Long-term outcome of unilateral adrenalectomy for primary bilateral macronodular adrenal hyperplasia

Purpose Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a form of Cushing's syndrome (CS) characterized by heterogeneous cortisol secretion and clinical comorbidities. Previously, bilateral adrenalectomy was the standard treatment for PBMAH, but this approach carried a high risk of primary adrenocortical insufficiency. In recent decades, unilateral adrenalectomy (U-Adx) has emerged as an effective alternative. However, limited research exists on its postoperative efficacy and prognostic predictors. Therefore, the present study aimed to investigate the long-term effectiveness and prognostic predictors of U-Adx in treating PBMAH. Methods A total of 61 patients with PBMAH diagnosis who underwent U-Adx at a single center between 2004 and 2022 were retrospectively evaluated. Patients were categorized into persistent hypercortisolism and remission groups based on postoperative biochemical outcomes at the last follow-up (>12 months after U-Adx). Clinical characteristics, comorbidities, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-h urinary-free cortisol (24-h UFC) levels were analyzed pre- and postoperatively. We further examined whether baseline plasma ACTH, serum cortisol, 24-h UFC levels, and the inhibition of cortisol and 24-h UFC after a low-dose dexamethasone suppression test (LDDST) could predict non-remission following U-Adx. Additionally, we explored the improvements in hypertension, abnormal glucose metabolism, osteoporosis, and other complications in patients with PBMAH post-U-Adx. Results After U-Adx, 22 of the 45 patients (48.89%) achieved initial remission within 6 months. At the last follow-up, 25 of the 45 patients underwent all required biochemical tests and cortisol assessment tests, among which eight of 25 (32.00%) were in remission and 17 of 25 (68.00%) were experiencing persistent hypercortisolism. Moreover, five of those 25 patients exhibited recurrence after initial remission. Baseline 24-h UFC level > 2 times the upper limit of normal (2ULN) and unsuppressed 24-h UFC after LDDST may predict persistent hypercortisolism postoperatively. Lastly, long-term postoperative follow-up revealed that hypertension decreased with hypercortisolism remission, whereas osteoporosis worsened with persistent hypercortisolism. Conclusion The short-term remission rate of hypercortisolism was 48.89% in patients with PBMAH treated with U-Adx, while a long-term remission rate of 32.00% was achieved after a median follow-up of 38.58 months. Furthermore, this finding suggests that baseline 24-h UFC level > 2ULN and unsuppressed 24-h UFC after LDDST predict persistent hypercortisolism in the long-term post-U-Adx. Finally, U-Adx improved cortisol circadian rhythm alterations and ACTH suppression in the patients in the remission group, thereby substantially alleviating hypertension and delaying the development of osteoporosis linked to PBMAH.