title: Adrenocorticotrophin (ACTH) deficiency undetected by standard dynamic tests of the hypothalamic-pituitary-adrenal axis.
abstract: Six patients (four females, two males; aged 18-65 years), previously treated by external pituitary irradiation (2000-4000 cGY in 8-15 fractions over 10-20 days) for pituitary tumours, presented with the symptoms of excessive and inappropriate tiredness suggestive of ACTH deficiency, despite a normal peak cortisol response to an insulin tolerance test (four cases) or to a glucagon stimulation test (two cases). These six patients were found to have significantly lower mean 24 h urinary free cortisol levels (100 +/- 40 nmol; mean +/- SD) compared with the mean value of 31 normal controls (210 +/- 70.8 nmol; P less than 0.01). In addition serum cortisol profiles based on a series of four timed samples between 0900-2300 h were subnormal (mean 130 nmol/l) in comparison with profiles obtained from 12 normal controls (mean 270 nmol/l) (P less than 0.001). Glucocorticoid replacement therapy promptly abolished their symptoms. These results suggest that a discordance between ACTH secretion under basal circumstances and ACTH response to pharmacological tests may exist in patients with ACTH deficiency. We speculate that defective endogenous corticotrophin-releasing hormone (CRF) secretion, due to radiation-induced damage at hypothalamic level, is one cause of this phenomenon.
authors.affiliation: Department of Endocrinology, Christie Hospital, Manchester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Tsatsoulis
authors.forename: S M
authors.initials: SM
authors.lastname: Shalet
authors.forename: J
authors.initials: J
authors.lastname: Harrison
authors.forename: W A
authors.initials: WA
authors.lastname: Ratcliffe
authors.forename: C G
authors.initials: CG
authors.lastname: Beardwell
authors.forename: E L
authors.initials: EL
authors.lastname: Robinson
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000172:deficiency*; D000328:Adult; D000368:Aged; D005260:Female; D005934:Glucagon; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology* / Q000528:radiation effects; D007328:Insulin; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000097:blood / Q000532:radiotherapy; D010913:Pituitary-Adrenal System / Q000503:physiopathology* / Q000528:radiation effects; D011832:Radiation Injuries / Q000097:blood / Q000503:physiopathology
chemical_list: D007328:Insulin; D000324:Adrenocorticotropic Hormone; D005934:Glucagon