Paradoxical response of plasma cortisol to pulse intravenous injection of synthetic corticotrophin and dibutyryl cyclic adenosine 3',5'-monophosphate in adult panhypopituitarism.

Abstract

ABSTRACT 250 μg of synthetic β-1-24 corticotrophin and 10 mg/kg of dibutyryl cyclic adenosine 3′,5′-monophosphate (Db-cAMP) were iv pulse injected into six patients with adult panhypopituitarism. The plasma cortisol levels were determined as 11-OHCS at zero time and then at 2.5, 5, 7.5, 10, 15, 30, 60 and 180 min after the injection. The data were compared with those obtained under the same experimental conditions in groups of normal subjects. A paradoxical pattern of early plasma cortisol response after the two stimuli was found in the case of hypopituitarism in comparison with that observed in normal subjects, that is a higher response after Db-cAMP than after corticotrophin. This was dependent on a selective impairment of adrenal steroidogenic response to iv injection of corticotrophin, whereas the response to iv injection of Db-cAMP was normal. Moreover in hypopituitaric patients the time course of cortisol response after ACTH was clearly different from the normal. The plasma 11-OHCS levels never showed an early peak followed by a fall and a second subsequent rise but rose progressively after the injection to a plateau between 15 and 180 min. By contrast, after Db-cAMP the time course of the response was also similar to that observed in normal subjects. It is suggested that after chronic failure of ACTH the reduced cortisol response to iv acute administration of corticotrophin may also depend on a defect localized before the synthesis of intracellular cyclic AMP, i. e. in the binding between ACTH and the specific cell membrane bound receptor and/or in the inactivation of the membrane associated adenyl cyclase.