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Low- and Standard-Dose Corticotropin and Insulin Hypoglycemia Testing in the Assessment of Hypothalamic-Pituitary-Adrenal Function after Pituitary Surgery

Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast BT12 6BA, United Kingdom

Address all correspondence and requests for reprints to: Professor A. B. Atkinson, Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, United Kingdom, BT12 6BA. E-mail: ab.atkinson{at}royalhospitals.n-i.nhs.uk.

The optimal means of assessing the integrity of the hypothalamic-pituitary-adrenal (HPA) axis after pituitary surgery remains controversial. We compared low-dose (1 µg iv) and standard-dose (250 µg im) corticotropin tests performed 1 and 4–6 wk after pituitary surgery with an insulin hypoglycemia test performed at 4–6 wk.

Forty-one patients (21 male and 20 female; median age, 52 yr; range, 23–73 yr) who had undergone pituitary surgery were studied (Cushing’s disease excluded). Twenty-two of the 41 patients had normal cortisol responses to all tests both at 1 and 4–6 wk after surgery. Eight patients had subnormal cortisol responses to all tests. Of the 11 patients with discrepant results, seven had subnormal responses only after the low-dose corticotropin test; the remaining four patients had borderline responses to one or more tests. At 4–6 wk after surgery, subjects with a 30-min serum cortisol after standard-dose corticotropin of less than 350 nmol/liter (12.7 µg/dl) consistently had a subnormal response to hypoglycemia, and those with a serum cortisol greater than 650 nmol/liter (23.6 µg/dl) had a normal response to hypoglycemia.

Definitive testing of the HPA axis using the standard-dose corticotropin test can be carried out provided it is performed at least 4 wk after pituitary surgery. A 30-min cortisol level greater than 650 nmol/liter (23.6 µg/dl) indicates adequacy of the HPA axis, and a level of less than 350 nmol/liter (12.7 µg/dl) indicates ACTH deficiency. No further testing is then required. An intermediate level of 350–650 nmol/liter (12.7–23.6 µg/dl) warrants further assessment using the insulin hypoglycemia test.

During the course of the study, C.H.C. was in receipt of a Royal Victoria Hospital Belfast Research Fellowship.

Abbreviation: HPA, Hypothalamic-pituitary-adrenal.

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