This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lamberts, S. W. J. Articles by de Jong, F. H. Search for Related Content PubMed PubMed Citation Articles by Lamberts, S. W. J. Articles by de Jong, F. H.

Familial and Iatrogenic Cortisol Receptor Resistance¹

Department of Medicine, Erasmus University, Rotterdam, The Netherlands

A family is described in which the father, a daughter, and two sons had cortisol receptor resistance. Hirsutism, skull baldness, and menstrual irregularities existed only in the female patient, while all three males were asymptomatic. The syndrome was transmitted via a dominant autosomal trait. A lowered dexamethasone affinity and a lowered number of glucocorticoid receptors were detected on the peripheral mononuclear leukocytes of the female patient.

Chronic administration of the glucocorticoid receptor-blocking agent mifepristone (RU 38486) to normal individuals resulted in resetting of the hypothalamo-pituitary-adrenal axis at a higher level, while the diurnal rhythm of cortisol and the responsiveness to corticotropin releasing factor remained present. In four postmenopausal women this resulted in a considerable increase in circulating androstenedione levels (and eventually of estradiol levels). This iatrogenic RU 38486-induced biochemical syndrome is similar and difficult to differentiate from familial cortisol receptor resistance.

Among a group of patients with so-called "idiopathic hirsutism," four patients were recognized with elevated androstenedione and (slightly) elevated cortisol levels which showed abnormalities in the affinity and/or number of glucocorticoid receptors on their peripheral mononuclear leukocytes. Therefore it is hypothesized that the syndrome of (partial) glucocorticoid receptor resistance is far more common than currently thought, especially among the group of patients with so-called "idiopathic hirsutism."