Alterations in hypothalamic-pituitary-adrenal function immediately after resection of adrenal adenomas in patients with Cushing’s syndrome and others with incidentalomas and subclinical hypercortisolism
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Patients with cortisol secreting adrenal adenomas present with Cushing’s syndrome (CS), while 5–15% of subjects with adrenal incidentalomas have subclinical hypercortisolism (SH) as they have biochemical abnormalities suggesting autonomous cortisol secretion without associated clinical features of CS.
Examine HPA function immediately after resection of either of these adenomas and utilize the data to decide on initiating glucocorticoid replacement.
ACTH, cortisol, and DHEA-S levels were measured frequently for 8 h after adrenalectomy in 14 patients with CS and 19 others with incidentalomas + SH. Glucocorticoids were withheld before/during surgery and administered 6–8 h postoperatively to those who had cortisol levels of <3 ug/dL (83 nmol/L).
Preoperatively, incidentalomas + SH patients had larger tumors, higher ACTH, and DHEA-S but lower dexamethasone-suppressed serum cortisol levels than those with CS. Postoperatively, ACTH levels increased in both groups: (90.1 ± 31.6; 24.1 ± 14.4 ng/L, respectively; P < 0.001). Postoperative ACTH levels correlated negatively with preoperative Dexamethasone-suppressed cortisol concentrations in both groups. Patients with CS had steeper decline in cortisol concentrations than those with incidentalomas + SH. All patients with CS had hypocortisolemia requiring glucocorticoid therapy for several months, while only 5/19 with incidentalomas + SH had cortisol levels <3 ug/dL;(83 nmol/L) 6–8 h after adrenalectomy and received hydrocortisone replacement therapy for ≤4 weeks.
Surgical stress stimulates HPA function even in patients with hypercortisolemia. Patients with incidentalomas + SH have incomplete HPA suppression that allows more robust response to surgical stress than that observed in patients with CS. HPA assessment immediately after surgical resection of adrenal incidentalomas identified those requiring glucocorticoid replacement before discharge.
KeywordsHPA ACTH Cortisol-secreting Adenomas Adrenal incidentalomas Adrenalectomy
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board and with the 1964 Helsinki declaration and later amendments or comparable ethical standards.
An informed consent was obtained from all participants in the study.
- 3.V. Morelli, B. Masserini, A.S. Salcuni, C. Eller-Vainicher, C. Savoca, R. Viti, F. Coletti, G. Guglielmi, C. Battista, L. Lorio, P. Beck-Peccoz, B. Ambrosi, M. Arosio, A. Scillitani, I. Chiodini, Subclinical hypercortisolism: correlation between biochemical diagnostic criteria and clinical aspects. Clin. Endocrinol. 73(2), 161–166 (2010)Google Scholar
- 8.I. Chiodini, V. Morelli, B. Masserini, A.S. Salcuni, C. Eller-Vainicher, R. Viti, F. Coletti, G. Guglielmi, C. Battista, V. Carnevale, L. Iorio, P. Beck-Peccoz, M. Arosio, B. Ambrosi, A. Scillitani, 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(9), 3207–3214 (2009)CrossRefGoogle Scholar
- 9.C. Eller-Vainicher, V. Morelli, F.M. Uliveri, S. Palmieri, V.V. Zhukouskaya, E. Cairoli, R. Pino, A. Naccarato, A. Scillitani, P. Beck-Peccoz, I. Chiodini, Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism. J. Bone Miner. Res. 27(10), 2223–2230 (2012)Google Scholar
- 10.V. Morelli, C. Eller-Vainicher, A.S. Salcuni, F. Coletti, L. Iorio, G. Muscogiuri, S. Della Casa, M. Arosio, B. Ambrosi, P. Beck-peccoz, I. Chiodini, Risk of new vertebral fractures in patients with adrenal incidentaloma with and without subclinical hypercortisolism: a multicenter longitudinal study. J. Bone Miner. Res. 26(8), 1816–1821 (2011)CrossRefGoogle Scholar
- 12.V. Morelli, G. Reimondo, Giordano, S. Della Casa, C. Policola, S. Palmieri, A.S. Salcuni, A. Dolci, M. Mendola, M. Arosio, B. Ambrosi, A. Scillitani, E. Ghigo, P. Beck-Peccoz, M. Terzolo, I. Chiodini, Long-term follow-up in adrenal incidentalomas: an Italian multicenter study. J. Clin. Endocrinol. Metab. 99(3), 827–834 (2014)CrossRefGoogle Scholar
- 13.I. Chiodini, V. Morelli, A.S. Salcuni, C. Eller-Vainicher, M. Torlontano, F. Coletti, L. Iorio, A. Cuttitta, A. Ambrosio, L. Vicentini, F. Pellegrini, M. Copetti, P. Beck-Peccoz, M. Arosio, B. Ambrosi, V. Trischitta, A. Scillitani, Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism. J. Clin. Endocrinol. Metab. 95(6), 2736–2745 (2010)CrossRefGoogle Scholar
- 16.I. Bancos, F. Alahdab, R.K. Crowley, V. Chortis, D.A. Delivanis, D. Erickson, N. Natt, M. Terzolo, W. Arlt, W.F.J.R. Young, M.H. Murad, Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: A systematic review and meta-Analysis. Eur. J. Endocrinol. 175(6), R283–R295 (2016)CrossRefGoogle Scholar
- 17.M. Iacobone, M. Citton, G. Viel, R. Boetto, I. Bonadio, I. Mondi, S. Tropea, D. Nitti, G. Favia, Adrenalectomy may improve cardiovascular and metabolic impairment and ameliorate quality of life in patients with adrenal incidentalomas and subclinical Cushing’s syndrome. Surgery 152(6), 991–997 (2012)CrossRefGoogle Scholar
- 18.M.C. Dennedy, A.K. Annmalai, O. Prankerd-Smith, N. Freeman, K. Vengopal, J. Graggaber, O. Koulouri, A.S. Powlson, A. Shaw, D.J. Halsall, M. Gunnell, Low DHEA-S: A sensitive and specific test for the detection of subclinical hypercortisolism in adrenal incidentalomas. J. Clin. Endocrinol. Metab. 102, 786–792 (2017)Google Scholar
- 19.C. Eller-Vainicher, V. Morelli, A.S. Salcuni, M. Torlontano, F. Coletti, L. Iorio, A. Cuttitta, A. Ambrosio, L. Vicentini, V. Carnevale, P. Beck-Peccoz, M. Arosio, B. Ambrosi, A. Scillitani, I. Chiodini, Post-surgical hypocortisolism after removal of an adrenal incidentaloma: is it predictable by an accurate endocrinological work-up before surgery? Eur. J. Endocrinol. 162(1), 91–99 (2010)CrossRefGoogle Scholar
- 21.C.M. Berr, G. Di Dalmazi, A. Osswald, K. Ritzel, M. Bidlingmaier, L.L. Geyer, M. Treitl, K. Hallfeldt, W. Rachinger, N. Reisch, R. Blaser, J. Schopohl, F. Beuschlein, M. Reincke, Time to recovery of adrenal function after curative surgery for Cushing’s syndrome depends on etiology. J. Clin. Endocrinol. Metab. 100(4), 1300–1308 (2015)CrossRefGoogle Scholar
- 22.M. Fassnacht, W. Arlt, I. Bancos, H. Dralle, J. Newell-Price, A. Sahdev, A. Tabarin, M. Terzolo, S. Tsagarakis, O.M. Dekkers, 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(2), G1–G34 (2016)CrossRefGoogle Scholar
- 25.D. Ortiz, J.W. Finding, T.B. Carroll, B.R. Javorsky, A.A. Carr, D.B. Evans, T.W. Yen, T.S. Wang, Cosyntropin stimulation testing on postoperative day 1 allows for selective glucocorticoid replacement therapy after adrenalectomy for hypercortisolism: Results of a novel, multidisciplinary institutional protocol. Surgery 159(1), 259–265 (2016)CrossRefGoogle Scholar
- 26.B.M. Arafah, O.H. Pearson. in Cushing’s syndrome. ed. by R.E. Rakel. Conn’s Current Therapy, 36th edn., (WB Saunders Co, Philadelphia, 1984), p. 472–477Google Scholar
- 31.V. Bansal, N. El Asmar, W.R. Selman, B.M. Arafah, Pitfalls in the diagnosis and management of Cushing’s syndrome. Neurological. Focus 38, 1–11 (2015)Google Scholar
- 34.R. Udelsman, J.A. Norton, S.E. Jelenich, D.S. Goldstein, W.M. Linehan, D.L. Loriaux, G.P. Chrousos, Responses of the hypothalamic-pituitary-adrenal and renin-angiotensin axes and the sympathetic system during controlled surgical and anesthetic stress. J. Clin. Endocrinol. Metab. 64, 986–994 (1987)CrossRefGoogle Scholar
- 38.A. Prete, R.M. Paragliola, F. Bottiglieri, C.A. Rota, A. Pontecorvi, R. Salvatori, S.M. Corsello, Factors predicting the duration of adrenal insufficiency in patients successfully treated for Cushing’s disease an nonmalignant primary adrenal Cushing’s syndrome. Endocrine 55, 969–980 (2017)CrossRefGoogle Scholar
- 39.M. Reincke, J. Nieke, G.P. Krestin, W. Saeger, B. Allolio, W. Winkelmann, Precrinical Cushing’s syndrome in adrenal incidentalomas: comparison with adrenal Cushing’s syndrome. J. Clin. Endocrinol. Metab. 75, 826–832 (1992)Google Scholar