Abstract 179

Abstract

Introduction: Primary generalized glucocorticoid resistance (PGGR) is a rare hereditary disease that was first described in 1976 by Vingerhoeds et al., and its molecular mechanism was elucidated in 1982 by Chrousos et al. It is characterized by -Generalized / partial target-tissue insensitivity to glucocorticoids with hyperactivation of the HP axis, adrenocortical hyperplasia/hypertrophy, increased adrenal cortical steroids. HPA axis circadian rhythm and responsiveness to stressors are intact in GRS. Case Report: 8 year-old boy was brought to hospital with C/O weakness of both UL and LL for past 4-5 days, was found to have hypokalaemia for which he received treatment. Noticed facial hair, pubic hair, axillary hair since last 3 years. Examination revealed Hypertension which needed enalapril and spironolactone for control. H/A was 11 yrs 6 months (> +3 SDS), W/A 10 years 10 months (@ 90th centile), SMR-A2 P3, B/L Testis- 25cc, Nodular & firm in consistency. Biochemical investigations suggestive of Elevated cortisol, ACTH and 24 hour- urine free cortisol, Androgen excess and Low PAC & PRA and metabolic alkalosis with hypokalemia. Bone age of 13 years, Imaging was suggestive of B/L bulky adrenals and B/L testicular adrenal rest tumours. Discussion: The clinical spectrum of GRS is broad. AVariable clinical phenotype is due to decreased receptor number, delayed translocation, DNA binding & transactivation, genetic or epigenetic factors. Dexamethasone activates the mutant and/or wild-type hGRα. Conclusion: GRS is a heterogenous disorder with very broad clinical spectrum. 11 beta hydroxylase deficiency and GRS are clinically indistinguishable. Genetic testing has a role. Serum and urinary cortisol, which are low/ low–normal in 11-BHD but elevated in GRS. Aim of treatment with dexamethasone is to suppress the excess secretion of ACTH and adrenal steroids.