21 Citations (Scopus)

Abstract

CONTEXT: Cardiovascular risk is increased in patients with secondary adrenal insufficiency (SAI), 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 (RAAS), 11β-hydroxysteroid dehydrogenase (11β-HSD) enzyme activity and circulating (nor)metanephrines.

DESIGN, SETTING AND PATIENTS: Forty-seven patients with SAI 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.

RESULTS: The higher hydrocortisone dose resulted in an increase in systolic BP of 5(12) mmHg (P=0.011), diastolic BP of 2(9) mmHg (P=0.050), and a median [interquartile range] drop in plasma potassium of -0.1[-0.3; 0.1] nmol/L (P=0.048). The higher hydrocortisone dose led to decreases in serum aldosterone of -28[-101; 9] pmol/L (P=0.020) and plasma renin of -1.3[-4.5; 1.2] pg/mL (P=0.051), and increased the ratio of plasma and urinary cortisol to cortisone (including their metabolites) (P<0.001 for all). Furthermore, on the higher dose plasma and urinary normetanephrine decreased by -0.101[-0.242; 0.029] nmol/L (P<0.001) and -1.48[-4.06; 0.29] μ mol/mol creatinine (P<0.001) respectively.

CONCLUSIONS: A higher dose of hydrocortisone increased systolic and diastolic BP and was accompanied by changes in the RAAS, 11β-HSD enzyme activity and circulating normetanephrine. This demonstrates that hydrocortisone dose even within the physiological range affects several pathways involved in BP regulation.

Original languageEnglish
Pages (from-to)3691-3699
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume101
Issue number10
Early online date4-Aug-2016
DOIs
Publication statusPublished - 1-Oct-2016

Keywords

  • TANDEM MASS-SPECTROMETRY
  • SOLID-PHASE EXTRACTION
  • 11-BETA-HYDROXYSTEROID DEHYDROGENASE
  • CARDIOVASCULAR-DISEASE
  • GLUCOCORTICOID REPLACEMENT
  • PREMATURE MORTALITY
  • INDUCED HYPERTENSION
  • INSULIN SENSITIVITY
  • SERUM CORTISOL
  • IN-VIVO

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