Original ArticleOutcome of Transsphenoidal Surgery for Cushing Disease: A Single-Center Experience over 20 Years
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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Cited by (22)
Presurgical predictive factors of surgical remission in Cushing's disease. Study of 32 cases
2022, Endocrinologia, Diabetes y NutricionCitation Excerpt :However, the predictive value of preoperative ACTH levels has not been widely accepted and remains controversial. In addition, no correlation between remission and preoperative 24-h UFC levels was detected in our study, consistent with previous studies’ results.9,29 Interestingly, Schernthaner-Reiter et al.30 reported that lower baseline UFC was associated with a higher number of long-term comorbidities, possibly due to the,more prolonged exposure to excess glucocorticoids in milder CD.
Pituitary neuroendocrine tumors: a model for neuroendocrine tumor classification
2021, Modern PathologyThe definition of remission and recurrence of Cushing's disease
2021, Best Practice and Research: Clinical Endocrinology and MetabolismCitation Excerpt :Multiple presurgical factors have repercussion over achievement of disease remission and the odds of recurrence. Most studies are consistent that microadenomas have higher remission rates than macroadenomas, although a recent single-center study reported the contrary [4,57,58]. The surgeon’s expertise, proper identification of the adenoma by imaging studies, lack of invasion to the cavernous sinuses and a patient’s age >35 years are also presurgical predictors for remission [59–62].
Cushing's syndrome – Disease monitoring: Recurrence, surveillance with biomarkers or imaging studies
2020, Best Practice and Research: Clinical Endocrinology and MetabolismCitation Excerpt :Furthermore, two of 4 children who regained normal cortisol production within 6 months after surgery developed recurrent CD [62]. Some patients with high early postoperative serum cortisol concentrations archive remission later without any further intervention, a phenomenon called delayed remission [30,55]. In a large multicentre study by Valassi et al., 35 of 620 (5.6%) patients who underwent transsphenoidal surgery for CD had a delayed remission after a median of 9 days (range 4–180) [30].
Development and validation of an MRI-based radiomic signature for the preoperative prediction of treatment response in patients with invasive functional pituitary adenoma
2019, European Journal of RadiologyCitation Excerpt :An increase in GH levels can cause cardiovascular and cerebrovascular diseases, and GH-secreting IFPAs carry a mortality rate at least twice as high as in the general population [29]. The chronic hypercortisolism caused by ACTH-secreting IFPAs can lead to serious complications and death, with a reported four-fold increased risk of mortality [30]. Therefore, in addition to the mass effect caused by the tumor size, IFPA patients may need individualized treatment for symptomatic elevated serum hormone levels.
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.