Serum Immunoreactive Corticotrophin and Response to Metyrapone in Old Age in Man

Abstract

Attempts have been made to establish the level of immunoreactive corticotrophin (IR-ACTH) in serum in healthy subjects with particular reference to the results in old age. A total of 146 subjects were investigated and the clinical and biochemical conditions of selection specified. Serum IR-ACTH was determined by a radioimmunoassay procedure using an N-terminal antibody produced against the 1–24 sequence of the corticotrophin molecule. The morning level of serum IR-ACTH was determined in 115 fasting healthy subjects, range < 16–210 pg/ml, median 94 pg/ml (3rd International Standard preparation). The level was found to be unchanged within the age interval 20–94 years, irrespective of sex. The nycterohemeral variation of the IR-ACTH concentration in serum was studied in 11 subjects. A rhythmic variation of the IR-ACTH level was not constantly found and age-related difference in the temporal pattern was not demonstrated. In 10 young and 10 elderly subjects a metyrapone test was carried out and the IR-ACTH response was determined. The rise in serum IR-ACTH concentration varied between 20 and 739 pg/ml. Any significant age-related difference in response was not found. The interpretation of the present results with respect to the decreased secretory activity of the glucocorticoid producing system in the aged is discussed. It was concluded that the findings in this study did not indicate a primary deficiency of the axis of the glucocorticoid producing system, neither at the pituitary level nor at the adrenocortical level, as a causal factor to the decreased glucocorticoid production in old age.

Changes in pituitary function with ageing and implications for patient care

“…29–31 At the mechanistic level, feedback disinhibition using a mineralocorticoid receptor antagonist also augments ACTH release more in ageing than young individuals. 32 Other factors that elicit ACTH secretion are equally effective in young and ageing volunteers, namely major surgery, insulin-induced hypoglycaemia, feedback disinhibition, 33–35 and opiate-receptor antagonism. 33,35 Ipsapirone (a serotonin receptor agonist) stimulates more ACTH release in older women than older men, 36 as do human CRH and naloxone.…”

“…32 Other factors that elicit ACTH secretion are equally effective in young and ageing volunteers, namely major surgery, insulin-induced hypoglycaemia, feedback disinhibition, 33–35 and opiate-receptor antagonism. 33,35 Ipsapirone (a serotonin receptor agonist) stimulates more ACTH release in older women than older men, 36 as do human CRH and naloxone. 29 Feedback suppression via glucocorticoid receptor agonists or a mineralocorticoid receptor agonist is less effective in ageing than young volunteers.…”

“…29 Feedback suppression via glucocorticoid receptor agonists or a mineralocorticoid receptor agonist is less effective in ageing than young volunteers. 37–39 Controversy exists regarding unstressed mean ACTH concentrations, which are reportedly unchanged across the age span of 20–100 years, 35,40 decreased with age or increased with age. 41 Comorbidities, assay nonuniformities and sampling inconsistencies may, in part, explain the discrepant reports.…”

Aging and Hypothalamic-Pituitary-Adrenal Response to Challenge in Humans*

“…Other challenges used to examine possible age differences in cortisol response have included insulin-induced hypoglycemia (111,152,153), metyrapone (112,154,155), and the cold pressor test (102). These latter studies have generally shown no significant age differences in patterns of initial cortisol response using both hospitalized (111,112,152,154,155) and healthier subjects (102,153). However, all were hampered by relatively small sample sizes.…”

“…102, 111, 112, 133, 134, 152-155, and 157). Where genderspecific results are reported, they most frequently relate only to basal levels where there appears to be no evidence for age-related gender differences (99,100,112,113,117,155). Overall, the paucity of gender-specific data on possible age-related differences in HPA response to challenge highlights a major area for future research.…”