Detailed MRI Analysis Provides Correlations with Clinical Features and Response to Treatment in Cushing’s Disease

Posted on May 1, 2026 by MaryO

Detailed imaging analysis of patients with Cushing’s disease (CD) and other disorders caused by pituitary adenomas (tumors that arise from the pituitary, a small gland in the brain) provides correlation with clinical characteristics and treatment response, a new Turkish study reports.

The research, “Clinicopathological significance of baseline T2-weighted signal intensity in functional pituitary adenomas,” appeared in the journal Pituitary.

Diagnosis of pituitary adenomas is often done with magnetic resonance imaging (MRI), which provides data on the tumor’s localization, its invasiveness, as well as cell death and other changes. However, MRI does not enable precise evaluation of the tumor’s hormone production and behavior.

Studies on T2-weighted signal intensity (T2-WSI) — one of the basic parameters in MRI scans that highlights fat and water in the body — shows that it correlates with collagen content, degree of fibrosis (scarring), amyloid protein accumulation, and granulation pattern of somatotroph adenomas, which produce excessive levels of growth hormone, causing acromegaly (a hormonal disorder that results from too much growth hormone in the body).

Evaluation of granulation patterns is key in predicting response to somatostatin analogues (SSAs) treatment, the researchers observed. SSAs are intended to stop excess hormone production.

In contrast, analysis of T2-WSI in corticotroph adenomas — benign tumors typical in Cushing’s disease patients that release elevated levels of adrenocorticotropin (ACTH) – is still lacking.

The research team assessed the correlation of T2-WSI with clinical features, granulation patterns, and response to treatment in patients with functional pituitary adenomas (FPAs), which are collectively characterized by excessive production of one or more hormones.

Specifically, scientists focused on 29 patients with Cushing’s disease, 87 with acromegaly, and 78 with prolactinoma, a type of benign pituitary tumor that produces elevated amounts of prolactin.

Results showed that while most somatotroph adenomas (53%) were hypointense, which means a darker image on MRI, the majority of prolactinomas (55%) and corticotroph adenomas (45%) were at least generally hyperintense, meaning lighter on image.

Data also revealed that hyperintense somatotroph adenomas were larger, sparsely granulated, and exhibited reduced shrinkage after treatment with SSAs.

In contrast, hypointense tumors were associated with higher levels of baseline insulin-like growth factor (IGF)-1% ULN, a predictor of insulin sensitivity, and a better response to SSAs.

In women with prolactinomas, hyperintensity correlated with smaller tumor diameter. In turn, hypointense prolactinomas were linked with younger age at diagnosis, higher baseline prolactin levels, and resistance to treatment with a dopamine agonist.

Scientists also found that hyperintense corticotroph adenomas correlated with larger tumor size and a sparsely granulated pattern. No difference was found between hyper and hypointense adenomas on cortisol and ACTH levels.

Investigators also reported that T2-WSI was not correlated with better surgical outcomes or with recurrent Cushing’s disease. Analysis of tumor shrinkage in these patients was not possible, the researchers noted.

“Although in present there is no immediate clinical application, we believe that if medical shrinkage of corticotrophs ever became a part of clinical practice, similar analyses could be performed in the future,” the researchers wrote.

“Further studies with larger series are required in order to make stronger suggestions,” they added.

From https://cushingsdiseasenews.com/2018/03/23/detailed-mri-analysis-correlates-with-cushings-disease-clinical-features/

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Adrenocortical carcinoma masquerading as Cushing’s disease

Posted on May 1, 2026 by MaryO

BMJ Case Reports 2017; doi:10.1136/bcr-2016-217519

Summary

Cushing’s syndrome (CS) can be classified as adrenocorticotropic hormone (ACTH)-dependent or ACTH-independent depending on the ACTH levels.

However, 30% of the patients with CS have ACTH levels in the ‘grey zone’ (5–20 pg/mL), thereby posing a challenge in establishing the aetiological diagnosis. In a patient with full-blown features of Cushing’s syndrome with equivocal ACTH levels, and a pituitary microadenoma on contrast-enhanced MRI sella, can falsely lead to a diagnosis of Cushing’s disease. Pituitary microadenoma, if <6 mm in size, may be an incidental finding (incidentaloma) in this scenario and can be present in ∼3–27% of the healthy population. Therefore, in a patient with CS with equivocal ACTH levels and a pituitary microadenoma, multiple samplings for ACTH and adrenal imaging should be performed to exclude ACTH-independent CS and if required, bilateral inferior petrosal sinus sampling to determine the source of ACTH excess.

Find the entire article here: http://casereports.bmj.com/content/2017/bcr-2016-217519.full

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A Faster Way to Diagnose Cushing’s Syndrome

Posted on May 1, 2026 by MaryO

Diagnosing Cushing’s syndrome can take 24 hours of complicated and repeated analysis of blood and urine, brain imaging, and tissue samples from sinuses. But that may soon be in the past: National Institutes of Health (NIH) researchers have found that measuring cortisol levels in hair samples can do the same job faster.

Patients with Cushing’s syndrome have a high level of cortisol, perhaps from a tumor of the pituitary or adrenal glands, or as a side effect from medications. In the study, 36 participants—30 with Cushing’s syndrome, six without—provided hair samples divided into three equal segments. The researchers found that the segments closest to the scalp had the most cortisol (96.6 ± 267.7 pg/mg for Cushing’s syndrome patients versus 14.1 ± 9.2 pg/mg in control patients). Those segments’ cortisol content correlated most closely with the majority of the initial biochemical tests, including in blood taken at night (when cortisol levels normally drop).

The study was small; Cushing’s syndrome is rare, and it’s hard to recruit large numbers of patients. Still, the researchers believe it is the largest of its kind to compare hair cortisol levels to diagnostic tests in Cushing’s patients. “Our results are encouraging,” said Mihail Zilbermint, MD, the study’s senior author and an endocrinologist at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. “We are hopeful that hair analysis may ultimately prove useful as a less-invasive screening test for Cushing’s syndrome or in helping to confirm the diagnosis.” The authors suggest the test is also a convenient alternative with the “unique ability” for retrospective evaluation of hypercortisolemia over months.

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From https://www.ptcommunity.com/journal/article/full/2017/4/271/research-briefs-april-2017

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Comparison of MRI techniques for detecting microadenomas in Cushing’s disease

Posted on April 29, 2026 by MaryO
1Department of Neurological Surgery and 2Department of Radiology, University of Virginia Health Science Center, University of Virginia, Charlottesville, Virginia
ABBREVIATIONS ACTH = adrenocorticotropic hormone; CMRI = conventional MRI; DMRI = dynamic contrast-enhanced MRI; FSH = follicle-stimulating hormone; IPSS = inferior petrosal sinus sampling; SE = spin echo; SGE = spoiled-gradient echo 3D T1 sequence; SPGR = spoiled gradient–recalled acquisition; VIBE = volumetric interpolated breath-hold examination.

INCLUDE WHEN CITING Published online April 28, 2017; DOI: 10.3171/2017.3.JNS163122.

Correspondence Edward H. Oldfield, Department of Neurological Surgery, University of Virginia, Box 800212, Charlottesville, VA 22908. email: .
OBJECTIVE

Many centers use conventional and dynamic contrast-enhanced MRI (DMRI) sequences in patients with Cushing’s disease. The authors assessed the utility of the 3D volumetric interpolated breath-hold examination, a spoiled-gradient echo 3D T1 sequence (SGE) characterized by superior soft tissue contrast and improved resolution, compared with DMRI and conventional MRI (CMRI) for detecting microadenomas in patients with Cushing’s disease.

METHODS

This study was a blinded assessment of pituitary MRI in patients with proven Cushing’s disease. Fifty-seven patients who had undergone surgery for Cushing’s disease (10 male, 47 female; age range 13–69 years), whose surgical findings were considered to represent a microadenoma, and who had been examined with all 3 imaging techniques were included. Thus, selection emphasized patients with prior negative or equivocal MRI on referral. The MRI annotations were anonymized and 4 separate imaging sets were independently read by 3 blinded, experienced clinicians: a neuroradiologist and 2 pituitary surgeons.

RESULTS

Forty-eight surgical specimens contained an adenoma (46 ACTH-staining adenomas, 1 prolactinoma, and 1 nonfunctioning microadenoma). DMRI detected 5 adenomas that were not evident on CMRI, SGE detected 8 adenomas not evident on CMRI, including 3 that were not evident on DMRI. One adenoma was detected on DMRI that was not detected on SGE. McNemar’s test for efficacy between the different MRI sets for tumor detection showed that the addition of SGE to CMRI increased the number of tumors detected from 18 to 26 (p = 0.02) based on agreement of at least 2 of 3 readers.

CONCLUSIONS

SGE shows higher sensitivity than DMRI for detecting and localizing pituitary microadenomas, although rarely an adenoma is detected exclusively by DMRI. SGE should be part of the standard MRI protocol for patients with Cushing’s disease.

Full text at http://thejns.org/doi/full/10.3171/2017.3.JNS163122

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Urinary free cortisol analyses: Enhancing their clinical performance in Cushing’s syndrome management by means of LC-MS/MS

Posted on April 10, 2026 by MaryO

Highlights

  • An LC-MS/MS method was developed for UFC, cortisone and dexamethasone monitoring.
  • Direct injection was found to be suitable, even in cases of hypocortisolism.
  • Cortisone and cortisol/cortisone ratio complementary role in UFC tests was proved.
  • Dexamethasone monitoring in urine allowed to exclude invalid samples.
  • Population-based LC-MS/MS reference ranges were established.

Abstract

24 h urinary free cortisol (UFC) analysis constitutes one of the three first level recommended tests in Cushing’s syndrome (CS) diagnostic confirmation work up. However, it occasionally leads to inaccurate results due to the use of immunoassays (IAs) or the concomitant administration of exogenous glucocorticoids, among others.
This study aimed to develop a rapid and accurate LC-MS/MS method which may ultimately replace the use of IAs, and also provide relevant clinical information through the simultaneous monitoring of UFC, cortisone, and dexamethasone.
An LC-MS/MS method based on direct injection approach was developed and fully characterized for the quantitation of the target analytes. A population-based reference range was established, and the potential supporting role of cortisone and cortisol/cortisone ratio was comprehensively assessed in patients under CS follow-up or clinical suspicion for hypercortisolism. The presence of dexamethasone was also assessed in order to exclude invalid samples from evaluation.
Significant differences were observed for cortisone and cortisol/cortisone ratio between the control group and patients with hyper−/hypocortisolism, and an ideal level of biochemical agreement was observed with UFC LC-MS/MS values when the combination of both biomarkers was considered. Dexamethasone was detected in up to 7.7% of the studied population.
The herein presented LC-MS/MS approach not only offers the possibility of discontinuing the use of IAs, but also provides additional biomarkers which are significantly relevant in CS management, thus enhancing the overall clinical performance of UFC analyses.

Introduction

Cushing’s syndrome (CS) is characterized by a state of hypercortisolism that can be detected and monitored by means of clinical laboratory tests, such as 24 h urinary freecortisol (UFC). UFC measurement constitutes one of the three first level recommended tests, along with overnight 1 mg dexamethasone suppression and late night salivary cortisol tests [1], [2].
UFC levels are in general highly variable, and at least two 24 h urine collections are necessary for screening/monitoring of CS [1], [2]. In addition to this, 24 h urine samples are often further required due to unexpected or biochemically inconsistent results. This makes the process even more tedious for the patient, and ultimately causes delays in CS diagnosis and management.
Such discordant results may derive from an undeclared use of exogenous glucocorticoids or analytical limitations, among other reasons. The latter occurs especially when UFC analyses are performed by immunoassays (IAs), due to their limited specificity.
Therefore, improvements in UFC tests concerning the analytical methodology, and the inclusion of complementary biomarkers that reinforce their clinical interpretation in the light of unexpected/inconsistent results, appear necessary.
Besides, the simultaneous monitoring of exogenous glucocorticoids in UFC analyses, which is not often considered in clinical practice, should be included.
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been suggested as the most suitable alternative for UFC quantification [3], [4], [5], [6], [7], since it overcomes IAs analytical limitations. Besides, it also allows for the simultaneous monitoring of different analytes.
In the context of CS management, the simultaneous LC-MS/MS determination of UFC and cortisone, as well as the use of cortisol/cortisone ratio have been previously suggested [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]. With regard to the monitoring of exogenous glucocorticoids, at our center (Hospital Universitario Son Espases, Palma, Spain), it would be of particular importance in the case of dexamethasone. This is because the UFC determination is often followed by an overnight 1 mg dexamethasone suppression test, and its intake may occur by mistake prior or during urine collection.
Despite their advantages, LC-MS/MS methods usually require time-consuming sample preparations, e.g. liquid-liquid extraction (LLE) protocols [20], thus not allowing to completely avoid using IAs in most clinical laboratories. In Spain, to the best of our knowledge, all hospitals in the public healthcare system still use IAs for UFC analysis. Mass spectrometry is only available at tertiary-care centers or academic hospitals, where is still used in combination with IAs to cope with the large volume of samples received on a daily basis. In this case, the use of complementary biomarkers in LC-MS/MS UFC analyses would be of particular interest, as discordant results may occur between methods due to IA analytical limitations.
For all these reasons, in the herein presented study, a novel, rapid and accurate LC-MS/MS method based on direct injection approach for the quantitation of UFC, cortisone, and dexamethasone was developed. Given the lack of standardization in reference ranges, appropriate population-based LC-MS/MS reference values were established.
Most research only focuses on the ability of cortisone and cortisol/cortisone ratio to discriminate ectopic ACTH production from other subtypes of CS [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]. For this reason, this study assessed their suitability as complementary biomarkers, and therefore their ability to reinforce the clinical interpretation of UFC analyses.
To the best of our knowledge, they have not been previously assessed in the context of hypocortisolism. This would be of substantial importance in the follow-up of CS since adrenal insufficiency secondary to adrenalectomy/pituitary surgery or pharmacological treatment (e.g. ketoconazole, metyrapone) may occur. Therefore, such scenario was further considered.

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