Cardiovascular risk is increased in patients with secondary adrenal insufficiency, which may be ascribed to an unfavorable metabolic profile consequent to a relatively high hydrocortisone replacement dose.Objective:
We determined the effects of a higher versus a lower glucocorticoid replacement dose on blood pressure (BP), the renin-angiotensin-aldosterone system, 11β-hydroxysteroid dehydrogenase enzyme activity and circulating (nor)metanephrines.Design, Setting, and Patients:
Forty-seven patients with secondary adrenal insufficiency from the University Medical Center Groningen participated in this randomized double-blind crossover study.Interventions:
Patients randomly received 0.2–0.3 mg hydrocortisone/kg body weight followed by 0.4–0.6 mg hydrocortisone/kg body weight, or vice versa, each during 10 weeks.Main Outcome Measure(s):
BP and regulating hormones were measured.Results:
The higher hydrocortisone dose resulted in an increase in systolic BP of 5 (12) mm Hg (P = .011), diastolic BP of 2 (9) mm Hg (P = .050), and a median [interquartile range] drop in plasma potassium of −0.1 [−0.3; 0.1] nmol/liter (P = .048). The higher hydrocortisone dose led to decreases in serum aldosterone of −28 [−101; 9] pmol/liter (P = .020) and plasma renin of −1.3 [−4.5; 1.2 ] pg/mL (P = .051), and increased the ratio of plasma and urinary cortisol to cortisone (including their metabolites) (P < .001 for all). Furthermore, on the higher dose, plasma and urinary normetanephrine decreased by −0.101 [−0.242; 0.029] nmol/liter (P < .001) and −1.48 [−4.06; 0.29] μmol/mol creatinine (P < .001) respectively.Conclusions:
A higher dose of hydrocortisone increased systolic and diastolic BP and was accompanied by changes in the renin-angiotensin-aldosterone system, 11β-hydroxysteroid dehydrogenase enzyme activity, and circulating normetanephrine. This demonstrates that hydrocortisone dose even within the physiological range affects several pathways involved in BP regulation.