Mortality in Cushing’s Syndrome: Declining Over Two Decades but Remaining Higher Than the General Population

Posted on April 18, 2025 by MaryO

Abstract

Objective

Patients with endogenous Cushing’s syndrome (CS) have elevated mortality, particularly during active disease. A recent meta-analysis reported reduced mortality rates after 2000 in adrenal CS and Cushing disease (CD), though many studies lacked population-matched controls.

Methods Nationwide retrospective study (2000–2023) in Israel using the Clalit Health Services database to assess all-cause mortality in patients with endogenous CS matched 1:5 with controls by age, sex, socioeconomic-status, and BMI. Primary outcome was all-cause mortality. Secondary outcomes included cause-specific mortality, impact of hypercortisolism remission, disease source, and mortality risk factors.

Results The cohort included 609 cases with CS (mean age 48.1±17.2 years; 65.0% women) and 3,018 matched controls (47.9±17.2 years; 65.4% women). Over a median follow-up of 16 years, 133 cases (21.8%) and 472 controls (15.6%) died (HR=1.44, 95% CI, 1.19–1.75). Both patients with CD (HR=1.73, 95% CI, 1.27–2.36) and adrenal CS (HR=1.31, 95% CI, 1.00–1.81) had increased mortality risk. Patients without remission within 2 years had a higher mortality risk than those achieving remission (HR=1.44, 95% CI, 1.00–2.17). Mortality was similar for CD and adrenal CS (HR=0.83, 95% CI, 0.56–1.24). Older age, male gender, and prior malignancy were independent risk factors for mortality.

Conclusion This is the largest national cohort study on mortality risk in CS over the past two decades, showing a significantly higher risk compared to matched controls in a homogeneous database. While etiology had no impact, remission significantly affected mortality, highlighting the importance of disease control for long-term survival.

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Efficacy and Safety of Pasireotide in Patients With Cushing’s Disease

Posted on April 16, 2025 by MaryO

Abstract

Purpose

Pasireotide is the first pituitary-directed approved therapy for Cushing’s disease (CD), effective in reducing 24 h urine free cortisol (UFC) > 50% in more than half of patients, with beneficial effects and with a relatively high incidence of hyperglycemia. The aim of this study was to evaluate efficacy and safety of long-term treatment with pasireotide (PAS) in CD patients, also according to gender.

Methods

We retrospectively evaluated 19 consecutive CD patients (13F; age at diagnosis: 34.9 ± 11.7 yrs) treated with PAS, referred to and followed-up at the Endocrine Unit of the University Hospital of Messina, from 2013 to 2023. We evaluated and compared, in the whole cohort and after gender stratification, anthropometric, clinical, neuroradiological, hormonal and metabolic parameters, along with CD-related comorbidities, before PAS treatment and at last follow-up visit. Side-effects and adverse events related to treatment were also assessed.

Results

Under PAS treatment: overall, 52.6% of patients achieved a normalization of UFCxULN from baseline without any difference in terms of UFC reduction and/or response to treatment according to gender; two females out of the 19 patients experienced tumor shrinkage. In the whole cohort, at last follow-up visit as compared to baseline: body weight, BMI, total cholesterol, LDL-cholesterol were significantly improved, while HbA1c significantly increased. Prevalence of CD-related comorbidities did not change significantly, while the number of patients with IGF-1 SDS below the sex/age adjusted normal range significantly increased. Stratifying patients by sex, at last follow-up visit vs. baseline, we observed lower total and LDL-cholesterol in men and lower waist circumference in women. Most common adverse events were related to hyperglycemia which led to treatment withdrawal in 3 cases, without any gender difference. Response to PAS correlated with younger age at diagnosis, longer duration of disease, lower Hb1Ac levels and absence of diabetes at baseline. Conclusion: PAS is effective in a significant number of patients with CD, regardless of gender, having a positive impact on lipid profile and on anthropometric parameters. Major adverse events are related to hyperglycemia which is more frequently associated with a worse baseline glycometabolic and lipid profile in both sexes.

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Ivory Tower: New PET Scan Molecule Offers Breakthrough in Detecting Cushing’s Syndrome

Posted on April 7, 2025 by MaryO

Asignificant advancement in medical imaging has been achieved by experts at the Postgraduate Institute of Medical Education and Research. Researchers from endocrinology and nuclear medicine departments have introduced a new PET scan molecule that enhances the detection of adenoma/small tumour causing Cushing’s syndrome. This development promises to improve surgical interventions and patient outcomes.

A collaborative effort between Dr Rama Walia from the endocrinology department and Dr Jaya Shukla from nuclear medicine department has resulted in the development of GA-68 MDEsMO, a specialised PET scan molecule. This innovative compound is designed to pinpoint tumors in the pituitary gland, which are often responsible for the excessive cortisol production characteristic of Cushing’s syndrome.

By providing a more precise visualisation of these tumours, the new technique enables neurosurgeons to operate with greater accuracy, preserving the normal functions of the pituitary gland and enhancing patients’ quality of life.

Recognising its potential, this pioneering technology was honoured at the institution’s recent Research Day.

Affects entire body

Cushing’s syndrome is a complex endocrine disorder that occurs due to an overproduction of cortisol, a hormone that influences multiple physiological processes. When cortisol levels surge beyond normal, it disrupts the body’s balance, leading to widespread health complications. The primary cause of this condition is a minuscule tumor within the pituitary gland, making diagnosis particularly challenging.

Currently, only 60 to 70 per cent of patients receive an accurate diagnosis due to the minuscule size of these tumors — often measuring less than a millimeter. The introduction of GA-68 MDEsMO is expected to bridge this diagnostic gap by facilitating early detection, thus enabling timely surgical intervention.

Hormonal disruptions

The pituitary gland, often referred to as the “master gland”, plays a crucial role in regulating hormone production. However, when affected by a tumor, it triggers an excessive release of hormones, leading to systemic damage.

Typical symptoms include unexplained weight gain, obesity and noticeable changes in skin texture. Many patients develop distinctive pink or purplish stretch marks on the abdomen, thighs and arms. Women may experience excessive hair growth, while men could suffer from reduced fertility and erectile dysfunction. Additionally, skin thinning, severe acne and heightened susceptibility to bruising are common indicators of the disease.

Understanding cortisol

Cortisol, a steroid hormone, is essential for stress regulation and overall metabolic balance. Produced by the adrenal glands, it influences numerous bodily functions through interactions with cortisol receptors present in most cells. The secretion of cortisol is managed by a complex system involving the hypothalamus, pituitary gland, and adrenal glands. Given its widespread presence, cortisol plays a vital role in multiple physiological processes, including immune response, metabolism, and blood pressure regulation.

However, any disruption in cortisol levels—whether an excess or deficiency—can lead to significant health challenges. This underscores the importance of precise diagnosis and timely treatment for disorders like Cushing’s syndrome. The introduction of GA-68 MDEsMO marks a crucial step in advancing medical science’s ability to manage and treat this condition effectively. —

https://www.tribuneindia.com/news/punjab/ivory-tower-new-pet-scan-molecule-offers-breakthrough-in-detecting-cushings-syndrome/

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Myocardial Work Impairment in Patients With Cushing’s Syndrome

Posted on April 4, 2025 by MaryO

The following is a summary of “Impact Of Hypercortisolism Beyond Metabolic Syndrome On Left Ventricular Performance: A Myocardial Work Analysis,” published in the March 2025 issue of Cardiovascular Diabetology by Sahiti et al.

Endogenous Cushing’s Syndrome (CS) is associated with an increased cardiovascular (CV) and metabolic risk profile, yet the specific impact of hypercortisolism on myocardial function remains inadequately understood. Myocardial Work analysis, a novel echocardiographic technique utilizing left ventricular pressure-strain loops, allows for the assessment of cardiac performance independently of afterload, offering valuable insight into myocardial function in CS. This cross-sectional study aimed to evaluate left ventricular function across four distinct groups: patients with overt endogenous CS (n = 31; mean age 47 ± 12 years; 71% women), patients in long-term remission following successful medical treatment (CS-LTR; n = 49; mean age 53 ± 12 years; 78% women), a healthy control group (n = 439; mean age 49 ± 11 years; 57% women), and individuals with metabolic syndrome (n = 305; mean age 59 ± 10 years; 37% women).

Both CS groups exhibited a more unfavorable metabolic and CV risk profile than healthy controls, although they presented a relatively better profile compared to individuals with metabolic syndrome. Adjusted analyses accounting for sex and age demonstrated significantly increased Wasted Work in both the overt CS group (median: 105 mmHg%; interquartile range: 74–147) and CS-LTR group (97 mmHg%; 69–158) when compared to healthy individuals (75 mmHg%; 54–109; p < 0.01). Additionally, wasted work values in patients with CS were slightly elevated in comparison to those observed in patients with metabolic syndrome (95 mmHg%; 65–136; p < 0.05), indicating persistent myocardial dysfunction. This impairment in myocardial performance translated into a significant reduction in Work Efficiency (p < 0.05), even in patients with CS who had achieved biochemical remission.

The findings suggest that hypercortisolism contributes to persistent left ventricular dysfunction beyond the effects of traditional CV risk factors. Furthermore, despite the biochemical resolution of CS, patients in long-term remission continue to exhibit myocardial abnormalities, reinforcing the notion that prior exposure to excess cortisol may induce lasting structural and functional cardiac alterations. These findings underscore the utility of Myocardial Work analysis in detecting subclinical yet clinically relevant myocardial dysfunction in patients with CS, both in its active state and after remission. Given the persistence of myocardial impairment even following the resolution of hypercortisolism, long-term cardiovascular monitoring may be warranted in this patient population. This study highlights the need for further research to determine whether targeted interventions could mitigate residual myocardial dysfunction in patients with a history of CS, ultimately improving their cardiovascular outcomes.

Source: cardiab.biomedcentral.com/articles/10.1186/s12933-025-02680-1`

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First-Episode Psychosis and Cushing Syndrome

Posted on March 28, 2025 by MaryO

Cushing syndrome, a state of hypercortisolism, has multiple etiologies, including ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). EAS is a frequently severe emergency related to the degree of hypercortisolism. Neuropsychiatric symptoms of Cushing syndrome are well documented, including irritability, anxiety, depressed mood, and cognitive impairment.1 A few prior case reports have described first episode psychosis associated with Cushing syndrome,2 sometimes leading to delayed or misdiagnosis of Cushing syndrome.

Here, we report a case of a 72-year old man diagnosed with EAS caused by excessive ACTH secretion by a metastatic neuroendocrine tumor. Our report aims to add to the body of evidence indicating that Cushing associated psychosis can cause acutely severe paranoia and delusions that significantly impact management.

Case Report

Mr A, a 72-year-old retired physician with no prior psychiatric history, was diagnosed with new-onset psychosis in the setting of hypercortisolism. He initially presented with weakness secondary to hypokalemia and was found to have Cushing syndrome. On psychiatric evaluation, he demonstrated paranoia and delusions as well as illogical, concrete, and limited thought content. Laboratory workup, neurocognitive examination, and collateral history ruled out delirium or dementias. His morning cortisol levels were up to 162 μg/dL, and ACTH levels were greater than 2,000 pg/mL.

Mr A’s cortisol levels were not suppressed with a high-dose dexamethasone test, supporting ectopic ACTH production. He was found to have a metastatic ACTH secreting large cell neuroendocrine tumor, responsible for his hypercortisolism. Magnetic resonance imaging of his brain demonstrated a pituitary mass, and a bilateral adrenalectomy revealed a small focus of neuroendocrine carcinoma on his left adrenal gland.

Mr A was treated with haloperidol for hallucinations, delusional features, and paranoia; ramelteon for delirium prophylaxis; and suvorexant for sleep initiation. His endocrinology team ultimately started him on osilodrostat (decreases cortisol synthesis via 11 β-hydroxylase inhibition), which led to improvements in his cortisol levels, and his psychotic features subsequently diminished and resolved by the fourth day. All medications for psychiatric symptoms were successfully discontinued without symptom recurrence.

Discussion

Hypothalamic-pituitary-adrenal axis abnormalities, including hypercortisolism, have been well documented in first-episode psychosis cases.3 This includes increased morning cortisol levels in the blood in individuals with first-episode psychosis and increased baseline cortisol levels in the saliva for individuals at a clinical high risk of psychosis.4 There are multiple proposed mechanisms for how excess exposure to cortisol leads to psychosis. Theories include structural and chemical changes such as abnormal regulation of neurotransmitters, impaired neurogenesis, decreased brain volume in the hippocampus, abnormal loss of synapses, and dendritic atrophy. However, these changes are typically in the setting of prolonged exposure to high levels of cortisol.

There are a limited number of case reports regarding Cushing syndrome and acute psychosis.2 Past case reports that have described Cushing syndrome and acute onset of psychosis endorse severely high levels of cortisol, which may be a driving factor, and patients presented with less profound delusional and paranoid content.2 In this case, the patient presented with severe paranoia and delusions in the setting of excess cortisol and metastatic malignancy. Similar cases have been reported and focus on reducing cortisol levels to help manage the psychiatric symptoms.2,5,6 Psychotropic management can assist with symptoms; however, the ultimate treatment remains to address the endocrinologic abnormality. While most cases have reported improvement of neuropsychiatric symptoms with resolution of hypercortisolism, others have described persisting or even exacerbation of psychiatric symptoms even after resolution of the high cortisol levels.5–7 Most importantly, we must recognize Cushing syndrome and its hormonal derangements as a possible underlying etiology of psychosis to guide effective diagnostics and therapeutic management.

Article Information

Published Online: March 25, 2025. https://doi.org/10.4088/PCC.24cr03886
© 2025 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2025;27(2):24cr03886
Submitted: November 4, 2024; accepted January 3, 2025.
To Cite: Gunther M, Jiang S. First-episode psychosis and Cushing syndrome. Prim Care Companion CNS Disord 2025;27(2):24cr03886.
Author Affiliations: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California (Gunther); Department of Psychiatry, University of Florida, Gainesville, Florida (Jiang).
Corresponding Author: Matthew Gunther, MD, MA, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Palo Alto, CA 94304 (guntherm@stanford.edu).
Relevant Financial Relationships: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect anonymity.

References:

  1. Santos A, Resmini E, Pascual JC, et al. Psychiatric symptoms in patients with Cushing’s syndrome: prevalence, diagnosis and management. Drugs. 2017;77(8):829–842. CrossRef
  2. Okumura T, Takayama S, Nishio S, et al. ACTH producing thymic neuroendocrine tumor initially presenting as psychosis: a case report and literature review. Thorac Cancer. 2019;10(7):1648–1653. CrossRef
  3. Misiak B, Pruessner M, Samochowiec J, et al. A meta-analysis of blood and salivary cortisol levels in first-episode psychosis and high-risk individuals. Front Neuroendocrinol. 2021;62:100930. CrossRef
  4. Chaumette B, Kebir O, Mam-Lam-Fook C, et al. Salivary cortisol in early psychosis: new findings and meta-analysis. Psychoneuroendocrinology. 2016;63:262–270. CrossRef
  5. Al-Harbi SD, Mashi AH, AlJohani NJ. A case of Cushing’s disease presenting with isolated suicidal attempt. Clin Med Insights Case Rep. 2021;14:11795476211027668.
  6. Mokta J, Sharma R, Mokta K, et al. Cushing’s disease presenting as suicidal depression. J Assoc Physicians India. 2016;64(11):82–83.
  7. Pivonello R, Simeoli C, De Martino MC, et al. Neuropsychiatric disorders in Cushing’s syndrome. Front Neurosci. 2015;9:129.

From https://www.psychiatrist.com/pcc/first-episode-psychosis-cushing-syndrome/

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

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