Imbalanced cortisol concentrations in glycogen storage disease type I: evidence for a possible link between endocrine regulation and metabolic derangement
Open Access
- 19 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Orphanet Journal of Rare Diseases
- Vol. 15 (1), 1-8
- https://doi.org/10.1186/s13023-020-01377-w
Abstract
Background Glycogen storage disease type I (GSDI) is an inborn error of carbohydrate metabolism caused by mutations of either the G6PC gene (GSDIa) or the SLC37A4 gene (GSDIb). Glucose 6-phosphate (G6P) availability has been shown to modulate 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1), an ER-bound enzyme catalyzing the local conversion of inactive cortisone into active cortisol. Adrenal cortex assessment has never been performed in GSDI. The aim of the current study was to evaluate the adrenal cortex hormones levels in GSDI patients. Methods Seventeen GSDI (10 GSDIa and 7 GSDIb) patients and thirty-four age and sex-matched controls were enrolled. Baseline adrenal cortex hormones and biochemical markers of metabolic control serum levels were analyzed. Low dose ACTH stimulation test was also performed. Results Baseline cortisol serum levels were higher in GSDIa patients (p = 0.042) and lower in GSDIb patients (p = 0.041) than controls. GSDIa patients also showed higher peak cortisol response (p = 0.000) and Cortisol AUC (p = 0.029). In GSDIa patients, serum cholesterol (p = 0.000), triglycerides (p = 0.000), lactate (p = 0.000) and uric acid (p = 0.008) levels were higher and bicarbonate (p = 0.000) levels were lower than controls. In GSDIb patients, serum cholesterol levels (p = 0.016) were lower and lactate (p = 0.000) and uric acid (p = 0.000) levels were higher than controls. Baseline cortisol serum levels directly correlated with cholesterol (rho = 0.65, p = 0.005) and triglycerides (rho = 0.60, p = 0.012) serum levels in GSDI patients. Conclusions The present study showed impaired cortisol levels in GSDI patients, with opposite trend between GSDIa and GSDIb. The otherwise preserved adrenal cortex function suggests that this finding might be secondary to local deregulation rather than hypothalamo-pituitary-adrenal axis dysfunction in GSDI patients. We hypothesize that 11 beta HSD1 might represent the link between endocrine regulation and metabolic derangement in GSDI, constituting new potential therapeutic target in GSDI patients.This publication has 40 references indexed in Scilit:
- Phosphorylation of FOXP3 controls regulatory T cell function and is inhibited by TNF-α in rheumatoid arthritisNature Medicine, 2013
- 11β-Hydroxysteroid Dehydrogenase Type 1, But Not Type 2, Deficiency Worsens Acute Inflammation and Experimental Arthritis in MiceEndocrinology, 2012
- G6PT-H6PDH-11βHSD1 triad in the liver and its implication in the pathomechanism of the metabolic syndromeWorld Journal of Hepatology, 2012
- Malformation syndromes caused by disorders of cholesterol synthesisJournal of Lipid Research, 2011
- Hexose-6-phosphate dehydrogenase: linking endocrinology and metabolism in the endoplasmic reticulumJournal of Molecular Endocrinology, 2008
- Physiological roles of 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenaseCurrent Opinion in Pediatrics, 2008
- Myasthenia gravis in a patient affected by glycogen storage disease type Ib: A further manifestation of an increased risk for autoimmune disorders?Journal of Inherited Metabolic Disease, 2008
- Inhibition of 11ß-hydroxysteroid dehydrogenase type 1 as a promising therapeutic targetDrug Discovery Today, 2007
- A Transgenic Model of Visceral Obesity and the Metabolic SyndromeScience, 2001
- The prevalence of polycystic ovaries in the hepatic glycogen storage diseases: its association with hyperinsulinismClinical Endocrinology, 1995