Glucocorticoid Resistance Syndrome in 2 Patients With Diverse Genotype
Abstract
Glucocorticoid resistance syndrome (GRS) is caused by inactivating pathogenic variants in the glucocorticoid receptor gene NR3C1. Reduced glucocorticoid receptor signaling leads to decreased tissue sensitivity to cortisol and resultant biochemical hypercortisolism without the classic clinical features of Cushing syndrome. Patients variably present with signs and symptoms of mineralocorticoid and androgen excess from ACTH overstimulation of the adrenal cortex. Neuropsychiatric symptoms, such as anxiety, depression, anorexia, and insomnia, have also been reported and may be related to CRH excess. Due to the broad clinical spectrum and genetic heterogeneity of the disorder, it remains a diagnostic and treatment challenge. In this report, we describe 2 cases of GRS that highlight the genetic diversity of the condition. Both patients had prominent neuropsychiatric symptoms. While 1 patient had no identifiable variant in the glucocorticoid receptor gene, the other was found to have a novel NR3C1 variant. Low-dose dexamethasone treatment led to clinical improvement in the patient with negative genetic testing, and the second patient continues to be monitored.
How strong is the evidence?
Evidence Hub reads this as a case report, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
Read the paper
Related studies
- Increased expression of circulating miRNA-93 in women with polycystic ovary syndrome may represent a novel, non-invasive biomarker for diagnosis
- Identification of key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis
- Identification of key pathways and genes in polycystic ovary syndrome via integrated bioinformatics analysis and prediction of small therapeutic molecules
- Regulation of Androgen Receptor Expression Alters AMPK Phosphorylation in the Endometrium: In Vivo and In Vitro Studies in Women with Polycystic Ovary Syndrome
- Effect of oral administration of low-dose follicle stimulating hormone on hyperandrogenized mice as a model of polycystic ovary syndrome
- Systems pharmacology to investigate the interaction of berberine and other drugs in treating polycystic ovary syndrome
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.