ACTH AND ADRENAL STEROID REPONSE TO CORTICOTRCPIN RELEASING FACTOR (CRF) STIMULATION IN PATIENTS WITH A GENETIC DEFECT IN ADRENAL STEROIDOGENESIS

Abstract

To investigate the pathophysiology of hypothalamic-pituitary-adrenal axis in patients (pt) with a mild defect in adrenal steroidogenesis, ACTH and adrenal steroid response (180 min) to ovine CRF (1 ug/kg IV bolus at 1600 hr) in 3 pt with late diagnosis of 11β-hydroxylase (11β-OH) deficiency (def) and in 7 pt with late-onset 21-hydroxylase def (21-OH) or 3β-ol dehydrogenase def (3β-HSD) were compared with the responses in 8 controls. In all pt, levels of adrenal precursor steroids proximal to the particular enzyme block were high following CRF. Basal and CRF-stimulated ACTH & F levels were normal irrespective of enzyme def or magnitude of the rise of the precursor steroid in all pt but 2 (11β-OH def) in whom ACTH response to CRF was high and F response low, with lower precursor steroid response than in the pt with normal ACTH and F. Conclusion: In pt with defects in adrenal steroidogenesis, compensatory ACTH hypersecretion occurs only when F secretion is inadequate. Normal ACTH secretion is seen in pt with normal F secretion despite increased precursor steroids. Mechanism for normal F without excess ACTH remains to be defined.