Tuesday, March 3, 2009

A subnormal peak cortisol response to stimulation testing does not predict a subnormal cortisol production rate

From http://jcem.endojournals.org/cgi/content/abstract/jc.2008-2392v1


Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2008-2392

A N Paisley, S V Rowles, D Brandon,  and P J Trainer*

Department of Endocrinology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK; Department of Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97201, USA

* To whom correspondence should be addressed. E-mail: peter.trainer@man.ac.uk.

Introduction: The decision to commence life-long glucocorticoid replacement therapy is often based on a cortisol stimulation test. We investigated the relationship between the peak cortisol response to insulin-induced hypoglycemia and daily cortisol production rate (CPR) to ascertain if provocative tests are accurate in indicating the need to initiate life-long glucocorticoid replacement.

Patients and Methods: Ten patients (5 male, mean age 44±13 yrs) with pituitary disease, with demonstrably suboptimal peak cortisol response (350–500 nmol/L) to insulin-induced hypoglycemia, underwent CPR measurement by isotope dilution using gas chromatography-mass spectrometry and 24 hour urinary free cortisol (UFC).

Results: The median baseline and peak cortisol attained with hypoglycemia was 284 (164–323) and 473.5 (366–494) nmol/L, respectively. A strong positive correlation was seen between peak stimulated cortisol and CPR (adjusted for body surface area)(r = 0.75, P = 0.02) and in all patients CPR (4.6 (2.9–15.1) mg/day per m2) was within the reference range (2.1–12 mg/day per m2) or elevated (1 patient). A wide range was found for 24 hr UFC (116.5 (20.5–265.9) nmol/L) in this group of patients, and this parameter lacked significant correlation with either serum cortisol concentration or CPR.

Conclusion: This is the first study to demonstrate a significant correlation between CPR and peak cortisol values during hypoglycemic challenge. An inadequate cortisol response to hypoglycemia suggests the need for glucocorticoid cover at times of stress, but these data indicate that a sub-optimal peak cortisol does not equate to a low CPR and should not be an automatic indication for life-long glucocorticoid replacement therapy. UFC bears no relation to serum cortisol or CPR and is therefore unhelpful in assessment of such patients.

Key words: Hypopituitarism • cortisol production rate