TY - JOUR
T1 - Hyperhomocysteinemia in patients with Cushing's syndrome
AU - Terzolo, Massimo
AU - Allasino, Barbara
AU - Bosio, Sandra
AU - Brusa, Elena
AU - Daffara, Fulvia
AU - Ventura, Massimo
AU - Aroasio, Emiliano
AU - Sacchetto, Gianna
AU - Reimondo, Giuseppe
AU - Angeli, Alberto
AU - Camaschella, Clara
PY - 2004/8
Y1 - 2004/8
N2 - We evaluated serum homocysteine concentrations and the C677T polymorphism of the gene encoding for methylene tetrahydrofolate reductase, a key enzyme for homocysteine metabolism, in 57 patients with Cushing's syndrome, 41 with active disease, and 16 in remission after successful surgery and 105 blood donors. The patients with active Cushing's syndrome had significantly higher serum homocysteine levels and lower folate concentrations than either the patients in remission or controls. The presence of a statistically significant difference in homocysteine concentrations among the three groups was confirmed after adjustment for confounding variables. In a multiple regression model, homocysteine levels were significantly associated with midnight serum cortisol levels (beta = 0.33, P = 0.01), which is the most sensitive marker of endogenous hypercortisolism, and serum folate levels (beta = -0.32, P = 0.02). The distribution of methylene tetrahydrofolate reductase genotypes was not different between patients and controls. In conclusion, active hypercortisolism is associated with hyperhomocysteinemia and reduced serum folate concentrations, whereas the patients in remission have homocysteine concentrations comparable with healthy subjects. Low serum folate concentrations do not fully account for the increase in homocysteine levels that are positively correlated with cortisol levels. Hyperhomocysteinemia may be key to the prothrombotic state and increased cardiovascular risk of Cushing's syndrome.
AB - We evaluated serum homocysteine concentrations and the C677T polymorphism of the gene encoding for methylene tetrahydrofolate reductase, a key enzyme for homocysteine metabolism, in 57 patients with Cushing's syndrome, 41 with active disease, and 16 in remission after successful surgery and 105 blood donors. The patients with active Cushing's syndrome had significantly higher serum homocysteine levels and lower folate concentrations than either the patients in remission or controls. The presence of a statistically significant difference in homocysteine concentrations among the three groups was confirmed after adjustment for confounding variables. In a multiple regression model, homocysteine levels were significantly associated with midnight serum cortisol levels (beta = 0.33, P = 0.01), which is the most sensitive marker of endogenous hypercortisolism, and serum folate levels (beta = -0.32, P = 0.02). The distribution of methylene tetrahydrofolate reductase genotypes was not different between patients and controls. In conclusion, active hypercortisolism is associated with hyperhomocysteinemia and reduced serum folate concentrations, whereas the patients in remission have homocysteine concentrations comparable with healthy subjects. Low serum folate concentrations do not fully account for the increase in homocysteine levels that are positively correlated with cortisol levels. Hyperhomocysteinemia may be key to the prothrombotic state and increased cardiovascular risk of Cushing's syndrome.
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U2 - 10.1210/jc.2004-0079
DO - 10.1210/jc.2004-0079
M3 - Article
C2 - 15292300
AN - SCOPUS:4043175422
VL - 89
SP - 3745
EP - 3751
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 8
ER -