Is Adrenal Insufficiency of Concern in Children with Disorders of Lipid and Lipoprotein Metabolism?

Background: Genetic mutations and newer lipid-lowering medications often result in very low plasma levels of LDL cholesterol. Low plasma cholesterol has the potential to negatively impact physiological processes, including steroidogenesis, but the adrenal employs several redundant mechanisms to minimize disparities. Although the likelihood of very low cholesterol impairing production of adrenocortical steroids is unlikely, our knowledge of adrenal function in affected patients is limited. Several genetic diseases including X-linked adrenoleukodystrophy have been reported to impact cholesterol metabolism leading to altered adrenal function. The case outlined below raises the question as to what extent impaired cholesterol transport could affect steroid hormone synthesis. We consider this question in the context of other disorders of cholesterol metabolism and their potential implications in adrenal insufficiency. Case Information: A 27-month-old male was referred to Endocrinology for evaluation of adrenal function following his diagnosis of X-linked adrenoleukodystrophy. Several labs were obtained including plasma ACTH, baseline cortisol, and peak cortisol. Monitoring over several years revealed impaired cholesterol metabolism and confirmed progressive failure of the adrenal cortex. Conclusions: Decreased intracellular cholesterol impaired adrenal function leading to decreased cortisol production. Several genetic disorders are characterized by abnormalities in cholesterol synthesis or metabolism, potentially limiting this key metabolite in providing proper adrenal hormone production and release. Due to the redundant mechanisms for utilizing cholesterol, it seems unlikely that hypocholesterolemia, secondary to genetic disorders and use of lipid-lowering medication that result in very low levels of LDL cholesterol, is of major concern.