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



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.

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Correspondence to Baha M Arafah.

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Khawandanah, D., ElAsmar, N. & Arafah, B.M. 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. Endocrine 63, 140–148 (2019).

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  • HPA
  • ACTH
  • Cortisol-secreting Adenomas
  • Adrenal incidentalomas
  • Adrenalectomy