Does subclinical hypercortisolism adversely affect the bone mineral density of patients with adrenal incidentalomas?
Open accessAbstract
OBJECTIVE: Subclinical hypercortisolism (SH) is detected increasingly in a substantial proportion of patients with incidentally discovered adrenal adenomas. The clinical implications of SH are currently unclear. Osteoporosis is a well-known complication of glucocorticoid excess. So far, the impact of SH on bone mineral density (BMD) has been studied in a limited number of reports with discordant results. In the present study we evaluated the BMD in a large cohort of post-menopausal women with adrenal incidentalomas. : patients and measurements Forty-two post-menopausal women with incidentally discovered adrenal masses and radiological features highly suggestive of benign adrenal adenomas were investigated. All patients underwent a standard low-dose dexamethasone suppression test (LDDST; 0.5 mg 6-hourly for 2 days). The diagnosis of subclinical hypercortisolism (SH) was based on post-LDDST cortisol concentrations of > 70 nmol/l. According to this criterion patients were subdivided into two groups: with (n = 18; group A) or without (n = 24; group B) SH. There was no significant difference in age, years since menopause and body mass index between these groups. BMD was measured at L2-L4 vertebrae and three sites of the proximal femur by the dual energy X-ray absorptiometry (DEXA) method. RESULTS: Post-menopausal women with SH (group A) exhibited slightly but significantly lower absolute and age-adjusted BMD values compared to group B patients in the femoral neck (BMD g/cm2: 0.72 +/- 0.08 vs. 0.79 +/- 0.09; Z-score: -0.20 +/- 0.82 vs. +0.43 +/- 0.94, P < 0.05) and trochanter (BMD g/cm2: 0.60 +/- 0.09 vs. 0.69 +/- 0.10; Z-score: -0.32 +/- 1.0 vs. +0.30 +/- 1.05, P < 0.01). BMD measurements of the Ward's triangle were also lower in group A patients but the difference did not reach statistical significance (BMD g/cm2: 0.60 +/- 0.10 vs. 0.68 +/- 0.13, P = 0.06). There was no difference in the lumbar vertebrae between the two groups (BMD g/cm2: 0.888 +/- 0.13 vs. 0.90 +/- 0.16, P = 0.78; z-score: +0.50 +/- 1.16 vs. +0.11 +/- 1.5, P = 0.36). The number of patients in the osteoporotic range was minimal with no significant difference between the two groups. However, the frequency of osteopenia in group A was significantly greater than in group B patients in the trochanter and Ward's triangle areas. Serum osteocalcin (BGP) levels were significantly lower in group A compared to group B patients (18.6 +/- 8.6 vs. 26.2 +/- 8.1 ng/ml, P < 0.01); no difference existed regarding parathyroid hormone (PTH) concentrations (43 +/- 15.6 vs. 41.2 +/- 14.8 pg/ml, P = 0.72). CONCLUSIONS: In this series, post-menopausal women with subclinical hypercortisolism had lower absolute and age-adjusted BMD values and a higher rate of osteopaenia in the trabecular loaded and mixed cortical-trabecular bone of proximal femur. These data demonstrate that the subtle hypercortisolism of patients with adrenal incidentalomas may have an adverse effect on the bone mass of these patients.
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Both trabecular and cortical bone loss have been described in patients with ACS.
“Both trabecular (65,261-263) and cortical (259,262,264-266) bone loss have been described in patients with ACS.”
From Adrenal incidentaloma (2020) · cites this paper as [262]
In patients with ACS, bone formation is reported as decreased, normal, or increased alongside normal bone resorption.
“However, in patients with ACS, a mixed picture is reported with either decreased, normal, or even increased bone formation reported alongside normal bone resorption (229,242,259-262).”
From Adrenal incidentaloma (2020) · cites this paper as [262]
In more than 25% of patients with adrenal incidentalomas, cortisol is not suppressed after 1-mg or 3-mg overnight dexamethasone suppression testing or 2-day low-dose dexamethasone suppression testing.
“In more than 25% of AI subjects, the lack of cortisol suppression after 1-or 3-mg overnight DST or 2-d low-dose DST (LDDST) (19,34,41,44,46,48,53,55,56,60,61)”
From Diagnosis and Treatment of Subclinical Hypercortisolism (2011) · cites this paper as [55]
Low-dose dexamethasone suppression testing has been used to diagnose subclinical hypercortisolism without advantages, except possibly in patients with alcoholism, psychiatric disorders, or diabetes.
“Similarly, LDDST has been used to diagnose SH (18,40,41,55) without advantages, with the exception of patients affected with alcoholism, psychiatric disorders, and diabetes in whom this test may be more accurate (1,14,66).”
From Diagnosis and Treatment of Subclinical Hypercortisolism (2011) · cites this paper as [55]
With lower 1-mg dexamethasone suppression test cutoffs of 1.8 and 2.2 g/dl, specificity decreased to 67-72% and sensitivity increased to 75-100%.
“However, if the lowest cutoffs were used [1.8 and 2.2 g/dl (50 and 60.6 nmol/liter), respectively], specificity decreased to 67-72%, whereas sensitivity increased to 75-100% (48 -62, 64 -67).”
From Diagnosis and Treatment of Subclinical Hypercortisolism (2011) · cites this paper as [55]
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References 34 · Cited by 60
Research works printed but not linked: 2
- Hadjidakis, D., Kokkinakis, E., Giannopoulos, G., Merakos, G. & Raptis, S.A. (1997) Bone mineral density of vertebrae, proximal femur and os calcis from Greek normal subjects: comparison with other populations. European Journal of Clinical Investigation, 27, 219 -227.
- Tsagarakis, S. (1998) The management of adrenal incidentalomas. In: Clinical Endocrinology, chapter 37 (ed. A. Grossman), pp. 484 -493.
- Authors
- Hadjidakis, D., Tsagarakis, S., Roboti, C., Sfakianakis, M., Iconomidou, V., Raptis, S. A., & Thalassinos, N.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Corresponding author
- Hadjidakis, D.
- ORCID
- Tsagarakis, S.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2003-01
- Volume
- 58
- Issue
- 1
- Pages
- 72-77
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2138202804
- Cited by
- 60
- References
- 34
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 2 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 2 · 2013: 2 · 2012: 6
- FWCI
- 4.15
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alexander von Humboldt-Stiftung
- Topics
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- subclinical hypercortisolism, adrenal incidentaloma, adrenal adenoma, bone mineral density, osteoporosis, glucocorticoid excess, postmenopausal women, low-dose dexamethasone suppression test, femoral neck, trochanter, Ward's triangle, vertebral bone density, Cushing's syndrome, bone loss risk factors
- MeSH terms
- Adrenal Cortex Neoplasms, Adrenocortical Hyperfunction, Aged, Anthropometry, Female, Femur Neck, Humans, Lumbar Vertebrae, Middle Aged, Bone Density, Postmenopause, Incidental Findings
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