Congenital adrenal hyperplasia (CAH) is a rare group of diseases of the adrenal cortex characterized by impaired cortisol production and accumulation of precursors steroids (PS) and adrenal androgens (AA). In this project we will focus on patients with CAH due to 21-hydroylase deficiency, the most common form of CAH with a prevalence of 1:15 000.

Patients require lifelong cortisol replacement treatment based on international guidelines, yet most adult patients develop short- and long-term complications. Patients are at risk to develop a life threatening adrenal crisis in situations of illness. Therefore, parents and patients have to be educated regularly to increase their cortisol dosages adequately in situations of stress. Well-known long-term complications in undertreated patients with chronically elevated AA are infertility, cardiovascular, and metabolic diseases with a reduced quality of life.

The excess of AA is an important hallmark responsible for many complications. Therefore, treatment aims to decrease AA concentrations within normal range with frequent monitoring. The current approach measuring androstenedione cannot differentiate between adrenal and gonadal origin of androgens. Notably, adrenal specific 11-oxygenated androgens (11OA) are the most abundant AA in 21OHD. Therewith, 11OA are promising biomarkers for treatment monitoring of CAH. For clinical implementation longitudinal studies are necessary, especially in children and infants.

In this project the measurement method of 11OA in saliva will be developed and the role of 11OA will be studied in a clinical cohort of patients with CAH. Salivary measurement of AA enables non-invasive home-based sample collection over several timepoints per day. To enable saliva collection in young children (<4 years), we will evaluate a new saliva collection tool. We want to investigate efficacy and clinical implementation of salivary 11OA as new biomarkers for treatment control in pediatric 21OHD. We hypothesize that measuring 11OA in saliva will improve treatment control and consequently long-term clinical outcome in patients with 21OHD.

Furthermore, to improve hormonal control and especially to lower AA new treatment options Since May 2021, a controlled-release cortisol preparation has been authorized by the EMA and available on the Dutch market since March 2022 and is registered for adults and adolescents aged 12 years and older. Dose recommendations for this age group are not given and treatment is based on recommendations based on adult schedules Therefore, there is a need for a more protocolized treatment to prospectively evaluate the effects of this preparation.

Tasks and responsibilities

• Unravelling the clinical importance of AA in CAH disease.
• Optimalization of treatment regimen for CAH patients.
• Correlation obtained research data with clinical data.
• Generate and critically analyze the data in order to prepare scientific publications and presents findings at scientific meetings.
• Supervise MSc and/or BSc students.
• Participation in the graduate school of Radboudumc.

Our new PhD candidate has an MSc degree in Biomedical Sciences or Molecular Life Sciences, Medicine or a related field and affinity with clinical research. You have affinity with LC-MSMS and measurement method development in clinical practice and an structured working style.

In addition you possess the profile below:

• A strong motivation, flexibility, and willingness to learn.
• Critical scientific attitude and be able to work both independently as well as in a group.
• Excellent communication skills; oral and in English writing.

Fixed-term contract: 3 years.

At Radboud university medical center, you build on your future. We are committed to providing the best care, education, and research. And we are true to our word, because we help you develop and seize opportunities and give you the room to grow. As an employer, we believe that employees should feel vital and happy at work in all stages of life. We are also committed to creating a healthy and safe working environment. Our employment conditions contribute to that. What we offer:

• Upon commencement of employment, you will start at scale 10A, step 0 (€ 3.017 based on a full-time appointment). Over a maximum period of 4 years, you will progress to scale 10A, step 3 (€3.824 based on a full-time appointment). You will also receive an 8% holiday allowance, an 8.3% end-of-year bonus, and a 47% to 72% bonus for working unsocial hours. This project is for 3 years.
• 172 vacation hours per year based on a 36-hour working week. (As of 1 January 2025, you will receive 176 vacation hours).

Radboudumc

This PhD position is available based at the department of Paediatrics at the Radboudumc, centre of expertise on Sex & Gender headed by Prof. dr. Hedi Claahsen. The research will be performed in close collaboration with the Department of Laboratory Medicine (dr. Teun van Herwaarden, Prof. Fred Sweep). You will join the Congenital Adrenal Hyperplasia (CAH) research group, with a longstanding experience of investigating pathophysiological mechanisms of CAH steroidogenesis.

Radboudumc
Welcome to Radboud university medical center (Radboudumc), where scientific breakthroughs are born through the curiosity and passion of our collaborating researchers in a vibrant environment. We believe trust and excitement are crucial elements to achieving our goals, and we approach our research as teams and with the utmost rigor to make a significant impact on health and healthcare. Our researchers are driven by their fascination with the biological, psychological, and sociological mechanisms underlying health and healthcare. They collaborate with partners from all over the world to improve health outcomes for all. Radboudumc unites patient care, research, education, and corporate learning, which allows us to approach our mission to shape the health and healthcare of the future in an innovative and person-centered way.

Our ambition is to lead the way in the pursuit of prevention, sustainability, meaningful care. We believe that through our research, we can significantly improve the health and well-being of society. Join us on our mission to make a difference in healthcare. Become a part of our community of gifted researchers, professionals or patient partners who are dedicated to making a real impact on population health and healthcare.

Read what it is like to do a PhD at the Radboud University Medical Center.