How to avoid pitfalls in interpretation of adrenal imaging

By Philip Ward, AuntMinnieEurope.com staff writer

January 15, 2019 — A clear understanding of the pitfalls in the performance and interpretation of adrenal CT can help prevent incorrect and inappropriate investigations, award-winning researchers from a top London facility have found. It’s essential to keep aware of the full range of pseudolesions and mimics, they said.

“Evaluation of adrenal tumor function is limited on imaging, but may be inferred from imaging findings,” noted Dr. Gurinder Nandra and colleagues from the department of radiology at St. George’s University Hospitals NHS Foundation Trust in an e-poster presentation that received a cum laude award at RSNA 2018 in Chicago.

Other adrenal pathology, including metastases and adrenocortical carcinoma, may be encountered, and this means it’s important to know about the imaging approaches to evaluate the adrenals, the authors pointed out.

Incidental adrenal nodules are identified in around 5% of patients who undergo CT. The prevalence of detecting incidentalomas increases with age, but most incidentally encountered adrenal pathology is benign and of little clinical relevance, they wrote. Adenomas are by far the most common adrenal pathology identified.

Among the technical aspects that deserve special attention are the following:

  • The region of interest (ROI): Changing the size of the ROI can alter the perceived attenuation of the nodule. The ROI should cover at least two-thirds of the circumference of the nodule, and exclude tiny areas of heterogeneity from the ROI (e.g., flecks of calcification) that are not representative of the adrenal pathology. Unenhanced attenuation of less than 10 Hounsfield units (HU) can be used to diagnose lipid-rich adrenal adenoma (sensitivity 71%, specificity of 98%).
  • Attenuation values on unenhanced CT: A homogenously dense lesion on unenhanced CT suggests a lack of microscopic lipid content. If attenuation on unenhanced CT is greater than 20 to 30 HU, evaluate the enhancement kinetics with CT.
  • Effect of kVp on attenuation values in a dual energy study: To use threshold of less than 10 HU to diagnose a lipid-rich adrenal adenoma, the kVp should be 120. Changing kVp can alter the attenuation values of soft tissues and adrenal glands.
  • Timing of post-contrast acquisitions: “Imaging needs to be performed at the correct times to allow sufficient time for enhancement and washout of contrast. Post-contrast images should be obtained at 60 to 75 seconds and 15 minutes,” the authors stated.
  • Assessment of washout on nondedicated studies: Relative washout can be calculated on nondedicated studies if more than one acquisition is made within 15 minutes post-intravenous contrast.
  • Suspicious attenuation: Attenuation of more than 43 HU on noncontrast CT is suspicious for malignancy, regardless of washout characteristics. PET/CT is of more use than CT and MRI in such cases, and adrenal hemorrhage also is a consideration at this attenuation.
  • Evaluation of small nodules: Minor nodularity of less than 1 cm in diameter does not require further radiological investigation. Also, CT evaluation of small adrenal nodules is limited by partial volume artifacts. MRI evaluation of small adrenal nodules is limited by the India ink artifact, or black boundary artifact, on an out-of-phase sequence. This artifact may give the impression of signal loss and lead to an incorrect diagnosis of a lipid-rich adenoma.
  • Evaluation of large adrenal masses: Malignancy risk increases with size (over 4 cm, 70%; over 6 cm, 85%) when excluding myelolipoma. In the absence of known malignancy, an adrenal lesion of less than 4 cm with indeterminate imaging features is likely to be benign.
  • Enhancement characteristics of metastases: Enhancement/washout characteristics of adrenal metastases are variable, and they can be confused with pheochromocytoma.
  • Adrenal calcification: Calcification is seen in benign adrenal pathology, but also can be seen in cases of malignancy, including adrenocortical carcinoma. “Look for ancillary features of malignancy including size, heterogeneity and invasion,” the authors recommended. “Evaluation of a predominantly calcified adrenal lesion will be limited with chemical shift MRI.”
  • Heterogeneous signal loss: Heterogeneous signal loss is not typical for a small lipid-rich adenoma and raises the possibility of malignant pathology. It also can be seen in larger adenomas because of calcification/cystic change/myelolipomatous metaplasia.

In their RSNA 2018 exhibit, Nandra and colleagues also identified the following list of mimics that can crop up:

  • Mimics arising from gastrointestinal tract: Gastric pathology can extend into the left suprarenal space and mimic adrenal pathology. The most common mimics include gastrointestinal stromal tumors and gastric diverticula. Pathology elsewhere in the gastrointestinal tract can mimic adrenal pathology (e.g., a fluid-filled colon).
  • Mimics arising from solid viscera: Pathology from the spleen, pancreas, liver, and kidneys can extend into the suprarenal space and mimic adrenal pathology. This includes splenic lobulation, splenunculi, upper pole renal pathology, pancreatic tail pathology, and exophytic hepatic lesions.
  • Mimics arising from vessels: Dilated, tortuous, or aneurysmal vessels may extend into the suprarenal space and mimic adrenal pathology. The most common mimics include splenic varices and splenic artery pseudoaneurysms.
  • Mimics arising from retroperitoneal tissues: Various retroperitoneal lesions can extend into the suprarenal space and mimic adrenal pathology, and normal anatomy in the retroperitoneum also can mimic adrenal pathology (e.g., a thickened diaphragmatic crus).

From https://www.auntminnieeurope.com/index.aspx?sec=ser&sub=def&pag=dis&ItemID=616803

Study Supports Midnight Salivary Cortisol Test to Diagnose Cushing’s in Chinese Population

A simple test that measures free cortisol levels in saliva at midnight — called a midnight salivary cortisol test — showed good diagnostic performance for Cushing’s syndrome among a Chinese population, according to a recent study.

The test was better than the standard urine free cortisol levels and may be an alternative for people with end-stage kidney disease, in whom measuring cortisol in urine is challenging.

The study, “Midnight salivary cortisol for the diagnosis of Cushing’s syndrome in a Chinese population,” was published in Singapore Medical Journal.

Cushing’s syndrome, defined by excess cortisol levels, is normally diagnosed by measuring the amount of cortisol in bodily fluids.

Traditionally, urine free cortisol has been the test of choice, but this method is subject to complications ranging from improper collection to metabolic differences, and its use is limited in people with poor kidney function.

Midnight salivary cortisol is a test that takes into account the normal fluctuation of cortisol levels in bodily fluids. Cortisol peaks in the morning and declines throughout the day, reaching its lowest levels at midnight. In Cushing’s patients, however, this variation ceases to exist and cortisol remains elevated throughout the day.

Midnight salivary cortisol was first proposed in the 1980s as a noninvasive way to measure cortisol levels, but its efficacy and cutoff value for Cushing’s disease in the Chinese population remained unclear.

Researchers examined midnight salivary cortisol, urine free cortisol, and midnight serum cortisol in Chinese patients suspected of having Cushing’s syndrome and in healthy volunteers. These measurements were then combined with imaging studies to make a diagnosis.

Overall, the study included 29 patients with Cushing’s disease, and 19 patients with Cushing’s syndrome — 15 caused by an adrenal mass and four caused by an ACTH-producing tumor outside the pituitary. Also, 13 patients excluded from the suspected Cushing’s group were used as controls and 21 healthy volunteers were considered the “normal” group.

The team found that the mean midnight salivary cortisol was significantly higher in the Cushing’s group compared to both control and normal subjects. Urine free cortisol and midnight serum cortisol were also significantly higher than those found in the control group, but not the normal group.

The optimal cutoff value of midnight salivary cortisol for diagnosing Cushing’s was 1.7 ng/mL, which had a sensitivity of 98% — only 2% are false negatives — and a specificity of 100% — no false positives.

While midnight salivary cortisol levels correlated with urine free cortisol and midnight serum cortisol — suggesting that all of them can be useful diagnostic markers for Cushing’s — the accuracy of midnight salivary cortisol was better than the other two measures.

Notably, in one patient with a benign adrenal mass and impaired kidney function, urine free cortisol failed to reach the necessary threshold for a Cushing’s diagnosis, but midnight salivary and serum cortisol levels both confirmed the diagnosis, highlighting how midnight salivary cortisol could be a preferable diagnostic method over urine free cortisol.

“MSC is a simple and non-invasive tool that does not require hospitalization. Our results confirmed the accuracy and reliability of [midnight salivary cortisol] as a diagnostic test for [Cushing’s syndrome] for the Chinese population,” the investigators said.

The team also noted that its study is limited: the sample size was quite small, and Cushing’s patients tended to be older than controls, which may have skewed the results. Larger studies will be needed to validate these results in the future.

From https://cushingsdiseasenews.com/2019/01/10/midnight-salivary-cortisol-test-helps-diagnose-cushings-chinese-study-shows/

FDA Approves High-resolution MRI, Better at Spotting Pituitary Tumors in Cushing’s Patients

The U.S. Food and Drug Administration has approved the clinical use of a magnetic resonance imaging (MRI) scanner — the ultra-high-field 7T Terra MRI — with unprecedented resolution that allows for more reliable images of the brain.

The approach recently allowed the precise localization of a small tumor in the pituitary gland, which standard MRI had failed to spot, in a patient with Cushing’s disease.

So far, only one scanner of this kind exists in the U.S.. It was installed in February 2017 at the Mark and Mary Stevens Neuroimaging and Informatics Institute (INI) of the Keck School of Medicine, University of Southern California (USC).

The new scanner has an increased magnetic field strength of 7 Tesla, which is more than four times that of conventional MRI. This property greatly improves the instrument’s signal-to-noise ratio, dramatically increasing the spatial resolution and contrast of its images so that scientists can visualize the human living brain in high-definition and with unprecedented detail.

The 7T Terra is ideal for high-resolution neuroimaging, exploration of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, and diagnosis and treatment of other brain diseases, a USC news story by Zara Greenbaum states.

Earlier this year, a report described the case of women with Cushing’s disease with a pituitary adenoma (slow-growing, benign tumor in the pituitary gland) that was possible to localize only with the new 7T MRI.

Based on laboratory analysis that revealed high levels of adrenocorticotropic hormone(ACTH) and cortisol, the doctors suspected a pituitary adenoma and recommended the patient for surgery. However, they ignored the precise location of the tumor, which failed to be detected by standard MRI scanners (1T and 3T).

    Two hours before surgery, the woman underwent a 7T MRI scan which finally identified with high precision the location of the adenoma, a very small tumor of 8 mm on the right side of the pituitary gland.

    “The 7T may save patients an invasive procedure. It also makes it easier for neurosurgeons to selectively remove a tumor without damaging surrounding areas,” said Gabriel Zada, MD, associate professor of neurological surgery at the Keck School.

    Since its arrival, the device has supported exploratory research into both healthy and diseased brains.

    Now the scanner’s advanced imaging technology can be used to help with diagnosis, treatment and monitoring of patients with neurological diseases, including Cushing’s disease.

    “This device, which has already made its mark as a powerful tool to advance research in the neurosciences, is now accessible to clinical populations in addition to researchers,” said Arthur W. Toga, PhD, provost professor and chair at the Keck School and director of the USC Stevens INI.

    “Clinicians across the university and beyond can now leverage all the benefits of increased spatial resolution to serve patients in need,” he said.

    Adapted from https://cushingsdiseasenews.com/2018/11/06/fda-oks-high-resolution-mri-better-spotting-pituitary-tumor-cushings/

    Night Cortisol Levels for Diagnosing Cushing’s Syndrome Less Accurate in Clinical Practice

    Salivary cortisol levels can be used to diagnose Cushing’s syndrome with relatively high reliability, but each test center should establish its own measurement limits depending on the exact method used for the test, a study from Turkey shows.

    Researchers, however, caution that late-night salivary cortisol measurements in clinical practice is likely to be less accurate than that seen in controlled studies, and some patients might require additional tests for a correct diagnosis.

    The study, “Diagnostic value of the late-night salivary cortisol in the diagnosis of clinical and subclinical Cushing’s syndrome: results of a single-center 7-year experience,” was published in the Journal of Investigative Medicine

    In healthy individuals, the levels of cortisol — a steroid hormone secreted by the adrenal glands — go through changes over a 24-hour period, with the lowest levels normally detected at night.

    But this circadian rhythm is disrupted in certain diseases such as Cushing’s syndrome, where night cortisol levels can be used as a diagnostic tool.

    Among the tests that can be used to detect these levels are late-night serum cortisol (LNSeC) and late-night salivary cortisol (LNSaC) tests. Since it uses saliva samples, LNSaC is more practical and does not require hospitalization, so it is often recommended for the diagnosis of Cushing’s syndrome.

    So far, though, there has been no consensus regarding cutoff values and the sensitivity of the test.

    Mustafa Kemal Balci, MD, and his team at the Akdeniz University in Turkey aimed to evaluate the diagnostic use of LNSaC in patients with clinical Cushing’s syndrome and in those with subclinical Cushing’s syndrome — people with excess cortisol but without signs of the disease.

    The study involved 58 patients with clinical Cushing’s syndrome (CCS), 53 with subclinical Cushing’s syndrome (SCS), and 213 patients without Cushing’s syndrome who were used as controls.

    Saliva and serum cortisol levels were measured in all patients, and statistical tests were used to study differences in these levels among the three groups of patients.

    In CSC patients, the median cortisol levels were 0.724 micrograms per deciliter of blood (µg/dL), which dropped to 0.398 and 0.18 in patients with subclinical disease and controls.

    The optimal cutoff point to distinguish patients with clinical Cushing’s was set at 0.288 µg/dL, where 89.6% of patients identified as positive actually have the disease (sensitivity), and 81.6% of patients deemed as negative were without the disease (specificity).

    With a lower cutoff point — 0.273 µg/dL — researchers were also able to identify patients with subclinical disease with high sensitivity and specificity.

    While the test showed high sensitivity and specificity values for clinical Cushing’s syndrome, its diagnostic performance was lower than expected in daily clinical practice, researchers said.

    “The diagnostic performance of late-night salivary cortisol in patients with subclinical Cushing’s syndrome was close to its diagnostic performance in patients with clinical Cushing’s syndrome,” researchers wrote.

    However, regarding the application of this test in other centers, they emphasize that “each center should determine its own cut-off value based on the method adopted for late-night salivary cortisol measurement, and apply that cut-off value in the diagnosis of Cushing’s syndrome.”

    From https://cushingsdiseasenews.com/2018/07/31/late-night-salivary-cortisol-levels-questioned-diagnosis-cushings-syndrome/

    Measuring TSH Levels Could Improve Diagnosis for Cushing’s Syndrome

    Measuring the variation in thyroid stimulating hormone blood levels between midnight and morning may be better for diagnosing Cushing’s syndrome than current approaches, a study suggests. 

    The study, “TSH ratio as a novel diagnostic method for Cushing’s syndrome,” was published in the Endocrine Journal

    Cushing’s syndrome (CS) is a condition characterized by excess cortisol in the blood, which can lead to a variety of issues, including obesity, high blood pressure, abnormal lipid levels, osteoporosis, depression, and cognitive impairments.

    In some cases, patients have high cortisol levels, but lack the typical physical features of Cushing’s syndrome. These patients are considered to have subclinical Cushing’s syndrome (SCS), and are at higher risk for cardiovascular disease.

    Being able to properly diagnose CS and SCS is of utmost importance for proper intervention and treatment of these patients.

    Current methods of diagnosis rely on dexamethasone suppressing tests or late-night salivary and blood cortisol tests, as well as measurements of cortisol in urine. However, because cortisol is a stress-hormone, it can be elevated in cases of mental or physical stress, leading to false positive results on these tests. 

    Researchers in this study examined if another hormone, called the thyroid stimulating hormone (TSH), could be used to diagnose Cushing’s syndrome with better accuracy.

    TSH is a hormone that stimulates the thyroid gland and whose secretion is affected by the body’s circadian rhythm. Its highest levels in the blood are usually seen in the late evening or early morning. However, patients with CS or SCS lack this nocturnal increase in TSH levels, which could be useful as a new diagnostic approach.

    The study recruited 142 patients with suspected CS and SCS, and 21 patients with depression, being treated at the Osaka University Hospital in Japan.

    Patients received the ordinal screening tests for Cushing’s syndrome, along with measurements of their midnight-to-morning TSH levels.

    After taking the tests, only 20 patients were diagnosed as having Cushing’s, including 12 with over (normal) Cushing’s syndrome and 10 with subclinical Cushing’s syndrome.

    Patients with Cushing’s had significantly lower midnight TSH levels than non-Cushing’s patients. No differences were seen in morning levels between the groups. Of note, TSH ratio was maintained in patients with depression, suggesting TSH levels could be used to diagnose Cushing’s in patients with depression.

    Researchers observed that serum TSH ratio had powerful diagnostic accuracy. Among patients identified as having Cushing’s, 90% actually had the disease. And among patients excluded for Cushing’s, 95% did not have the condition. These sensitivity and specificity rates were better than with current diagnostic approaches.

    However, when considering this test, patients with a severe TSH deficiency must be taken into account.

    Overall, these results suggest that the midnight-to-morning serum TSH ratio is a potential new way to diagnose both CS and SCS with a higher specificity than the current diagnostic methods

    “The strength of our current survey is its prospective design and the evaluation of not only overt CS but also SCS. The limitation is the relatively small number of CS group patients, especially overt CD,” the researchers wrote.

    “New prospective studies will be needed with a larger number of patients in order to further clarify the optimal TSH ratio in the diagnosis of CS,” the study concluded. 

    From https://cushingsdiseasenews.com/2018/06/28/measuring-tsh-levels-may-improve-cushings-syndrome-diagnosis-study/

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