Temporal changes in cortisol secretion and their association with long-term outcomes in benign adrenal incidentalomas: a retrospective cohort study

Suntornlohanakul, O; Reimondo, G; Ghislieri, M; Petramala, L; Coscia, K; Kraljevic, I; Perini, A; Ceccato, F; Palmieri, S; Rengarajan, L; Bobrowicz, M; Altieri, B; Rahimi, L; Matrozova, J; Aloini, ME; Rivas-Otero, D; Löndahl, M; Marina, LV; Alexandraki, KI; Falhammar, H; Gallego, NV; Morelli, V; Angelousi, A; Ueland, GÅ; Isidori, AM; Pignatelli, D; Favero, V; Theiler-Schwetz, V; Circosta, F; Tucci, L; Đukić, M; Puglisi, S; Bovo, G; Mangone, A; Ronchi, CL; Gladka, A; Detomas, M; Vasilev, V; Servello, AD; Donnarumma, F; Botto, C; Elhassan, YS; Ivović, M; Lindgren, O; Torre, EM; Stigliano, A; Bancos, I; Ambroziak, U; Mantovani, G; Scaroni, C; Kastelan, D; Di Dalmazi, G; Letizia, C; Deutschbein, T; Terzolo, M; Fassnacht, M; Agostini, V; Prete, A

doi:10.1016/s2213-8587(26)00098-7

Adrenal disease

Temporal changes in cortisol secretion and their association with long-term outcomes in benign adrenal incidentalomas: a retrospective cohort study

Lancet Diabetes EndocrinolPublished 7 Jul 2026Retrospective cohort study

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Authors' conclusion

Longitudinal 1-mg DST changes are common. MACS-to-MACS patients had worsening hypertension, but rates of mortality and cardiovascular or thrombotic events were not significantly associated with 1-mg DST trajectories after adjustment for age and cardiovascular risk factors.

Study context

Population: Adults (≥18 years) with benign adrenal incidentalomas diagnosed Jan 2000–Dec 2020, ≥2 1-mg DSTs and follow-up ≥36 months; excluded CS, PA, phaeochromocytoma, androgen-secreting tumour, active malignancy, interfering drugsmedian follow-up 80 months
Participants: 2,525 adults

Exposure: Longitudinal 1-mg DST trajectories: Mild autonomous cortisol secretion (MACS)-to-MACS vs NFAT-to-NFAT
MACS-to-MACSn = 839
NFAT-to-NFATn = 1,103reference
Outcome: All-cause mortality and cardiovascular and thrombotic events by longitudinal 1-mg DST results

Methodological detailsmulticentre, 25 adrenal centres, 14 countries (ENS@T consortium), multivariable Cox models, restricted mean survival time, Data from electronic health records of all eligible patients at each centre

Multicentre
25 adrenal centres, 14 countries (ENS@T consortium)
Multivariable Cox models
Restricted mean survival time
Data from electronic health records of all eligible patients at each centre

Main finding

As reported in the abstract

Worsening hypertension, MACS-to-MACS vs NFAT-to-NFAT

Adjusted hazard ratio

1.34

95% CI 1.03–1.73

By group

MACS-to-MACS60.410-year RMST · CI 56.8–75.5 · months

NFAT-to-NFAT86.110-year RMST · CI 79.1–93.4 · months

MACS-to-MACSvs NFAT-to-NFAT

aHR 1.34 (95% CI 1.03–1.73)

Observational data: associations, not effects.

Further findings

Change in 1-mg DST results leading to change in diagnosis · most within 3 years of baseline 1-mg DST

Patients with diagnosis change: 563 (22.3%)

Baseline characteristics

MACS-to-MACS patients were older and had greater cardiometabolic burden than NFAT-to-NFAT

Reference

Authors: Suntornlohanakul O, Reimondo G, Ghislieri M, Petramala L, Coscia K, Kraljevic I, et al.
All 58 authors
Suntornlohanakul O, Reimondo G, Ghislieri M, Petramala L, Coscia K, Kraljevic I, Perini A, Ceccato F, Palmieri S, Rengarajan L, Bobrowicz M, Altieri B, Rahimi L, Matrozova J, Aloini ME, Rivas-Otero D, Löndahl M, Marina LV, Alexandraki KI, Falhammar H, Gallego NV, Morelli V, Angelousi A, Ueland GÅ, Isidori AM, Pignatelli D, Favero V, Theiler-Schwetz V, Circosta F, Tucci L, Đukić M, Puglisi S, Bovo G, Mangone A, Ronchi CL, Gladka A, Detomas M, Vasilev V, Servello AD, Donnarumma F, Botto C, Elhassan YS, Ivović M, Lindgren O, Torre EM, Stigliano A, Bancos I, Ambroziak U, Mantovani G, Scaroni C, Kastelan D, Di Dalmazi G, Letizia C, Deutschbein T, Terzolo M, Fassnacht M, Agostini V, Prete A
Journal: The Lancet Diabetes & Endocrinology
Published: 7 Jul 2026
DOI: 10.1016/s2213-8587(26)00098-7
PubMed: 42413529

Topic: Adrenal disease

Exposure definitions

MACS-to-MACS: persistently abnormal 1-mg DST results
NFAT-to-NFAT: persistently normal 1-mg DST results (non-functioning adrenal tumours)

Key notes

Mortality and cardiovascular or thrombotic events not significantly associated with 1-mg DST trajectories after adjustment for age and cardiovascular risk factors
Higher baseline post-1-mg DST cortisol, greater cumulative cortisol exposure and MACS-to-MACS associated with shorter survival and event-free time in crude analyses only; not independent of age and baseline cardiometabolic risk factors

Original publication

Temporal changes in cortisol secretion and their association with long-term outcomes in benign adrenal incidentalomas: a retrospective cohort study. Lancet Diabetes Endocrinol. Published 7 July 2026. doi:10.1016/s2213-8587(26)00098-7

Read the original article ↗

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