Elsevier

World Neurosurgery

Volume 119, November 2018, Pages e106-e117
World Neurosurgery

Original Article
Outcome of Transsphenoidal Surgery for Cushing Disease: A Single-Center Experience over 20 Years

https://doi.org/10.1016/j.wneu.2018.07.055Get rights and content

Highlights

  • The overall remission rate in our center (mainly 1 surgeon) was 83%. Highest remission rate in patients with macroadenomas (92%).

  • Successful first MN-TSS was correlated with a high final remission rate (95%), failed first MN-TSS remained associated with a low final remission rate (36%) even after additional surgery.

  • For patients with CD for many years, a high-level day 1 cortisol level was regularly observed even if followed by long-term remission.

  • Less than 10% of postoperative pituitary long-term hypofunction.

Background

This study investigated the outcome of transsphenoidal surgery (TSS) for Cushing disease (CD) and the influence of our surgical strategy on remission rates and postoperative pituitary function.

Patients and Methods

We retrospectively reviewed data from 71 patients with CD who underwent microscope navigation TSS (MN-TSS) in Saint-Luc Hospital between 1996 and 2017. True remission was defined as normal fasting cortisol level, normal 24-hour urinary free cortisol, or continued need for hydrocortisone replacement for 1 year after surgery.

Results

Overall remission rate after 1 or repeated MN-TSS was 83%. Highest remission rate was found in patients with macroadenomas (92%). Successful first MN-TSS was correlated with a high final remission rate (95%), whereas failed first MN-TSS was correlated with a low final remission rate (36%). Although day 1 cortisol levels were significantly lower in patients with long-term remission, high levels were still observed in a few patients, especially those who had had CD for many years. We found a low rate of postoperative pituitary long-term hypofunction (9.7%).

Conclusions

MN-TSS is a safe and effective procedure to treat CD, allowing remission rates of 83%. One-year remission period after first surgery is correlated with a final remission rate of 95%. Although day 1 morning cortisol value is the most significant predictor for long-term remission, some patients with CD for many years may keep high postoperative cortisol levels and be in later remission, likely because of secondary adrenal hyperplasia. Our focused approach with microscope navigation resulted in low rates of postoperative pituitary hypofunction and kept a recurrence rate comparable to that in the literature.

Introduction

Cushing disease (CD) is a severe endocrine disorder resulting from hypersecretion of adrenocorticotrophin hormone (ACTH) by a pituitary tumor. Excluding administration of exogenous steroids, pituitary adenoma is the most frequent cause (80%) of endogenous Cushing syndrome (CS).1, 2 Disease prevalence is estimated to be 40 cases per million inhabitants and incidence is 2.4 cases per million inhabitants per year.1, 3

Chronic hypercortisolism can lead to serious complications and death, with a reported 4-fold increased risk of mortality.3, 4 Therefore, early diagnosis and treatment (which normalize the mortality risk) are recommended for all patients.5, 6

Surgical resection remains the gold standard for this condition.7 Given that most ACTH adenomas are microadenomas, the usual primary goal of resection is to cure the underlying endocrinopathy. Most rarely, in large and invasive corticotroph adenomas, mass effect can also justify a debulking surgery.7

Transsphenoidal surgery (TSS) usually leads to remission rates ranging from 68% to 95%.8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 Rates are variable depending on location and type of tumor, neurosurgeon's expertise, duration of the follow-up, and criteria used to define the remission.19

The aim of this study was to retrospectively analyze the outcome of 71 patients with CD who underwent their first microscope navigation-TSS (MN-TSS) in Saint-Luc Hospital between 1996 and 2017. It allowed us to update our previously reported data.8

Section snippets

Population

Seventy-one patients with CD underwent MN-TSS in our department between 1996 and 2017. All patients presented with typical characteristics of chronic hypercortisolism. The signs and symptoms most frequently reported were weight gain and truncal obesity, cervical and supraclavicular fat pad, red and rounded face, hirsutism and acne, stretch marks, tendency toward bruising (all previous were grouped into cushingoid features in Table 1), fatigue, muscular weakness, hypertension, depression,

Results

The main characteristics of our 71 patients are shown in Table 1. Fifty-seven patients (80.3%) were female and 14 were male (19.7%) (female/male ratio, 4:1). The age of patients ranged from 15 to 84 years (mean, 43 ± 14 years). Preoperative pituitary MRI showed 13 macroadenomas (18%), 41 microadenomas (58%), and 17 nonvisible adenomas (24%). Among the 17 patients with nonvisible adenomas, there were 2 patients for whom MRI could not be performed: in these 2 patients, computed tomography also

Discussion

A clear and universal definition of remission of CD still does not exist: each center defines it according to its own criteria. Although bias could be avoided by a very long-term remission study (e.g., 10 years), the average follow-up is only around 72 months in the literature, and 82 months in our series. Therefore, differences between several studies should be interpreted with caution and criteria used to define remission must be taken into account (Table 6). Most restrictive criteria of

Conclusions

MN-TSS is a safe and effective primary treatment for CD, allowing high remission rates, as much for noninvasive macroadenomas as for visible microadenomas, and a reasonable success rate is also obtained for MRI-negative adenomas. The 1-year remission period after first surgery is associated with a final remission rate of 95%, whatever the number of recurrences and repeat surgeries. On the other hand, failed first MN-TSS (persistent disease) is correlated with a final low remission rate.

Acknowledgments

We thank Viorica Radian for assistance with statistical analyzes.

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    Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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