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Blood pressure increases with high hydrocortisone doses
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High-dose hydrocortisone therapy — even within physiologic levels — increases blood pressure and affects several related systems, including the renin-angiotesnin-aldosterone system, 11 beta-hyroxysteroid dehrydrogenase enzyme activity and sympathetic nerve activity in patients with secondary adrenal insufficiency.
In a subanalysis of a double blind, cross-over study designed to evaluate cognitive effects of two doses of hydrocortisone, Jorien Werumeus Buning, MSc, of the University of Gronigen, University Medical Center Gronigen in the Netherlands, and colleagues evaluated effects on blood pressure and BP-regulation systems. Researchers analyzed data from 47 adults (29 men; mean age, 51 years) with secondary adrenal insufficiency randomly assigned to 0.2 mg to 0.3 mg hydrocortisone/kg body weight followed by 0.4 mg to 0.6 mg hydrocortisone/kg body weight, or the reverse, each for 10 weeks.
On average, during the low-dose condition participants received 17.9 mg hydrocortisone per day and 35.8 mg hydrocortisone per day during the high-dose condition.
Compared with the lower hydrocortisone dose, the higher dose resulted in higher plasma total cortisol levels 1 hour (median difference, 233 nmol/L) and 5 hours (100 nmol/L) after administration (P < .001 for both), and higher plasma free cortisol levels 1 hour (median difference, 31 nmol/L) and 5 hours (median difference, 4 nmol/L) after administration (P < .01 for both).
Following the higher hydrocortisone dose, systolic BP increased by 5 mm Hg (P = .011) and diastolic BP increased by 2 mm Hg (P = .05) compared with the lower dose.
Compared with the lower dose, the higher dose led to decreases in plasma renin (-1.3 pg/mL; P = .051), aldosterone (-28 pmol/L; P = .02) and aldosterone-to-renin ratio (-2.7 pmol/ng; P = .044).
Compared with the lower dose, the higher dose yielded a decrease in plasma free normetanephrine concentrations (median decrease, -0.101 nmol/L (P < .01), in free normetanephrine in 24-hour urinary samples (median difference, -1.48 µmol/mol creatinine; P < .011), and in free 3-methoxytyramine (median difference, -2.2 µmol/mol creatinine; P < .001).
“A complex balancing of the harms and benefits needs to be made in the individualization of substitution therapy in patients with [secondary adrenal insufficiency],” the researchers wrote. “We suggest to use the lowest dose possible that relieves symptoms of [glucocorticoid] deficiency, to prevent the observed negative side effects of higher doses of [glucocorticoids]. However, in light of our previous paper that showed improved [quality of life] after higher substitution doses, an increase in dose should be considered when necessary or desirable.”– by Amber Cox
Disclosure: The researchers report no relevant financial disclosures.
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