Authors: Merza Z. Rostami-Hodjegan A. Memmott A. Doane A. Ibbotson V.

Newell-Price J. Tucker GT. Ross RJ.

Institution: Division of Clinical Sciences (North), The University of Sheffield,

Sheffield, UK.

Title: Circadian hydrocortisone infusions in patients with adrenal insufficiency

and congenital adrenal hyperplasia.

Source: Clinical Endocrinology. 65(1):45-50, 2006 Jul.

Abstract:

OBJECTIVE: Conventional hydrocortisone therapy in adrenal insufficiency

cannot provide physiological replacement. We have explored the potential

of circadian delivery of hydrocortisone as proof of concept for such

therapy delivered in modified-release tablet formulation. METHODS: We

investigated whether the circadian intravenous infusion of hydrocortisone

could improve control of ACTH and androgen levels. Two healthy subjects,

two patients with Addison’s disease and two patients with congenital

adrenal hyperplasia (CAH) were studied. RESULTS: In patients on thrice

daily oral hydrocortisone, peak serum cortisol levels were higher than in

normal subjects and overnight levels were very low. Patients had very high

plasma ACTH levels before their morning dose of hydrocortisone, both at

the beginning and at the end of their conventional oral therapy: mean +/-

SEM 311.8 +/- 123.2 and 311.2 +/- 85.4 ng/l, respectively. In the patients

with CAH, serum 17-hydroxyprogesterone levels were also elevated: 550 and

642 nmol/l at the beginning and 550 and 777 nmol/l at the end of

conventional treatment, respectively. The overall 24-h mean cortisol

levels were similar for conventional oral hydrocortisone and the circadian

infusion. At 0700 h, ACTH levels were much higher on conventional

treatment than after circadian infusion: mean +/- SEM 311.2 +/- 85.4 vs.

70.5 +/- 45.0 ng/l, respectively (P < 0.05). The same pattern was observed

in 17-hydroxyprogesterone levels, which were 550 and 777 nmol/l after

conventional treatment and 3 and 64 nmol/l after circadian infusion.

CONCLUSIONS: In patients with poor biochemical control of Addison’s

disease and CAH, a 24-h circadian infusion of hydrocortisone can decrease

morning ACTH and 17-hydroxyprogesterone levels to near normal.