February 2016 – The Endocrine Post

Rare Disease Day takes place on the last day of February each year. With this in mind, we bring you a new post focusing on congenital adrenal hyperplasia (CAH). This is a rare endocrine condition affecting only around 1 in 14,000 births, and a focus for a UK-wide Society-led project to develop clinical outcomes and treatment for CAH patients.

RareDiseaseDay

CAH Adult Study Exercise (CaHASE) is one of five research and audit projects which the committee works on with the Society’s UK-wide network of members. The study aims to address clinical outcomes, quality of life and sexual function in adults with CAH.

CAH is one of the most common inherited diseases and is associated with enlarged (hyperplasic) adrenal glands, cortisol-deficiency and overproduction of androgen. Consequently, patients may have an inability to respond effectively to stress, a lowered metabolic efficiency and early or inappropriate sexual development. See our public-facing website, You and Your Hormones, for more information on the causes, symptoms and treatment of CAH.

CaHASE, set up in 2004, is led by Society member Professor Richard Ross, Head of the Unit of Diabetes and Endocrinology at the University of Sheffield.

“Most of the published literature on CAH is centred on CAH in childhood,” says Richard, “But with the development of advanced hormone treatment in the 50s, many patients now live into adulthood. We had a feeling these adults needed better care – so we set up CaHASE to look at how well they were being treated.”

Since the project was set up, a great deal has been invested in the development of CaHASE. Through our extensive member network, over 200 patients were recruited into the largest study ever of adults with CAH, the results of which demonstrated that new treatments were required. The study has provided a wealth of peer-reviewed literature which has fed directly into clinical practice at participating centres. For example, in Oxford, clinicians managed to bring back the majority of CAH patients who had been lost to follow-up, reducing ‘did not attend’ rates and expanding the number of CAH patients they see.

When asked what he hopes CaHASE will achieve in the future, Richard said, “It will continue to inform and develop clinical practice. We hope to bring new therapies to patients and improve the quality of life of those patients.”

CaHASE is one five projects supported and developed by our Society Clinical Committee: read an overview on these projects in the latest edition of the Society magazine, The Endocrinologist. We are proud to support Rare Disease Day in its aim to raise awareness amongst the general public and decision-makers about rare diseases and their impact on patients’ lives. The political momentum resulting from Rare Disease Day also serves advocacy purposes, aiming to contribute to the advancement of national plans and policies for rare diseases in a number of countries.

The Society for Endocrinology is a member of Rare Disease UK – the organisation coordinating Rare Disease Day.

Follow Rare Disease Day on Twitter using the hashtag #RareDiseaseDay

Coinciding with World Cancer Day, this month’s issue of our journal Endocrine-Related Cancer includes an exciting new review of cutting edge research on a putative new oncogene TERT, and its role in affecting clinical outcomes in thyroid cancer. Journal editor Charis Eng is here to tell us why this is such a significant piece of work.

Over the last 10 years, thyroid cancer has been the fastest rising incident cancer in women and second fastest in men, without clear aetiology. In the January 2016 issue of Endocrine-Related Cancer, Liu and Xing from Johns Hopkins University School of Medicine provided an authoritative review article on “TERT promoter mutations and their role in predicting clinical outcome in thyroid cancer”.

Up until recently, BRAF and RAS somatic mutations were utilized to predict outcome in thyroid cancer. Two years ago, Prof Xing was the first to show that TERT promoter mutations were associated with the most aggressive thyroid cancers. Now, the authors bring us an erudite and comprehensive review on this new and cutting edge field.

The oncogenic role of TERT promoter mutations involve creation of consensus binding sites for ETS transcriptional factors. The mutations occur with an increasing prevalence from low- to high-grade thyroid tumours, namely, on average, 0%, 11.3%, 17.1%, 43.2%, and 40.1% in benign thyroid tumours, papillary thyroid cancer (PTC), follicular thyroid cancer, poorly differentiated thyroid cancer, and anaplastic thyroid cancer, respectively (Figure 1). They are strongly associated with aggressive clinicopathological outcomes, including aggressive pathological features, tumour recurrence, and patient mortality. Importantly, TERT promoter mutations are also associated with BRAF and RAS mutations, and their coexistence has a robust synergistic effect on the poor clinicopathological outcomes of thyroid cancer.

This review by Liu and Xing conclude that the mutated TERT gene is a prominent new oncogene that plays an important role in thyroid tumorigenesis and represents a novel diagnostic and prognostic molecular marker and therapeutic target in this cancer.

Fig 1

Figure 1. Prevalence of TERT promoter mutations increases with the grade of the thyroid tumour and is associated with more aggressive clinicopathological outcomes.

To find out more on the latest endocrine cancer research across all our journals, visit our new website Hormone-Related Cancer.

Month: February 2016

Rare Disease Day: improving patient outcomes for rare endocrine diseases

Oncogenes and predicting clinical outcomes in thyroid cancer