Endocrine Abstracts

Introduction

Corticosteroids are included in the maintenance immunosuppressive regimen in most kidney transplant recipients. Studies evaluating the effect of chronic low-dose glucocorticoid treatment on the hypothalamic-pituitary-adrenal (HPA) axis and the metabolic profile of these patients are limited.

Aim

The objective of the study was to evaluate the metabolic effects and the alterations of HPA axis regulation in stable kidney transplant recipients treated with long-term low-dose glucocorticoids.

Methods

A cross-sectional study was conducted including adult kidney transplant recipients on a stable immunosuppressive regimen followed in our center. Selected patients were transplanted for over a year and maintained an estimated glomerular filtration rate (eGFR)>54 ml/min/1.73 m² (CKD-EPI equation). Examined metabolic abnormalities included new-onset diabetes mellitus after transplantation (NODAT), central obesity and dyslipidemia as defined by IDF criteria. HPA axis evaluation encompassed measurements of morning (0800 hours) serum cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone-sulphate (DHEAS) levels; 24-hour urine free cortisol excretion (UFC) and hair cortisol levels (HC). HC samples (2 cm length) were collected according to SoHT guidelines and measured by liquid chromatography tandem–mass spectrometry (LC–MS/MS). All hormonal functional tests were performed in the same laboratory. An intergroup analysis between patients who received glucocorticoids and those who did not was performed.

Results

Sixty-four kidney transplant recipients (males 67.2%) with a mean age of 53 ± 13.4 years and a median time from transplantation of 71 (IQR 25–147) months were included in the study. The mean eGFR was 70.1 ± 15.1 ml/min/1.73 min². Most patients (81.3%) were on a tacrolimus-based regimen, while prednisolone was used by 84.4% of subjects with a mean dose of 5 ± 1 mg/d. NODAT was observed in 17.2% of patients, 81.8% of whom were on glucocorticoids. Dyslipidemia was found in 67.2% of patients and central obesity in 62.5% of men and 50% of women. Glucocorticoid-treated patients had significantly lower median serum cortisol (P < 0.001), DHEAS (P = 0.002) and UFC (P = 0.012). ACTH and HC levels were also lower although not statistically significant (P = 0.644 and P = 0.285, respectively). Markedly suppressed UFC levels ( < 6 µg/24 h) were found in 29.4% of glucocorticoid-treated patients correlating with decreased morning serum cortisol < 5 µg/dl) (P = 0.01), DHEAS (P = 0.021) and HC levels (P = 0.899). Among metabolic parameters, NODAT was associated with suppressed levels of UFC (P = 0.041) and HC (P = 0.042) in glucocorticoid-treated patients.

Conclusions

Chronic low-dose steroid-treated kidney transplant recipients exhibited HPA axis suppression and increased prevalence of NODAT. HC could be a potential adjunctive biomarker of adrenal insufficiency, although more studies are required to establish this marker.