Effect of ACTH deficiency and hydrocortisone replacement dose on mortality in patients with acromegaly
M Sherlock1, RC Reulen2, A Aragon Alonso1, J Ayuk1, RN Clayton3, MC Sheppard1, MM Hawkins2, A Bates4 & PM Stewart1
Author affiliations
1School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham, UK; 2Department of Public Health & Epidemiology, Centre for Childhood Cancer Survivor Studies, University of Birmingham, Birmingham, UK; 3Department of Postgraduate Medicine, University of Keele, Hartshill, Stoke-on-Trent, UK; 4Birmingham Heartlands and Solihull NHS Trust, Birmingham, UK.
Acromegaly and hypopituitarism are associated with elevated standardised mortality ratios (SMR) of between 1.3–3 and 1.2–2.17, respectively. There is little data on the role of hypopituitarism and in particular ACTH deficiency on mortality in patients with acromegaly and less still known about the role of hydrocortisone (HC) replacement. There is data to suggest that previous HC regimens may have overestimated normal cortisol production rates and recent data that higher doses of HC are associated with detrimental cardiovascular risk profiles.
Using the west midlands acromegaly database (n=501, 275 female) we assessed the influence of ACTH deficiency and hydrocortisone therapy on mortality in patients with acromegaly. Of 214/501 were ACTH deficient (ACTHD), 79 received hydrocortisone (HC) at doses of <25 mg/ day and 135 received HC at doses of >25 mg/day. The median duration of follow up was 13.9 years (IQR 7.9–21 years).
The SMR in the ACTHD group was 2.5 (1.9–3.2, P<0.0005). On internal analysis (adjusted for age, sex, calendar period, follow up period, radiotherapy) within the acromegaly cohort the relative risk of mortality was 1.7 (1.2–2.4) in the ACTHD group (P=0.004). In the ACTHD group a higher dose of hydrocortisone was associated with increased mortality (with a threshold for increased mortality of >25 mg/day (Table 1).
In summary, ACTHD is associated with significantly increased mortality in patients with acromegaly. In ACTHD patients a daily dose of >25 mg hydrocortisone is associated with increased mortality. This data raises important questions regarding optimum hydrocortisone therapy for patients with acromegaly.
Likelihood ratio test for linear trend in relative risks P=0.002.