digoxin and Cushing-Syndrome

We encountered a case of a pregnant woman with adrenal causes of Cushing's syndrome who exhibited congestive heart failure as an initial symptom. Since the patient was also a diabetic, we treated her with high levels of diuretics and insulin. Echocardiography revealed a remarkable thickening of the left ventricle without asymmetric hypertrophy. The diagnosis of Cushing's syndrome caused by adrenal adenoma was confirmed by the endocrinological data and magnetic resonance imaging. The right adrenal adenoma was removed in the 28th week of pregnancy. After the operation, her congestive heart failure and hyperglycemia dramatically improved. Five weeks after the operation, she delivered a normal infant by caesarean section without complications. Only 4 months after delivery, the thickening of her left ventricle was normalized. We consider that the progression of her left ventricular hypertrophy induced by the changes in hemodynamic load during pregnancy may have been augmented by the excess of plasma cortisol. Operative therapy may be recommended for pregnant Cushing's syndrome patients with severe hypercortisolism complicating congestive heart failure.

Topics: Adenoma; Adrenal Gland Neoplasms; Adrenalectomy; Adult; Antihypertensive Agents; Cardiotonic Agents; Circadian Rhythm; Cushing Syndrome; Digoxin; Diuretics; Dopamine; Echocardiography; Electrocardiography; Female; Furosemide; Heart Failure; Humans; Hydrocortisone; Hypoglycemic Agents; Insulin; Oxygen Inhalation Therapy; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Neoplastic; Pregnancy in Diabetics

We here report a reversed-phase HPLC method for the determination of free cortisol in human urine, using methylprednisolone as the internal standard. Before chromatography, samples were extracted with a C18 solid-phase extraction column and the steroids were separated on a LiChrospher 100 C18 column with a mobile phase of methanol/acetonitrile/water (43/3/54 by vol). Linearity, precision, and accuracy of the method were established. The detection limit was 10 pmol of cortisol, and total CVs were < 8%. With various solid-phase extraction columns the recovery of cortisol was 36-97%; recovery of the internal standard was 43-85%. Study of interference by 6 other steroids and metabolites and 24 drugs showed that carbamazepine and digoxin partly overlapped with cortisol, but this interference could be reduced by modification of the mobile phase. The HPLC method was compared with an RIA and an automated immunoassay method. The results obtained by HPLC averaged 40% of the RIA values.

Topics: Calibration; Carbamazepine; Chromatography, High Pressure Liquid; Cushing Syndrome; Digoxin; Humans; Hydrocortisone; Immunoassay; Methylprednisolone; Radioimmunoassay; Reference Values; Regression Analysis; Reproducibility of Results; Sensitivity and Specificity; Steroids

In order to investigate the effect of chronic hypercortisolaemia on endogenous natriuretic factors (atrial natriuretic hormone (ANH) and the Na+/K+ pump inhibitor) digitalis-like substance (DLS), and their relation to hypertension, 28 patients with pituitary- or adrenal-dependent Cushing's syndrome and six patients on high-dose prednisone treatment were studied. Plasma ANH levels were increased in patients with Cushing's syndrome (36.0 +/- 1.4 (S.E.M.) ng/l) compared with those in healthy controls (28.6 +/- 1.3 ng/l, P less than 0.01). In prednisone-treated patients, ANH levels (43.8 +/- 4.5 ng/l) were higher than those in patients with Cushing's syndrome and in controls (P less than 0.05 and P less than 0.01 respectively). DLS measured by radioimmunoassay and binding of [3H]ouabain to erythrocytes was not altered in patients with hypercortisolaemia. Slightly decreased DLS activity in the erythrocyte 86Rb uptake inhibition assay was found in patients with Cushing's syndrome (52.9 +/- 2.7%) compared with that in controls (60.9 +/- 1.8%, P less than 0.02). With the exception of cortisol (r = 0.52, P less than 0.01), none of the other factors determined correlated with the mean arterial pressure in patients with Cushing's syndrome. Thus, a chronic excess of endogenous and exogenous glucocorticoids increases plasma levels of ANH, but does not substantially influence DLS activity or plasma levels. Neither natriuretic factor is directly related to hypertension in Cushing's syndrome.

Topics: Adult; Blood Proteins; Cardenolides; Cushing Syndrome; Digoxin; Female; Humans; Hydrocortisone; Hypertension; Male; Middle Aged; Natriuretic Agents; Prednisolone; Saponins; Sodium-Potassium-Exchanging ATPase