Endocrine Abstracts

Background: Germline mutations in SDHB, SDHC, and SDHD cause hereditary phaeochromocytoma and paraganglioma (PGL) syndromes. The genotype-phenotype correlation of these mutations and relationship to penetrance is poor. Our objective was to assess characteristics of patients with SDH mutations seen in our dedicated multidisciplinary clinic.

Methods: A retrospective observational study of patients attending from May 2005 to May 2010, approved as an institutional case notes review. Clinical, genetic, biochemical and radiological characteristics were recorded. All patients underwent yearly biochemical screening with urinary catecholamines/metanephrines, and plasma metanephrines, and 2–3 yearly MRI of the sympathetic and parasympathetic chain using axial and coronal T1/T2 spin-echo sequences, with 18FDG-PET if needed for clinical decision making if abnormalities found

Results: From a total of forty-five mutation carriers, tumours were detected by MRI in eighteen patients (median age): 11/34 (26) SDHB (8 secreting), 2/4 SDHC (36) (1 secreting), 5/7 (48) SDHD (all non secreting). 4/11 SDHB patients belonged to one large family of 17 with frame-shift mutation c.379dupA(p.LLe127AsnfsX28) in exon 4 of SDHB Gene. Only one patient had a metastatic phaeochromocytoma at presentation. One patient with an aggressive glomus tumour (SDHC) secreted high levels of dopamine in isolation, treated effectively with Gamma knife. The SDHD associated glomus tumour was nonsecreting and SDHB glomus tumour secreted noradrenaline. Six SDHB patients had false positive biochemistry, most commonly urine metanephrine and normetanephrine, which subsequently normalized. Two new tumours were detected on screening (SDHB,SDHD).

Conclusion: MRI is effective to monitor these patients. False positive biochemistry is common in SDHB, but normal in SDHD despite the presence of tumours. SDHB present at a younger age with abdominal PGL. Dopamine can be the only biochemical abnormality in some aggressive tumors. Gamma knife radiosurgery can be considered for glomus tumours. No new tumours were missed by an interval of MRI imaging every 2–3 years.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.