Subcommittee (CGS), ten additional clinicians experienced in treating CAH, a methodologist, and a medical writer. Additional experts were also consulted. The authors received no corporate funding or remuneration.
Consensus Process: Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society’s CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments.
Conclusions: We recommend universal newborn screening for severe steroid 21-hydroxylase deficiency followed by confirmatory tests. We recommend that prenatal treatment of CAH continue to be regarded as experimental. The diagnosis rests on clinical and hormonal data; genotyping is reserved for equivocal cases and genetic counseling. Glucocorticoid dosage should be minimized to avoid iatrogenic Cushing’s syndrome. Mineralocorticoids and, in infants, supplemental sodium are recommended in classic CAH patients. We recommend against the routine use of experimental therapies to promote growth and delay puberty; we suggest patients avoid adrenalectomy. Surgical guidelines emphasize early single-stage genital repair for severely virilized girls, performed by experienced surgeons. Clinicians should consider patients’ quality of life, consulting mental health professionals as appropriate. At the transition to adulthood, we recommend monitoring for potential complications of CAH. Finally, we recommend judicious use of medication during pregnancy and in symptomatic patients with nonclassic CAH.
Presented is The Endocrine Society Guideline for the evaluation and management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
Skillful streamflow forecasts provide key support to several water‐related applications. Because of the critical impact of initial conditions (ICs) on forecast accuracy, ever‐growing interest is ...focused on improving their estimates via data assimilation (DA). This study aims to assess the sensitivity of the DA‐based estimation of forecast ICs to several sources of uncertainty and the update of different model states and parameters of a lumped conceptual rainfall–runoff model over 232 watersheds in France. The performance of two sequential ensemble‐based techniques, namely, the ensemble Kalman filter (EnKF) and the particle filter (PF), is compared in terms of efficiency and temporal persistence (up to 10 days) of the updating effect through the assimilation of observed discharges. Several experiments specifically address the impact of the meteorological, state, and parameter uncertainties. Results show that an accurate estimate of the initial level of the routing store of the conceptual model ensures the most benefit to the DA‐based estimation of forecast ICs. While EnKF‐based forecasts outperform PF‐based ones when accounting for meteorological uncertainty, the more comprehensive representation of the state uncertainty makes it possible to greatly improve the accuracy of PF‐based predictions, with a longer‐lasting updating effect. Conversely, forecasting skill is undermined when accounting for parameter uncertainty, owing to the change in hydrological responsiveness. This study extensively addresses several sensitivity analyses in order to provide useful recommendations for designing DA‐based streamflow forecasting systems and for diagnosing possible deficiencies in existing systems.
Plain Language Summary
Accurate streamflow forecasts are of critical importance to several real‐time applications, such as water resource management and flood prevention. The predictive accuracy critically depends on the quality of the forecast initial conditions. Data assimilation (DA) techniques are increasingly being implemented to obtain the most likely estimation of forecast initial conditions through the assimilation of observed hydrological variables. This study compares the performances of two DA techniques, namely the Ensemble Kalman filter and the Particle filter, in terms of both efficiency and temporal persistence (up to 10 days) of the updating effect. The analysis addresses the impact of different sources of uncertainty and the update of different model states and parameters of a lumped conceptual hydrological model, when assimilating observed discharges over 232 watersheds in France. Results show that an accurate estimation of the initial level of the routing store ensures the most benefit of DA, as this state variable is the most correlated with observations. A comprehensive representation of the state uncertainty generally improves the estimation of the forecast initial conditions resulting from the assimilation. While the Ensemble Kalman filter outperforms the Particle filter in the short term, this latter guarantees a longer‐lasting updating effect over the forecast horizon.
Key Points
Estimation of forecast initial level of the routing store of a conceptual hydrological model ensures the most benefit from data assimilation
Updating forecast initial conditions using the ensemble Kalman filter results in a greater improvement in predictive accuracy in the short term
The particle filter guarantees a longer‐lasting effect of the update of initial conditions over the forecast horizon
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