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Surgical outcomes in patients with Cushing’s disease: the Cleveland clinic experience

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Abstract

Context

Transsphenoidal surgery (TSS) to resect a pituitary adenoma is considered first-line treatment for patients with Cushing’s disease (CD). Early, post-operative remission rates >80% are expected for patients with a microadenoma (≤ 10 mm) visible on magnetic resonance (MR) imaging.

Objective

To report surgical outcomes and predictors of remission in a specialist center for patients with CD.

Patients and methods

Clinical data was obtained from a prospective CD database in addition to review of all electronic medical, laboratory and surgical patient records. Patients who underwent their first TSS by one neurosurgeon between 2004 and 2013, and had a minimum 1 year follow up, were evaluated.

Results

One hundred and one consecutive patients with CD (73F, 28M) underwent TSS. Median (range) age and follow-up were 47 (15–87) and 4.33 (1–9.8) years, respectively. At surgery, 74 (73.2%) patients had a microadenoma, 27 a macroadenoma; six of the latter patients had a planned, subtotal resection to control neurological signs due to mass effect. Initial remission rates were: microadenoma, 89% (66/74); macroadenoma, 63% (17/27); and 81% (17/21) in those macroadenomas where complete surgical removal was anticipated. Initial non-remission occurred in 18 patients, ten macro- and eight microadenoma; six of 18 had residual disease on most recent follow up. Six (2 macro, 4 micro) of the 83 patients with initial remission have had late (>12 months) recurrence of hypercortisolism that required either repeat TSS or adjunctive therapy, three of whom have persistent hypercortisolism. Macroadenoma (p = 0.003) and tumor invasion beyond the pituitary and sella (p < 0.001) were associated with failure to obtain remission with the initial TSS and greater likelihood of late recurrence. Patients in whom no lesion was seen on neuroimaging had rates of initial remission (21/25 or 84%) and a similar late recurrence rate of 4% (1/25) in comparison with those with MR-visible microadenomas (3/49, or 6%).

Conclusions

A team-based approach, in a specialized pituitary center, can lead to initial and durable, long-term remission in patients with CD. The presence of a macroadenoma and tumor extension beyond the pituitary and sella were predictive of initial non-remission as well as risk of late recurrence.

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Abbreviations

TSS:

Transsphenoidal tumor resection

ACTH:

Adrenocorticotropic hormone

UFC:

Urinary free cortisol

CD:

Cushing’s disease

CS:

Cushing’s syndrome

IPSS:

Inferior petrosal sinus sampling

ULN:

Upper limit of normal

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Author information

Author notes

  1. Philip C. Johnston

    Present address: Regional Center for Endocrinology and Diabetes, Royal Victoria Hospital, Grosvenor Road, Belfast, UK

  2. Robert J. Weil

    Present address: National Clinical Enterprise, Catholic Health Initiatives, Englewood, CO, USA

Authors and Affiliations

  1. Department of Endocrinology, Diabetes and Metabolism, Cleveland Clinic, 9500 Euclid Avenue Desk F20, Cleveland, OH, 44195, USA

    Philip C. Johnston, Laurence Kennedy, Amir H. Hamrahian, Zahrae Sandouk & Betul Hatipoglu

  2. Department of Endocrinology, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

    Amir H. Hamrahian

  3. Department of Biostatistics, Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA

    James Bena

  4. Department of Neurosurgery, the Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

    Robert J. Weil

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  1. Philip C. Johnston
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Corresponding author

Correspondence to Philip C. Johnston.

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Conflict of interest

All authors on this manuscript have declared that they have no conflict of interest.

Disclosure

All authors of this manuscript have no conflicts of interest to disclose Acknowledgments: We thank the physician staff at Cleveland Clinic including Dr Leann Olanksy who referred patients for surgery.

Ethical approval

Informed consent was obtained from all individual participants included in the study. This article does not contain any studies with human participants or animals performed by any of the authors.

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Johnston, P.C., Kennedy, L., Hamrahian, A.H. et al. Surgical outcomes in patients with Cushing’s disease: the Cleveland clinic experience. Pituitary 20, 430–440 (2017). https://doi.org/10.1007/s11102-017-0802-1

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