title: Effects of Hydrocortisone on the Regulation of Blood Pressure: Results From a Randomized Controlled Trial.
abstract: 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.
  
  
  
  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.
  
  
  
  Forty-seven patients with secondary adrenal insufficiency from the University Medical Center Groningen participated in this randomized double-blind crossover study.
  
  
  
  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.
  
  
  
  BP and regulating hormones were measured.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jorien
authors.initials: J
authors.lastname: Werumeus Buning
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: van Faassen
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Pauline
authors.initials: P
authors.lastname: Brummelman
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: van den Berg
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Melanie M
authors.initials: MM
authors.lastname: van der Klauw
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Michiel N
authors.initials: MN
authors.lastname: Kerstens
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Coen A
authors.initials: CA
authors.lastname: Stegeman
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Muller Kobold
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Ido P
authors.initials: IP
authors.lastname: Kema
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.affiliation: Department of Endocrinology (J.W.B., P.B., R.P.F.D., G.v.d.B., M.M.v.d.K., M.N.K., A.P.v.B.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Laboratory Medicine (M.v.F., A.C.M.K., I.P.K.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands; Department of Nephrology (C.A.S.), University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: André P
authors.initials: AP
authors.lastname: van Beek
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000187:drug effects*; D000309:Adrenal Insufficiency / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008875:Middle Aged; D009647:Normetanephrine / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D009647:Normetanephrine; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone