Research led by the University of Birmingham has found that increased levels of hormones including testosterone could cause a brain condition that can lead to blindness in women.
Idiopathic Intracranial Hypertension - also known as IIH - is caused by high pressure in the brain with consequences from blindness to incapacitating daily long-term headaches. IIH was originally identified over 100 years ago yet the cause of the condition has remained unknown although there has been much speculation about why more than 95 per cent of total incidence is in women with obesity.
Once regarded as rare, incidence of IIH is now rising dramatically in line with the global rise in obesity and there has been a 150 per cent rise in incidence in last 10 years. Currently there are very limited treatment options.
Scientists at the University of Birmingham carried out research, funded by the National Institute of Health Research (NIHR), the Medical Research Council UK, and Wellcome Trust and published today in JCI Insight, exploring the role of hormones known as androgens in the way IIH develops.
The researchers examined the levels of androgens in blood and urine, as well as in brain fluid known as cerebrospinal fluid (CSF), in 55 women with IIH aged 18 to 45. They then compared the results with the levels observed in women with obesity of the same age and body mass index (BMI), as well as a cohort of women with polycystic ovary syndrome (PCOS).
PCOS is a common condition and is classically associated with increased levels of specific types of androgens, which can cause excess hair and irregular periods.
The researchers found that IIH patients had a very different profile of raised levels of androgens compared to women of a similar age with obesity and women with PCOS. Most notable were the high levels of the androgen 'testosterone' found in the blood in IIH women. Crucially, levels of androgens were uniquely increased in the brain fluid (CSF) of women with IIH. When the researchers, analysed human choroidal plexus tissue, which is the site in the brain where CSF is produced, they confirmed that androgens could increase the rate of CSF secretion, a potential driver for increased brain pressure.
Corresponding and senior author Dr Alex Sinclair, NIHR Clinician Scientist at the University of Birmingham, said: "For over 100 years the cause of IIH has been unknown.
"These findings mark a key step forward; for the first time we have found a pattern of androgen dysregulation that is unique to IIH and potentially a driver of abnormal brain pressure in people with the condition.
"Taken together this provides the first evidence that IIH may be a manifestation of female androgen excess."
Lead author Dr Michael O'Reilly, Hoffenberg Clinician Scientist in Endocrinology and Human Metabolism at the University of Birmingham, said: "These findings, for the first time, implicate androgens as a potential cause of IIH."
Professor Wiebke Arlt, Director of the University of Birmingham's Institute of Metabolism and Systems Research, added: "These findings mark a significant step forward in a previously poorly understood disabling condition.
"Understanding the cause of a disease is a vital step to ultimately refine treatments which improved patient care and outcomes."
Michelle Williamson, Chair of the patient charity IIHUK, added: "The recent patient and doctor research Priority Setting Partnership identified that uncovering the cause of IIH was the number one priority for IIH. We are delighted by this discovery. It is vital for the patients to see that progress is being made."
This latest study comes after experts led by the University of Birmingham recently produced the first internationally collaborative guidelines aimed at improving the treatment and diagnosis of IIH.
Created by a group of specialists in neurology, neurosurgery, neuro-radiology, ophthalmology and neuroradiology, who have had expertise in managing IIH, the team envisage that the new guidelines, published last October in Journal of Neurology Neurosurgery and Psychiatry, will step change the treatment of the condition.
For more information please contact Emma McKinney, Communications Manager (Health Sciences), University of Birmingham, Email: firstname.lastname@example.org or tel: +44 (0) 121 414 6681, or contact the press office on +44 (0) 7789 921 165 or email@example.com
Notes to Editors:
- The University of Birmingham is ranked amongst the world's top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 6,500 international students from over 150 countries.
- O'Reilly et al (2019). 'A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics'. JCI Insight. DOI: [insert here]
- Dr Alex Sinclair is also an Honorary Consultant Neurologist and Clinician Scientist at University Hospitals Birmingham NHS Foundation Trust.
- This study was funded by the National Institute of Health Research (NIHR), the Medical Research Council UK, and Wellcome Trust.
- This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme
- Nurses of the National Institute of Health Research/Wellcome Trust Clinical Research Facility at University Hospital Birmingham NHS Foundation Trust, Birmingham, helped with patient recruitment and running of the study.
- The views expressed in this publication are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, or the Department of Health UK.
- University Hospitals Birmingham NHS Foundation Trust (UHB) runs the Queen Elizabeth Hospital Birmingham, Birmingham Chest Clinic, Heartlands Hospital, Good Hope Hospital, Solihull Hospital and various community services across the region. The Trust has regional centres for trauma, burns, plastics, neurosciences, dermatology and cancer. It also has centres of excellence for vascular, headache, bariatric and pathology services, as well as the treatment of MRSA and other infectious diseases. We also have expertise in HIV/AIDS, premature baby care, bone marrow transplants and thoracic surgery. UHB has the largest solid organ transplantation programme in Europe and runs Umbrella, the sexual health service for Birmingham and Solihull. It is also home to the West Midlands Adult Cystic Fibrosis Centre and a nationally-renowned weight management clinic and research centre. The Queen Elizabeth Hospital Birmingham is a Major Trauma Centre treating the most severely injured casualties from across the region. The hospital's single site 100-bed critical care unit is the largest in Europe. The Trust hosts the Institute of Translational Medicine (ITM) and leads the West Midlands Genomics Medicine Centre as part of the national 100,000 Genomes Project. UHB is also proud to host the Royal Centre for Defence Medicine (RCDM) at the Queen Elizabeth Hospital Birmingham. The RCDM provides dedicated training for defence personnel and is a focus for medical research.
The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR:
- Funds, supports and delivers high quality research that benefits the NHS, public health and social care
- Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
- Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
- Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
- Partners with other public funders, charities and industry to maximise the value of research to patients and the economy.
The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR commissions applied health research to benefit the poorest people in low- and middle-income countries, using Official Development Assistance funding.
About Idiopathic Intracranial Hypertension
- Idiopathic Intracranial Hypertension is a rare condition, with an incidence in the general population rising rapidly from 2 per 100,000 in 2002, to 5 per 100,000 by 2016. The incidence is highest in women with obesity. https:/
/ www. nature. com/ articles/ s41433-018-0238-5
- The cause of IIH has, to date, been unknown but is characterised by raised intracranial pressure, resulting in disabling chronic daily headaches and optic disc swelling which cause blindness in up to 25%.
- A previous study by the University of Birmingham research team has shown that weight loss is successful in relieving IIH. https:/
/ www. bmj. com/ content/ 341/ bmj. c2701. long
- New guidelines for treating IIH: Mollan et al (2018).'Idiopathic intracranial hypertension: consensus guidelines on management'. Journal of Neurology Neurosurgery and Psychiatry. DOI: 10.1136/jnnp-2017-317440 https:/
/ www. ncbi. nlm. nih. gov/ pubmed/ 29903905