Bone density and risk of osteoporosis in Klinefelter syndrome.

UNLABELLED: Different mechanisms in Klinefelter syndrome contribute to reduced bone mass and osteoporosis, which have a precocious onset and are detected in up to 40% of patients, irrespectively of testosterone levels. Androgen receptor, X chromosome inactivation and INSL3 levels are hypothesized to cooperate with and modulate the effect of testosterone on the bone. CONCLUSION: New perspectives on genetic topics are opening exciting areas of research on the pathophysiology of reduced bone mass in Klinefelter patients.

Osteoporosis in Klinefelter's syndrome.

Hypogonadism represents one of the most important causes of male osteoporosis. Testosterone regulates male bone metabolism both indirectly by aromatization to estrogens and directly through the androgen receptor (AR) on osteoblasts, promoting periosteal bone formation during puberty and reducing bone resorption during adult life. Early onset of testosterone deficiency, as observed in Klinefelter's syndrome (KS), is an important risk factor for precocious osteoporosis. Osteoporosis is present in up to 40% of subjects with KS and has usually been attributed to low testosterone levels. However, reduced bone mass might be present also in KS men with normal testosterone levels and testosterone replacement therapy does not always restore bone density in KS patients. Possible new determinants for osteoporosis in KS might be related to the AR function and insulin-like factor 3 (INSL3) levels. The CAG length and inactivation pattern of the AR in KS have been related to osteoporosis, but definitive proof is lacking. INSL3 has an anabolic role on bone metabolism by acting on osteoblasts and INSL3 levels are low in KS. Therefore, low INSL3 concentrations might represent a possible new pathogenic mechanism for reduced bone mass in KS.

Male hypogonadism in cirrhosis and after liver transplantation.

Liver is deeply involved in the metabolism of proteins, hormones, enzymes, cytokines, as well as in sex hormones catabolism. Gonadal function requires a normal liver function, and it is well known that clinical signs of hypogonadism are common in patients with liver cirrhosis. Few studies have focused on hypothalamic- pituitary-gonadal alterations in male cirrhotic patients or after orthotopic liver transplantation (OLT). The pathogenesis of hypogonadism in cirrhotic patients is complex and not well explained. It involves both a gonadal and a hypothalamic- pituitary dysfunction. After OLT the hypothalamic-pituitary-gonadal function partially improves, showing that the hepatic dysfunction before OLT is deeply involved in its pathogenesis. After OLT some alterations persist in some patients, both because of pre-existing gonadal alterations (toxic-metabolic damage) and immunosuppressive pharmacological side effects. Further studies will explain the relationship between hypogonadism and OLT outcome, and the role of androgen therapy in hypogonadism after OLT, in the early months and in the long term.

Portal hypertension and portal hypertensive gastropathy in patients with liver cirrhosis: a haemodynamic study.

BACKGROUND/AIM: The relationships between the levels of portal hypertension and the morphologic alterations of gastric mucosa in patients with liver cirrhosis--generally described as portal hypertensive gastropathy--are poorly defined. PATIENTS: In total, 62 patients with cirrhosis of different aetiologies, were examined by endoscopy and measurement of portal hypertension by hepatic venous pressure gradient. RESULTS: Portal hypertensive gastropathy was observed in 49 cases; six patients showed gastric antral vascular ectasia always associated with gastric lesions described as severe portal hypertensive gastropathy with different localizations. Hepatic venous pressure gradient showed severe portal hypertension in 37 cases, and averaged 17.7 +/- 4.3 mmHg. It was much higher in patients with severe lesions (p=0.0004). Hepatic venous pressure gradient in patients with endoscopic signs of isolated antral gastropathy was lower (p=0.04) than in those with isolated lesions in body-fundus. No relationship was found between hepatic function, as assessed by the Child-Pugh score, and portal hypertensive gastropathy. CONCLUSIONS: The present data suggest that the severity of portal hypertensive gastropathy is related to portal hypertension, but portal hypertension is not the sole determinant of the occurrence of endoscopic abnormalities of gastric mucosa. The derangement of liver function does not appear to play any role in the occurrence of portal hypertensive gastropathy.