The effect of lead intoxication on endocrine functions

Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders. (J. Endocrinol. Invest. 32: 175-183, 2009) © 2009, Editrice Kurtis

The impact of sex hormone changes on bone mineral deficit in chronic renal failure

In chronic renal failure several factors affect bone homeostasis leading to the development of renal osteodystrophy. Common calcitropic hormone derangements in renal failure play a central role in bone structure and mineral defects, which in turn accompany osteodystrophy frequently resulting in low bone mineral density (BMD) values. However, patients with end-stage renal disease (ESRD) suffer from several comorbidities, which may partly account for renal bone disease lesions. Hypogonadism in particular accompanies chronic renal failure frequently and exerts an additive effect on bone loss potential. Sex hormones contribute to the equilibrium of osteotropic hormones and cytokines, exerting a protective action on bone tissue. Estrogens have a regulatory effect on bone metabolism in women with renal failure as well. Hypogonadal ESRD women experience a higher bone turnover and more significant bone mass decrements than ESRD women with relatively normal hormone profile and menstrual habits. Female hemodialysis patients have lower BMD values than male patients on average, probably because of menstrual cycle irregularities. However, hypogonadal ESRD men may also experience bone mineral deficits and the severity of hypogonadism may correlate to their bone mineral status. Hormone replacement therapy (HRT) appears to reverse bone mineral loss to some extent in both sexes. In conclusion hypogonadism in renal failure contributes to the bone structure and mineral defects as well as the low-energy fracture risk, reflected in BMD measurements. HRT in ESRD patients should therefore not be overlooked in these patients in the face of their significant comorbidities

sRANKL/osteoprotegerin complex and biochemical markers in a cohort of male and female hemodialysls patients

Objective: The processes involved in bone remodeling are under the control of a multitude of systemic and local factors. Receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) complex seems to be one of the major modulators of bone remodeling. In chronic renal failure, the cytokine systems involved in the regulation of bone turnover may be influenced, and are therefore likely to contribute to the pathogenesis of renal bone disease. The aim of the present study was the evaluation of RANKL/OPG complex in concert with other biochemical parameters in hemodialysis (HD) patients and the investigation of possible correlations between the serum levels of its components and several clinical parameters of these patients. Methods: We measured serum levels of intact PTH (iPTH), total serum RANKL (sRANKL), osteoprotegerin (OPG), alkaline phosphatase, osteocalcin (OC), and tartrate-resistant acid phosphatase (TRAP) in 104 HD patients and in 40 healthy controls. Results: The average serum OPG level was significantly higher, whereas the average serum concentration of RANKL was nonsignificantly lower in patients on HD therapy than in age-matched healthy controls. Consequently, the mean sRANKL/OPG ratio was significantly lower in patients. Among HD patients, serum level of OPG increased significantly with aging and with a longer duration of hemodialysis. RANKL levels were inversely correlated with age nonsignificantly in the whole group of patients and significantly in the female subgroup (r=-0.322, p=0.035), whereas RANKL/OPG ratio declined significantly with age in the entire cohort of patients (r=-0.259, p=0.008). In addition, iPTH, OC, TRAP were significantly higher in female, whereas RANKL/OPG ratio was significantly higher in male than female patients. Conclusions: Lower values of sRANKL/OPG ratio in HD patients, as well as the age and duration of HD dependent increase of serum OPG and the age-dependent decrease of sRANKL concentration especially in women cannot be explained by the elimination of renal clearance only. Alterations in sRANKL/OPG ratio might reflect a compensatory mechanism to modulate bone remodeling in these patients. © 2007, Editrice Kurtis