Impaired cortisol secretion in abetalipoproteinemia

In the adrenal gland cholesterol for steroid biosynthesis is derived from both de novo biosynthesis and receptor mediated uptake of plasma low density lipoproteins (LDL). In the present study we have compared ACTH stimulated adrenal production of cortisol in four control subjects and one adult male patient with abetalipoproteinemia, a disorder in which LDL is absent. Basal morning cortisol levels in the plasma in the control subjects (13.3 +/- 1.6 microgram/dl) and abetalipoproteinemic patient (14.6 micrograms/dl) were similar. During infusion of alpha 1, 24 ACTH however, plasma cortisol levels were higher in the control subjects than in the abetalipoproteinemic patient and this difference was significant at times after 4 hours. Urinary excretion of both 17-hydroxy and 17-ketosteroids over the 24 hour infusion period was also significantly lower in the abetalipoproteinemia patient indicating that cortisol production rates were reduced. Our results suggest that in the absence of plasma low density lipoproteins, as occurs in abetalipoproteinemia, the maximal production of adrenal corticosteroids is impaired. By inference, these findings lend in vivo support to the view that plasma low density lipoproteins serve as an important source of cholesterol for adrenal steroidogenesis in man.