Further analysis of the disturbed adrenocortical function in the cerebro-hepato-renal syndrome of Zellweger.

Plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-desoxycortisol, cortisol and cortisone were determined simultaneously in small plasma samples obtained during an i.v. ACTH (Synacthen) stimulation test in five patients (age 4-7 years) with Zellweger syndrome. The response of all ACTH-dependent steroids to Synacthen was severely impaired in all patients, despite normal basal levels. It can be concluded that the biochemical defect in adrenal steroidogenesis causing the inadequate response to ACTH injection is located proximal to progesterone. We propose that the lack of responsiveness to ACTH is secondary to an abnormality of ACTH receptors on the adrenocortical cell. The extremely low levels of non-specific lipid transfer protein may be a contributing factor.