Effects of Hydrocortisone on the Regulation of Blood Pressure: Results From a Randomized Controlled Trial

• Published in: The journal of clinical endocrinology and metabolism 2016-10, Vol.101 (10), p.3691-3699
• Main Authors: Werumeus Buning, Jorien, van Faassen, Martijn, Brummelman, Pauline, Dullaart, Robin P. F, van den Berg, Gerrit, van der Klauw, Melanie M, Kerstens, Michiel N, Stegeman, Coen A, Muller Kobold, Anneke C, Kema, Ido P, Wolffenbuttel, Bruce H. R, van Beek, André P
• Format: Article
• Language: English
• Subjects: 11-beta-Hydroxysteroid Dehydrogenases - drug effects; Adrenal Insufficiency - drug therapy; Adult; Aged; Blood Pressure - drug effects; Cross-Over Studies; Glucocorticoids - administration & dosage; Glucocorticoids - adverse effects; Glucocorticoids - pharmacology; Hormone Replacement Therapy - adverse effects; Humans; Hydrocortisone - administration & dosage; Hydrocortisone - adverse effects; Hydrocortisone - pharmacology; Middle Aged; Normetanephrine - blood; Renin-Angiotensin System - drug effects; Treatment Outcome; Young Adult
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2016-2216

Context: 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. This randomized double-blind crossover study showed that two different physiological doses of hydrocortisone affect blood pressure and regulatory mechanisms.