Endocrine Abstracts

The role of environmental and occupational toxins in the aetiology of unexplained infertility remains to be fully explored. Epidemiological studies have implicated heavy metals, including cadmium as having a pathogenic role with studies demonstrating associations between serum levels, testicular function and gonadotrophin levels in large cohort studies. Cadmium toxicity is associated with a complex spectrum of effects. Whilst the renal complications are well described, putative effects upon gonadal and endocrine function have not been reported. Studies in rodents have suggested that cadmium exposure is associated with sertoli cell destruction with consequent elevation of FSH, normal LH and testosterone. In addition in vitro studies suggest that cadmium can directly activate the androgen receptor.

We present the case of a 68-year old man who attended the endocrine clinic complaining of decreased libido, erectile dysfunction, lethargy and tiredness. In addition, he suffered from benign prostatic hypertrophy and renal impairment (GFR 40 ml/min). He was a non-smoker. On examination he had decreased testicular volumes bilaterally (4 ml right and 2 ml left). FBC, liver chemistry, thyroid function, prolactin, and IGF-1, were normal. Testosterone was low (6.2 nmol/l (10–28)), with elevated FSH (33 IU/l (2–12)) but normal LH (5.6 IU/l (2–9)). SHBG was also low (13.8 nmol/l (18–84)). On further direct questioning, the patient admitted that he had been exposed to cadmium, working in a battery factory for >20 years. His last exposure was ∼19 years previously. Despite the long time period since exposure, and consistent with its long biological half-life (17–30 years), serum cadmium levels were elevated (4.2 μg/ml (<3)).

We therefore propose that the endocrinology presented in this case is a direct result of cadmium exposure and represents the first description of toxic effects upon the hypothalamo–pituitary–gonadal axis in humans. Sertoli cell failure after cadmium administration is well described in rodents with associated decreases in testicular volume and elevation of FSH. The fact that cadmium is able to bind, and activate the androgen receptor may explain the relatively normal LH concentration in the context of low testosterone as well as the low SHBG. It is also interesting to speculate that this may account for the prostatic hypertrophy in this patient – a feature also reported in rodents exposed to cadmium. This case highlights the fact that unusual causes for atypical endocrinological presentations should always be considered.