The association of cortisol and adrenal androgen with trabecular bone score in patients with adrenal incidentaloma with and without autonomous cortisol secretion
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Despite ethnic differences in cortisol sensitivity, only one study in Caucasians has assessed trabecular bone score (TBS) in patients with subclinical hypercortisolism (SH). We showed that both subtle cortisol excess and reduced adrenal androgen may contribute to impaired bone quality in Asian women with SH.
One study in Caucasians has assessed trabecular bone score (TBS), an index of bone microstructure, in adrenal incidentaloma (AI) patients with subclinical hypercortisolism (SH). There are ethnic differences in cortisol sensitivities between Caucasian and Asian populations. We investigated the associations of cortisol and the adrenal androgen dehydroepiandrosterone-sulfate (DHEA-S) with TBS in AI patients with SH, adrenal Cushing’s syndrome (CS), and nonfunctional AI (NFAI).
We measured TBS, cortisol levels after the overnight 1 mg dexamethasone suppression test (1 mg DST), and cortisol/DHEA-S in 61 patients with SH (30 men; 31 women), 19 with adrenal CS (4 men; 15 women), and 355 with NFAI (213 men; 142 women).
After adjusting for confounders, the serum cortisol level after 1 mg DST was inversely correlated with TBS in men (β = −0.133, P = 0.045) and women (β = − 0.140, P = 0.048). Higher cortisol/DHEA-S ratio was associated with lower TBS in women (β = − 0.252, P < 0.001), but not men. This inverse association of cortisol/DHEA-S ratio in women remained statistically significant after adjusting for the serum cortisol level after 1 mg DST (β = − 0.221, P = 0.008). Compared with women with NFAI, women with SH had 2.2% lower TBS (P = 0.040). Deteriorated bone microstructure (TBS < 1.230) was associated with the serum cortisol level after 1 mg DST (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.04–4.53) and cortisol/DHEA-S ratio (OR, 2.05; 95% CI, 1.03–4.08).
Subtle cortisol excess in both genders and reduced DHEA-S, especially in women, may contribute to impaired bone quality in Asian patients with SH.
KeywordsBone mineral density Cortisol Dehydroepiandrosterone-sulfate Subclinical hypercortisolism Trabecular bone score
This study was supported by grants from the Asan Institute for Life Sciences, Seoul, Republic of Korea (Project No. 2014-1215) and from the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (Project HI15C0377).
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Conflicts of interest
- 1.Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, Tabarin A, Terzolo M, Tsagarakis S, Dekkers OM (2016) Management of adrenal incidentalomas: European Society of Endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors. Eur J Endocrinol 175:G1–G34. https://doi.org/10.1530/EJE-16-0467 CrossRefPubMedGoogle Scholar
- 2.Chiodini I (2011) Clinical review: diagnosis and treatment of subclinical hypercortisolism. J Clin Endocrinol Metab 96:1223–1236. https://doi.org/10.1210/jc.2010-2722
- 6.Chiodini I, Morelli V, Masserini B, Salcuni AS, Eller-Vainicher C, Viti R, Coletti F, Guglielmi G, Battista C, Carnevale V, Iorio L, Beck-Peccoz P, Arosio M, Ambrosi B, Scillitani A (2009) Bone mineral density, prevalence of vertebral fractures, and bone quality in patients with adrenal incidentalomas with and without subclinical hypercortisolism: an Italian multicenter study. J Clin Endocrinol Metab 94:3207–3214. https://doi.org/10.1210/jc.2009-0468 CrossRefPubMedGoogle Scholar
- 7.Morelli V, Eller-Vainicher C, Salcuni AS, Coletti F, Iorio L, Muscogiuri G, Della Casa S, Arosio M, Ambrosi B, Beck-Peccoz P, Chiodini I (2011) Risk of new vertebral fractures in patients with adrenal incidentaloma with and without subclinical hypercortisolism: a multicenter longitudinal study. J Bone Miner Res 26:1816–1821. https://doi.org/10.1002/jbmr.398 CrossRefPubMedGoogle Scholar
- 8.Eller-Vainicher C, Morelli V, Ulivieri FM, Palmieri S, Zhukouskaya VV, Cairoli E, Pino R, Naccarato A, Scillitani A, Beck-Peccoz P, Chiodini I (2012) Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism. J Bone Miner Res 27:2223–2230. https://doi.org/10.1002/jbmr.1648 CrossRefPubMedGoogle Scholar
- 10.Morelli V, Donadio F, Eller-Vainicher C, Cirello V, Olgiati L, Savoca C, Cairoli E, Salcuni AS, Beck-Peccoz P, Chiodini I (2010) Role of glucocorticoid receptor polymorphism in adrenal incidentalomas. Eur J Clin Investig 40:803–811. https://doi.org/10.1111/j.1365-2362.2010.02330.x CrossRefGoogle Scholar
- 11.Siggelkow H, Etmanski M, Bozkurt S, Grobeta P, Koepp R, Brockmoller J, Tzvetkov MV (2014) Genetic polymorphisms in 11beta-hydroxysteroid dehydrogenase type 1 correlate with the postdexamethasone cortisol levels and bone mineral density in patients evaluated for osteoporosis. J Clin Endocrinol Metab 99:E293–E302. https://doi.org/10.1210/jc.2013-1418 CrossRefPubMedGoogle Scholar
- 12.Szappanos A, Patocs A, Gergics P, Bertalan R, Kerti A, Acs B, Feldmann K, Racz K, Toth M (2011) The 83,557insA variant of the gene coding 11beta-hydroxysteroid dehydrogenase type 1 enzyme associates with serum osteocalcin in patients with endogenous Cushing’s syndrome. J Steroid Biochem Mol Biol 123:79–84. https://doi.org/10.1016/j.jsbmb.2010.11.009 CrossRefPubMedGoogle Scholar
- 13.Tauchmanova L, Pivonello R, De Martino MC, Rusciano A, De Leo M, Ruosi C, Mainolfi C, Lombardi G, Salvatore M, Colao A (2007) Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism. Eur J Endocrinol 157:359–366. https://doi.org/10.1530/EJE-07-0137 CrossRefPubMedGoogle Scholar
- 14.Lee SH, Song KH, Kim J, Park S, Ahn SH, Kim H, Cho YY, Suh S, Kim BJ, Kim JH, Koh JM (2017) New diagnostic criteria for subclinical hypercortisolism using postsurgical hypocortisolism: the co-work of adrenal research study. Clin Endocrinol 86:10–18. https://doi.org/10.1111/cen.13145 CrossRefGoogle Scholar
- 23.Chiodini I, Viti R, Coletti F, Guglielmi G, Battista C, Ermetici F, Morelli V, Salcuni A, Carnevale V, Urbano F, Muscarella S, Ambrosi B, Arosio M, Beck-Peccoz P, Scillitani A (2009) Eugonadal male patients with adrenal incidentalomas and subclinical hypercortisolism have increased rate of vertebral fractures. Clin Endocrinol 70:208–213. https://doi.org/10.1111/j.1365-2265.2008.03310.x CrossRefGoogle Scholar
- 27.Ghebre MA, Hart DJ, Hakim AJ, Kato BS, Thompson V, Arden NK, Spector TD, Zhai G (2011) Association between DHEAS and bone loss in postmenopausal women: a 15-year longitudinal population-based study. Calcif Tissue Int 89:295–302. https://doi.org/10.1007/s00223-011-9518-9 CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Baulieu EE, Thomas G, Legrain S, Lahlou N, Roger M, Debuire B, Faucounau V, Girard L, Hervy MP, Latour F, Leaud MC, Mokrane A, Pitti-Ferrandi H, Trivalle C, de Lacharriere O, Nouveau S, Rakoto-Arison B, Souberbielle JC, Raison J, le Bouc Y, Raynaud A, Girerd X, Forette F (2000) Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge study to a sociobiomedical issue. Proc Natl Acad Sci U S A 97:4279–4284CrossRefGoogle Scholar
- 33.Nair KS, Rizza RA, O'Brien P, Dhatariya K, Short KR, Nehra A, Vittone JL, Klee GG, Basu A, Basu R, Cobelli C, Toffolo G, Man CD, Tindall DJ, Melton LJ III, Smith GE, Khosla S, Jensen MD (2006) DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 355:1647–1659. https://doi.org/10.1056/NEJMoa054629 CrossRefPubMedGoogle Scholar
- 34.Tauchmanova L, Rossi R, Nuzzo V, del Puente A, Esposito-del Puente A, Pizzi C, Fonderico F, Lupoli G, Lombardi G (2001) Bone loss determined by quantitative ultrasonometry correlates inversely with disease activity in patients with endogenous glucocorticoid excess due to adrenal mass. Eur J Endocrinol 145:241–247CrossRefGoogle Scholar