Mild Autonomous Cortisol Secretion (MACS) – Related Osteoporosis

Abstract

Mild autonomous cortisol secretion (MACS) has thus far been associated with several comorbidities, among which osteoporosis and fractures appear to be highly prevalent. Recent guidelines for adrenal incidentalomas have updated the definition of MACS, currently formulated on serum cortisol after a 1-mg dexamethasone test above 1.8 µg/dL or 50 nmol/L. Previous studies on bone health in adrenal incidentalomas had adopted different definitions of MACS, producing heterogeneous results in terms of fracture prevalence. This review aims to summarize the clinical impact of MACS in relation to fractures, bone quantity and quality, by providing a thorough update on MACS-related osteoporosis (MACS-ROP). This area has a large room for research, and management of this comorbidity still needs to be elucidated.

Keywords

adrenal tumors - osteoporosis - MACS - hypercortisolism - mild autonomous cortisol secretion - fractures

Publikationsverlauf

Eingereicht: 13. Januar 2024
Eingereicht: 02. April 2024

Angenommen: 17. Mai 2024

Accepted Manuscript online:
17. Mai 2024

Artikel online veröffentlicht:
11. Dezember 2024

• References

• 1 Fassnacht M, Tsagarakis S, Terzolo M. et al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 2023; 189: G1-G42
• 2 Fassnacht M, Arlt W, Bancos I. et al. European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 2016; 175: G1-G34
• 3 Zavatta G, Vicennati V, Altieri P. et al. Mild autonomous cortisol secretion in adrenal incidentalomas and risk of fragility fractures: A large cross-sectional study. Eur J Endocrinol 2023; 188: 343-352
• 4 Favero V, Eller-Vainicher C, Morelli V. et al. Increased risk of vertebral fractures in patients with mild autonomous cortisol secretion. J Clin Endocrinol Metab 2023; 109: e623-e632
• 5 Chotiyarnwong P, McCloskey EV. Pathogenesis of glucocorticoid-induced osteoporosis and options for treatment. Nat Rev Endocrinol 2020; 16: 437-447
• 6 Kanis JA, Johansson H, Oden A. et al. Guidance for the adjustment of FRAX according to the dose of glucocorticoids. Osteoporos Int 2011; 22: 809-816
• 7 Chiodini I, Vainicher CE, Morelli V. et al. Mechanisms in endocrinology: Endogenous subclinical hypercortisolism and bone: A clinical review. Eur J Endocrinol 2016; 175: R265-R282
• 8 Cooper MS, Rabbitt EH, Goddard PE. et al. Osteoblastic 11beta-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure. J Bone Miner Res 2002; 17: 979-986
• 9 Kimberg DV, Baerg RD, Gershon E. et al. Effect of cortisone treatment on the active transport of calcium by the small intestine. J Clin Invest 1971; 50: 1309-1321
• 10 Favus MJ, Kimberg DV, Millar GN. et al. Effects of cortisone administration on the metabolism and localization of 25-hydroxycholecalciferol in the rat. J Clin Invest 1973; 52: 1328-1335
• 11 Suzuki Y, Ichikawa Y, Saito E. et al. Importance of increased urinary calcium excretion in the development of secondary hyperparathyroidism of patients under glucocorticoid therapy. Metabolism 1983; 32: 151-156
• 12 Mazziotti G, Formenti AM, Adler RA. et al. Glucocorticoid-induced osteoporosis: pathophysiological role of GH/IGF-I and PTH/VITAMIN D axes, treatment options and guidelines. Endocrine 2016; 54: 603-611
• 13 Li D, Zhang CD, Saini J. et al Determinants of muscle function and health-related quality of life in patients with endogenous hypercortisolism: A cross-sectional study. Eur J Endocrinol 2023; 10 188: 603-612
• 14 Humphrey EL, Williams JH, Davie MW. et al. Effects of dissociated glucocorticoids on OPG and RANKL in osteoblastic cells. Bone 2006; 38: 652-661
• 15 Zavatta G, Clarke BL. Glucocorticoid- and transplantation-induced osteoporosis. Endocrinol Metab Clin North Am 2021; 50: 251-273
• 16 Zavatta G, Di Dalmazi G. Recent advances on subclinical hypercortisolism. Endocrinol Metab Clin North Am 2018; 47: 375-383
• 17 Chiodini I, Guglielmi G, Battista C. et al. Spinal volumetric bone mineral density and vertebral fractures in female patients with adrenal incidentalomas: The effects of subclinical hypercortisolism and gonadal status. J Clin Endocrinol Metab 2004; 89: 2237-2241
• 18 Tauchmanovà L, Pivonello R, De Martino MC. et al. Effects of sex steroids on bone in women with subclinical or overt endogenous hypercortisolism. Eur J Endocrinol 2007; 157: 359-366
• 19 Chiodini I, Morelli V, Masserini B. et al. 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 2009; 94: 3207-3214
• 20 Chiodini I, Viti R, Coletti F. et al. Eugonadal male patients with adrenal incidentalomas and subclinical hypercortisolism have increased rate of vertebral fractures. Clin Endocrinol (Oxf) 2009; 70: 208-213
• 21 Tauchmanova L, Guerra E, Pivonello R. et al. Weekly clodronate treatment prevents bone loss and vertebral fractures in women with subclinical Cushing's syndrome. J Endocrinol Invest 2009; 32: 390-394
• 22 Morelli V, Eller-Vainicher C, Salcuni AS. et al. Risk of new vertebral fractures in patients with adrenal incidentaloma with and without subclinical hypercortisolism: A multicenter longitudinal study. J Bone Miner Res 2011; 26: 1816-1821
• 23 Eller-Vainicher C, Morelli V, Ulivieri FM. et al. Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism. J Bone Miner Res 2012; 27: 2223-2230
• 24 Morelli V, Palmieri S, Salcuni AS. et al. Bilateral and unilateral adrenal incidentalomas: Biochemical and clinical characteristics. Eur J Endocrinol 2013; 168: 235-241
• 25 Lasco A, Catalano A, Pilato A. et al. Subclinical hypercortisol-assessment of bone fragility: Experience of single osteoporosis center in Sicily. Eur Rev Med Pharmacol Si 2014; 18: 352-358
• 26 Salcuni AS, Morelli V, Eller Vainicher C. et al. Adrenalectomy reduces the risk of vertebral fractures in patients with monolateral adrenal incidentalomas and subclinical hypercortisolism. Eur J Endocrinol 2016; 174: 261-269
• 27 Kim B-J, Kwak MK, Ahn SH. et al. The association of cortisol and adrenal androgen with trabecular bone score in patients with adrenal incidentaloma with and without autonomous cortisol secretion. Osteoporos Int 2018; 29: 2299-2307
• 28 Ahn SH, Kim JH, Cho YY. et al. The effects of cortisol and adrenal androgen on bone mass in Asians with and without subclinical hypercortisolism. Osteoporos Int 2019; 30: 1059-1069
• 29 Moraes AB, De Paula MP, De Paula Paranhos-Neto F. et al. Bone evaluation by high-resolution peripheral quantitative computed tomography in patients with adrenal incidentaloma. J Clin Endocrinol Metab 2020; 105: e2726-e2737
• 30 Ishida A, Igarashi K, Ruike Y. et al. Association of urinary free cortisol with bone formation in patients with mild autonomous cortisol secretion. Clin Endocrinol (Oxf.) 2021; 94: 544-550
• 31 Li D, Kaur RJ, Zhang CD. et al. Risk of bone fractures after the diagnosis of adrenal adenomas: A population-based cohort study. Eur J Endocrinol 2021; 184: 597-606
• 32 Izawa S, Matsumoto K, Matsuzawa K. et al. Sex difference in the association of osteoporosis and osteopenia prevalence in patients with adrenal adenoma and different degrees of cortisol excess. Borretta G, ed. Int J Endocrinol. 2022. 2022. 1-9
• 33 Dogra P, Šambula L, Saini J. et al. High prevalence of frailty in patients with adrenal adenomas and adrenocortical hormone excess: A cross-sectional multi-centre study with prospective enrolment. Eur J Endocrinol 2023; 189: 318-326
• 34 Deutschbein T, Reimondo G, Di Dalmazi G. et al. Age-dependent and sex-dependent disparity in mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: An international, retrospective, cohort study. Lancet Diabetes Endocrinol 2022; 10: 499-508
• 35 Martineau P, Leslie WD, Johansson H. et al. In which patients does lumbar spine trabecular bone score (TBS) have the largest effect?. Bone 2018; 113: 161-168
• 36 Vinolas H, Grouthier V, Mehsen-Cetre N. et al. Assessment of vertebral microarchitecture in overt and mild Cushing’s syndrome using trabecular bone score. Clin Endocrinol (Oxf.) 2018; 89: 148-154
• 37 Schini M, Vilaca T, Gossiel F. et al. Bone turnover markers: Basic biology to clinical applications. Endocr Rev 2023; 44: 417-473
• 38 Athimulam S, Delivanis D, Thomas M. et al. The impact of mild autonomous cortisol secretion on bone turnover markers. J Clin Endocrinol Metab 2020; 105: 1469-1477
• 39 Shoback D, Rosen CJ, Black DM. et al. Pharmacological management of osteoporosis in postmenopausal women: An Endocrine Society Guideline pdate. J Clin Endocrinol Metab 2020; 105: dgaa048
• 40 Camacho PM, Petak SM, Binkley N. et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis- 2020 update executive summary. Endocr Pract 2020; 26: 564-570
• 41 Humphrey MB, Russell L, Danila MI. et al. 2022 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatol 2023; 75: 2088-2102
• 42 Braun LT, Fazel J, Zopp S. et al. The effect of biochemical remission on bone metabolism in Cushing's syndrome: A 2-year follow-up study. J Bone Miner Res 2020; 35: 1711-1717