Profile: Wiebke Arlt
University of Birmingham researcher Wiebke Arlt received many bouquets of flowers for establishing that male hormones affect women’s libidos. Now she’s developing a urine test for adrenal cancer, as she told Sarah Harrop in the fourth of a series of profiles taken from our Annual Review 2011/12.
Cancer of the adrenal glands is hard to detect because the glands are hidden deep inside the body and the disease can be symptomless in its early stages — so new diagnostic tests are urgently needed.
In 2011, with MRC funding, Professor Wiebke Arlt developed the first urine test for adrenal cancer which could replace expensive CT scans and avoid the need for surgery in suspected cases that turn out to be benign. Wiebke is fascinated by hormones — in fact she’s built her career around studying them.
Early on in her career, as a young doctor in Germany, she was the first to establish that male hormones (androgens) affect libido and feelings of wellbeing in women. During a trial to restore these hormones in women with androgen deficiency she began to receive thank-you gifts of flowers and wine from their husbands, which she says “was an early sign of what was going on”.
She’s been hooked on endocrinology (hormone research) ever since and today she is head of the Centre for Endocrinology, Diabetes and Metabolism at the University of Birmingham. One of her particular interests is a group of hormones called steroids, which are made by the adrenal glands that sit just above our kidneys.
It was while studying rare conditions caused by under- or over-production of steroid hormones that Wiebke came up with the idea of using a technique called gas chromatography/mass spectrometry (GC/MS) to measure the individual steroid hormones in the body.
Wiebke realised that this technique might also be useful for diagnosing cancer of the adrenal glands, because she had a hunch that adrenal cancer cells might lose the ability to produce normal levels of steroid hormones. She wanted to see if it was possible to distinguish adrenal cancer patients from healthy people by measuring the products of hormones broken down by the body and excreted in urine.
“In the UK a lot of imaging is done for people who complain of non-specific tummy pain, and during these procedures we often discover nodules on the adrenal glands. In a small number of cases a nodule can turn out to be cancer and needs to be taken out. But diagnosis takes multiple tests and CT scans, and that can mean huge costs,” explains Wiebke.
“Also, up to 60 per cent of surgical removals of large adrenal nodules end up revealing that the nodule is benign. So in the vast majority of these cases, a urine test would completely avoid the need for expensive surgery and the associated risks to the patient,” she adds.
With MRC funding, Wiebke and her colleagues carried out a trial of 45 patients who were known to have adrenal cancer that had spread and compared them with 100 patients who had adrenal tumours that turned out to be benign nodules.
“We ran GC/MS tests on their urine collected over 24 hours and analysed the results. This revealed that there is a specific ‘steroid fingerprint’ for adrenal cancer in the urine of some of the molecules that go on to become a steroid hormone, and these so-called precursors are not detectable in the blood.
This work, funded with a biomarker grant from the MRC, has shown that the test detects the malignancy with 90 per cent sensitivity and specificity.”
This discovery will have a huge impact for patients and for the NHS because it offers the possibility of replacing expensive scans with a quick, simple urine test.
A big research study is about to start to see whether the test can be transferred to a faster type of technology called high throughput LC/MS, which could rapidly analyse urine for up to 10 steroids in less than five minutes.
“In theory, the patient could just bring the urine to the clinic and in the afternoon we would already know whether the fingerprint for malignancy is in their urine or not,” explains Wiebke. “This would also avoid the need for expensive top-to-toe CT scans to check for cancer recurrence in patients who’ve had an adrenal cancer removed, as the urine test may prove to be more sensitive than imaging. Our team are currently studying whether this is the case.”
Together with diagnostics company Bioscience Ventures, Wiebke and her team are carrying out a prospective study of the test and hope to launch it as a diagnostic product in 2013.
“The MRC biomarker grant funding was critical to the translation of my ideas to clinical application because it funded a biochemist, a mass spectrometrist who did the analysis and a computer science postdoctoral researcher who did the computational analysis. So it was absolutely key to the development of the test,” says Wiebke.
“For me, the highlight of my work is to combine clinical practice with discovery research and translational research that has lab aspects and clinical aspects to it. It’s incredibly satisfying because you can see something through from the start to the finish, such as with the adrenal tumour test, and hopefully end up helping more patients than you could ever hope to treat in your career.”
Wiebke was also featured in ‘What’s in a work space?’ in September.