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Letter re: HPA Axis Testing after Pituitary Surgery

Consultant Physician/Reader in Medicine (P.L.P.); Moncrieff-Arnott Professor of Molecular Medicine (J.R.S.); British Heart Foundation Senior Research Fellow and Professor of Endocrinology (B.R.W.); and Specialist Registrar in Diabetes and Endocrinology (H.K.G.), Western General Hospital, The University of Edinburgh, Edinburgh EH4 2XU, Scotland, United Kingdom

Address correspondence to: Dr. P. L. Padfield, Endocrine Unit, Department of Medical Sciences, Western General Hospital, The University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, Scotland, United Kingdom. E-mail: Paul.Padfield{at}luht.scot.nhs.uk.

To the editor:

Courtney et al. (1) describe testing of the hypothalamic-pituitary-adrenal (HPA) axis 4–6 wk after pituitary surgery and report discrepancies between the plasma cortisol response to a standard (250 µg) short synacthen test (SST) and to insulin-induced hypoglycemia (ITT) in 11 of 41 patients. However, there were only three patients (I, J, and K in Table 1) in whom the 30-min cortisol result during the SST was discrepant from the ITT. To argue that patients would have been mismanaged if decisions had been based on their SST result is critically dependent on the cut-off used to define a "normal" cortisol. For the SST, their figure of 500 nmol/liter (18.1 µg/dl) was based on studies in 16 normal volunteers, whereas for the ITT they used the "historical" cut-off at 550 nmol/liter (19.9 µg/dl). Our earlier survey of UK endocrinologists (2) suggested that 550 was an archaic figure based upon very different assays for cortisol than are used currently. Our cut-off for the standard SST is a 30-min cortisol of 460 nmol/liter (16.7 µg/dl), extrapolated from previous normative data and corrected for changes in assay methodology. Thus, it is our contention that these three patients probably had normal HPA axes and repeat testing might have been a better management plan for J and K than lifelong glucocorticoid therapy.

Courtney et al. (1) advised practicing endocrinologists that patients who have recently had pituitary surgery and undergone a standard SST should be considered normal if their cortisol response is above 650 nmol/liter (23.6 µg/dl) and subnormal if less than 350 nmol/liter (12.7 µg/dl). For intermediate values, they argue that an ITT is indicated. Our own experience (3) suggests that by following this advice 24% of patients (21 in our series of 80) undergoing a standard SST after pituitary surgery would require an ITT; however, only one patient out of 14 with a cortisol response to SST above 460 nmol/liter (16.7 µg/dl) but less than 650 nmol/liter (23.6 µg/dl) required hydrocortisone replacement in the year after surgery. We conclude that the clinical gain of performing an ITT in such patients is small, whereas the hazards are significant. We agree with Courtney et al. (1), however, that there may be benefit in further testing of patients with a borderline "fail" SST to ensure that lifelong hydrocortisone replacement is justified.

We believe that the data from Courtney et al. (1) emphasize that the SST is a safe and effective measure of HPA axis function a few weeks after pituitary surgery. Overreliance on arbitrary threshold "pass-fail" cortisol levels overvalues the precision of assays and "normal ranges." The algorithm presented would lead to many unnecessary ITTs.

Footnotes

A response to this letter was invited, but the authors of the original article chose not to provide one.

Received December 15, 2004.

References

1. Courtney CH, McAllister AS, Bell PM, McCance DR, Leslie H, Sheridan B, Atkinson AB 2004 Low- and standard-dose corticotropin and insulin hypoglycemia testing in the assessment of hypothalamic pituitary-adrenal function after pituitary surgery. J Clin Endocrinol Metab 89:1712–1717[Abstract/Free Full Text]
2. Stewart PM, Corrie J, Seckl JR, Edwards CR, Padfield PL 1988 A rational approach for assessing the hypothalamo-pituitary-adrenal axis. Lancet 1:1208–1210[CrossRef][Medline]
3. Gleeson HK, Walker BR, Seckl JR, Padfield PL 2003 Ten years on: safety of short synacthen tests in assessing adrenocorticotropin deficiency in clinical practice. J Clin Endocrinol Metab 88:2106–2111[Abstract/Free Full Text]

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