THERAPY OF ENDOCRINE DISEASE: Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: a systematic review and meta-analysis

Abstract

Objective: Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushing's syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor. Methods: MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate. Results: We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3-27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5-9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97-7.2) or obesity (RR 3.4,. Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS. Conclusions: Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.

Extensive clinical experience: Hypothalamic‐pituitary‐adrenal axis recovery after adrenalectomy for corticotropin‐independent cortisol excess

“…Patients presented with varying degrees of biochemical and clinical cortisol excess. Guided by Endocrine Society guidelines on the diagnosis of CS, ENSAT/ESE guidelines on adrenal incidentalomas and a systematic review on MACE, we created a scoring system to classify biochemical and clinical abnormalities as mild, moderate or severe.…”

“…Whilst overt adrenal CS is rare, biochemical abnormalities suggestive of mild autonomous cortisol excess (MACE, also known as “subclinical” CS) are much more common and are reported in at least 30% of patients with adrenal cortical adenomas . Whilst patients with MACE lack the classic physical features of CS, they present with significantly higher rates of metabolic abnormalities that increase cardiovascular risk, morbidity and mortality, when compared to the general population …”

Nonfunctional Adrenal Adenomas: Truth or Myth? Presentation and Treatment of 2 Patients

“…In addition to the diagnostic challenges, inconsistent data on the treatment benefits of adrenalectomy in patients with cortisol-secreting adenomas without florid Cushing syndrome (CS) have also been reported (14). A recent systematic review and meta-analysis was conducted that included 584 patients from 26 studies (mostly retrospective) with "mild" CS (14).…”

“…A recent systematic review and meta-analysis was conducted that included 584 patients from 26 studies (mostly retrospective) with "mild" CS (14). Although criteria defining hypercortisolism varied, results found statistically significant improvement in hypertension and diabetes for patients treated surgically versus conservative management (relative risk [RR], 11; 95% confidence interval [CI], 4.3 to 27.8 vs. RR 3.9; 95% CI, 1.5 to 9.9).…”

Cushing's syndrome: a practical approach to diagnosis and differential diagnoses

“…SCS is defined as a state of inappropriate cortisol overproduction that may be associated with alterations in the HPA axis, without the overt manifestations of classic CS such as striae, adiposity, proximal myopathy and metabolic abnormalities 40. The disease may be present in 5–30% of patients with adrenal incidentalomas, which is found in 4–7% of the adult population 9.…”