Corticosteroids in human blood: IX. Evidence for adrenal secretion of sulfate-conjugated cortisol, 11β,17α-dihydroxy-4-pregnene-3,20-dione-21-yl-sulfate

Ludwig Kornel*, Suresh K. Patel, Ezeroug Ezzeraimi, Cedric H.L. Shackleton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


A method was developed for the estimation of levels of cortisol-21-sulfate (FKS), cortisone-21-sulfate (EKS), and 20(α + β)-reduced cortisol-21-sulfates in blood plasma. Levels of these conjugates were determined in peripheral vein plasma of 42 normal subjects, 21 men, and 21 women (age range 20-64 years) and in adrenal vein plasma of patients with various adrenocortical disorders, six patients with primary hyperaldosteronism, five patients with Cushing's syndrome, and in two obese patients, suspected to have Cushing's syndrome, but with inconclusive laboratory findings. Adrenal vein blood was obtained by percutaneous, trans-femoral adrenal vein catheterization. Levels of non-conjugated (free) cortisol were determined in all plasma samples along with those of the sulfated steroids. FKS was found in all plasma samples, both in men and women. The variation in FKS levels paralleled that in the free cortisol levels, thus the ratio of FK FKS was the same in the blood samples drawn at 8 AM as in those drawn at 4 PM or 5 PM (ranges: 17.5-36.3 in men, 23.6-45.8 in women). The levels of FKS were relatively lower in women than in men (women 610-880 ng/100 mL at AM, 300-510 ng/100 mL at PM; men: 760-1,220 ng/100 mL at AM, 380-760 ng/100 mL at PM). Plasma levels of total sulfate-conjugated Δ4-3-keto-C-21 steroids (FKS + EKS + 20(α + β)-dihydrocortisol-21-sulfates) were 30-40% higher than those of the levels of cortisol-21-sulfate alone (separated by thin-layer chromatography). In the adrenal vein plasma, levels of Δ4-3-keto-C-21-steroid-21-yl sulfates were 20 to 40 times higher than levels of these steroids in the peripheral blood. The bulk of the steroid sulfate measured in the adrenal vein plasma consisted of cortisol-21-sulfate. The ratio of FK FKS in the adrenal vein plasma was markedly smaller than in the peripheral vein plasma; it was 6.9-12.3 in males and 4.9-6.7 in females, whereas in the peripheral vein of the same subjects it was 19.2-43.7 in males and 21.4-48.3 in females. Cortisol-21-sulfate isolated from adrenal vein plasma was identified by mass spectrometry. The data presented provide evidence for the secretion of this conjugate by the adrenal cortex. Its secretion appears to be markedly elevated in patients with Cushing's syndrome, both due to hyperplasia and due to adrenal adenoma, as compared with normal subjects and patients with primary aldosteronism, both males and females. However, the FK FKS ratio was markedly lower in Cushing's patients due to adrenal adenoma than due to adrenal hyperplasia, this suggesting that ACTH is stimulating intra-adrenal hydrolysis of cortisol sulfate.

Original languageEnglish (US)
Pages (from-to)817-823
Number of pages7
Issue number12
StatePublished - Dec 1995


  • Cushing's syndrome
  • cortisol-21-sulfate
  • plasma levels
  • primary aldosteronism

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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