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Outcomes of pituitary surgery for Cushing’s disease: a systematic review and meta-analysis

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Abstract

Purpose

Transsphenoidal surgery (TSS) is the first-line treatment for Cushing’s disease (CD). This review aimed to synthesize the remission and recurrence rates following TSS for CD and identify predictors of these outcomes.

Methods

Medline (1946-) and Embase (1947-) were searched until 23rd January 2019 for original studies. A meta-analysis was performed of remission and recurrence rates. Studies were excluded if patients had prior radiosurgery/radiotherapy, mixed pathologies or interventions without separated data, follow-up not reported or population size < 20. For recurrence rate syntheses, studies with follow-up < 6 months were excluded.

Results

The search produced 2663 studies, of which n = 68 were included, involving 5664 patients. Remission rates after primary and revision TSS were 80% [77–82] and 58% [50–66] at last follow-up. After primary TSS, predictors of remission were micro- v macroadenomas (83% v 68%, p < 0.01), imaging-visible adenomas (81% v 69%, p < 0.01), adenomas confirmed on histopathology (87% v 45%, p < 0.01), absence of cavernous sinus invasion (80% v 30%, p < 0.01), postoperative serum cortisol (MSeC) nadir < 2 μg/dL (< 55 nmol/L; 95% v 46%, p < 0.01) and lower preoperative 24-h urine free cortisol (1250 nmol v 1726 nmol, p < 0.01). For revision TSS, predictors of remission were postoperative MSeC nadir < 2 μg/dL (< 55 nmol/L; 100% v 38%, p < 0.01) and operations for recurrence v persistence (80% v 54%, p < 0.01). Recurrence rates after primary and revision TSS were 18% [14–22] and 28% [16–42].

Conclusions

TSS is most effective in primary microadenomas, visible on preoperative imaging and without CS invasion, lower preoperative 24-h urine free cortisol and postoperative MSeC nadir < 2 μg/dL (< 55 nmol/L).

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Acknowledgements

The authors thank the staff of the Sydney Ear Nose and Throat Clinic and members of the Rhinology and Pituitary Research Groups for their feedback and support.

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This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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Correspondence to Anna Stroud.

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Richard J Harvey is consultant with Medtronic, Stryker, Novartis, Meda, and NeilMed pharmaceuticals. Research grant funding received from Glaxo-Smith-Kline and Stallergenes. He has been on the speakers’ bureau for Glaxo-Smith-Kline, Meda Pharmaceuticals and Seqirus. Ann McCormack has received speaker honorarium for IPSEN, Pfizer and Novartis. Benjamin P Jonker has received speaker fees from Integra LifeSciences Corporation. All other authors declare that they have no conflicts of interest.

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Stroud, A., Dhaliwal, P., Alvarado, R. et al. Outcomes of pituitary surgery for Cushing’s disease: a systematic review and meta-analysis. Pituitary 23, 595–609 (2020). https://doi.org/10.1007/s11102-020-01066-8

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