Effect of decreased plasma low-density lipoprotein levels on adrenal and testicular function in man

Objective: The study assessed whether serum LDL cholesterol levels affect adrenal and Leydig cell function in man. Design and Methods: A 24-h continuous ACTH infusion was performed in 15 consecutive chronically ill patients. Serum cortisol and DHEA-s were measured at baseline and at 3, 6, 12, 20, and 24 h during the infusion. Fasting serum lipoprotein levels including LDL cholesterol, HDL cholesterol as well as FSH, LH, total and free testosterone concentrations were also measured on the baseline morning samples prior to the infusion. Results: The initial 3 and 6 h percent rise in cortisol values during 24-h ACTH infusion were significantly diminished in patients with LDL-C values <1.55 mmol/L as compared with patients with higher LDL-C levels (127 ± 17% (SE) vs. 199 ± 31% (SE); p< 0.02 and 115 ± 17% vs. 213 ± 32%; p< 0.02. However, the 24-h areas of cortisol under the curve were comparable the 2 groups. Basal and ACTH stimulated DHEA-s levels and percent increases tended to be lower in the low LDL-C group but the differences were not statistically significant. The mean total testosterone was lower in the low LDL-C group (5.30 ± 1.78 vs. 15.60 ± 1.95 nmol/L; p< 0.0005). Free testosterone levels were also lower in the low LDL-C group (0.03 ± 0.009 nmol/L vs. 0.08 ± 0.01 nmol/L; p< 0.001). Five of six patients with low LDL-cholesterol had low testosterone values, but variable LH levels. Conclusions: Our results suggest that severe acquired LDL cholesterol insufficiency impairs slightly the initial glucocorticoid response to ACTH stimulation but not the overall cortisol production during sustained ACTH stimulation. It also may contribute to the reduction in testosterone seen in chronically ill patients.