Sex Difference in the Association of Osteoporosis and Osteopenia Prevalence in Patients with Adrenal Adenoma and Different Degrees of Cortisol Excess

Abstract

Objective. Osteoporosis and osteopenia (OS/OP) are frequent in patients with adrenal adenomas associated with cortisol excess (CE). However, the relationship between OS/OP and CE severity considering sex differences is unknown. Design. A cross-sectional observational study from January 2006 to December 2015. Patients. 237 patients with adrenal adenoma associated with CE, including Cushing’s syndrome and mild autonomous cortisol secretion (MACS), diagnosed in 10 referral centers in Japan. MACS was defined by 1 mg overnight dexamethasone suppression test (DST) cortisol level >1.8 μg/dL. Measurements. Prevalence of fragility fractures, medication for osteoporosis, and bone mineral density. Results. In total, 112 of 237 patients, who were predominantly female ( P < 0.001 ) and had lower BMI ( P = 0.013 ), had OS/OP. Patients with OS/OP was significantly affected by CE ( P < 0.01 ) than those without. The adjusted odds ratio (OR) for predicting OS/OP was obtained in multivariate logistic regression analysis. Clinical measures of CE, 1 mg DST cortisol levels, were positively associated with OS/OP in total cases (OR 1.124, 95% CI: 1.070–1.181, P < 0.001 ) and the cases with MACS (OR 1.156, 95%CI: 1.046–1.278, P = 0.005 ). A cutoff value of 1 mg DST cortisol level >5.0 μg/dL was associated with OS/OP differently between men and women. OS/OP risk in men with MACS was significantly affected only by 1 mg DST cortisol levels. However, OS/OP risk in women with MACS was significantly affected by 1 mg DST cortisol levels and age. Conclusions. CE severity in adrenal adenoma is positively associated with OS/OP. However, the associated factors of OS/OP in the patients with MACS are different between men and women.

Mild Autonomous Cortisol Secretion (MACS) – Related Osteoporosis

“…Older studies [17][18][19][20][21][22][23][24][25][26][27][28][29] with a 1-mg DST cortisol cut-off > 3 mcg/dL showed a highly variable prevalence of vertebral fractures ranging from 43% to 100%. More recent studies performed with 1-mg DST cortisol cut-off >1.8 mcg/dL (50 nmol/L) [3,4,[30][31][32][33], demonstrated similar rates regardless of the size of the cohort, with fracture prevalence in larger cohorts ranging from 31.7% to 62.6% (Table 1).…”

Management of Adrenal Cortical Adenomas: Assessment of Bone Status in Patients with (Non-Functioning) Adrenal Incidentalomas

“…The mentioned studies used various endocrine criteria in order to define the cortisol excess as seen in ACS (or equivalent) [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. ( Table 2 ).…”

“…As mentioned, ACS (or SCS or SH) involves a distinct type of tumour with positive (yet mild, not overt) cortisol (persistent) excess, and consecutive DXA-BMD evaluations depend on the criteria for defining this hormonal activity, on the age and sex of the studied population (including the menopausal status of women), and on the sample size of the cohort. Except for three, 37 cohorts provided data in terms of DXA and/or VFs [ 43 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ], and a confirmation of a negative impact of bone status was generally confirmed.…”

“…Overall, we identified 40 original studies on patients diagnosed with AI and/or ACS (or SCS) for whom bone assessments of various types were provided; a total of 3046 patients were included, with a higher prevalence of women (female-to-male ratio of 1921:1125, aged between 20.5 and 95.5 years old) [ 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ] ( Figure 1 ).…”

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“…The previous studies showed that the female sex is a risk factor related to osteoporosis and is associated with a lower BMD. [21][22][23][24] Osteoporosis has a significant hormonal influence, particularly in postmenopausal women, where reduced estrogen levels have a negative effect on the formation of the bone by increasing the sensitivity to the bone resorption effect of parathyroid hormone. This can cause rapid bone loss as compared to bone formation leading to osteoporosis.…”