Why do children get adrenocortical tumours (ACTs)?
Children and young people may develop adrenocortical tumours (ACT) either randomly or due to faulty genes (‘genetic mutations’). If they are born with these faulty genes, they are more likely to get ACTs at younger age. The most common gene change is a TP53 mutation, which may cause Li-Fraumeni Syndrome. Another genetic condition called Beckwith-Wiedemann Syndrome, also increases the risk.
What symptoms do children experience due to adrenocortical tumours?
Most children with ACT have hormone imbalances because their tumour makes too much of certain hormones. Symptoms depend on which hormones are affected:
• Early puberty in boys (e.g. pubic hair, growth of the penis, deeper voice, large muscles)
• Girls developing male traits (early pubic and facial hair, deep voice, growth of the clitoris)
• Fast growth and strong bones
• Weight gain (especially in the face and belly)
• Weak muscles and thin skin
• High blood pressure
• High blood pressure
• Headaches, blurry vision, dizziness, racing or fluttering heartbeat
• Boys may develop breasts
• Girls may start puberty too early
• Stomach pain or a lump in the belly
• Tiredness and weight loss
At what age do children usually develop adrenocortical tumours?
ACTs mostly affects two age groups:
- Children under 5 years old – Nearly half of all cases happen before age 4. These cases are often linked to genetic conditions.
- Older children (10 years and up) – Tumours in this group are usually bigger and more aggressive.
ACTs are more common in girls than boys (about 2 girls for every 1 boy).
How are adrenocortical tumours treated in children?
Treatment depends on if the tumour is cancer and how advanced the cancer is. Because paediatric adrenocortical tumours are rare, treatment should be managed by specialised cancer centres with experience in adrenal tumours.
• If the tumour is small and hasn’t spread, surgery to remove it is the best option.
• Open surgery is recommended to avoid breaking the tumour, which can spread cancer.
• If the tumour has spread or isn’t fully removed, doctors use chemo to kill cancer cells.
• The most common drugs used are Mitotane on its own or, in advanced stages, the combination of Etoposide, Doxorubicin, Cisplatin, and Mitotane (EDP-M).
• Radiation is usually not recommended because it may cause other cancers later.
Outlook
• Early-stage ACT: High survival rate (about 90% % if caught early).
• Late-stage ACT: Poor survival rate (less than 20% if it spreads).
Children who have had an ACT need regular check-ups to make sure the cancer doesn’t come back.
What is the Future for Treatment for Adrenocortical Tumours (ACT) in Children?
Currently, most treatments for paediatric ACT are based on adult treatments, but researchers are working on better options. The future of ACT treatment focuses on:
Instead of general chemotherapy, new treatments aim to attack specific cancer cells while sparing healthy ones. Promising options include:
• Cabozantinib – A drug that blocks signals that help cancer grow. It is currently in trial for ACT in children.
• Pembrolizumab (Immunotherapy) – Boosts the immune system to fight cancer. A small number of children have already responded well to this treatment.
• IGF2/IGF1R Inhibitors – Since many adrenocortical tumours have too much IGF2, drugs targeting this protein could help.
CAR-T therapy uses genetically modified immune cells to attack cancer. Scientists are testing B7-H3 CAR-T cells for ACC, which could provide a new, effective treatment.
• Liquid Biopsies – A simple blood test that can track cancer cells without surgery.
• Single-Cell Sequencing – Helps doctors understand how tumours change over time, leading to more personalized treatments.
Because ACT is rare, global studies like the International Paediatric Adrenocortical Tumour Registry (IPACTR) help collect data and improve treatment plans. Doctors need to work together across the world to share experience and develop research projects; one of those initiatives is the European Network for the Study of Adrenal Tumours (ENS@T) Kids’ Group (https://ensat.wildapricot.org).
New research will focus on:
• Understanding paediatric ACTs better by collecting data across the globe
• Safer chemotherapy combinations
• Radiation alternatives for children with TP53 mutations
• New drug combinations to improve survival
What This Means for the Future
In the next 5-10 years, we can expect:
- More effective and less toxic treatments
- More personalized medicine based on each child’s tumour
- Higher survival rates and better quality of life
While surgery and chemotherapy remain the standard today, research is paving the way for better, targeted treatments with fewer side effects.
Useful Childhood Cancer Organisations
- Children with Cancer UK (UK)
- Grace Kelly Childhood Cancer Trust (UK)
- Teenage Cancer Trust (UK)
- Cancer Research UK List of Organisations Supporting Children with Cancer
References
- M Ilanchezhian et al; Pediatric adrenocortical carcinoma, Frontiers in Endocrinology, 31 October 2022 (base article summarised to produce the initial draft of this information using ChatGPT in March 2025)
- Pinto EM, Zambetti GP, Rodriguez-Galindo C. Pediatric adrenocortical tumours. Best Pract Res Clin Endocrinol Metab. 2020 May;34(3):101448. doi: 10.1016/j.beem.2020.101448. Epub 2020 Jul 3. PMID: 32636100.
- Virgone C, Roganovic J, Vorwerk P, Redlich A, Schneider DT, Janic D, Bien E, López-Almaraz R, Godzinski J, Osterlundh G, Stachowicz-Stencel T, Brugières L, Brecht IB, Thomas-Teinturier C, Fresneau B, Surun A, Ferrari A, Bisogno G, Orbach D. Adrenocortical tumours in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations. Pediatr Blood Cancer. 2021 Jun;68 Suppl 4:e29025. doi: 10.1002/pbc.29025. PMID: 34174161.
- Riedmeier M, Antonini SRR, Brandalise S, Costa TEJB, Daiggi CM, de Figueiredo BC, de Krijger RR, De Sá Rodrigues KE, Deal C, Del Rivero J, Engstler G, Fassnacht M, Fernandes Luiz Canali GC, Molina CAF, Gonc EN, Gültekin M, Haak HR, Guran T, Hendriks Allaird EJ, Idkowiak J, Kuhlen M, Malkin D, Meena JP, Pamporaki C, Pinto E, Puglisi S, Ribeiro RC, Thompson LDR, Yalcin B, Van Noesel M, Wiegering V. International consensus on mitotane treatment in pediatric patients with adrenal cortical tumors: indications, therapy, and management of adverse effects. Eur J Endocrinol. 2024 Mar 30;190(4):G15-G24. doi: 10.1093/ejendo/lvae038. PMID: 38552173.
ACT in Children Website Information Authors/Reviewers:
- Joanna Grey (AMEND CEO)
- Dr Jan Idkowiak (Clinical Associate Professor and Honorary Consultant in Paediatric Endocrinology, Programme Director NIHR Clinical Research Facility (Paediatrics), Department of Metabolism and Systems Sciences, School fio Mecdical Sciences, College of Medicine & Health, University of Birmingham & Department of Endocrinology, Birmingham Women’s and Children’s NHS Foundation Trust)
- Dr Renuka Dias (Honorary Associate Clinical Professor, Consultant Paediatric Endocrinologist, Department of Applied Health Sciences at the University of Birmingham and at the Department of Paediatric Endocrinology and Diabetes at Birmingham Children’s Hospital (BCH))
- The ACC Support Medical Advisory Team