Background: Adrenal suppression is a clinically concerning side effect of inhaled corticosteroid (ICS) treatment in patients with asthma. Increased susceptibility to ICS-induced adrenal suppression has previously been identified in those with the rs591118 polymorphism in platelet-derived growth factor D (PDGFD). The mechanism underpinning this relationship is not known.
Methods: H295R cells were genotyped for rs591118 using a validated Taqman PCR allelic discrimination assay. H295R cell viability was determined after treatment with beclometasone and fluticasone (range 0-330 μM). Cortisol was measured in cell culture medium using competitive enzyme immunoassay.
Results: PDGFD protein expression in H295R cells was confirmed using Western blotting. When ACTH and forskolin were added to H295R cells, a reduction in PDGFD expression was seen, which was then restored by incubation with prochloraz, a known inhibitor of steroidogenesis. A dose-dependent, decrease in PDGFD expression was observed with beclometasone (over a 24 h incubation period) but not with beclometasone incubations beyond 24 h nor with fluticasone (at 24 or 48 h).
Conclusions: H295R cells express PDGFD protein, which can be modulated by incubation with steroidogenesis agonists and antagonists and additionally with exogenous beclometasone.
Impact: PDGFD is expressed in the human adrenal cell line, H295R, and expression can be modulated by beclometasone as well as agonists/antagonists of steroidogenesis. This builds on previous research that identified a SNP in PDGFD (rs591118) as an independent risk factor for adrenal suppression in adults and children with obstructive airway disease treated with inhaled corticosteroids. First in vitro experiments to support a link between the PDGF and cortisol production pathways, supporting the hypothesis that PDGFD variants can affect an individual's sensitivity to corticosteroid-induced adrenal suppression.
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http://dx.doi.org/10.1038/s41390-022-02094-9 | DOI Listing |
Arch Dis Child
December 2024
Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK.
Objective: To determine the incidence and describe the presentation and management of unexpected symptomatic glucocorticoid-induced adrenal suppression (AS) in children and young people aged 0-15 years.
Setting And Design: Surveillance study of symptomatic glucocorticoid (GC)-induced AS with supportive biochemical evidence or presenting as an adrenal crisis, reported via the British Paediatric Surveillance Unit (BPSU) from September 2020 to September 2022.
Results: Over a 25-month period, 190 reports of symptomatic GC-induced AS/adrenal crisis were made, of which 22 were confirmed cases: 18 AS and 4 adrenal crises.
Pediatr Nephrol
January 2025
Department of Pediatrics, Chacha Nehru Bal Chikitsalaya, Delhi, 110031, India.
Background: Hypothalamic-pituitary-adrenal (HPA) axis recovery after cessation of steroid therapy in children with nephrotic syndrome (NS) has hardly been studied in the literature.
Methods: This 22-month cross-sectional study recruited children (2-14 years) with NS, having received a minimum 3 months of prednisolone, now in remission, and off steroids for 1, 3, or 6 months. Serum cortisol-basal and stimulated (with long-acting intramuscular adrenocorticotropic hormone), and factors affecting them, were assessed.
Zhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Department of Endocrinology &Metabolism, West China Hospital, Sichuan University, Chengdu 610041.
Cushing's disease is a rare endocrine disorder characterized by hypercortisolism. Chronic elevated cortisol levels can lead to dysfunction or complications in multiple organs of systems, including cardiovascular, glucose, and bone metabolism, severely impacting patients' quality of life and posing life-threatening risks. Surgery is the first-line treatment for Cushing's disease.
View Article and Find Full Text PDFSheng Li Xue Bao
December 2024
College of Life Sciences, Fujian Normal University; Fujian Key Laboratory of Developmental and Neuro Biology, Fuzhou 350117, China.
Cancer pain is one of the most common symptoms in patients with advanced cancer. In this study, we aimed to investigate the effects of the -related gene C (MrgC) receptors on bone cancer pain. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured after the inoculation of Walker 256 mammary gland carcinoma cells into the tibia of adult Sprague-Dawley rats.
View Article and Find Full Text PDFClin Transl Med
January 2025
Department of Physiology, School of Basic Medicine, Shandong Second Medical University, Weifang, China.
Background: Distant metastasis occurs in the majority of adrenocortical carcinoma (ACC), leading to an extremely poor prognosis. However, the key genes driving ACC metastasis remain unclear.
Methods: Weighted gene co-expression network analysis (WGCNA) and functional enrichment analysis were conducted to identify ACC metastasis-related genes.
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