Mild autonomous cortisol secretion in adrenal incidentalomas and risk of fragility fractures: a large cross-sectional study

Abstract

Objective Mild autonomous cortisol secretion (MACS) has been associated with a higher prevalence of osteoporosis, although most data rely on single-center studies with limited sample size. We aimed to assess the prevalence of fragility fractures and contributing factors in a large cohort of patients with adrenal incidentalomas. Design and Methods Medical records of 1023 patients with adrenal incidentalomas from 1990 to 2019 were reviewed, and 735 patients were selected. Clinically-obtained electronic radiological images closest to first endocrine evaluation, such as lateral views of spine X-rays or CT thoraco-abdominal scans, were reviewed to screen for asymptomatic morphometric vertebral fractures. Clinical fragility fractures, hormonal and DXA indices were also recorded. Results 474 patients had non-functioning (NF) adrenal incidentalomas, 238 had MACS and 23 Adrenal Cushing’s Syndrome (AC). Prevalence of fragility fractures was different (P = 0.018) between groups, respectively 24.1% (NF), 34.0% (MACS) and 30.4% (AC), with significant difference between NF and MACS (P = 0.012). When analyzed separately by sex and menopausal status, this difference remained significant in post-menopausal women (P = 0.011), with a fracture prevalence of 22.2% (NF), 34.6% (MACS). Fracture prevalence was similar in males. Women with MACS aged ≥65 years reported a 48.8% prevalence of fractures, as compared with 29.5% in NF (P < 0.01). In post-menopausal women, fragility fractures were associated with age (OR 1.1, P < 0.001), smoking (OR 1.8, P = 0.048) and 1mg-DST cortisol (OR 3.1, P = 0.029), while in men, only age was associated with fragility fractures. Conclusions A considerable fracture burden was shown in post-menopausal women with adrenal incidentalomas and MACS, with clinical implications for the evaluation and management of bone metabolism.

Prevalence and Incidence of Fractures in Patients With Nonfunctional Adrenal Tumors

“…Previous studies in patients with adrenal tumors have found increased fracture risk in individuals with higher cortisol levels . In contrast to the current study, these studies did not exclude individuals with MACS.…”

“…However, Li et al had medical records available since 1966 in their examined county, whereas we had only national data using ICD-10 , which was introduced in Sweden in 1997 (ie, an almost 20-year difference, which may explain the prevalence difference). Moreover, our vertebral fracture prevalence rate of 1.5% in patients with NFATs (compared with 0.9% in controls) was also much lower than the 6.4% reported by Li et al but even lower compared with the rates of 22.9% to 24.7% reported by other recent studies . We suspect that this drastic difference in prevalence is due to inclusion of asymptomatic vertebral fractures in the previous studies because all patients with NFATs had their spines evaluated radiologically, whereas our study and the study by Li et al possibly included only symptomatic vertebral fractures.…”

“…There were both increased prevalence of vertebral and hip fractures and increased incidence of the same fracture type in younger men. An increased risk of vertebral fractures has been seen in men compared with women with NFATs . The explanation is somewhat unclear.…”

“…An increased risk of vertebral fractures has been seen in men compared with women with NFATs. 11 The explanation is somewhat unclear. Women's risk of fractures increases after menopause, and premenopausal women with NFATs may be protected by their eugonadism, but this cannot be the case for men.…”

Cushing Syndrome

“…Testing for Cushing syndrome can be considered in select patients with clinical features strongly associated with Cushing syndrome (Table 1), such as osteoporosis and vertebral fractures, among those younger than 50 years and those with incidentally identified asymptomatic adrenal tumors …”