Urinary Cadmium Excretion Is Associated With Increased Synthesis of Cortico- and Sex Steroids in a Population Study

J Clin Endocrinol Metab. 2018 Feb 1;103(2):748-758. doi: 10.1210/jc.2017-01540.

Abstract

Context: Urinary cadmium (Cd) excretion is associated with cancer and cardiovascular morbidity. A potential mechanism could be disturbance of steroidogenesis in gonads and adrenal glands.

Objective: We tested whether urinary excretion of Cd is correlated with that of cortico- and sex steroid metabolites in the general adult population.

Setting: The Swiss Kidney Project on Genes in Hypertension is a multicentric, family-based population study.

Measures: Urinary excretions of steroid hormone metabolites and Cd were measured with separate day and night collections. Associations were analyzed by mixed linear models.

Results: Urinary Cd and testosterone excretions in men were significantly correlated (respective day and night β values [standard error (SE)], 1.378 [0.242], P < 0.0005; and 1.440 [0.333], P < 0.0005), but not in women [0.333(0.257), P = 0.2; and 0.674 (0.361), P = 0.06]. Urinary Cd and cortisol excretions were positively associated in both sexes [day: β = 0.475 (SE, 0.157), P = 0.0025, and 0.877 (SE, 0.194), P < 0.0005, respectively; night: β = 0.875 (SE, 0.253), P < 0.0005 and 1.183 (SE, 0.277), P = 0.00002, respectively]. Cd excretion was correlated with mineralocorticoid metabolites excretion, except tetrahydroaldosterone, in both sexes (P < 0.01). There was an independent effect of Cd on sex hormone and corticosteroid synthesis and an interdependent effect on gluco- and mineralcorticoid production.

Conclusion: Our findings provide evidence for a global stimulating effect on steroid synthesis already at low-dose Cd exposure. These findings might explain the association of Cd with diseases such as steroid-sensitive cancers or metabolic disorders.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones / metabolism*
  • Adult
  • Aged
  • Aldosterone / analogs & derivatives
  • Aldosterone / urine
  • Cadmium / urine*
  • Cohort Studies
  • Family
  • Female
  • Gonadal Steroid Hormones / metabolism*
  • Gonadal Steroid Hormones / urine
  • Humans
  • Hypertension / metabolism*
  • Hypertension / urine
  • Kidney / metabolism
  • Male
  • Middle Aged
  • Mineralocorticoids / urine
  • Testosterone / urine

Substances

  • Adrenal Cortex Hormones
  • Gonadal Steroid Hormones
  • Mineralocorticoids
  • Cadmium
  • tetrahydroaldosterone
  • Testosterone
  • Aldosterone