Background: SDH mutations cause about 80% of familial pheochromocytomas / paragangliomas (1). Although mutations in each subunit are associated with a particular clinical spectrum of disease, there is no clear genotype-phenotype correlation of a specific mutation, nor with penetrance of disease. We report characteristics of patients with SDH mutations seen in a single dedicated tertiary referral clinic.
Methods: A retrospective observational study of patients attending the Endocrine Genetics clinic from May 2005 to May 2010. All patients had yearly clinical assessments with biochemistry and 2 to 3 yearly imaging with MRI with 18FDG PET if needed for clinical decision making.
Results: From a total of 37 patients, MRI detected all 16 tumours at baseline: SDHB 9/26, SDHC 2/4, and SDHD 5/8. Biochemistry was positive in all confirmed SDH B tumours, in 1/2 patients with SDHC (with tumour) and negative in all SDHD with tumours. 5/17 SDHB without tumours had abnormal urine but not plasma metanephrines on at least one occasion, which normalised subsequently. Only one patient (SDHB) presented with a new tumour at follow up. One patient with SDHB had a metastatic phaeochromocytoma at presentation which was fatal. Gamma knife radiosurgery was highly effective for glomus tumours, with reduction in catecholamine secretion and resolution of symptoms.
Conclusion: MRI is effective to monitor these patients. No new tumours were missed by an interval of imaging every 2-3 years. SDHB can be potentially fatal. False positive biochemistry is common in SDHB. Biochemistry is normal in SDHD despite the presence of tumours. Gamma knife radiosurgery can be considered for glomus tumours. Timing of intervention once an abnormality is identified requires an individualised approach.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.