Adrenal insufficiency is common amongst kidney transplant recipients receiving maintenance prednisolone and can be predicted using morning cortisol

Abstract

Background Long-term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTR), leading to significant cumulative glucocorticoid exposure. The aims of this study are to investigate the prevalence of adrenal insufficiency (AI) in KTR taking prednisolone and to develop a screening algorithm to identify patients at highest risk of AI. Methods In this cross-sectional cohort study, 67 KTR receiving prednisolone underwent a short synacthen test (SST) and measurement of cumulative glucocorticoid exposure. Results 72% (n = 48) of participants failed the SST. Participants with AI had a higher daily prednisolone dose (4.9 vs 4.2mg/day, p = 0.002) and greater cumulative glucocorticoid exposure (289 vs 111mg/kg, p = 0.03) than those with intact adrenal function. Participants with AI had a lower baseline cortisol than participants with intact adrenal function (143 vs 303nmol/l, p < 0.001). Morning cortisol of > 288nmol/l predicted a normal SST with 100% specificity (95% CI 92–100%) and 70% sensitivity (95% CI 56–78%), therefore excluding AI. Conclusions Our results suggest KTR are at higher risk for AI than previously reported. A morning serum cortisol measurement is a useful screening tool in this cohort, reducing the need for stimulatory testing by 44%. KTR with AI need education regarding glucocorticoid sick rules similar to patients with other forms of AI.

Adrenal insufficiency in hemodialysis patients—An under‐recognized problem: A case series

“…The gold standard for diagnosing adrenal insufficiency is the short synacthen test, 1 however there are challenges to its widespread use and interpretation. Resource limitations restrict use as a screening tool and it is best performed when glucocorticoid therapy is stopped which may not be feasible 9 . There is limited data regarding the best time to perform the test, with dialysis clearance of free cortisol causing lower cortisol concentration during hemodialysis compared with after the session 6 .…”

“…9 The pharmacokinetic interaction between exogenous glucocorticoids and calcineurin inhibitors has been suggested as a risk factor, with in vitro studies linking high prednisone tissue exposure in patients receiving tacrolimus to alterations in corticosteroid metabolism. 9 While a causal link remains unclear, B2 microglobulin amyloid depositions have been found on adrenal biopsy of patients who required hemodialysis. 10 As such, patients with renal disease are at risk for the development of adrenal hypofunction.…”

“…Resource limitations restrict use as a screening tool and it is best performed when glucocorticoid therapy is stopped which may not be feasible. 9 There is limited data regarding the best time to perform the test, with dialysis clearance of free cortisol causing lower cortisol concentration during hemodialysis compared with after the session. 6 Increased cortisol levels have been noted during the subsequent 4 h due to counterregulatory ACTH secretion.…”

“…Additional risk factors for the development of adrenal insufficiency in patients with renal disease include the presence of uremia, hypoalbuminemia and reduced protein binding which causes increased free prednisone bioavailability 9 . The pharmacokinetic interaction between exogenous glucocorticoids and calcineurin inhibitors has been suggested as a risk factor, with in vitro studies linking high prednisone tissue exposure in patients receiving tacrolimus to alterations in corticosteroid metabolism 9 . While a causal link remains unclear, B2 microglobulin amyloid depositions have been found on adrenal biopsy of patients who required hemodialysis 10 .…”

Hyponatraemia and the syndrome of inappropriate antidiuresis (SIAD) in cancer

“…A largely unexplored field of oncology is the potential for high-dose corticosteroid therapy, used to supplement chemotherapy, to cause adrenal suppression. Immunosuppressive steroids have been reported to cause adrenal suppression in a spectrum of clinical conditions ( Dineen et al 2019 , Tomkins et al 2022 ), which is often unrecognised. Patients prescribed immunosuppressive steroids for inflammatory conditions are also much less likely than endocrine patients to be made aware of sick day rules or to carry steroid warning cards ( Salehmohamed et al 2018 ), so the potential vulnerability to adrenal crisis in this situation is considerable ( Dineen et al 2019 ).…”