Endocrine Abstracts

A 19-year-old student was referred with a history of increasing anxiety attacks, palpitations and breathlessness. Blood pressure and urinary catecholamine levels were elevated. MRI imaging confirmed a para-aortic paraganglionoma and MIBG scan highlighted bony metastases. The patient underwent surgery for the primary lesion and targeted MIBG therapy for metastases.

Age of onset, malignant disease and metastases increase the likelihood of a genetic cause and family history revealed a paternal uncle had died from renal cell cancer aged 22. The patient underwent genetic counselling and testing and a heterozygous SDHB splice site mutation was found (c.423+1G>A).

DNA testing of relatives to date has identified another 7 mutation carriers (age 7–74 years) who are undergoing assessment screening. SDHB mutation carriers are more likely to develop malignant disease including renal cell and thyroid cell carcinomas.

Paraganglionomas and phaeochromocytomas are rare complex tumours requiring tertiary care and a multidisciplinary approach, and genetic classification of these tumours is key to follow-up screening and treatment protocols. 25–30% may be familial associated with one of six genes inherited in an autosomal dominant pattern, (SDHB, C or D, VHL, RET or rarely NF1).

With the establishment of our joint endocrine genetic clinic, and open access to an endocrine genetic clinical nurse specialist, patients and families receive optimum streamlined care and management.

Costly and time consuming genetic testing is prioritised according to clinical risk factors such as age at onset, sex, tumour site and number and accurate family history.

15/26 phaeochromocytoma/ paraganglionoma patients tested in our clinic between 2007 and 2009 were sporadic in origin. 9/26 were familial tumours and prompted 21 pre-symptomatic cascade relative tests. Ten (47.6%) of these were found to have a mutation.

Accurate and supportive counselling is essential prior to genetic screening. Cascade screening/pre-symptomatic testing for relatives of gene positive patients provides early diagnosis and best practise preventative medicine in a specialist clinic setting.