Impact of Remission Status in Endogenous Cushing’s Syndrome on Cancer Incidence

Posted on March 4, 2025 by MaryO

Abstract

Objective
Endogenous Cushing’s syndrome (CS) has been linked with an increased risk of cancer. We aimed to evaluate the association between cancer risk and disease remission post-surgery in adrenal CS and Cushing’s disease (CD).
Design
A nationwide retrospective matched-cohort study of patients with CS diagnosed between 2000-2023 in Israel, using Clalit Health Services’ database. Methods Patients with CS were matched 1:5 with controls by age, sex, socioeconomic status, and BMI. Remission status post-surgery was assessed within two years after the diagnosis of CS. The outcome measured was time to first diagnosis of malignancy, at least three years post-CS diagnosis, excluding those who died or developed cancer earlier. Malignancy risk, stratified by remission status, was evaluated using Cox proportional hazards with death as a competing event.
Results
The cohort comprised 388 cases and 1,862 controls [mean age at diagnosis, 47.4±16.8 years; 1,534 (68.2%) women]. Among patients with CD, those who did not achieve remission within 2 years post diagnosis (n=69) had a higher risk of malignancy compared to those who achieved remission (n=99) (HR 3.89, 95% CI 1.41-10.75). Cancer risk in patients with CD who achieved remission was similar to that of the controls (HR 0.58, 95% CI 0.23-1.47). In patients with adrenal CS, the risk of cancer was comparable between those who did not achieve early remission (n=39) and those who did (n=113) (HR 1.68, 95% CI 0.83-3.40).
Conclusion
Though cancer risk is higher in both CD and adrenal CS, we have shown that achieving surgical remission within 2 years may attenuate cancer risk in patients with CD, but not in those with adrenal CS.

Filed under: Cancer, Clinical trials, Cushing's | Tagged: , , , , , | Leave a comment »

Sterotherapeutics begins Phase II trial for ST-002 targeting Cushing’s Syndrome

Posted on March 2, 2025 by MaryO

US-based clinical-stage company Sterotherapeutics has announced the commencement of a Phase II clinical trial for its drug candidate, ST-002, for treating Cushing’s Syndrome, a rare endocrine disorder.

The trial will assess the drug’s efficacy, tolerability, and safety in individuals with this condition. It is set to be conducted in several European clinical sites.

Sterotherapeutics CEO Manohar Katakam said: “After extensive preparations and based on a large body of scientific data, we are excited to convene this important Investigator Meeting as we progress to the next stage of our clinical development programme.

“This trial represents a significant step forward in our mission to develop transformative therapies for unmet medical needs. Collaboration with our expert investigators is essential to ensuring the highest standards of scientific rigour and patient safety.”

An orphan drug designation was granted by the US Food and Drug Administration (FDA) to the drug underscoring the requirement for new treatments alternatives for this rare condition.

Through this designation, Sterotherapeutics is eligible for various development incentives. These include assistance in the drug development process, certain FDA fee exemptions, post-approval marketing exclusivity of seven years, and tax credits for clinical expenses.

Characterised by longer exposure to high cortisol levels, Cushing’s Syndrome is stated to result in serious health complications like diabetes, osteoporosis, and hypertension.

Sterotherapeutics concentrates on the orphan diseases therapy development. The company stated that its leading programmes, ST-002 for Cushing’s Syndrome and ST-003 for primary sclerosing cholangitis, have shown promise in prior animal and human studies. ST-003 has also been granted an orphan drug designation by the US regulator.

From https://www.clinicaltrialsarena.com/news/sterotherapeutics-trial-st-002/?cf-view&cf-closed

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

Oncocytic Pituicytoma in a Patient with Cushing’s Disease

Posted on February 20, 2025 by MaryO

The final, formatted version of the article will be published soon.

1) Background: Posterior pituitary tumors (PPTs) are extremely rare, with fewer than 400 cases reported to date. In 2022, the WHO classified four types of tumors originating from the posterior pituitary: traditional pituicytoma, oncocytic pituicytoma, granular pituicytoma, and ependymal pituicytoma. To our knowledge, only one subject with coexistence of Cushing’s disease and oncocytic pituicytoma (spindle cell oncocytoma) has been reported, but the clinical features of this patient were not described in detail.

2) Case presentation: We presented a case of a patient with Cushing’s syndrome and a pituitary mass. Transsphenoidal surgery was performed, and pathologic examination revealed two distinct tumors: a corticotroph adenoma with a diameter of less than 2mm and a larger oncocytic pituicytoma. Post-surgery serum cortisol was 51 nmol/L, indicating complete remission. Corticotroph adenoma or corticotroph hyperplasia were identified after surgery in less than half of the subjects with Cushing’s disease and PPT. (3)

Conclusions: Our study indicates that Cushing’s disease in patients with PPT may be caused by the existence of collision lesions, with corticotroph adenoma or hyperplasia being difficult to detect due to their small dimensions.

Keywords: Cushing’s disease, oncocytic pituicytoma, Spindle cell oncocytoma, pituitary adenoma, Posterior pituitary tumors

Received: 27 Aug 2024; Accepted: 17 Feb 2025.

Copyright: © 2025 Li, Chen, Tan, Yu, Tang, Cai and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Huiwen Tan, Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China
Ying Tang, Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
Bowen Cai, Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
Jianwei Li, Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, Chengdu, China

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

 

From https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1487120/abstract

 

Filed under: Clinical trials, Cushing's, pituitary, Rare Diseases, Treatments | Tagged: , , , | Leave a comment »

Cushing Disease Clinical Phenotype and Tumor Behavior Vary With Age

Posted on January 24, 2025 by MaryO

Abstract

Context

Little is known about presenting clinical characteristics, tumor biology, and surgical morbidity of Cushing disease (CD) with aging.

Objective

Using a large multi-institutional data set, we assessed diagnostic and prognostic significance of age in CD through differences in presentation, laboratory results, tumor characteristics, and postoperative outcomes.

Methods

Data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) were reviewed for patients with CD treated with transsphenoidal tumor resection at 11 centers between 2003 and 2023. Outcomes assessed included comorbidities, presenting features, preoperative endocrine evaluations, perioperative characteristics, postoperative endocrine laboratory values, and complications.

Results

Of the 608 patients evaluated, 496 (81.6%) were female; median age at surgery was 44 years (range, 10-78 years). Increasing age was associated with increasing comorbidities, frailty, rates of postoperative thromboembolic disease, Knosp grade, tumor size, and postoperative cortisol and adrenocorticotropin nadirs. Conversely, increasing age was associated with decreased hallmark CD features, preoperative 24-hour urinary free cortisol, Ki-67 indices, and arginine vasopressin deficiency. Younger patients presented more frequently with weight gain, facial rounding/plethora, abdominal striae, hirsutism, menstrual irregularities, dorsocervical fat pad, and acne. Obstructive sleep apnea and infections were more common with increasing age.

Conclusion

There are age-dependent differences in clinical presentation, tumor behavior, and postoperative outcomes in patients with CD. Compared to younger patients, older patients present with a less classic phenotype characterized by fewer hallmark features, more medical comorbidities, and larger tumors. Notably, age-related differences suggest a more indolent tumor behavior in older patients, potentially contributing to delayed diagnosis and increased perioperative risk. These findings underscore the need for tailored diagnostic and therapeutic approaches across age groups, with a focus on managing long-term comorbidities and optimizing surgical outcomes.

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

Can We Predict the Risk of Venous Thromboembolism in Patients With Cushing’s Syndrome

Posted on January 22, 2025 by MaryO

Purpose

Patients with Cushing’s syndrome (CS) have an increased venous thromboembolism (VTE) risk with most studies focusing on the perioperative period. The purpose of this study was to assess the 5-year VTE risk and identify predictors of VTE at CS diagnosis.

Methods

A comparative nationwide retrospective cohort study of 609 patients (mean age 48.1 ± 17.2 years, 65.0% women) with CS, and 3018 age-, sex-, body mass index-, and socioeconomic status-individually matched controls. Ectopic CS and adrenal cancer were excluded. The time-to-event of pulmonary embolism (PE) or deep vein thrombosis (DVT) within 5 years of CS diagnosis was examined. VTE risk was calculated with death as competing event.

Results

VTE occurred in 16 cases (2.6%), compared to 17 (0.56%) controls (hazard ratio [HR] 4.71, 95% CI, 2.38–9.33). The 5-year HRs for PE and DVT were 7.47 (95% CI, 2.66–20.98) and 3.32 (95% CI, 1.36–8.12), respectively. After excluding patients and controls with current or prior malignancy the risk for VTE was 7.57 (95% CI, 2.98–19.20). Patients with CS ≥ 60 years at diagnosis (HR, 3.49; 95% CI, 1.30–9.35), with hypertension (HR, 5.53; 95% CI, 1.26–24.27), ischemic heart disease (HR, 3.60; 95% CI, 1.25–10.36), kidney disease (HR, 4.85; 95% CI, 1.39–16.90), or VTE event prior to CS diagnosis (HR, 33.65; 95% CI, 10.07–112.42) had an increased risk of VTE within five years.

Conclusions

In this large cohort of patients with CS, the 5-year VTE risk was 5 times higher compared with matched controls. Key baseline predictors included age ≥ 60, hypertension, heart/kidney disease, and prior VTE.

From https://link.springer.com/article/10.1007/s11102-024-01482-0

 This is a preview of subscription content, log in via an institution  to check access.

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

« Previous Page — Next Page »