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Adrenocortical Response to Adrenocorticotropin in Heterozygous Familial Hypercholesterolemia^*

D. ROGER ILLINGWORTH, NARGIS A. ALAM and SARALYN LINDSEY

Division of Endocrinology, Metabolism, and Clinical Nutrition, Departments of Medicine and Biochemistry, The Oregon Health Sciences University Portland, Oregon 97201

Address all correspondence and requests for reprints to: D. Roger Illingworth, M.D., Ph.D., Department of Medicine, L465, The Oregon Health Sciences University, Portland, Oregon 97201.

Receptor-mediated uptake of low density lipoproteins (LDL) provides an important source of cholesterol for corticosteroid synthesis by human adrenocortical cells grown in tissue culture. Recent studies have indicated an impaired adrenocortical response to prolonged ACTH stimulation in patients with abetalipoproteinemia (who lack plasma LDL) and in patients with homozygous familial hypercholesterolemia (FH), who have a virtual absence of high affinity LDL receptors. In the present study we examined parameters of adrenocortical function in four women with well characterized heterozygous FH to asses whether a 50% reduction in the number of LDL receptors measured in vitro influenced the response of the adrenal cortex to prolonged stimulation with ACTH. Biochemical studies of the binding, internalization, and degradation of [¹²⁵I]LDL were undertaken in cultured skin fibroblasts from each patient, and all patients had reduced LDL receptor activity. The adrenocortical response to a 36-h iv infusion of ACTH-(l–24) (Cortrosyn) was evaluated in the four patients with heterozygous FH and in five normalwomen. Stimulation with iv ACTH resulted in rapid increases in the serum concentrations of cortisol in both groups and plateau concentrations of 55–60 µg/dl. The rates of increase and the plateau concentrations were similar in the control and FH patients. Similarly, rates of excretion of 17-hydroxycorticosteroids and cortisol were similar in the normal subjects and FH patients. These results indicate that a 50% reduction in the number of high affinity LDL receptors due to the presence of one abnormal gene at the LDL receptor locus does not result in any impairment in the delivery of cholesterol to the adrenal cortex during conditions of maximal corticosteroid production.

^* This work was supported in part by USPHS Grants HL-28399 and HL-29074 and by the General Clinical Research Centers Program (RR-334), NIH.

Recipient of a NIH Research Career Development Award (HL-00953).

Received July 29, 1983.

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