Blood Lipid Levels Linked to High Blood Pressure in Cushing’s Disease Patients

Posted on April 25, 2026 by MaryO

High lipid levels in the blood may lead to elevated blood pressure in patients with Cushing’s disease, a Chinese study shows.

The study, “Evaluation of Lipid Profile and Its Relationship with Blood Pressure in Patients with Cushing’s Disease,” appeared in the journal Endocrine Connections.

Patients with Cushing’s disease often have chronic hypertension, or high blood pressure, a condition that puts them at risk for cardiovascular disease. While the mechanisms of Cushing’s-related high blood pressure are not fully understood, researchers believe that high levels of cortisol lead to chronic hypertension through increased cardiac output, vascular resistance, and reactivity to blood vessel constrictors.

In children and adults with Cushing’s syndrome, the relationship between increased cortisol levels and higher blood pressure has also been reported. Patients with Cushing’s syndrome may remain hypertensive even after surgery to lower their cortisol levels, suggesting their hypertension is caused by changes in blood vessels.

Studies have shown that Cushing’s patients have certain changes, such as increased wall thickness, in small arteries. The renin-angiotensin system, which can be activated by glucocorticoids like cortisol, is a possible factor contributing to vascular changes by increasing the uptake of LDL-cholesterol (LDL-C) — the “bad” cholesterol — in vascular cells.

Prior research showed that lowering cholesterol levels could benefit patients with hypertension and normal lipid levels by decreasing the stiffness of large arteries. However, the link between blood lipids and hypertension in Cushing’s disease patients is largely unexplored.

The study included 84 patients (70 women) referred to a hospital in China for evaluation and diagnosis of Cushing’s disease. For each patient, researchers measured body mass index, blood pressure, lipid profile, and several other biomarkers of disease.

Patients with high LDL-cholesterol had higher body mass index, blood pressure, cholesterol, triglycerides, and apolipoproteinB (apoB), a potential indicator of atherosclerosis and cardiovascular disease.

Data further revealed an association between blood pressure and lipid profile, including cholesterol, triglycerides, apoB and LDL-c. “The results strongly suggested that CHO (cholesterol), LDL-c and apoB might predict hypertension more precisely in [Cushing’s disease],” the scientists wrote.

They further add that high cholesterol, LDL-cholesterol, and apoB might be contributing to high blood pressure by increasing vessel stiffness.

Additional analysis showed that patients with higher levels of “bad” cholesterol — 3.37 mmol/L or higher — had higher blood pressure. This finding remained true, even when patients were receiving statins to lower their cholesterol levels.

No association was found between blood pressure and plasma cortisol, UFC, adrenocorticotropic hormone, or glucose levels in Cushing’s disease patients.

These findings raise some questions on whether lipid-lowering treatment for high blood pressure and cardiovascular disease would be beneficial for Cushing’s disease patients. Further studies addressing this question are warranted.

Adapted from https://cushingsdiseasenews.com/2018/04/24/blood-pressure-linked-lipid-levels-cushings-disease-study/

Filed under: adrenal, Clinical trials, Cushing's, pituitary, symptoms | Tagged: , , , , , , , , | Leave a comment »

Fluorescent Metabolite Might Help Surgeons Remove Pituitary Tumors

Posted on April 14, 2026 by MaryO

The resection of microadenomas — small, benign tumors in the pituitary gland underlying Cushing’s disease — could be aided by a fluorescent marker that is naturally produced by the tumor, a new study shows.

The findings were presented recently at the 2018 George Washington Research Days in a poster titled, “Enhanced 5-ALA Induced Fluorescence in Hormone Secreting Pituitary Adenomas.”

Cushing’s disease is characterized by high cortisol levels that cause debilitating physical, mental, and hormonal symptoms. The excess cortisol is caused by tiny benign tumors in the pituitary gland, called microadenomas, with a size of less than 10 millimeters.

On account of their small size, these microadenomas pose imaging challenges to physicians. Up to 40 percent of microadenomas remain undetected in the gold-standard magnetic resonance imaging (MRI).

Pituitary adenomas, however, have a characteristic that distinguishes them from the surrounding healthy tissue. They process (metabolize) a natural haemoglobin metabolite, called 5-aminolevulinic acid (5-ALA), into protoporphyrin IX (PpIX) at much higher rates — up to 20 to 50 times higher — than normal tissues.

Importantly, PpIX emits red fluorescence when excited with blue light.

This means that exogenous 5-ALA is taken up by the adenoma cells and rapidly metabolized into the fluorescent metabolite, PpIX, which may establish its use for fluorescence-guided resection of pituitary adenomas.

To test this, researchers incubated human-derived corticotropinoma, as well as the adjacent normal gland cells with 5-ALA. They did the same with mouse model normal pituitary cells and a mouse model pituitary tumor cell line, called AtT20.

They then analyzed the cells’ fluorescence profile by microscopy and with a technique called flow cytometry.

The analysis showed that compared to normal pituitary tissue, human-derived adenomatous cells had a significant increase of tenfold in 5-ALA-induced PpIX fluorescence intensity.

Similarly, mouse pituitary tumor cells (AtT20 cell line) fluoresced seven times more intensely than normal murine pituitary tissue.

The microscopy analysis revealed that the 5-ALA localized in subcellular organelles called mitochondria.

On June 6, 2017, the U.S. Food and Drug Administration approved the use of 5-ALA (under the brand name Gleolan) as an optical imaging agent for patients with gliomas (brain tumors), as an add-on compound to assist surgeons in identifying the malignant tissue during surgery.

Now, these findings suggest that 5-ALA also may be used for fluorescence-guided surgery of microadenomas in Cushing’s disease.

“The supraphysiological levels of glucocorticoids, as seen in CD [Cushing’s disease], may enhance the 5-ALA fluorescence in corticotropinomas,” researchers wrote.

From https://cushingsdiseasenews.com/2018/04/13/fluorescent-metabolite-might-help-surgeons-removepituitary-tumors/

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

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 »

Identification Of Potential Markers For Cushing’s Disease

Posted on January 27, 2026 by MaryO

Endocr Pract. 2016 Jan 20. [Epub ahead of print]

Broder MS1, Chang E1, Cherepanov D1, Neary MP2, Ludlam WH2.

Author information

Abstract

OBJECTIVE:

Cushing’s disease (CD) causes a wide variety of nonspecific symptoms, which may result in delayed diagnosis. It may be possible to uncover unusual combinations of otherwise common symptoms using ICD-9-CM codes. Our aim was to identify and evaluate dyads of clinical symptoms or conditions associated with CD.

METHODS:

We conducted a matched case-control study using a commercial healthcare insurance claims database, designed to compare the relative risk (RR) of individual conditions and dyad combinations of conditions among patients with CD versus matched non-CD controls.

RESULTS:

With expert endocrinologist input, we isolated 10 key conditions (localized adiposity, hirsutism, facial plethora, polycystic ovary syndrome, abnormal weight gain, hypokalemia, deep venous thrombosis, muscle weakness, female balding, osteoporosis) with RR varying from 5.1 for osteoporosis to 27.8 for hirsutism. The RR of dyads of these conditions ranged from 4.1 for psychiatric disorders/serious infections to 128.0 for hirsutism/fatigue in patients with vs. without CD. Construction of uncommon dyads resulted in further increases in RR beyond single condition analyses, such as osteoporosis alone had RR of 5.3, which increased to 8.3 with serious infections and to 52.0 with obesity.

CONCLUSION:

This study demonstrated that RR of any one of 10 key conditions selected by expert opinion was ≥5 times greater in CD compared to non-CD, and nearly all dyads had RR≥5. An uncommon dyad of osteoporosis and obesity had an RR of 52.0. If clinicians consider the diagnosis of CD when the highest-risk conditions are seen, identification of this rare disease may improve.

KEYWORDS:

Cushing’s disease; delay in diagnosis; disease markers; insurance claims; relative risk

PMID:
26789346
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/26789346

Filed under: adrenal, Cushing's, Diagnostic Testing, pituitary, symptoms | Tagged: , , , , , , , , , , , , , , , , , , , , , | Leave a comment »

Cushing’s Syndrome Subtype Affects Postoperative Time to Adrenal Recovery

Posted on January 25, 2026 by MaryO

Berr CM. J Clin Endocrinol Metab. 2014;doi:10.1210/jc.2014-3632.

January 16, 2015

In patients undergoing curative surgical tumor resection for Cushing’s syndrome, the time to recovery of adrenal function is contingent upon the underlying etiology of the disease, according to recent findings.

In the retrospective study, researchers reviewed case records of 230 patients with Cushing’s syndrome. All patients were seen at a tertiary care center in Munich between 1983 and 2014, whose cases were documented in the German Cushing’s Registry. Patients were divided into three subgroups of Cushing’s syndrome: Cushing’s disease, adrenal Cushing’s syndrome and ectopic Cushing’s syndrome.

After applying various exclusion criteria, the researchers identified 91 patients of the three subgroups who were undergoing curative surgery at the hospital. The patients were followed for a median of 6 years. The researchers defined adrenal insufficiency as the need for hydrocortisone replacement therapy, and collected this information from patient records and laboratory results.

The duration of adrenal insufficiency was calculated as the interval between successful surgery and the completion of hydrocortisone replacement therapy. Cushing’s syndrome recurrence was defined as biochemical and clinical signs of hypercortisolism.

The researchers found a significant difference between Cushing’s syndrome subtypes in the likelihood of regaining adrenal function within 5 years of follow-up: The probability was 82% in ectopic Cushing’s syndrome, 58% in Cushing’s disease and 38% in adrenal Cushing’s syndrome (P=.001). Among the 52 participants who recovered adrenal function, the median type to recovery also differed between subtypes and was 0.6 years in ectopic Cushing’s syndrome, 1.4 years in Cushing’s disease and 2.5 years in adrenal Cushing’s syndrome (P=.002).

An association also was found between younger age and adrenal recovery in the Cushing’s disease participants (P=.012).

This association was independent of sex, BMI, symptom duration, basal adrenocorticotropic hormone and cortisol levels. No association was seen between adrenal recovery and length of hypercortisolism or postoperative glucocorticoid replacement dosage.

“It is the main finding of this series that the median duration of tertiary adrenal insufficiency was dependent on the etiology of [Cushing’s syndrome]: It was shortest in the ectopic [Cushing’s syndrome], intermediate in [Cushing’s disease] and longest in adrenal [Cushing’s syndrome] caused by unilateral cortisol producing adenoma,” the researchers wrote. “The significant difference to [Cushing’s disease] is an unexpected finding since by biochemical means cortisol excess is generally less severe in adrenal [Cushing’s syndrome]. If confirmed by others, our data have clinical impact for the follow-up of patients after curative surgery: Patients should be informed that adrenocortical function may remain impaired in benign conditions such as cortisol-producing adenoma.”

Disclosure: The study was funded in part by the Else Kröner-Fresenius Stiftung.

The original article is here: Healio

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

Next Page »