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Adrenal insufficiency is an insidious diagnosis that can be initially misdiagnosed as other life-threatening endocrine conditions, as well as sepsis, metabolic disorders, or cardiovascular disease. In newborns, cortisol deficiency causes delayed bile acid synthesis and transport maturation, determining prolonged cholestatic jaundice. Subclinical ad...
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Domestic horses are widely used for physically demanding activities but the effect of exercise on their learning abilities has not been explored. Horses are also frequently exposed to stressors that may affect their learning. Stress and exercise result in the release of glucocorticoids, noradrenaline and other neurotransmitters that can influence l...
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... For patients with Addison's disease, long-term glucocorticoid and mineralocorticoid replacement therapy is necessary, using daily hydrocortisone and flu-drocortisone. Additionally, thyroid substitution with levothyroxine is indicated when hypothyroidism is associated, but it is initiated only after the initiation of glucocorticoid substitution therapy to prevent the precipitation of an adrenal crisis [60,61]. ...
Hypocalcemia is a common occurrence in pediatric patients, attributed to various causes and presenting with diverse clinical manifestations. A prompt evaluation is necessary to determine its underlying cause, whether it presents acutely or chronically, and to tailor treatment based on its severity. Among the potential causes of chronic hypocalcemia, primary hypoparathyroidism stands out. The case of a seven-year-old male patient with hypocalcemia reported in this article serves as an illustration, wherein targeted next-generation sequencing revealed a homozygous p.R257X mutation in the AIRE gene, indicative of autoimmune polyendocrine syndrome type 1 (APS-1). It poses challenges due to its multisystemic nature and involvement of specific autoantibodies, often leading to underdiagnosis, owing to its rarity, varied manifestations, and incomplete penetrance. A comprehensive review of the APS-1 literature was conducted to provide insights into the clinical manifestations, genetic spectrum, potential immunological mechanisms, and current medical strategies. Additionally, the recognition of AIRE gene mutations is crucial for facilitating genetic diagnosis, prognosis, and potential treatment strategies for APS-1. The management of such cases involves individualized approaches to treatment, regular monitoring, medication adjustments, and the early identification of associated conditions.
... Eine CH kann aber auch im Rahmen anderer genetischer syndromaler Erkrankungen wie dem Prader-Willi-, Kallmann-, Laurence-Moon-, Bardet-Biedl-, Pasqualini-, Sheehan-, Pickardt-, oder Richards-Rundle-Syndrom auftreten. Isolierte ACTH-Defizienz kann, wenn sie durch inaktivierende POMC-Mutationen ausgelöst wird, zusammen mit roten Haaren und Hyperphagie syndromal auftreten [8]. ...
... Being an observation study, we did not standardize TBI management practices between sites, which may have confounded our analysis. Although rare in children, we did not exclude children with previous endocrine and renal diseases, which may predispose them to sodium disorders [26]. Future studies that specifically investigate sodium dysregulation in TBI should exclude these patients. ...
Purpose We aimed to investigate the association between initial dysnatremia (hyponatremia and hypernatremia) and in-hospital mortality, as well as between initial dysnatremia and functional outcomes, among children with traumatic brain injury (TBI). Method We performed a multicenter observational study among 26 pediatric intensive care units from January 2014 to August 2022. We recruited children with TBI under 18 years of age who presented to participating sites within 24 h of injury. We compared demographics and clinical characteristics between children with initial hyponatremia and eu-natremia and between those with initial hypernatremia and eu-natremia. We defined poor functional outcome as a discharge Pediatric Cerebral Performance Category (PCPC) score of moderate, severe disability, coma, and death, or an increase of at least 2 categories from baseline. We performed multivariable logistic regression for mortality and poor PCPC outcome. Results Among 648 children, 84 (13.0%) and 42 (6.5%) presented with hyponatremia and hypernatremia, respectively. We observed fewer 14-day ventilation-free days between those with initial hyponatremia [7.0 (interquartile range (IQR) = 0.0-11.0)] and initial hypernatremia [0.0 (IQR = 0.0-10.0)], compared to eu-natremia [9.0 (IQR = 4.0-12.0); p = 0.006 and p < 0.001]. We observed fewer 14-day ICU-free days between those with initial hyponatremia [3.0 (IQR = 0.0-9.0)] and initial hypernatremia [0.0 (IQR = 0.0-3.0)], compared to eu-natremia [7.0 (IQR = 0.0-11.0); p = 0.006 and p < 0.001]. After adjusting for age, severity, and sex, presenting hyponatremia was associated with in-hospital mortality [adjusted odds ratio (aOR) = 2.47, 95% confidence interval (CI) = 1.31-4.66, p = 0.005] and poor outcome (aOR = 1.67, 95% CI = 1.01-2.76, p = 0.045). After adjustment, initial hypernatremia was associated with mortality (aOR = 5.91, 95% CI = 2.85-12.25, p < 0.001) and poor outcome (aOR = 3.00, 95% CI = 1.50-5.98, p = 0.002). Conclusion Among children with TBI, presenting dysnatremia was associated with in-hospital mortality and poor functional outcome, particularly hypernatremia. Future research should investigate longitudinal sodium measurements in pediatric TBI and their association with clinical outcomes.
... Hydrocortisone was selected as the model drug due to its requirements for dose personalisation [54][55][56]. Hydrocortisone is the recommended glucocorticoid during childhood and puberty for the treatment of cortisol deficiency (adrenal insufficiency) [57]. In clinical practice, the hydrocortisone dose is calculated based on the patient's body surface area and is commonly 8-10 mg/m 2 /day, administered between 2 and 4 times a day [58]. ...
... Conversely, myeloneuropathy's differential diagnosis encompasses multiple sclerosis, amyotrophic lateral sclerosis, vitamin B12 deficiency, and progressive spastic paraparesis. Finally, primary adrenal insufficiency can arise from diverse causes such as congenital adrenal hyperplasia, autoimmune and infectious adrenalitis, and some drugs [2,15]. ...
... If the patient exhibits normal aldosterone secretion, there is no requirement for mineralocorticoid replacement. However, if there is confirmed aldosterone deficiency, fludrocortisone should be initiated (0.1-0.2 mg/day) [15]. ...
Adrenoleukodystrophy, a rare genetic disease associated with the X chromosome (X-ALD - X-linked adrenoleukodystrophy), predominantly affects males and stems from mutations in the ABCD1 gene, responsible for transporting very long chain fatty acids (VLCFA) into peroxisomes. It leads to adrenal insufficiency (AI) and axonal demyelination. In males, the phenotype varies from isolated adrenocortical insufficiency and progressive myelopathy to cerebral adrenoleukodystrophy (CALD). The aim of this case series is to characterize patients with different clinical presentations of X-ALD with follow-up at a tertiary Portuguese hospital.
All four patients were males, and the median age at the diagnosis was 5 years. Three patients were diagnosed through family screening, with the oldest already displaying hyperpigmentation. Two distinct forms were identified: adolescent CALD (25%) and isolated primary adrenal insufficiency (75%). Analytical studies revealed elevated plasma VLCFA levels in all cases, and genetic analysis demonstrated two different mutations in the ABCD1 gene.
This disorder requires early diagnosis for improved prognosis. Screening male children with primary AIfor X-ALD using a VLCFA panel should be considered, particularly after ruling out the most common causes or when learning difficulties are evident. Genetic confirmation of the diagnosis is essential, enabling genetic counseling, family planning, and preimplantation genetic diagnosis.
... In is otherwise uneventful without additional physiologic stressors. 62,63 Then, consider cosyntropin stimulation testing 48-72 h after the operation as this informs ongoing dosing/management. 62 • 4H: Calcium channel blockers are valuable adjunctive agents when acutely treating catecholamine-induced hypertension and sinus tachycardia. ...
Paediatric phaeochromocytomas and paragangliomas (PPGLs), though rare tumours, are associated with significant disability and death in the most vulnerable of patients early in their lives. However, unlike cryptogenic and insidious disease states, the clinical presentation of paediatric patients with PPGLs can be rather overt, allowing early diagnosis, granted that salient findings are recognized. Additionally, with prompt and effective intervention, prognosis is favourable if timely intervention is implemented. For this reason, this review focuses on four exemplary paediatric cases, succinctly emphasizing the now state-of-the-art concepts in paediatric PPGL management.
... Particular attention is still needed for the pediatric population with subclinical AI requiring dynamic tests since a random cortisol assay might not be relevant. 38 New methods of plasma renin activity are being developed, this being an essential assessment in primary aldosteronism, but also in AD, CAH, Bartter syndrome, etc. One study introduced a semiautomated method of assay based on liquid chromatography and tandem mass spectrometry. ...
We aim to overview Addison’s disease (AD) with regard to current diagnosis and management. This is a narrative review of full-length articles published in English between January 2022 and December 2022 (including online ahead of print versions) in PubMed-indexed journals. We included original studies in living humans regardless of the level of statistical significance starting from the key search terms “Addison’s disease” or “primary adrenal insufficiency” in title or abstract. We excluded articles with secondary adrenal insufficiency. Briefly, 199 and 355 papers, respectively were identified; we manually checked each of them, excluded the duplicates, and then selected 129 based on their clinical relevance in order to address our 1-year analysis. We organized the data in different subsections covering all published aspects on the subject of AD. To our knowledge, this is the largest AD retrospective from 2022 on published data. A massive role of genetic diagnosis especially in pediatric cases is highlighted; the importance of both pediatric and adult awareness remains since unusual presentations continue to be described. COVID-19 infection is a strong player amid this third year of pandemic although we still not do have large cohorts in this particular matter as seen, for instance, in thyroid anomalies. In our opinion, the most important topic for research is immune checkpoint inhibitors, which cause a large panel of endocrine side effects, AD being one of them.
... Hyperpigmentation from ACTH excess may occur in primary AI. Secondary AI is 24 Rushworth et al (2019) 25 Nowotny et al (2021) 26 Nisticò et al (2021) 27 Bornstein et al (2016) 28 BNFc 10 ...
... Adrenal crisis 50-100 mg/m 2 intravenously or intramuscularly initially Followed by 50-100 mg/m 2 per day either as a continuous infusion or in four divided doses given every 6 hours intravenously (or intramuscularly) 24 24 Nowotny et al (2021) 26 Bornstein et al (2016) 28 Nisticò et al (2021) 27 Woodcock et al (2020) 29 Surgery 50-100 mg/m 2 intravenously or intramuscularly initially Followed by 50-100 mg/m 2 per day either as a continuous infusion or in four divided doses given every 6 hours intravenously (or intramuscularly) 24 26 28 Major surgery: 2 mg/kg intravenously at induction, then 2 mg/kg intravenously every 4 hours or by infusion based on weight ranges: ► Up to 10 kg: 25 mg/24 hours; 11-20 kg: 50 mg/24 hours ► Over 20 kg: prepubertal 100 mg/24 hours, pubertal 150 mg/24 hours Postoperative dose: 2 mg/kg every 4 hours intravenously 27 29 Minor surgery: ► 2 mg/kg intravenously or intramuscularly at induction, followed by double normal doses for at least 24 hours 27 ► 50 mg/m 2 or hydrocortisone replacement doses doubled or tripled 28 Shulman et al (2006) 24 Nowotny et al (2021) 26 Nisticò D et al (2021) 27 Bornstein et al (2016) 29 Oral sick day doses 30-50 mg/m 2 /day divided into three or four doses. Gradually reduce to maintenance level 24 26 Doubling or tripling oral glucocorticoid doses 27 29 Simpson et al (2020) 2 (Society for Endocrinology (adult guidelines)) ...
... Adrenal crisis 50-100 mg/m 2 intravenously or intramuscularly initially Followed by 50-100 mg/m 2 per day either as a continuous infusion or in four divided doses given every 6 hours intravenously (or intramuscularly) 24 24 Nowotny et al (2021) 26 Bornstein et al (2016) 28 Nisticò et al (2021) 27 Woodcock et al (2020) 29 Surgery 50-100 mg/m 2 intravenously or intramuscularly initially Followed by 50-100 mg/m 2 per day either as a continuous infusion or in four divided doses given every 6 hours intravenously (or intramuscularly) 24 26 28 Major surgery: 2 mg/kg intravenously at induction, then 2 mg/kg intravenously every 4 hours or by infusion based on weight ranges: ► Up to 10 kg: 25 mg/24 hours; 11-20 kg: 50 mg/24 hours ► Over 20 kg: prepubertal 100 mg/24 hours, pubertal 150 mg/24 hours Postoperative dose: 2 mg/kg every 4 hours intravenously 27 29 Minor surgery: ► 2 mg/kg intravenously or intramuscularly at induction, followed by double normal doses for at least 24 hours 27 ► 50 mg/m 2 or hydrocortisone replacement doses doubled or tripled 28 Shulman et al (2006) 24 Nowotny et al (2021) 26 Nisticò D et al (2021) 27 Bornstein et al (2016) 29 Oral sick day doses 30-50 mg/m 2 /day divided into three or four doses. Gradually reduce to maintenance level 24 26 Doubling or tripling oral glucocorticoid doses 27 29 Simpson et al (2020) 2 (Society for Endocrinology (adult guidelines)) ...
Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, weight loss, abdominal pain, vomiting and lingering illnesses. AI is treated with replacement doses of hydrocortisone. At times of physiological stress such as illness, trauma or surgery, there is an increased requirement for exogenous glucocorticoids, which if untreated can lead to an adrenal crisis and death. There are no unified guidelines for those <18 years old in the UK, leading to substantial variation in the management of AI. This paper sets out guidance for intercurrent illness, medical, dental and surgical procedures to allow timely and appropriate recognition and treatment of AI and adrenal crisis for children and young people.
... It requires overnight hospitalization and increases the risk of adrenal crisis, while the insulin tolerance test (ITT) is related to the risk of significant hypoglycemia, especially in children at risk such as PWS patients. Given the considerable safety profile, corticotropin analogs such as tetracosactrin (Synacthen ® ), which is a synthetic ACTH, are recommended as first-line stimulation tests, especially the low-dose tetracosactrin stimulation test (LDSST) (1 µg), which is usually very well tolerated (7). ...
... It should be suspected in case of decreased basal cortisol levels with elevated ACTH levels. Standard dose Synacthen stimulation test (SDSST) with 250 µg of tetracosactrin is recommended to confirm the diagnosis (7). Cortisol value of ≥ 500 nmol/l at 0, 30 or 60 min. ...
... It should be repeated if symptoms occur. The proposed hydrocortisone replacement doses are given in Table 4 (7,20). At present, however, there are no (6)) nmol/l rules out the diagnosis of CAI (23) Metyrapone test 30 mg/kg -easy to perform -high sensitivity -increases the risk of adrenal crisis -limited availability (unavailable in the USA) leads to the lack of standardization -according to some authors, a single test is of limited diagnostic value ACTH level >17 pmol/l (23) and/or 11-deoxycortisol level >200 nmol/l rules out the diagnosis of CAI (6, 23) ...
The generalized dysfunction of the hypothalamic-pituitary axis in patients with Prader-Willi syndrome (PWS) is the most likely cause of hypogonadism, inadequate growth hormone secretion, excessive appetite and associated obesity, impaired body temperature regulation, and hypothyroidism. The syndrome is also related to an increased risk of central adrenal insufficiency, although its prevalence remains unknown. The results of the studies in which different methods of pharmacological stimulation were used do not provide conclusive outcomes. As a result, there are no clear guidelines with regard to diagnosis, prevention, or long-term care when adrenal insufficiency is suspected in patients with PWS. Currently, most patients with PWS are treated with recombinant human growth hormone (rhGH). It has been confirmed that rhGH therapy has a positive effect on growth, body composition, body mass index (BMI), and potentially on psychomotor development in children with PWS. Additionally, rhGH may reduce the conversion of cortisone to cortisol through inhibition of 11β-hydroxysteroid dehydrogenase type 1. However, its influence on basal adrenal function and adrenal stress response remains unexplained in children with PWS. This paper reviews the literature related to the hypothalamic-pituitary-adrenal axis dysfunction in the PWS patient population with a focus on children.
... Conditions associated with hypoglycemia may require a bolus of dextrose, and if hyperkalemia occurs, ECG abnormalities should be monitored (Hubby et al. 2016). If misdiagnosed, the disease can be fatal, causing coma and unexplained infant death (Nisticò et al. 2022). It can be challenging to diagnose and manage a case. ...
Highlight:
• The diagnosis and therapy of Congenital Adrenal Hyperplasia (CAH) children with Adrenal crisis (AC) case report.
• Adrenal crisis (AC) is a life-threatening emergency that contributes to the high death rate of children with adrenal insufficiency.
• The early detection and prompt treatment can improve the outcomes of patients with CAH and AC.
Abstract:
Adrenal crisis is the acute complication of the patient with congenital adrenal hyperplasia. Congenital adrenal hyperplasia (CAH) is a rare condition. Children with CAH commonly come to the emergency room due to acute complications. The condition has high mortality and thus needs early recognition. Newborn screening for CAH in Indonesia is not routinely performed and has not been suggested yet. The purpose of this case report was to report a case of adrenal crisis in a congenital adrenal hyperplasia patient focused on diagnosis and therapy. A female, 10 months old infant, was admitted to the emergency department with a chief complaint of a decrease of consciousness for 3 hours before admission and frequent vomiting since born. On physical examination, there was clitoromegaly. Laboratory showed 17-OH progesterone: 173 ng/dL (7-77 ng/dL) and karyotyping: 46 XX. Management of adrenal crisis is a stress dose of hydrocortisone and rehydration. Education is the key to optimal outcomes and normal growth and development.
