Disease Remission and Surgical Outcomes of Endoscopic Transsphenoidal Surgery for Cushing Disease: A Single Center Experience

Posted on February 1, 2026 by MaryO

Introduction

Transsphenoidal surgery is the primary treatment for patients with Cushing disease (CD). This study assessed the surgical and endocrinologic outcomes of patients with CD following endoscopic pituitary surgery using strict biochemical criteria to guide surveillance in patients not achieving early remission.

Methods

The medical records of all patients with CD who underwent endoscopic transsphenoidal surgery at a single institution between 2004 and 2025 were reviewed. Remission was defined as a fasting serum cortisol level <50 nmol/L (1.8 μg/dL) either basal or after 1 mg dexamethasone.

Results

A total of 125 patients were diagnosed with CD and had a primary endoscopic transsphenoidal surgery during the study period (median age 48 years [range: 14–79 years; M:F 93:32). Fifty-seven patients (45.6%) had a microadenoma, 41 (32.8%) had a macroadenoma, and 26 (20.8%) had no demonstrable focal lesion on pituitary magnetic resonance imaging (MRI) (MRI-negative CD). The median length of follow-up was 3.1 years (range: 1 month to 16.7 years). Initial remission rates 3 months after surgery were: 72.0% for patients with MRI-negative CD, 77.2% for microadenomas, and 48.7% for macroadenomas. Age, male sex, MRI-negative, and single operation were predictors of remission. Patients who achieved remission at 3 months were significantly more likely to be in remission at last follow-up after accounting for patient and tumor characteristics. The 5-year recurrence rate following remission was 6.9%.

Conclusion

Endoscopic transsphenoidal surgery is an effective first-line treatment for patients with CD but a significant minority will relapse. Close biochemical surveillance of patients who fail to achieve remission may support the use of early adjuvant radiotherapy.

Key words

Cushing disease
Endoscopic transsphenoidal surgery
Remission

Abbreviations

CD

Cushing’s Disease
CSF

Cerebrospinal fluid
DI

Diabetes insipidus
MRI

Magnetic Resonance Imaging

Introduction

Cushing disease (CD) is a rare endocrine disease caused by the circulation of excess cortisol due to hypersecretion of adrenocorticotrophic hormone from a pituitary adenoma. The annual incidence of CD is estimated to be between 1.2 and 2.4 million cases per year1, 2, 3 although it may be higher in selected patient populations such as those with poorly controlled diabetes and young patients with osteoporosis or hypertension.4 Untreated CD is associated with a very poor prognosis and a significantly reduced 5-year survival mandating prompt and effective treatment.5 Nevertheless, long-term management of patients with CD remains challenging.
In most cases of CD, the pituitary adenoma is benign and excellent remission rates have been reported with surgical treatment.6, 7, 8 Comparable remission rates of around 80% have been reported with both microscopic and endoscopic transsphenoidal pituitary surgery,7,8 however the basal serum cortisol level used to define remission varies significantly in the literature (50–138 nmol/L). Several previous studies have also excluded macroadenomas and invasive tumors from longitudinal analysis. As such, there is a paucity of long-term clinical data for an unselected population undergoing endoscopic transsphenoidal pituitary surgery for CD. Furthermore, there is little evidence concerning the optimal management of patients who fail to enter complete biochemical remission (basal serum cortisol level <50 nmol/L [1.8 μg/dL]) following their initial surgical treatment.
The aim of this study was to assess the treatment pathway and long-term outcomes of consecutive patients treated at a regional treatment center over a 20-year period. All surgical cases were performed using a purely endoscopic approach and we evaluated the impact surgical experience on clinical outcomes. We assessed biochemical remission rates immediately following surgery (within 2 weeks of surgery), at 3 months and at the patient’s most recent follow-up appointment and analyzed predictors of successful remission in our patient group. For those who did not achieve biochemical remission, we detail the treatment course of patients placed under surveillance and those who underwent adjuvant therapy. In doing so, we illustrate a complete picture of the surgical outcomes and subsequent management of an unselected population that may be encountered during the treatment of patients with CD at a dedicated regional center.

Methods

Study Population

We analyzed the medical records of all patients diagnosed with CD who underwent primary surgical treatment at King’s College Hospital, London, between January 2004 and January 2025. Patients were identified from our prospective pituitary multidisciplinary database and cross-referenced with data from the hospital’s clinical coding department and operative database.

Preoperative Investigations

Serum cortisol was measured by chemiluminescent assay (Siemens ADVIA Centaur XP) with a sensitivity of 0.0362 nmol/L. A diagnosis of Cushing syndrome was confirmed by a serum cortisol measurement of >50 nmol/L after administering a 1-mg low-dose dexamethasone suppression test. Additional 24-hour urinary free cortisol measurements (>50 μg/24 hours), late night salivary cortisol measurements (>4 nmol/L), plasma adrenocorticotrophic hormone levels (pg/mL), and 48-hour 2-mg low-dose dexamethasone suppression tests were performed as required. All patients with confirmed Cushing syndrome underwent magnetic resonance imaging (MRI) of the pituitary gland and in equivocal cases patients also underwent corticotrophin-releasing hormone stimulation, high-dose dexamethasone suppression test, and/or inferior petrosal sinus sampling before proceeding to surgery.

Surgical Procedure

Surgery was performed via an endoscopic transnasal transsphenoidal approach in all study patients as described by Jho9 and Cappabianca.10 Image guidance was used in patients with complex or atypical sinus or vascular anatomy, those with very small microadenomas, and in patients undergoing repeat surgery. Complete hypophysectomy (sellar clearance) was performed for patients with MRI-negative Cushing disease. The histological pseudocapsular technique was employed to permit wide exposure of the sella, pituitary, and parasellar region.11,12 If a cerebrospinal fluid (CSF) leak was identified intraoperatively, an autologous adipose tissue graft was positioned in the pituitary fossa and sphenoid sinus and in selected cases a vascularized naso-septal flap was also positioned over the defect.

Postoperative Investigations and Follow-up

Our postoperative protocol included endocrinologic assessment in the early postoperative period, within 72 hours of surgery, and again within the first 2 weeks following surgery. The patient’s initial treatment strategy was defined as any surgical management within 30 days of the patient’s first surgical procedure. If a postoperative CSF leak was suspected, samples of fluid were sent for confirmatory testing of β-2-transferrin. Management of the CSF leak was determined by its severity and included observation alone, insertion of a lumbar drain and a period of bed rest, and surgical repair. Postoperative diabetes insipidus was defined as patients with polyuria requiring ongoing desmopressin therapy 6 months after surgery.
Long-term biochemical assessment of cortisol status was performed on an annual basis, or more frequently depending on the patient’s individual status. A routine postoperative MRI scan was also performed 3 months postoperatively. Remission was defined as an early morning serum cortisol of <50 nmol/L (1.8 μg/dL) requiring substitutive therapy at 3 months postoperatively. Patients who failed to enter remission were considered for further pituitary surgery, radiotherapy, medical treatment, and/or bilateral adrenalectomy. Recurrence was defined as the re-emergence of clinical features of cortisol excess supported by biochemical evidence of cortisol excess as described above. Persistent disease was defined as such was defined as a postoperative basal cortisol(s) > 50 nmol/.

Data Collection

We reviewed the biochemical, radiologic, medical, and surgical records of all study patients. The following data were collected: demographic features, preoperative endocrinologic measurements, radiologic MRI features of the tumor (including tumor visibility on MRI and size), procedural complications (including CSF leak, meningitis, diabetes insipidus [DI], hematoma, visual complications, or new cranial nerve deficits), postoperative endocrinologic assessments, and any further treatments performed.

Statistical Analysis

Categorical data are summarized using frequencies and percentages and continuous data are described using means, standard deviations, medians, and ranges. Associations between categorical variables were assessed using Fisher’s Exact test. Multivariable logistic regression models were performed in which remission statuses at (i) 3 months and (ii) last follow-up were used as outcome variables. The list of predictors of each outcome included patient characteristics (sex, age), tumor category, number of operations performed, and the presence of postoperational complications, which were decided a priori. Subgroup analyses were also performed based on tumor category—microadenomas, macroadenomas, and MRI-negative CD.
Data were collated in Microsoft Excel (Microsoft, Redmond, WA). All statistical analyses were performed using R software version 4.2.1 (R Foundation for Statistical Computing, 2022; r-project.org). P-values less than 0.05 were considered statistically significant.

Ethics Statement

This study was approved by King’s College Hospital’s research committee without the need for informed consent. The study was conducted in accordance with the ethics standards of the institution’s research committee and with the 1964 Helsinki declaration and its later amendments.

Results

Baseline Characteristics

A total of 125 patients including 93 (74.4%) female patients and 32 (25.6%) male patients were diagnosed with CD and had primary endoscopic transsphenoidal surgery during the study period. The median age was 48 years (range: 14–79 years). Fifty-seven patients (45.6%) had a microadenoma, 41 (32.8%) had a macroadenoma, and 26 (20.8%) had no demonstrable focal lesion on pituitary MRI (MRI-negative CD). The median length of follow-up was 3.1 years (range: 1 month to 16.7 years). Of the 125 patients included in our study, 88 patients (70.4%) had a single operation during their initial treatment strategy. Thirty-seven patients (29.6%) had more than 1 operation; 4 patients (3.2%) had 3 operations during the study period. A summary of the baseline characteristics of our patients can be found in Table 1.

Table 1. Baseline Characteristics of the Study Population

Number of Patients 125
Patient variables
 Age Median 48 (range: 14–79) years
 Male 32 (25.6%)
Pituitary characteristics
 Microadenoma 57 (45.6%)
 Macroadenoma 41 (32.8%)
 No focal lesion on pituitary MRI (MRI-negative Cushing’ disease) 26 (20.8%)
Operative variables
 Single operation 88 (70.4%)
 More than 1 operation 33 (26.4%)
 3 operations 4 (3.2%)

Perioperative Complications

Forty patients (32.0%) had a complication following their surgery (Table 2). The overall complication rate for patients undergoing a single procedure was 23.9% (21 of 88) and was significantly lower than the complication rate in patients who had multiple operations: 51.3% (19 of 37) (P = 0.002). The complication rates for different tumor types were not significantly different: microadenoma 33.3% (19 of 57), macroadenoma 36.6% (15 of 41), MRI-negative CD 23.1% (6 of 26) (P = 0.274). There was a significant difference between complications in the second period; Period 1: 8.7% (2 of 23) and Period 2: 37.3% (38 of 102) (P = 0.008).

Table 2. Procedural Complications Encountered in Our Series

Complication N (%)
Any complication 40 (32.0%)
Persistent diabetes insipidus 18 (14.4%)
Cerebrospinal fluid leak 17 (13.6%)
Meningitis 2 (1.6%)
Ventriculitis 1 (0.8%)
Bleeding/haematoma 4 (3.2%)
Visual deterioration 2 (1.6%)
Death 3 (2.4%)
Eighteen patients (14.4%) developed persistent DI following surgery (requiring treatment for more than 6 months which we considered as a complication). Separately, in 12 patients (9.6%) the DI was transient and resolved spontaneously within 6 months of surgery, and 34 patients (27.2%) recovered from transient DI before discharge.
A confirmed postoperative CSF leak occurred in 17 patients (13.6%) and was significantly higher in patients who had multiple procedures; the CSF leak rate was 16.2% (6 of 37) in patients who had multiple procedures versus 12.5% (11 of 88) in those who only had a single procedure (P = 0.004). The type of tumor did not affect the CSF leak rate (P = 0.737). In 3 (2.4%) patients, the leak settled with observation alone. Three (2.4%) patients were managed with only a lumbar drain and 11 (8.8%) patients underwent surgical repair either as an executive decision or after failed lumbar drain. There were 2 (1.6%) cases with new cranial nerve deficits following surgery presenting with visual deterioration and a partial sixth nerve palsy. Two patients developed meningitis (1.6%), 1 (0.8%) developed ventriculitis. Four patients (3.2%) developed postoperative bleeding or hematoma requiring surgical attention.
Three (2.4%) patients died in the immediate perioperative period. One (0.8%) patient developed acute respiratory failure and suffered a cardiac arrest. Significant intraoperative bleeding was encountered in the other 2 cases (1.6%); 1 (0.8%) subsequently died of acute cardiorespiratory instability and the other (0.8%) died because of multiorgan failure following a prolonged stay on the intensive care unit.

Disease Remission

The overall remission rate 2 weeks following surgery was 59.0% (72 of 122), increasing to 60.7% (74 of 122) at 3 months. The remission rate 3 months following surgery was 72.0% (18 of 25) for patients with MRI-negative CD, 77.2% (44 of 57) for microadenomas, and 48.7% (19/39) for macroadenomas. Following adjuvant treatment and further surgery, the overall remission rate at last follow up was 68.0% (85 of 125).
Age, patient sex, tumor category and the number of operations were significant predictors of remission at three months. Age (adjusted odds ratio [aOR]: 1.04, 95% CI: 1.01–1.07, P = 0.009), male sex (aOR: 4.15, 95% CI: 1.64–10.53, P = 0.003), MRI-negative CD (aOR: 2.25, 95% CI: 1.24–4.07, P = 0.008), and single operation (aOR: 3.87, 95% CI: 1.56–9.61, P = 0.004), were predictors of remission at 3 months (Table 3).

Table 3. Multivariable Logistic Regression for Predictors of Remission at Last Follow-up

Outcome Predictor Multivariable Analysis
Adjusted OR (95% CI) P Value
Remission at 3 months Age 1.04 (95%CI: 1.01–1.07) 0.009
Sex† 3.31 (95%CI: 1.31–8.40) 0.011
MRI-negative Cushing disease‡ 1.88 (95%CI: 1.06–3.35) 0.031
Single operation§ 3.87 (95%CI: 1.56–9.61) 0.004
Remission at last follow-up Age 1.00 (95%CI: 0.97–1.04) 0.904
Sex† 2.92 (95%CI: 0.89–9.62) 0.003
MRI-negative Cushing disease‡ 1.84 (95%CI: 0.89–3.79) 0.008
Single operation§ 1.24 (95%CI: 0.36–4.24) 0.730
Remission at 3 months∗ 27.0 (95%CI: 8.47–83.33) <0.001
∗
No remission is used as the reference group.
†
Female is used as the reference group.
‡
Microadenoma is used as the reference group.
§
Multiple operation is used as the reference group.
Additionally, patients were more likely to be in remission at last follow-up if they had achieved remission at 3 months, compared with those who had not (aOR: 31.25, 95% CI: 11.2–90.9, P < 0.001). On multivariable analysis, this remained significant (aOR: 27.0, 95% CI: 8.47–83.33, P < 0.001).
Of the 72 patients who entered remission following surgery, 5 patients (6.9%) had relapsed at their last follow-up. Further intervention was performed/planned in all patients exhibiting recurrence, including repeat surgery and radiotherapy. Four of the 5 recurrences (80.0%) happened within the first 5 years.

Growth Hormone Replacement Therapy

In total, 48.0% (60 of 125) and 40.8% (51 of 125) patients required growth hormone replacement therapy at three months and at last endocrine follow up. Nine (15.0%) patients who initially needed growth hormone replacement, no longer required it at last endocrine follow-up.

Secondary Intervention

Patients with persistent disease are very likely to require a secondary intervention within a short time after initial surgery. The rate of secondary endoscopic transsphenoidal surgery was more common in patients with persistent disease (22 of 53, 41.5%) than those in initial remission (15 of 72, 20.8%) (aOR: 3.52, 95% CI: 1.48–8.38, P = 0.004). The ongoing management of patients with active disease with was tailored to the patient and included medical therapy with metyrapone, chemotherapy (temozolamide), bilateral adrenalectomy, and radiotherapy; either alone or in combination.

DISCUSSION

In one of the largest modern series in the literature, we reviewed the treatment pathway and long-term outcomes of consecutive patients treated for CD at a single regional treatment center over a 20-year period. Several previous studies have examined the surgical outcomes of patients undergoing microscopic surgery and a recent meta-analysis compared the early clinical outcomes of patients undergoing endoscopic surgery.7 However, there remains little evidence concerning the optimal long-term management of CD patients who do not immediately enter remission following surgery. Given the potential complications of CD and the challenges in managing recurrent disease, our center considers treating any patient with a cortisol of >50 nmol/L (1.8 μg/dL).

Remission

A postoperative cortisol of <50nmol/L is a good predictor of remission but not a guarantee and patients should be advised accordingly. The most conclusive finding of our study was that patients who achieved remission at 3 months were 3 times as likely to still be in remission at their last follow-up, having accounted patient and tumor characteristics. The overall initial 3-month remission rate for patients in our series was 60.7% and is comparable to other studies that have used a similarly low early morning serum cortisol level of <50 nmol/L (1.8 μg/dL) to define remission.13, 14, 15 Despite this, patients achieving early remission remain at risk of relapse with a 5-year recurrence rate of 6.9%. In addition, those with persistent disease are very likely to require a secondary intervention within a short time after initial surgery.
Using an early morning serum cortisol level of 50 nmol/L(1.8 μg/dL). to define remission enabled us to label a subgroup of patients with moderately lowered cortisol levels (50–150 nmol/L [1.8–5.4 μg/dL]) that were placed under close surveillance. It has been demonstrated that patients with postoperative cortisol of 55–137nmol/L (equivalent to 2–5.4 μg/dL) have a higher risk of late recurrence.12 We considered patients with a cortisol of greater than 150 nmol/L to be candidates for early secondary intervention without delay.
Radiotherapy, delivered by conventional external beam radiotherapy or via stereotactic radiosurgery, is typically used as a second-line treatment in CD patients after failure of initial or repeat pituitary surgery.8 In other centers, patients with similar moderately lowered cortisol level would have been labeled as being in remission and would not have been offered adjuvant radiotherapy. However, by closely observing the biochemical trends of these patients in the months following surgery we were able to offer further intervention at an earlier stage, thus avoiding the potentially harmful sequelae of untreated CD. In future work, it would be helpful to compare the long-term clinical outcomes of patients with moderately lowered serum cortisol levels who received early adjuvant therapy with patients who had similar biochemical results but did not receive adjuvant treatment.
Finally, we observed a statistically and clinically significant association between patient sex and tumor type on remission—a finding not previously reported. The underlying reasons for this result are unclear but further work should examine if, and how, the biology and histologic characteristics of adenomas changes with sex and age.9,16, 17, 18

Complications

Previous studies elected not to report the overall complication rate, hence at first sight, our overall complication rate of 32.0% may appear high even though the rate of individual specific complications are similar to those previously reported (Table 2).7, 8,15, 19 Postoperative complications were significantly higher in patients who underwent more procedures.
The overall perioperative mortality rate of 2.4% (n = 3) observed in this series is comparable with other published studies.7,8 One patient developed acute respiratory failure in the early postoperative period and died on day 3 following surgery. In the other cases significant intracavernous and intracranial bleeding was encountered and controlled; one patient subsequently developed acute cardiorespiratory instability and died on day 5; the other developed multiorgan failure and died following a prolonged stay on the intensive care unit. Following an internal review of these deaths we lowered our threshold for giving preoperative medical treatment such as ketoconazole or metyrapone in potential high-risk cases, particularly in those patients presenting with more severe clinical features at diagnosis. Preoperative medical treatment improves the quality of the tissues and increases the patient’s physiological reserve in preparation for surgery.14 In the ERCUSYN study, patients with severe clinical features who were treated preoperatively experienced comparable outcomes to those patients with milder features who were not treated with medical treatment before surgery. This justifies our approach to treat the more severe cases medically in the first instance. Nevertheless, preoperative medical treatment may confound the interpretation of early postoperative serum cortisol levels so close monitoring of these patients is required in the first few months following surgery.14 Since this change in practice, no deaths have occurred in patients undergoing surgery for CD at our unit.

Limitations

CD is a rare disease, and this study offers one of the larger modern series with practical illustrations of multidisciplinary practice at a tertiary pituitary center. Despite its size, this study did confirm that patients who achieved remission at 3 months were more likely to be in remission at the last follow-up. Patient and tumor characteristics were also important factors to consider. This study is nonetheless limited by lack of data on residual tumors found in postoperative MRIs. As such, we were unable to investigate further on the subgroup of patients without biochemical remission who had residual tumors. Furthermore, we do not fully know the proportion of MRI-negative patients who harbored an adenoma on histopathology, which may have skewed our findings. Further multi-institutional research is required to determine if patients with moderately lowered serum cortisol levels who receive early adjuvant radiotherapy have improved long-term clinical outcomes.

Conclusions

Despite good initial remission rates following endoscopic transsphenoidal surgery, this study demonstrated significant recurrence of CD. Nevertheless, patients who achieved initial biochemical remission (serum cortisol <50 nmol/L [1.8 μg/dL]) at 3 months were significantly more likely to achieve long-term biochemical remission. Selected patients with moderately lowered serum cortisol (serum cortisol 50–150 nmol/L [1.8–5.4 μg/dL]) responded well to early adjuvant radiotherapy but further research is required to determine their long-term clinical outcomes.

CRediT authorship contribution statement

Jonathan Shapey: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Writing – original draft, Writing – review & editing. Keng Siang Lee: Data curation, Formal analysis, Visualization, Writing – original draft. Vanitha Karunakaran: Formal analysis, Visualization, Writing – review & editing. Mohamed Okasha: Data curation, Writing – review & editing. Proma Dey: Data curation. Sabina Pate: Data curation. Mariusz T. Grzeda: Formal analysis, Writing – review & editing. Jackie Gilbert: Data curation, Writing – review & editing. Paul V. Carroll: Data curation, Writing – review & editing. Benjamin Whitelaw: Data curation, Writing – review & editing. Konstantinos Barkas: Data

curation, Writing – review & editing. Eleni Maratos: Data curation, Writing – review & editing. Sinan Barazi: Data curation, Writing – review & editing. Simon Aylwin: Data curation, Methodology, Supervision, Writing – original draft, Writing – review & editing. Nick WM. Thomas: Conceptualization, Data curation, Methodology, Supervision, Writing – review & editing.

References

Filed under: Cushing's, pituitary, Treatments | Tagged: , , , , | Leave a comment »

BIPSS Diagnostic Method May Cause False Positive in Some Cases of Cyclic Cushing’s Syndrome

Posted on January 31, 2026 by MaryO

A diagnostic technique called bilateral inferior petrosal sinus sampling (BIPSS), which measures the levels of the adrenocorticotropic hormone (ACTH) produced by the pituitary gland, should only be used to diagnose cyclic Cushing’s syndrome patients during periods of cortisol excess, a case report shows.

When it is used during a spontaneous remission period of cycling Cushing’s syndrome, this kind of sampling can lead to false results, the researchers found.

The study, “A pitfall of bilateral inferior petrosal sinus sampling in cyclic Cushing’s syndrome,” was published in BMC Endocrine Disorders.

Cushing’s syndrome is caused by abnormally high levels of the hormone cortisol. This is most often the result of a tumor on the pituitary gland that produces too much ACTH, which tells the adrenal glands to increase cortisol secretion.

However, the disease may also occur due to adrenal tumors or tumors elsewhere in the body that also produce excess ACTH — referred to as ectopic Cushing’s syndrome.

Because treatment strategies differ, doctors need to determine the root cause of the condition before deciding which treatment to choose.

BIPSS can be useful in this regard. It is considered a gold standard diagnostic tool to determine whether ACTH is being produced and released by the pituitary gland or by an ectopic tumor.

However, in people with cycling Cushing’s syndrome, this technique might not be foolproof.

Researchers reported the case of a 43-year-old woman who had rapidly cycling Cushing’s syndrome, meaning she had periods of excess cortisol with Cushing’s syndrome symptoms — low potassium, high blood pressure, and weight gain — followed by normal cortisol levels where symptoms resolved spontaneously.

In general, the length of each period can vary anywhere from a few hours to several months; in the case of this woman, they alternated relatively rapidly — over the course of weeks.

After conducting a series of blood tests and physical exams, researchers suspected of Cushing’s syndrome caused by an ACTH-producing tumor.

The patient eventually was diagnosed with ectopic Cushing’s disease, but a BIPSS sampling performed during a spontaneous remission period led to an initial false diagnosis of pituitary Cushing’s. As a result, the woman underwent an unnecessary exploratory pituitary surgery that revealed no tumor on the pituitary.

Additional imaging studies then identified a few metastatic lesions, some of which were removed surgically, as the likely source of ACTH. However, the primary tumor still hasn’t been definitively identified. At the time of publication, the patient was still being treated for Cushing’s-related symptoms and receiving chemotherapy.

There is still a question of why the initial BIPSS result was a false positive. The researchers think that the likely explanation is that BIPSS was performed during an “off phase,” when cortisol levels were comparatively low. In fact, a later BIPSS performed during a period of high cortisol levels showed no evidence of ACTH excess in the pituitary.

This case “demonstrates the importance of performing diagnostic tests only during the phases of active cortisol secretion, as soon as first symptoms appear,” the researchers concluded.

From https://cushingsdiseasenews.com/2020/01/02/cushings-syndrome-case-study-shows-drawback-in-bipss-method/

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Metabolomic Biomarkers in Urine of Cushing’s Syndrome Patients

Posted on January 29, 2026 by MaryO
Int. J. Mol. Sci. 2017, 18(2), 294; doi:10.3390/ijms18020294 (registering DOI)

Alicja Kotłowska 1,* , Tomasz Puzyn 2, Krzysztof Sworczak 3, Piotr Stepnowski 4 and Piotr Szefer 1

1 Department of Food Sciences, Faculty of Pharmacy, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland
2 Laboratory of Environmental Chemometrics, Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland
3 Department of Endocrinology and Internal Medicine, Medical University of Gdańsk, ul. Dębinki 7, 80-211 Gdańsk, Poland
4 Department ofEnvironmental Analytics, Institute for Environmental and Human Health Protection, Faculty of Chemistry, University of Gdańsk, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland
* Author to whom correspondence should be addressed.
Academic Editor: Ting-Li (Morgan) Han
Received: 5 December 2016 / Revised: 9 January 2017 / Accepted: 19 January 2017 / Published: 29 January 2017
(This article belongs to the Section Molecular Diagnostics)
Download PDF [1853 KB, uploaded 29 January 2017]

Abstract

Cushing’s syndrome (CS) is a disease which results from excessive levels of cortisol in the human body. The disorder is associated with various signs and symptoms which are also common for the general population not suffering from compound hypersecretion. Thus, more sensitive and selective methods are required for the diagnosis of CS.

This follow-up study was conducted to determine which steroid metabolites could serve as potential indicators of CS and possible subclinical hypercortisolism in patients diagnosed with so called non-functioning adrenal incidentalomas (AIs).

Urine samples from negative controls (n = 37), patients with CS characterized by hypercortisolism and excluding iatrogenic CS (n = 16), and patients with non-functioning AIs with possible subclinical Cushing’s syndrome (n = 25) were analyzed using gas chromatography-mass spectrometry (GC/MS) and gas chromatograph equipped with flame ionization detector (GC/FID). Statistical and multivariate methods were applied to investigate the profile differences between examined individuals. The analyses revealed hormonal differences between patients with CS and the rest of examined individuals.

The concentrations of selected metabolites of cortisol, androgens, and pregnenetriol were elevated whereas the levels of tetrahydrocortisone were decreased for CS when opposed to the rest of the study population. Moreover, after analysis of potential confounding factors, it was also possible to distinguish six steroid hormones which discriminated CS patients from other study subjects.

The obtained discriminant functions enabled classification of CS patients and AI group characterized by mild hypersecretion of cortisol metabolites. It can be concluded that steroid hormones selected by applying urinary profiling may serve the role of potential biomarkers of CS and can aid in its early diagnosis.

 

Keywords: Cushing’s syndrome; metabolomics; multivariate analysis; biomarkers; steroid hormones; urinary profiling; gas chromatography; linear discriminant analysis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

From http://www.mdpi.com/1422-0067/18/2/294

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Froedtert and MCW researchers investigate Cushing syndrome incidence in bariatric surgery patients

Posted on January 29, 2026 by MaryO

Researchers at the Medical College of Wisconsin determined that Cushing syndrome, an endocrine disorder, may be the potential cause for weight gain and metabolic complications for patients who have undergone bariatric surgery for obesity. The study, published in the journal Obesity Surgery, was conducted by Ty B. Carroll, MD, assistant professor of endocrinology; James W. Findling, MD, FACP, professor of endocrinology ; and Bradley R. Javorsky, MD, assistant professor of endocrinology. The physicians practice at Froedtert Hospital in Wauwatosa and Community Memorial Hospital in Menomonee Falls.

Cushing syndrome can occur when the human body is exposed to high levels of cortisol for an extended period of time. Cortisol is a hormone in the body which affects blood pressure regulation and cardiovascular system functions. Cortisol also helps regulate the body’s conversion of proteins, carbohydrates and fats from diet into usable energy. However, when the level of cortisol becomes too high, Cushing syndrome can develop.

Cushing syndrome is associated with a variety of symptoms including weight gain and fatty tissue deposits in the body. According to the American Association of Neurological Surgeons, 10 to 15 million people are affected each year by Cushing syndrome.

Bariatric surgery is a procedure performed to help with extreme cases of obesity. Weight loss is achieved by reducing the size of the stomach with a gastric band, removal of a portion of the stomach or resecting and rerouting the small intestine to a small stomach pouch. Bariatric surgery is often used as an option for individuals unable to lose weight through diet and exercise, or have serious health problems caused by obesity.

According to the American Society for Metabolic and Bariatric Surgery, 179,000 bariatric surgeries were performed in the U.S. in 2013. However, despite successes in normal weight loss cases, bariatric surgery does not provide long term weight loss for individuals diagnosed with Cushing syndrome. Cushing syndrome often goes undiagnosed as a potential cause for weight gain and metabolic complications until after the surgery is performed.

MCW researchers in this study analyzed the incidence of Cushing syndrome in patients who underwent bariatric surgery for weight loss. During the investigation, the researchers performed a retrospective chart review on a series of 16 patients diagnosed with Cushing syndrome from five tertiary care centers in the U.S. who underwent bariatric surgery. The results from the study found 12 of the analyzed patients were not diagnosed with Cushing syndrome prior to their bariatric surgery. The remaining four patients had Cushing syndrome surgery prior to bariatric surgery, without recognition that their Cushing syndrome was persistent until after the weight loss surgery. The findings from the research indicate that Cushing syndrome may be often overlooked in patients undergoing bariatric surgery.

According to the researchers, testing for Cushing syndrome should be performed prior to bariatric surgery in patients with persistent hypertension, diabetes mellitus or excessive weight regain.

From http://www.lakecountrynow.com/usersubmittedstories/366480371.html

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Imaging Technique Measures Tumor Stiffness to Aid Surgical Planning

Posted on January 28, 2026 by MaryO

screenshot-2017-01-27-11-04-44

 

Important steps in planning tumor surgery include identifying borders between tumor and healthy tissue and assessing the tumor stiffness, e.g. hard and calcified or soft and pliant. For decades, tumors near the surface of the body have been evaluated for stiffness by simple palpation—the physician pressing on the tissue. Because tumors within the skull cannot be palpated, researchers used Magnetic Resonance Elastography (MRE) to assess pituitary tumor stiffness by measuring waves transmitted through the skull into pituitary macroadenomas (PMAs). MRE reliably identified tumors that were soft enough for removal with a minimally-invasive suction technique versus harder tumors requiring more invasive surgery.

“The group developed brain MRE several years ago and is now successfully applying it to clinical diagnosis and treatment,” explained Guoying Liu, Ph.D., Director of the NIBIB Program in Magnetic Resonance Imaging. “This development of a new imaging technique followed by its practical application in surgical planning for better patient outcomes is an outstanding example of one of the main objectives of NIBIB-funded research.”

MRE is a special magnetic resonance imaging technique that captures snapshots of shear waves that move through the tissue and create elastograms—images that show tissue stiffness. John Huston III, M.D., Professor of Radiology at the Mayo Clinic in Rochester, MN, and senior author of the study, explains how MRE works. “MRE is similar to a drop of water hitting a still pond to create the ripples that move out in all directions. We generate tiny, harmless ripples, or shear waves, that travel through the brain of the patient. Our instruments measure how the ripples change as they move through the brain and those changes give us an extremely accurate measure–and a color-coded picture–of the stiffness of the tissue.”

MRE data enables non-invasive surgical planning

Ninety percent of PMAs are soft—nearly the consistency of toothpaste. Therefore, without MRE, surgeons would routinely plan for a procedure called transphenoidal resection that employs very thin instruments that are threaded through the nasal cavity to the pituitary gland at the base of the skull, where suction is used to remove the tumor. However, in about 10% of the cases, the surgeon will encounter a hard tumor. At that point an attempt is made to break-up the tumor—essentially chipping away at it with sharp instruments. If that is not successful, the surgeon must perform a fully-invasive craniotomy that involves removing a piece of the skull bone in order to fully expose the tumor.

The more extensive procedure means added risk and discomfort for patients, and up to a week-long recovery in the hospital compared to the transphenoidal approach that allows patients to leave the hospital in a day or two. Using MRE, hard PMAs can be identified and the more extensive craniotomy can be planned before starting the surgery, which makes the more invasive procedure less taxing for both the surgeon and patient. Similarly, MRE showing a soft PMA gives surgeons confidence that the nasal entry and removal by suction will be successful-eliminating the likelihood that the surgeon may need to perform a second fully-invasive craniotomy.

In the study of PMA reported in the January 2016 issue of the journal Pituitary, the group performed pre-surgical MRE evaluation of the PMAs of 10 patients.The MRE measurements were compared to tumor classifications made by inspection of the tumor during surgery. The surgeons categorized six tumors as soft and four tumors as medium. No tumors were deemed to be hard. The comparison of the MRE results and reports of stiffness by the surgeons when the tumor was removed and inspected were in close agreement, which was confirmed by statistical analysis.

Future plans

Although brain MRE is not yet widely available, Huston explained that the surgeons at the Mayo Clinic are now routinely using MRE to plan the best procedure for the removal of PMAs as well as several other types of brain tumor. And, even though this study of the 10 PMA patients is a very small set, Huston believes that as Mayo surgeons continue to use MRE in planning, the technique will likely begin to be adopted by other surgical centers.

Huston explained that an important aspect of some of the other brain tumor types, which the surgeons are finding extremely useful, is the ability of MRE to identify tumor adhesion to the brain. Adhesion refers to whether the brain tumor and healthy brain tissue are connected by an extensive network of blood vessels and connective tissue. This is in comparison with a tumor that is in the brain but is isolated from healthy tissue.

When MRE is used to analyze this aspect of the tumor, it clearly identifies those that are non-adhered, showing a border around the tumor through which there are no vascular connections. Conversely, MRE of adhered tumors show no border between the tumor and healthy brain, indicating extensive vascular and soft tissue connections between brain and tumor. Mutual blood vessels make removal of adherent tumors much more difficult, with a much higher chance of damage to healthy tissue and potential loss of function for the patient.

Huston and his colleagues are continuing to apply MRE, often called “palpating by imaging” to diagnosis of other brain disorders. In addition to characterizing focal brain disorders such as tumors, the group is testing the potential for MRE to provide diagnostic information about diffuse brain disease, and are currently using MRE brain stiffness patterns to identify different types of neural disorders including dementia.

This research was funded by the National Institutes of Health through the National Institute of Biomedical Imaging and Bioengineering grant EB001981.

Magnetic resonance elastography detects tumoral consistency in pituitary macroadenomas. Hughes JD, Fattahi N, Van Gompel J, Arani A, Ehman R, Huston J 3rd. Pituitary. 2016 Jun;19(3):286-92

From http://www.rdmag.com/news/2017/01/imaging-technique-measures-tumor-stiffness-aid-surgical-planning

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