International consensus on initial screening and follow-up of asymptomatic SDHx mutation carriers

Abstract

Approximately 20% of patients diagnosed with a phaeochromocytoma or paraganglioma carry a germline mutation in one of the succinate dehydrogenase (SDHx) genes (SDHA, SDHB, SDHC and SDHD), which encode the four subunits of the SDH enzyme. When a pathogenic SDHx mutation is identified in an affected patient, genetic counselling is proposed for first-degree relatives. Optimal initial evaluation and follow-up of people who are asymptomatic but might carry SDHx mutations have not yet been agreed. Thus, we established an international consensus algorithm of clinical, biochemical and imaging screening at diagnosis and during surveillance for both adults and children. An international panel of 29 experts from 12 countries was assembled, and the Delphi method was used to reach a consensus on 41 statements. This Consensus Statement covers a range of topics, including age of first genetic testing, appropriate biochemical and imaging tests for initial tumour screening and follow-up, screening for rare SDHx-related tumours and management of elderly people who have an SDHx mutation. This Consensus Statement focuses on the management of asymptomatic SDHx mutation carriers and provides clinicians with much-needed guidance. The standardization of practice will enable prospective studies in the near future.

Fig. 1. Screening and follow-up proposed during childhood.

An initial tumour screening should be performed after the discovery of an SDHA, SDHB, SDHC or SDHD-pi mutation relying on blood pressure measurements, a symptoms or signs questionnaire, assessment of metanephrines in plasma or urine, and imaging work-up by MRI of head and neck, thorax, abdomen and pelvis. Even after an initial negative work-up, all asymptomatic mutation carriers should be clinically followed up every year, by biochemical assessments every 2 years and by MRI every 2–3 years.

Fig. 2. Screening and follow-up proposed during adulthood.

An initial tumour screening should be performed after the discovery of an SDHA, SDHB, SDHC and SDHD-pi mutation relying on blood pressure measurements, a symptoms or signs questionnaire, assessment of metanephrines in plasma or urine, and imaging work-up by MRI of head and neck, abdomen, pelvis, and a whole-body PET–CT. Even after an initial negative work-up, all asymptomatic mutation carriers should be followed clinically and by biochemistry assessments every year and by MRI every 2–3 years. Thoracic MRI is not mandatory at the first initial work-up if PET–CT does not show any abnormality but is recommended for subsequent follow-up.