title: Hypopituitaric patients with corticotropin insufficiency show marked impairment of the cortisol response to ACTH (1-24) independently of the duration of the disease.
abstract: It is widely accepted that the classical dose of 250.0 microg ACTH (1-24) (tetracosactin) is clearly supra-maximal while 1.0 and 0.03 microg have been shown as the maximal and the lowest stimulatory ACTH doses for cortisol (F) secretion in normal young subjects. Testing with low ACTH dose would better evaluate adrenal sensitivity to corticotropin. The aims of the present study were: a) to clarify the adrenal sensitivity to ACTH in patients with different duration of corticotroph insufficiency by testing with low and very low tetracosactin doses; and b) to evaluate diagnostic implication regarding the ability of ACTH tests to distinguish patients with corticotroph insufficiency from normal subjects. In 24 hypopituitaric patients (HYPOPIT, 15 male and 9 female, age 22-50 yr, BMI: 22-26 kg/m2) with corticotrophin deficiency we studied the F, DHEA and aldosterone (A) responses to challenges with low ACTH doses (0.06 or 0.5 microg iv at 0 min) followed by 250 microg iv (at +60 min). The results in HYPOPIT were compared with those recorded in 12 normal controls (NS, 6 male and 6 female, age 22-34 yr, BMI: 20-25 kg/m2). Basal F and DHEA levels in HYPOPIT were lower than in NS, while A levels were similar in both groups. The F responses to ACTH in HYPOPIT were dose-independent and markedly lower (p < 0.0001) than in NS. After the 0.06 and 0.5 microg ACTH dose, 16% of HYPOPIT patients showed AF peak within the range of normal response. No HYPOPIT showed AF peak within the normal range after 250 microg ACTH. The DHEA responses to ACTH in HYPOPIT were dose-independent and markedly lower than in NS (p < 0.0001). Overlap between individual DHEA responses in HYPOPIT and NS was present after 0.06 microg and 0.5 microg but not after 250 microg tetracosactin. The A responses in HYPOPIT were dose-dependent and overlapped with those in NS. The adrenal responses to ACTH in HYPOPIT were not associated with the duration of the disease. In conclusion, the present study shows that the mean F and DHEA but not the A responses to ACTH (1-24) are markedly impaired in hypopituitaric patients with corticotroph insufficiency independently of the duration of the disease. The impaired F and DHEA response to ACTH is also independent of the dose, suggesting the existence of relatively enhanced sensitivity of the fasciculata and reticularis adrenal zone to ACTH but meantime remarkable impairment of the adrenal function due to corticotrophin deficiency. In the present study, testing with submaximal ACTH doses did not distinguish patients with secondary adrenal insufficiency from normal subjects.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Aimaretti
authors.forename: C
authors.initials: C
authors.lastname: Baffoni
authors.forename: L
authors.initials: L
authors.lastname: Di Vito
authors.forename: S
authors.initials: S
authors.lastname: Grottoli
authors.forename: D
authors.initials: D
authors.lastname: Gaia
authors.forename: V
authors.initials: V
authors.lastname: Gasco
authors.forename: R
authors.initials: R
authors.lastname: Giordano
authors.forename: Z
authors.initials: Z
authors.lastname: Zadik
authors.forename: F
authors.initials: F
authors.lastname: Camanni
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
authors.forename: E
authors.initials: E
authors.lastname: Arvat
mesh_terms: D000309:Adrenal Insufficiency / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000172:deficiency*; D000328:Adult; D000450:Aldosterone / Q000097:blood; D019540:Area Under Curve; D003366:Cosyntropin / Q000008:administration & dosage; D003687:Dehydroepiandrosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007018:Hypopituitarism / Q000150:complications / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: D003366:Cosyntropin; D003687:Dehydroepiandrosterone; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone