Predictability of hypoadrenalism occurrence and duration after adrenalectomy for ACTH-independent hypercortisolism
To evaluate if the parameters of hypothalamic–pituitary–adrenal (HPA) axis activity could predict the occurrence and duration of post-surgical hypocortisolism (PSH) in patients with Cushing’s syndrome (CS) and with adrenal incidentaloma (AI).
We studied 80 patients (54 females, age 53.3 ± 11 years), who underwent adrenalectomy for CS (17 patients) or for AI (53 patients). Before surgery, we measured adrenocorticotroph hormone (ACTH), urinary free cortisol (UFC) and serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST) levels. After surgery, all patients were given a steroid replacement therapy, and PSH was searched after 2 months by a low-dose (1 µg, iv) corticotropin stimulation test, that was repeated every 6 months in PSH patients for at least 4 years.
The PSH occurred in 82.4 and 46% of CS and AI patients, respectively. In the whole sample and in AI patients separately considered, the PSH was independently predicted by the preoperative cortisol levels after 1 mg-DST, however, with a low (< 70%) accuracy. In AI patients the PSH occurrence was not ruled out even by the cortisol levels after 1 mg-DST lower than 1.8 μg/dL (50 nmol/L). In the 50% of CS patients and in 31% of AI patients the PSH lasted more than 18 months and in 35.7% of CS patients it persisted for more than 36 months. In AI patients, the PSH duration was not predictable by any parameter. However, a PSH duration of at least 12 months was significantly predicted before adrenalectomy (sensitivity 91.7%, specificity 41.2%, positive predictive value 52.4%, negative predictive value 87.5%, p = 0.05) by the presence of at least 2 out of low ACTH levels, increased UFC levels and cortisol levels after 1 mg-DST ≥ 3.0 µg/dL (83 nmol/L).
The PSH occurrence and its duration are hardly predictable before surgery. All patients undergoing unilateral adrenalectomy should receive a steroid substitutive therapy.
KeywordsAdrenal incidentalomas Hypocortisolism Adrenalectomy
Compliance with ethical standards
Conflict of interest
The authors state that they have no conflicts of interest.
This work did not receive any funding.
All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.
Informed consent was obtained from all individual participants included in the study.
- 2.Arnaldi G, Angeli A, Atkinson AB, Bertagna X, Cavagnini F, Chrousos GP, Fava GA, Findling JW, Gaillard RC, Grossman AB, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman LK, Sonino N, Vance ML, Giustina A, Boscaro M (2003) Diagnosis and complications of Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 88:5593–5602CrossRefPubMedGoogle Scholar
- 7.Di Dalmazi G, Vicennati V, Rinaldi F, Morselli-Labate AM, Giampalma E, Mosconi C, Pagotto U, Pasquali R (2012) Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: a large cross-sectional study. Eur J Endocrinol 166:669–677CrossRefPubMedGoogle Scholar
- 8.Morelli V, Reimondo G, Giordano R, Della Casa S, Policola C, Palmieri S, Salcuni AS, Dolci A, Mendola M, Arosio M, Ambrosi B, Scillitani A, Ghigo E, Beck-Peccoz P, Terzolo M, Chiodini I (2014) Long-term follow-up in adrenal incidentalomas: an Italian multicenter study. J Clin Endocrinol Metab 99:827–834CrossRefPubMedGoogle Scholar
- 9.Di Dalmazi G, Vicennati V, Garelli S, Casadio E, Rinaldi E, Giampalma E, Mosconi C, Golfieri R, Paccapelo A, Pagotto U, Pasquali R (2014) Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing’s syndrome: a 15-year retrospective study. Lancet Diabetes Endocrinol 2:396–405CrossRefPubMedGoogle Scholar
- 11.Morelli V, Palmieri S, Lania A, Tresoldi A, Corbetta S, Cairoli E, Eller-Vainicher C, Arosio M, Copetti M, Grossi E, Chiodini I (2017) Cardiovascular events in patients with mild autonomous cortisol secretion: analysis with artificial neural networks. Eur J Endocrinol. https://doi.org/10.1530/EJE-17-0047 (Epub ahead of print) PubMedGoogle Scholar
- 12.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–G34CrossRefPubMedGoogle Scholar
- 16.Eller-Vainicher C, Morelli V, Salcuni AS, Battista C, Torlontano M, Coletti F, Iorio L, Cairoli E, Beck-Peccoz P, Arosio M, Ambrosi B, Scillitani A, Chiodini I (2010) Accuracy of several parameters of hypothalamic-pituitary-adrenal axis activity in predicting before surgery the metabolic effects of the removal of an adrenal incidentaloma. Eur J Endocrinol 163:925–935CrossRefPubMedGoogle Scholar
- 18.NIH State-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”) (2002) NIH Consensus and State-of-the-Science Statements 19:1–23Google Scholar
- 23.Prete A, Paragliola RM, Bottiglieri F, Rota CA, Pontecorvi A, Salvatori R, Corsello SM (2016) Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing disease and nonmalignant primary adrenal Cushing syndrome. Endocrine. https://doi.org/10.1007/s12020-016-1007-5 (Epub ahead of print) Google Scholar
- 29.Kazlauskaite R, Evans AT, Villabona CV, Abdu TA, Ambrosi B, Atkinson AB, Choi CH, Clayton RN, Courtney CH, Gonc Maghnie M, Rose SR, Soule SG, Tordjman K, Consortium for Evaluation of Corticotropin Test in Hypothalamic–Pituitary Adrenal Insufficiency (2008) Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 93:4245–4253CrossRefPubMedGoogle Scholar
- 30.Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). J Am Med Ass 285:2486–2497CrossRefGoogle Scholar
- 33.Reincke M, Nieke J, Krestin GP, Saeger W, Allolio B, Winckelmann W (1991) Preclinical Cushing’s syndrome in adrenal “incidentaloma”: comparison with adrenal Cushing’s syndrome. J Clin Endocrinol Metab 75:826–832Google Scholar
- 34.Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, Husebye ES, Merke DP, Murad MH, Stratakis CA, Torpy DJ (2016) Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 101:364–389CrossRefPubMedGoogle Scholar