Mass spectrometric detection of neutrophil elastase cleaved corticosteroid binding globulin and its association with Asn347 site glycosylation, in septic shock patients.

Background: Corticosteroid-binding globulin (CBG) modulates tissue cortisol availability via modification of cortisol:CBG binding affinity in response to multiple factors, including neutrophil elastase (NE) cleavage of the reactive centre loop (RCL), converting high affinity CBG (haCBG) to low affinity CBG (laCBG). In vitro, glycosylation of the RCL at Asn347 affects NE cleavage susceptibility. To date, no direct measurement of laCBG, which would verify NE cleavage, has been reported.

Adrenal Crisis and Adrenal Insufficiency Admissions in Patients 30-59 Years: Contribution of Psychosocial Factors.

Background And Objective: Adrenal crises (AC) occur in middle aged adults with adrenal insufficiency (AI). Psychosocial difficulties may impede effective self-management in some cases. This study aimed to investigate associations between psychosocial problems and hospital admissions for AI/AC in middle aged adults.

17α-hydroxylase/17,20-lyase deficiency (17-OHD): A Meta-analysis of Reported Cases.

Purpose: Homozygous pathogenic variants in the CYP17A1 gene result in defective activity of the steroidogenic enzymes 17α-hydroxylase/17,20-lyase resulting in the clinical syndrome 17-OHD characterised by hypertension, hypokalaemia, and disorders of sexual development. Pathogenic variants of CYP17A1 lead to complete or partial loss of enzymatic activity and clinical presentations of varying severity. This study aimed to examine relationships between CYP17A1 genotype and clinical presentation in a global cohort.

In Vivo Formation of Adrenal Organoids in a Novel Porcine Model of Adrenocortical Cell Transplantation.

Recognizing the limitations of current therapies for Addison's disease, novel treatments that replicate dynamic physiologic corticosteroid secretion, under control of ACTH, are required. The aim of these experiments was to evaluate the feasibility of adrenocortical cell transplantation (ACT) in a large animal model, adapting methods successfully used for intracutaneous pancreatic islet cell transplantation, using a fully biodegradable temporizing matrix. Autologous porcine ACT was undertaken by bilateral adrenalectomy, cell isolation, culture, and intracutaneous injection into a skin site preprepared using a biodegradable temporizing matrix (BTM) foam.

Cortisol, Stress, and Disease-Bidirectional Associations; Role for Corticosteroid-Binding Globulin?

Selye described stress as a unified neurohormonal mechanism maintaining homeostasis. Acute stress system activation is adaptive through neurocognitive, catecholaminergic, and immunomodulation mechanisms, followed by a reset via cortisol. Stress system components, the sympathoadrenomedullary system, hypothalamic-pituitary-adrenal axis, and limbic structures are implicated in many chronic diseases by establishing an altered homeostatic state, allostasis.

Triiodothyronine supplementation in a sheep model of intensive care.

Triiodothyronine (T3) concentrations in plasma decrease during acute illness and it is unclear if this contributes to disease. Clinical and laboratory studies of T3 supplementation in disease have revealed little or no effect. It is uncertain if short term supplementation of T3 has any discernible effect in a healthy animals.

Is high salt intake inducing obesity via production of cortisol? A novel working hypothesis and pilot study.

Purpose: Evidence is growing that high salt intake is an independent risk factor for obesity, but the mechanisms are unknown. Our novel working hypothesis is that high salt intake drives cortisol production, which in turn, drives obesity. The current study aimed to demonstrate an acute cortisol response following a single high salt meal.

Novel agents to treat adrenal insufficiency: findings of preclinical and early clinical trials.

Introduction: Adrenal insufficiency currently affects over 300/million population, with higher morbidity and mortality compared to the general population. Current glucocorticoid replacement therapy is limited by a lack of reliable biomarkers to guide dosing, inter-patient variation in metabolism and narrow therapeutic window. Increased morbidity and mortality may relate to unappreciated under- or over-exposure to glucocorticoids and impaired cortisol circadian rhythm.

The Learning Curve for Endoscopic Endonasal Transsphenoidal Pituitary Surgery: Evaluating Endocrine Outcomes.

Objective: In South Australia endoscopic endonasal approach (EEA) pituitary surgery has been practiced since 2006, largely by two neurosurgeons with a small fellowship-trained otolaryngology team. The aim of this cohort study was to determine if a "learning curve" can be established over this time period, as represented by structural and endocrine patient outcomes.

Method: Retrospective cohort study of patients undergoing EEA surgery between 2006 and 2021 in Adelaide, South Australia at three tertiary teaching hospitals.

A clinical perspective on ectopic Cushing's syndrome.

Cushing's syndrome (CS) refers to the clinical features of prolonged pathological glucocorticoid excess. About 10-20% of individuals with CS have ectopic CS (ECS), that is, an adrenocorticotropin (ACTH)-producing tumour outside the pituitary gland. ACTH-secreting neuroendocrine neoplasia (NENs) can arise from many organs, although bronchial NEN, small cell lung cancer (SCLC), pancreatic NEN, thymic NEN, medullary thyroid cancer (MTC), and pheochromocytoma are the most common.

variants in patients with thyrotrophinomas, cyclical Cushing's disease and prolactinomas.

Introduction: Germline loss-of-function variants in , encoding peptidylglycine α-amidating monooxygenase (PAM), were recently discovered to be enriched in conditions of pathological pituitary hypersecretion, specifically: somatotrophinoma, corticotrophinoma, and prolactinoma. PAM is the sole enzyme responsible for C-terminal amidation of peptides, and plays a role in the biosynthesis and regulation of multiple hormones, including proopiomelanocortin (POMC).

Methods: We performed exome sequencing of germline and tumour DNA from 29 individuals with functioning pituitary adenomas (12 prolactinomas, 10 thyrotrophinomas, 7 cyclical Cushing's disease).

Factors underlying a disproportionate increase in hospital admissions for adrenal insufficiency in women aged 20-29 years.

Since the year 2000, admissions for adrenal insufficiency (AI) and adrenal crises (AC) have shown a particular increase in young adult females. We examined data on acute non-surgical hospitalisations for AI/AC from New South Wales, Australia, to determine relevant factors that may have contributed to this increase. Data were analysed to ascertain associations between various comorbid psychosocial issues, identified by relevant ICD-10-AM codes in each record, and ACs.

Approach to the Patient: Reninoma.

A reninoma is a functional tumor of afferent arteriolar juxtaglomerular cells that secretes the enzyme renin, leading to hyperactivation of the renin-angiotensin-aldosterone system. Reninoma is a potentially curable cause of pathological secondary hyperaldosteronism that results in often severe hypertension and hypokalemia. The lack of suppression of plasma renin contrasts sharply with the much more common primary aldosteronism, but diagnosis is often prompted by screening for that condition.

Cabergoline-associated valvulopathy of the tricuspid valve in the treatment of prolactinoma.

Cabergoline-associated valvulopathy (CAV) is defined by the echocardiographic triad of moderate or severe regurgitation, valvular thickening and restricted valvular motion. While it is a well-described complication of dopamine agonist therapy in Parkinson's disease, only three convincing cases of CAV have previously been described in the treatment of prolactinoma, with none involving the tricuspid valve. We describe a case of CAV affecting the tricuspid valve, ultimately resulting in the patient's death.

Adrenal Medullary Hyperplasia: A Systematic Review and Meta-analysis.

Context: Adrenal medullary hyperplasia (AMH) is a rare, incompletely described disorder of the adrenal medulla that is associated with catecholamine excess.

Objective: To increase knowledge about AMH by reviewing the reported cases of this disorder.

Design: Systematic review and meta-analysis of the genotype/phenotype relationship in all reported cases of AMH.

The Changing Epidemiology of Adrenal Insufficiency: Iatrogenic Factors Predominate.

Context: Adrenal insufficiency (AI)-related morbidity persists despite efforts to minimize its effect. Reasons for this are unknown and warrant examination.

Objective: This work aimed to investigate trends in AI hospitalizations and glucocorticoid (GC) replacement therapy use.

Corticosteroid-binding globulin (CBG): spatiotemporal distribution of cortisol in sepsis.

Corticosteroid-binding globulin (CBG) is a 50-60 kDa circulating glycoprotein with high affinity for cortisol. CBG is adapted for sepsis; its cortisol binding is reduced reversibly by pyrexia and acidaemia, and reduced irreversibly by neutrophil elastase (NE) cleavage, converting high cortisol-binding affinity CBG to a low affinity form. These characteristics allow for the targeted delivery of immunomodulatory cortisol to tissues at the time and body site where cortisol is required in sepsis and septic shock.

Future Directions for Adrenal Insufficiency: Cellular Transplantation and Genetic Therapies.

Primary adrenal insufficiency (PAI) occurs in 1 in 5 to 7000 adults. Leading etiologies are autoimmune adrenalitis in adults and congenital adrenal hyperplasia (CAH) in children. Oral replacement of cortisol is lifesaving, but poor quality of life, repeated adrenal crises, and dosing uncertainty related to lack of a validated biomarker for glucocorticoid sufficiency persists.