Adrenocortical carcinoma masquerading as Cushing’s disease

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

A Faster Way to Diagnose Cushing’s Syndrome

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

Scalp Hair Cortisol Accurate in Cushing’s Syndrome Diagnosis

Scalp hair cortisol measurement is an accurate first-line diagnostic test for Cushing’s syndrome in adults and offers several advantages over other first-line diagnostic procedures, according to findings published in the European Journal of Endocrinology.

“[Hair cortisol content] has practical advantages over currently used diagnostic tests, since sample collection can easily be performed in an outpatient setting and is not dependent on patient adherence to sampling instructions,” Elisabeth F. C. van Rossum, MD, PhD, professor at Erasmus MC, University Medical Center Rotterdam in the Netherlands, and colleagues wrote. “Furthermore, [hair cortisol content] measurement offers retrospective information about cortisol levels over months of time in a single measurement, thereby potentially circumventing the limitations posed by the variability in cortisol secretion in endogenous [Cushing’s syndrome].”

Van Rossum and colleagues analyzed data from 43 patients with confirmed endogenous Cushing’s syndrome and 35 patients with suspected Cushing’s syndrome in whom diagnosis was excluded after testing (patient controls), all evaluated between 2009 and 2016 at an endocrinology outpatient clinic at Erasmus MC. Adults from a previously published validation study served as healthy controls (n = 174). Researchers measured scalp hair samples, 24-hour urinary free cortisol, serum cortisol and salivary cortisol, and used Pearson’s correlation to determine associations between hair cortisol content and first-line screening tests for Cushing’s syndrome.

Hair cortisol content was highest in patients with Cushing’s syndrome (geometric mean, 106.9 pg/mg; 95% CI, 77.1-147.9) and higher compared with both healthy controls (mean, 8.4 pg/mg; 95% CI, 7-10) and patient controls (mean, 12.7 pg/mg; 95% CI, 8.6-18.6). Using healthy controls as the reference population, researchers found that the optimal cutoff for diagnosis of Cushing’s syndrome via hair cortisol content was 31.1 pg/mg; sensitivity and specificity were 93% and 90%, respectively (area under the curve = 0.958). Results were similar when using patient controls as the reference population, according to the researchers.

Hair cortisol content was correlated with urinary free cortisol (P < .001), serum cortisol (P < .001) and late-night salivary cortisol (P < .001). In addition, in two patients with ectopic Cushing’s syndrome, researchers observed a gradual rise in hair cortisol content in the 3 to 6 months before disease diagnosis.

“Together with a straightforward sample collection procedure, this method may prove to be a convenient noninvasive screening test for [Cushing’s syndrome],” the researchers wrote. “Additionally, our results indicate that hair cortisol measurements provide clinicians a tool to retrospectively assess cortisol secretion in patients with [Cushing’s syndrome], months to years back in time. This also offers the opportunity to estimate the onset of hypercortisolism and thus the duration of the disease before diagnosis.” – by Regina Schaffer

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B72da0183-e1a8-48cb-a1fd-332c7999beb5%7D/scalp-hair-cortisol-accurate-in-cushings-syndrome-diagnosis

What You Should Know About Pituitary Tumors

Ask the Experts

Igor Kravets, MD
Endocrinologist, Assistant Professor Division of Endocrinology,
Diabetes and Metabolism
Stony Brook Medicine
Raphael Davis, MD
Neurosurgeon, Professor and Chair Department of Neurosurgery
Co-Director, Stony Brook University Neurosciences Institute

 

Where do pituitary tumors form?
Dr. Kravets: A pituitary tumor is an abnormal growth of cells in the pituitary gland, which is a small, pea-sized organ located in the center of the brain, behind the nose and eyes. The pituitary is a “master gland” of the body; it produces many hormones that control other endocrine glands and certain functions of the body.
Are they mostly benign or malignant?
Dr. Davis: Most pituitary tumors are benign (non-cancerous). However, because of the location of the pituitary gland at the base of the skull, pituitary tumors can cause problems since they grow upward. Eventually some will press against the area where the optic nerves intersect, causing vision problems. They can also cause hormonal imbalance.What causes pituitary tumors?
Dr. Kravets: No one knows for sure what causes pituitary tumors. About one to five percent of pituitary tumors occur within families. Most are not inherited, however there are certain, rare, inherited conditions such as multiple endocrine neoplasia type 1 (MEN 1), that carry a higher risk of pituitary tumors.

What are the different types of pituitary tumors?
Dr. Davis: Adenomas are benign tumors that develop on the pituitary gland behind the eyes. These tumors can change levels in hormone production or cause vision loss. Craniopharyngiomas are benign tumors that develop at the base of the brain where it meets the pituitary gland. They commonly affect children 5 to 10 years of age, but adults can sometimes be affected in their 50s and 60s.

What are the symptoms?
Dr. Kravets: Symptoms vary depending on the type and size of a pituitary tumor but not all pituitary tumors cause symptoms. Many pituitary tumors are not diagnosed until symptoms appear. Some pituitary tumors are found incidentally on brain imaging obtained for a reason unrelated to the pituitary. Certain symptoms may develop when pituitary tumors grow so large that they exert pressure on surrounding structures.

Such symptoms include:
• Changes in vision (particularly loss of peripheral/outer edge vision)
• Headache

Other symptoms are related to either deficiency or excessive production of certain hormones. Common symptoms caused by such hormonal disturbances include:
• Menstrual cycle changes (irregular or lack of menstrual periods
• Erectile dysfunction or loss of sex drive
• Weight changes
• Production of breast milk by a woman who has not given birth
• Accelerated or stunted growth in a child or teenager
• Growth of the hands, feet, forehead and jaw in adults
• Development of a round face, a hump between the shoulders or both

How is a pituitary tumor diagnosed?
Dr. Kravets: An endocrinologist will ask you about the symptoms you are experiencing, and about your personal and family health history. He or she will perform a physical exam and order tests of your blood and urine. A magnetic resonance imaging (MRI) scan or computerized tomography (CT or CAT) scan may also be ordered to obtain detailed images of the brain and the pituitary gland. In rare instances, a biopsy (surgical procedure to remove a small sample of the tumor for examination) is required.

What treatments are available?
Dr. Davis: Treatments may include surgery, radiation therapy or medication. Transsphenoidal surgery is surgery performed through the nose and sphenoid sinus (located in the very back part of the nose, just beneath the base of the brain) to remove a pituitary tumor. It can be performed with an endoscope, microscope or both and is a team effort between neurosurgeons and ear, nose and throat (otolaryngology/ENT) surgeons. Radiation therapy uses high-energy x-rays to kill the tumor cells and is recommended when surgery is not an option, if the pituitary tumor remains, or if the tumor causes symptoms that are not relieved by medicine.

Why choose Stony Brook?
Dr. Kravets: Our Pituitary Care Center provides access to all of the coordinated expert care you need in one location, close to home — which can make the course of your treatment easier. Our team includes specialists from endocrinology, neurosurgery, otolaryngology (ENT), radiation oncology, neuropathology, neuroradiology, neuro-ophthalmology, and patient education and support.

To make an appointment with one of our Pituitary Care Center endocrinologists, call
(631) 444-0580. To make an appointment with one of our Pituitary Care Center neurosurgeons,
call (631) 444-1213. To learn more, visit stonybrookmedicine.edu/pituitary.

All health and health-related information contained in this article is intended to be general and/or educational in nature and should not be used as a substitute for a visit with a healthcare professional for help, diagnosis, guidance, and treatment. The information is intended to offer only general information for individuals to discuss with their healthcare provider. It is not intended to constitute a medical diagnosis or treatment or endorsement of any particular test, treatment, procedure, service, etc. Reliance on information provided is at the user’s risk. Your healthcare provider should be consulted regarding matters concerning the medical condition, treatment, and needs of you and your family. Stony Brook University/SUNY is an affirmative action, equal opportunity educator and employer.

From https://www.stonybrookmedicine.edu/patientcare/pituitarytumors

Hair Test for Cushing Syndrome?

Cortisol levels in hair correlated strongly with standard tests

by Jeff Minerd
Contributing Writer, MedPage Today

Analyzing the levels of cortisol in hair may aid in the diagnosis of Cushing syndrome, perhaps one day replacing invasive blood tests, scientists said.

Cortisol levels in the proximal ends of hair samples taken from patients with the syndrome correlated strongly with blood tests (R=0.4; P=0.03) and urine tests (R=0.5; P=0.005) for cortisol, reported Mihail Zilbermint, MD, of the National Institute of Child Health and Human Development in Bethesda, Md., and colleagues.

“The diagnosis of Cushing syndrome is often challenging and inconclusive, despite numerous tests used for the detection of hypercortisolemia and its origin, and is associated with high morbidity and high risk for mortality, if undiagnosed and untreated,” Zilbermint and colleagues wrote online in Endocrine: International Journal of Basic and Clinical Endocrinology.

“As a potential solution to the limitations of these tests, hair cortisol has been increasingly studied as an additional means to diagnose patients with Cushing Syndrome. Much like hemoglobin A1C is a longitudinal marker of blood glucose levels, hair cortisol can be a measure of the body’s glucocorticoid levels over the previous several weeks to months.”

“Our results are encouraging,” Zilbermint said in a statement. “We are hopeful that hair analysis may ultimately prove useful as a less-invasive screening test for Cushing syndrome or in helping to confirm the diagnosis.”

The study included 30 patients with Cushing syndrome and six control individuals without the disease. The participants’ average age was 26, and 75% were female and 75% were Caucasian.

The investigators took 3 cm-long hair samples from all patients, analyzed the proximal, medial, and distal segments of the samples for cortisol, and compared the results with results of standard blood and urine tests. Cortisol levels were highest in the proximal segments and correlated best with the standard tests, the investigators reported.

“We found that proximal hair cortisol directly correlates with late night serum cortisol and UFC [urinary free cortisol] in patients with and without Cushing syndrome. The most proximal 1 cm of hair was the best section of hair for stratifying the two groups of patients in our cohort.

“These findings support further research on the use of this modality in the workup for Cushing syndrome.”

Regarding the study’s limitations, the team pointed to the small control group of only six patients. Another limitation is that more than half of the participants (58%) were younger than age 18, and pubertal status on cortisol metabolism may be a factor in hair cortisol measurement.

“However, our study’s strengths are that it is the largest sample so far to analyze segmental hair cortisol in Cushing syndrome, and that it is the largest study to compare hair cortisol to any biochemical test for hypercortisolemia in patients with Cushing syndrome,” Zilbermint and colleagues said. “Our study also included a large cohort of Cushing Disease patients, which has been under-represented in prior studies on hair cortisol.”

The study was funded by the National Institutes of Health. Zilbermint and colleagues reported having no relevant financial relationships with industry.

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