Sulfur amino acids in Cushing's disease: insight in homocysteine and taurine levels in patients with active and cured disease.
BACKGROUND
Cushing's syndrome is associated with an increased cardiovascular risk. Although a series of cardiovascular risk factors have been identified, sulfur amino acids (SAAs), recently indicated as independent cardiovascular risk factors, have been poorly investigated in patients with Cushing's syndrome.


OBJECTIVE
The aim of this cross-sectional controlled study was to evaluate serum and urinary levels and urinary excretion rate (ER) of SAAs in patients with Cushing's disease (CD) during the active disease and after long-term disease remission.


METHODS
Forty patients with CD (20 with active disease and 20 with cured disease for at least 5 yr) and 40 controls entered the study. Serum and urinary concentrations and urinary ER of SAAs, namely methionine, cystine, homocysteine, and taurine, were measured by means of cationic exchange HPLC. Serum folic acid and vitamin B12 levels were also evaluated in patients and controls and correlated to SAA levels.


RESULTS
CD patients with active disease had higher serum and urinary concentrations of cystine and homocysteine, and lower serum and higher urinary concentrations and ER of taurine than cured patients and controls. Vitamin B12 levels were significantly decreased in patients with active disease compared with cured patients and controls, whereas folic acid levels were slightly decreased in patients than in controls. In patients with active CD, urinary cortisol concentrations were significantly and inversely correlated to serum taurine and directly correlated to taurine urinary ER, and fasting serum glucose levels were significantly correlated to taurine urinary ER. At the multiple regression analysis, urinary cortisol concentrations were the best predictors of taurine ER.


CONCLUSIONS
CD is associated with hyperhomocysteinemia and hypotaurinemia. Glucocorticoid excess, acting directly or indirectly, seems to be the most responsible for this imbalance in SAA levels. The long-term disease remission is accompanied by normalization of SAA levels. Hyperhomocysteinemia and hypotaurinemia might contribute to the increased cardiovascular risk of CD.
Faggiano
Antongiulio
A
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Via Sergio Pansini 5, 80131 Naples, Italy.
Melis
Daniela
D
Alfieri
Raffaele
R
De Martino
MariaCristina
M
Filippella
Mariagiovanna
M
Milone
Francesco
F
Lombardi
Gaetano
G
Colao
Annamaria
A
Pivonello
Rosario
R
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D003553:Cystine / Q000097:blood; D003555:Cystinuria; D005215:Fasting / Q000097:blood; D005260:Female; D006710:Homocysteine / Q000097:blood* / Q000652:urine*; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D047748:Pituitary ACTH Hypersecretion / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy; D012074:Remission Induction; D013654:Taurine / Q000097:blood* / Q000652:urine*
D001786:Blood Glucose; D006710:Homocysteine; D013654:Taurine; D003553:Cystine; D006854:Hydrocortisone