ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2012) 29 OC7.5

Continuous subcutaneous hydrocortisone infusion (CSHI) as replacement therapy in Addison's disease (AD)

M. Øksnes1,4, S. Bjørnsdottir2, P. Methlie1,4, E. Bratland4, M. Isaksson3, O. Kämpe3, A. Hulting2, S. Bensing2, E. Husebye1,4 & K. Løvås1,4

1Haukeland University Hospital, Bergen, Norway; 2Karolinska Institutet, Stockholm, Sweden; 3Uppsala University Hospital, Uppsala, Sweden; 4University of Bergen, Bergen, Norway.

Background: Conventional glucocorticoid replacement therapy is unphysiological, and does not restore quality-of-life in AD. Here we evaluated the dosing regimens and glucocorticoid metabolism in 10 patients undergoing 24 h sampling during oral replacement therapy and CSHI.

Design, Subjects, Measurements: We set up a cross-over randomised multi-centre clinical trial to evaluate dosage and effects of CSHI in 40 Scandinavian AD patients, comparing 3 months of thrice daily oral hydrocortisone with 3 months on CSHI (NCT 01063569). Doses were adjusted according to serum cortisol 4 h after the morning dose (weight-adjusted oral treatment), and salivary cortisol (body-surface-area(BSA)-adjusted CSHI). Ten of the patients were admitted for 24 h blood sampling to determine whether circadian cortisol rhythm was restored, and to analyse the effects on ACTH levels.

Results: Oral treatment doses (median 0.24 mg/kg/day, range 0.2–0.5; median 10.4 mg/BSA/d, range 7.9–19.3) were slightly lower than CSHI doses (median 0.31 mg/kg/24 h, 0.26–0.5; median 13.1 mg/BSA/24 h, range 10.1–20.1).

Oral treatment yielded high post-dose serum cortisol peaks, whereas CSHI created a smooth circadian cortisol curve with median serum cortisol 472 nmol/L (interquartile range 467–589; 08 h), 336 nmol/L (291–415; 14 h), 141 nmol/L (126–212; 20 h) and 60 nmol/L (42.5–78.2; 02 h). The cortisone rhythm resembled the cortisol rhythm; the principal difference between the treatments was non-detectable levels during night-time on oral treatment, as opposed to a rise in the levels from 02 h on CSHI. Compared with oral treatment CSHI resulted in significantly lower ACTH levels from 06 h (median 49.1 pmol/L (interquartile range 9.0–271) vs 4.0 (1.0–28.6), P=0.011) to 12 h (21.5 pmol/L (2.1–91.6), vs 1.8 (1.0–5.9), P=0.008). Three patients on CSHI had morning ACTH values below the reference range.

Conclusion: CSHI safely established circadian cortisol rhythm in AD patients, which resulted in more normal ACTH levels. We suggest that with physiological replacement therapy ACTH is the appropriate effect parameter for individualisation of dose.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.

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