Adrenalectomy reduces the risk of vertebral fractures in patients with mild autonomous cortisol secretion

Valentina Morelli; Vittoria Favero; Sofia Frigerio; Carmen Aresta; Flavia Pugliese; Antonio Stefano Salcuni; Alessandro Risio; Cristina Eller-Vainicher; Serena Palmieri; Elisa Cairoli; Sabrina Corbetta; Giovanna Mantovani; Alfredo Scillitani; Iacopo Chiodini

doi:10.1210/clinem/dgaf227

Adrenalectomy reduces the risk of vertebral fractures in patients with mild autonomous cortisol secretion

J Clin Endocrinol Metab. 2025 Apr 11:dgaf227. doi: 10.1210/clinem/dgaf227. Online ahead of print.

Authors

Valentina Morelli¹, Vittoria Favero^{2

3}, Sofia Frigerio⁴, Carmen Aresta³, Flavia Pugliese⁵, Antonio Stefano Salcuni⁶, Alessandro Risio², Cristina Eller-Vainicher⁴, Serena Palmieri⁴, Elisa Cairoli¹, Sabrina Corbetta^{1

7}, Giovanna Mantovani^{4

8}, Alfredo Scillitani⁵, Iacopo Chiodini^{1

2}

Affiliations

¹ Endocrinology Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, 20100 Milan, Italy.
² Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy.
³ Unit of Endocrinology, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
⁴ Unit of Endocrinology, Fondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico Milan, Italy.
⁵ Unit of Endocrinology, "Casa Sollievo della Sofferenza Hospital", IRCCS, San Giovanni Rotondo, Foggia, Italy.
⁶ Unit of Endocrinology and Metabolism, University-Hospital S. Maria Della Misericordia, Udine, Italy.
⁷ Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.
⁸ Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

PMID: 40214048
DOI: 10.1210/clinem/dgaf227

Abstract

Objective: Mild autonomous cortisol secretion (MACS) is associated with increased risk of vertebral fractures (VFx). The impact of recovery from MACS on bone health remains unclear.

Design: Retrospective intervention Study (Study1): 53 patients with MACS were followed for 35.2±18.6 months; 31 patients underwent surgery (Study1-GroupA, 74.2% women, age 63 years [57-67]), while 22 patients received conservative treatment (Study1-GroupB, 45.5% women, age 64 years [61-72]).Prospective Randomized Study (Study 2): Fifty-one outpatients with MACS were randomly assigned to either adrenalectomy (Study2-GroupA, 21 patients, 67% women, age 63 [56.5-72.5]) or conservative approach (Study2-GroupB, 28 patients, 78% women, age 69 [61-73]) and were followed for 24 months.

Methods: MACS was diagnosed in patients with adrenal incidentalomas (AI)>1 cm and cortisol after 1-mg dexamethasone suppression test (F-1mgDST) ≥1.8 µg/dL (50 nmol/L). At baseline and at the end of follow-up we assessed: calcium-phosphorus metabolism, bone mineral density (BMD) at the lumbar spine (LS), total hip (TH) and femoral neck (FN) using Dual-energy X-ray Absorptiometry, and the presence of VFx.

Results: Study 1: At the end of the follow-up, Study1-GroupB showed an increased incidence of VFx (n=11, 50%) than Study1-GroupA (n=3, 9.7%, p<0.005). In both groups BMD at LS, FN and TH was comparable between baseline and the end of follow-up.Study 2: After 24 months in Study2-GroupA, but not in Study2-GroupB, calcium and phosphorus levels increased compared to baseline (p=0.03 and p=0.04, respectively). At the end of follow up, BMD remained stable across both groups, but Study2-GroupB showed a significantly higher incidence of VFx (n=7, 25%) compared to Study2-GroupA (n=1, 4.8%, p=0.04).

Conclusions: In patients with AI and MACS, adrenalectomy significantly reduces the risk of VFx.

Keywords: bone mineral density; mild autonomous cortisol secretion; vertebral fracture.