Older Adults With Cushing’s Disease Present With Fewer Symptoms Than Younger Patients

Posted on March 7, 2025 by MaryO

Key takeaways:

  • Older age was tied to a higher prevalence of 10 comorbidities among a group of 608 people with Cushing’s disease.
  • Younger age was associated with most hallmark features of Cushing’s disease.

The presentation of Cushing’s disease varies by age, with older adults having fewer hallmark features of the condition and more comorbidities, according to study findings published in The Journal of Clinical Endocrinology & Metabolism.

Researchers assessed data from 608 people diagnosed with Cushing’s disease and treated with a transsphenoidal tumor resection at 11 academic pituitary centers in the U.S. from 2003 to 2023 (82% women; 77.3% white). Patients were divided into 10-year age interval groups, with the youngest group consisting of those aged 10 to 19 years and the oldest containing adults aged 70 to 79 years. Researchers found Cushing’s disease presents differently as adults age, with older adults experiencing more comorbidities and complications, but fewer hallmark features such as weight gain, facial rounding and hirsutism.

“The diagnosis of Cushing’s disease remains challenging, particularly with age,” Won Kim, MD, associate clinical professor of neurosurgery and radiation oncology at the David Geffen School of Medicine at UCLA, told Healio. “The older a patient is, the more likely that he or she may have a slower-growing tumor with fewer classic manifestations of the disease.”

Kim and colleagues obtained data from the Registry of Adenomas of the Pituitary and Related Disorders. Hallmark features of Cushing’s disease were identified by consensus opinion.

The number of comorbidities increased with patient age (beta = 0.0466; P < .001), according to the researchers.

Older age was associated with several comorbidities for patients with Cushing’s disease, including hypertension (P < .001), diabetes (P < .001), hyperlipidemia (P < .001), cancer (P < .001), coronary artery disease (P < .001), chronic obstructive pulmonary disease (P = .044), cardiac arrhythmia (P = .023), hepatitis (P = .038), anxiety (P = .039) and osteopenia (P = .024). The most common comorbidity was hypertension, which was prevalent in 67.2% of participants.

In an analysis of presenting hallmark features of Cushing’s disease, younger age was positively associated with weight gain (P < .001), facial rounding (P < .001), abdominal striae (P < .001), hirsutism (P < .001), menstrual irregularities (P < .001) and acne (P < .001). Older age was positively tied to obstructive sleep apnea (P = .007). The most common hallmark feature of Cushing’s disease was weight gain, prevalent in 80.2% of patients.

“Our work highlights that we must lower our threshold for suspecting Cushing’s disease in patients without the classic physical manifestations as the age of the patient increases,” Kim said in an interview. “Subtle clues, such as increasingly difficult to control medical conditions such as hypertension and diabetes, may be the only things we see.”

Older age was associated with lower preoperative 24-hour urinary free cortisol levels (beta = –0.0256; P = 6.89 x 10-7), but higher postoperative nadir cortisol (beta = 0.0342; P = 1.03 x 10-4) and higher adrenocorticotropin (beta = 0.0204; P = 5.22 x 10-4).

In an assessment of tumor characteristics, older age was tied to having a higher Knosp grade tumor (beta = 0.011; P = .00435), greater tumor volume (beta = 0.0261; P = .0233) and higher maximum tumor dimension (beta = 0.009; P = 3.82 x 10-4). Older age was inversely associated with Ki-67 index, which is a measure of tumor’s proliferation (beta = –0.0459; P = 1.39 x 10-4).

Age was not associated with a patient’s number of surgical complications. Older age was linked to a greater prevalence of deep vein thrombosis or venous thromboembolism (beta = 0.07; P = .014). Younger age was tied to a higher prevalence of postoperative arginine vasopressin (beta = –0.02; P = .048).

Kim said the study’s findings should encourage health care professionals to adjust their methods for screening for Cushing’s disease in older adults.

“Improving our diagnostic sensitivity through our standardized assessments for the disease should account for these new findings,” Kim told Healio.

For more information:

Won Kim, MD, can be reached at wonkim@mednet.ucla.edu.

Published by:endocrine today logo

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

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 »

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 »

Personalized Noninvasive Diagnostic Algorithms Based on Urinary Free Cortisol in ACTH-dependant Cushing’s Syndrome

Posted on November 9, 2024 by MaryO

Julie Lavoillotte, Kamel Mohammedi, Sylvie Salenave, Raluca Maria Furnica, Dominique Maiter, Philippe Chanson, Jacques Young, Antoine Tabarin
The Journal of Clinical Endocrinology & Metabolism, Volume 109, Issue 11, November 2024, Pages 2882–2891
https://doi.org/10.1210/clinem/dgae258

Abstract

Context

Current guidelines for distinguishing Cushing’s disease (CD) from ectopic ACTH secretion (EAS) are questionable, as they use pituitary magnetic resonance imaging (MRI) as first-line investigation for all patients. CRH testing is no longer available, and they suggest performing inferior petrosal sinus sampling (BIPPS), an invasive and rarely available investigation, in many patients.

Objective

To establish noninvasive personalized diagnostic strategies based on the probability of EAS estimated from simple baseline parameters.

Design

Retrospective study.

Setting

University hospitals.

Patients

Two hundred forty-seven CD and 36 EAS patients evaluated between 2001 and 2023 in 2 French hospitals. A single-center cohort of 105 Belgian patients served as external validation.

Results

Twenty-four-hour urinary free cortisol (UFC) had the highest area under the receiver operating characteristic curve for discrimination of CD from EAS (.96 [95% confidence interval (CI), .92–.99] in the primary study and .99 [95% CI, .98–1.00] in the validation cohort). The addition of clinical, imaging, and biochemical parameters did not improve EAS prediction over UFC alone, with only BIPPS showing a modest improvement (C-statistic index .99 [95% CI, .97–1.00]). Three groups were defined based on baseline UFC: < 3 (group 1), 3–10 (group 2), and > 10 × the upper limit of normal (group 3), and they were associated with 0%, 6.1%, and 66.7% prevalence of EAS, respectively. Diagnostic approaches performed in our cohort support the use of pituitary MRI alone in group 1, MRI first followed by neck-to-pelvis computed tomography scan (npCT) when negative in group 2, and npCT first followed by pituitary MRI when negative in group 3. When not combined with the CRH test, the desmopressin test has limited diagnostic value.

Conclusion

UFC accurately predicts EAS and can serve to define personalized and noninvasive diagnostic algorithms.

Read the article here: https://academic.oup.com/jcem/article/109/11/2882/7645065

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

« Previous Page — Next Page »