Mild Autonomous Cortisol Secretion is Associated with Impaired Kidney Function

Objective:
Patients with mild autonomous cortisol secretion (MACS) have been reported to have a higher prevalence of chronic kidney disease (CKD). However, it is unclear whether this is due to a direct effect of hypercortisolism on kidney function or indirect effect of MACS on CKD risk factors, including hypertension, diabetes, obesity, and dyslipidemia. We aimed to determine the prevalence of CKD in patients with MACS as compared to patients with nonfunctioning adrenal adenomas (NFA) and discern the impact of hypercortisolism versus comorbidities on kidney function.

Methods:
We conducted a retrospective single center study, from 1999 to 2022, and included adult patients with NFA and MACS, diagnosed based on a post-dexamethasone cortisol (DST) cutoff of 1.8 mcg/dL. Estimated glomerular filtration rate (eGFR) and advanced CKD (eGFR <30 ml/min/1.73 m² consistent with stage 4 and 5 CKD) were the primary outcomes. Demographics and comorbidities such as hypertension, diabetes mellitus, dyslipidemia, and obesity (BMI ≥ 30 kg/m²) were included in univariable and multivariable analysis.

Results:
Of 972 patients, 429 (44%) were diagnosed with MACS and 543 (56%) were diagnosed with NFA. The proportion of women was high in patients with MACS and NFA (66% vs 63%, p=0.32); however, patients with MACS were older (median age 62.8 vs 59.4 years in NFA, p<0.001). The prevalence of hypertension (58% vs 49%, p=0.005) and smoking (71% vs 63%, p=0.02) was higher in MACS vs NFA, while the prevalence of diabetes (25% vs 20%, p=0.13) and dyslipidemia (44% vs 44%, p=0.86) was similar. BMI was lower in patients with MACS (median 30.7 vs 31.4 kg/m² in NFA, p=0.04). Patients with MACS had lower eGFR (median 79.6 vs 83.8 ml/min/1.73m², p< 0.001) and a higher prevalence of advanced CKD (17.6% vs 11.7%, p<0.001). Post dexamethasone cortisol level was negatively correlated with eGFR (r = -0.15, p<0.001). After adjusting for age, sex, BMI, hypertension, dyslipidemia, diabetes and smoking, the correlation between post dexamethasone cortisol level and eGFR decreased (r=-0.07) but remained statistically significant (p = 0.027). In addition, patients with MACS were at higher risk of developing stage 4 and 5 CKD (adjusted OR 3.38, 95% CI 1.1-12.4) when compared to patients with NFA. Hypertension was the only other independent risk factor for advanced CKD (OR 11.8, 95% CI 2.1-220.8).

Discussion/Conclusion:
Higher post-DST cortisol was associated with lower eGFR independent of cardiovascular risk factors such as BMI, hypertension, diabetes, and dyslipidemia. Patients with MACS were at 3.3-fold higher risk of developing advanced CKD.