Evidence suggesting that cadmium induces a non-thyroidal illness syndrome in the rat

The effect of in vivo administration of cadmium chloride on the pituitary-thyroidal axis was assessed in 200 g body weight Wistar rats. A dose of 2·5 mg/kg body weight was injected i.v. 24 h before the experiments were initiated. Plasma thyroxine (T4) and tri-iodothyronine (T3) concentrations in cadmium-treated rats were significantly (P<0·01) decreased, whereas plasma TSH failed to increase in response to low T4 and T3. However, the TSH response to TRH and the pituitary content of TSH in these rats were both normal. Cadmium induced a significant (P<0·01) decrease in 4-h thyroidal 131I uptake and in thyroid/plasma radioactivity ratio. The in vitro conversion of T4 to T3 in the pituitary was significantly (P<0·01) blocked by cadmium whereas there was no in vivo effect. Parameters of peripheral T4 kinetics in cadmium-treated rats, such as metabolic clearance rate (P<0·01), fractional turnover rate (P<0·01), absolute disposal rate (P<0·05), urinary clearance (P<0·05) and faecal clearance (P<0·05), were all decreased by cadmium. The lack of response of TSH to low plasma T4 and T3 and the normal response to exogenous TRH in this and in other non-thyroidal illness syndromes produced by other pathologies suggest a decreased stimulation of pituitary thyrotrophs by endogenous TRH. Journal of Endocrinology (1997) 154, 113–117

A stable isotope study of zinc kinetics in Irish setters with gluten-sensitive enteropathy

The short-term kinetics of Zn turnover were studied in Irish setters with gluten-sensitive enteropathy and control dogs following intravenous injection of 0·25 mg 96·5% enriched 70ZnCl2. The 70Zn enrichment of serum was found closely to obey two-compartment kinetics and the derived two-compartment decay equation was used to calculate the size and turnover of the two initial rapidly exchanging pools of body Zn. In normal Irish setters isotopic Zn initially equilibrates with a pool (a) of size 1·27 (SD 0·46) μmol/kg and then with a second pool (b) of size 6·83 (SD 1·72) μmol/kg. The fractional turnover of pool (b) was approximately one eighth that of pool (a). Enteropathic dogs showed no reduction in the size of either rapidly exchangeable Zn pool, reduction in serum Zn concentration or abnormality in Zn balance and hence these results do not support the possibility of an underlying Zn deficiency in this disorder.

Studies of human zinc kinetics using the stable isotope 70Zn

1. The short-term (120 min) kinetics of Zn turnover has been studied in control subjects and patients with alcoholic liver disease after intravenous injection of 0.5 mg of 96.5% enriched 70ZnCl2. 2. The 70Zn enrichment of plasma was found closely to obey two-compartment kinetics and the derived two-component decay equation has been used to calculate the size and turnover of the initial two rapidly exchanging pools of body Zn. 3. In normal subjects isotopic Zn appears initially to equilibrate with the whole of the plasma Zn which comprises the first metabolic compartment, pool a. This has a size of 0.72 ± 0.1 μmol/kg. 70Zn equilibration then occurs with a second compartment, pool b, consistent with a rapidly exchanging liver Zn pool of size 3.60 ± 0.93 μmol/kg. The fractional turnover rate of pool b was found to be fivefold slower than that of pool a. 4. In the alcoholic group an expansion of pool a was observed (1.63 ± 0.39 μmol/kg), but the size of the second pool was not significantly different from that of control subjects (5.55 ± 1.0 μmol/kg), although its fractional turnover was significantly increased (Kab: control subjects, 0.018 ± 0.002 min−1, alcoholic patients, 0.031 ± 0.006 min−1). 5. These data therefore demonstrate that kinetic studies using stable isotopes of Zn can provide novel information on exchangeable Zn pools in man, but provide no support for the possibility of an underlying Zn depletion in patients with alcoholic liver disease.