The low-dose (1 mg) adrenocorticotropin stimulation test in kidney and kidney–pancreas transplant patients: a potential guideline for steroid withdrawal M Baz-Hecht a , E Osher a , T Yachnin b , R Nakache b , G Nakache b , K Tordjman a and NStern a a Institute of Endocrinology, Metabolism and Hypertension and b The Unit of Organ Transplantation, Sackler Faculty of Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel Baz-Hecht M, Osher E, Yachnin T, Nakache R, Nakache G, Tordjman K, Stern N. The low-dose (1 mg) adrenocorticotropin stimulation test in kidney and kidney–pancreas transplant patients: a potential guideline for steroid withdrawal. Clin Transplant 2005 DOI: 10.1111/j.1399-0012.2005.00443.x r Blackwell Munksgaard, 2005 Abstract: Chronic steroid treatment is known to impair the hypothalamic–pituitary adrenal axis (HPA) but the need to assess HPA function prior to withdrawal of steroid therapy in post-transplant patients has not been uniformly accepted. We evaluated the status of the HPA axis in 48 kidney or kidney–pancreas transplant patients who were considered for possible discontinuation of glucocorticoid therapy using a recently validated dynamic test of HPA integrity, the low-dose (1 mg) adrenocorticotropin (ACTH) test. HPA suppression was detected in 29 (60%) of the patients, four of which had severe hypoadrenalism prohibitive of steroid withdrawal. Neither the duration of steroid treatment nor 8:00 AM serum cortisol was a useful marker of hypoadrenalism. 8:00 AM cortisol in subjects with normal HPA reserve and subjects with partial hypoadrenalism overlapped considerably but levels o5 mg/dL were indicative of severe hypoadrenalism. Pre-withdrawal diagnosis of partial hypoadrenalism allowed the identification of subjects requiring no further steroid replacement under regular daily circumstances. However glucocorticoid supplementation was prescribed in the event of stress such as infection, exceptional effort, trauma or surgery. Individuals with partial HPA impairment, but not patients with severe HPA suppression, improved upon retesting 3 months later. Patients exhibiting normal response to 1 mcg ACTH enjoyed an uneventful course following steroid withdrawal. Since hypoadrenalism is extremely common in post-transplant patients, we recommend the use of the low-dose ACTH test as a convenient method to identify patients with various degrees of hypoadrenalism prior to steroid withdrawal. Long-term treatment with corticosteroids may sup- press normal pituitary–adrenal axis function and expose the patient to risk if corticosteroids are with- drawn, especially under stressful conditions such as surgery or severe infection. Corticosteroids have been a part of anti-rejection treatment since the be- ginning of solid organ transplantation. To minimize unfavorable metabolic side effects with long-term treatment, multiple protocols have been proposed for the withdrawal of corticosteroids at various intervals after transplantation (1–7). The adrenocorticotropin (ACTH) test is used to assess hypothalamic–pituitary–adrenal (HPA) reserve. Traditionally, this test was based on the use of a high dose of ACTH (250 mg). Following the intravenous administration of this dose, circulating ACTH levels increase much above the concen- trations of endogenous ACTH observed under Clin Transplant 2005 DOI: 10.1111/j.1399-0012.2005.00443.x Copyright r Blackwell Munksgaard 2005 Clinical Transplantation Key words: adrenocorticotropin test – kidney/ kidney–pancreas transplantation – steroid withdrawal Corresonding author: Merav Baz Hecht MD, 15 Winthrop Rd, Brookline, MA, 02445, USA. Tel.: 1 1 617 566 1131; fax: 1 1 413 502 4628; e-mail: meravbh@comcast.net Accepted for publication 29 July 2005 72