fludrocortisone-acetate and Body-Weight

Escape from the sodium-retaining action of mineralocorticoids coincides with the suppression of plasma renin and angiotensin II levels. The purpose of this study was to evaluate whether blockade of the renin system accelerates this escape. Eight male normotensive volunteers, aged 24--33 yr, were maintained during two subsequent periods of 12 days each, separated by 3--4 weeks, on a constant intake of sodium and potassium of 140 mmol/day. During both periods, fludrocortisone acetate (0.2 mg) was administered orally three times a day on days 4--12. In addition, on days 3--12, either a converting enzyme inhibitor (MK 421;20 mg orally, twice daily) or a placebo was added in double blind fashion and randomized sequence. During both periods, blood pressures were similar; they tended to increase slightly toward day 12. The weight increase did not differ between the two periods. With MK 421, angiotension II levels were significantly lower than with placebo on days 3--6 (P less than 0.001). On the same days, PRA was increased due to converting enzyme blockade. Despite the significantly different angiotensin II levels on days 3--6, daily urinary sodium excretion on all individual days as well as cumulative sodium balance were the same during both periods. Therefore, we could find no evidence in man that suppression of circulating angiotensin II levels is causally related to escape from mineralocorticoid excess.

Topics: Adult; Aldosterone; Angiotensin II; Blood Pressure; Body Weight; Creatinine; Dipeptides; Enalapril; Fludrocortisone; Humans; Male; Natriuresis; Osmolar Concentration; Potassium; Renin

The impact of patient's characteristics on glucocorticoid (GC) replacement therapy in adrenal insufficiency (AI) is poorly evaluated. Aims of this study were to assess the influence of sex and body weight on GC dosing and to describe the choice of GC in AI of different etiologies.. We retrospectively evaluated hydrocortisone (HC) equivalent total daily dose (HC-TDD) and per-kg-daily dose (HC-KDD) in 203 patients (104 primary AI [pAI], 99 secondary AI [sAI]) followed up for ≥ 12 months. They were treated with HC, modified-release HC (MRHC) or cortisone acetate (CA) and fludrocortisone acetate (FCA) in pAI.. At baseline, CA was preferred both in pAI and sAI; at last visit, MRHC was most used in pAI (49%) and CA in sAI (73.7%). Comparing the last visit with baseline, in pAI, HC-TDD and HC-KDD were significantly lower (p = 0.04 and p = 0.006, respectively), while FCA doses increased during follow-up (p = 0.02). The reduction of HC-TDD and HC-KDD was particularly relevant for pAI women (p = 0.04 and p = 0.002, respectively). In sAI patients, no change of HC-KDD and HC-TDD was observed, and we found a correlation between weight and HC-TDD in males (r 0.35, p = 0.02).. Our real-life study demonstrated the influence of etiology of AI on the type of GC used, a weight-based tailoring in sAI, a likely overdosage of GC treatment in pAI women at the start of treatment and the possibility to successfully increase FCA avoiding GC over-treatment. These observations could inform the usual clinical practice.

Topics: Adrenal Insufficiency; Body Weight; Cortisone; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Fludrocortisone; Follow-Up Studies; Glucocorticoids; Hormone Replacement Therapy; Humans; Italy; Male; Middle Aged; Patient Care Management; Retrospective Studies; Risk Adjustment; Risk Assessment; Sex Factors