Endocrine Abstracts (2017) 49 OC13.5 | DOI: 10.1530/endoabs.49.OC13.5

Urinary cadmium excretion is associated with increased synthesis of cortico- and sex steroids in a family-based Swiss population study

Murielle Bochud1, Judith Jenny-Burri2, Menno Pruijm3, Belen Ponte4, Idris Guessous1, Georg Ehret5, Dusan Petrovic1, Vincent Dudler2, Max Haldimann2, Geneviève Escher7, Bernhard Dick7, Markus Mohaupt7, Fred Paccaud1, Michel Burnier3, Antoinette Péchère-Bertschi6, Pierre-Yves Martin4, Bruno Vogt7 & Daniel Ackermann7

1Institute of Social and Preventive Medicine (IUMSP), Lausanne, Switzerland; 2Federal Food Safety and Veterinary Office, Bern, Switzerland; 3Service of Nephrology, Lausanne, Switzerland; 4Service of Nephrology, Geneva, Switzerland; 5Cardiology, Department of Specialities of Internal Medicine, Geneva, Switzerland; 6Endocrinology, Department of Specialities of Internal Medicine, Geneva, Switzerland; 7University Clinic for Nephrology and Hypertension, Bern, Switzerland.

Background: Cadmium (Cd) is considered as a human carcinogen. A potential intermediate mechanism could be hormone-related by disturbing steroidogenesis in gonads and adrenal glands. We tested whether urinary Cd excretion, as a marker of long-term exposure, is associated with the urinary steroid profile in the general adult population.

Methods and Findings: The Swiss Kidney Project on Genes in Hypertension (SKIPOGH) is a multicentric family-based population study with a response rate of 25.6%. We measured 24-h urinary excretions of Cd and steroid hormone metabolites by gas chromatography and mass spectrometry in 1000 participants (473 men, 527 women), with separate day and night collections. Mixed linear models were used to analyse the associations of each steroid metabolite with Cd excretion.

Cd and testosterone excretions were positively associated in men (β[SE, P]: 1.378[0.242, <0.00001] and 1.440[0.333, 0.00002] for day and night, respectively), but not in women (0.333[0.257, 0.2] and 0.674[0.361, 0.06]). There was a strong positive association of the urinary excretion of Cd and cortisol (0.475[0.157, 0.0025] and 0.877[0.194, 0.00001], for day and 0.875[0.253, 0.00053] and 1.183[0.277, 0.00002] for night, respectively). Cd excretion was not associated with the excretion of tetrahydroaldosterone, the major metabolite of aldosterone, but with other mineralocorticoid metabolites (P<0.01 in men and women). Further adjustment revealed an independent effect between the synthesis of sex hormones and corticosteroids and an interdependent effect of Cd on gluco- and mineralcorticoid synthesis.

Conclusions: Our findings provide evidence for a global stimulating effect of low-dose Cd exposure on sex and corticosteroid synthesis in the general adult population. Further studies are needed to explore the health consequences of chronic low-dose exposure to Cd on selected diseases such as steroid-sensitive cancers or metabolic disorders.

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