Outcomes of annual surveillance imaging in an adult and paediatric cohort of succinate dehydrogenase B mutation carriers

Tufton, Nicola; Shapiro, Lucy; Srirangalingam, Umasuthan; Richards, Paula J.; Sahdev, Anju; Kumar, V K Ajith; Chew, Shern L.; Drake, William M; Storr, Helen; Akker, Scott

doi:10.1530/endoabs.44.p5

Cited by 13 publications

(30 citation statements)

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“…Others have recommended screening every 1 to 2 years in a similar population. 28,29 We found that patients with carotid body tumors were at greater risk of a second primary paraganglioma compared to glomus vagale, glomus typanicum, and glomus jugulare tumors combined. This propensity for multicentricity has been suggested in several small case series, but this is the first study to our knowledge to demonstrate this increased risk.…”

Section: Discussionmentioning

confidence: 85%

Second primary tumors in patients with a head and neck paraganglioma

et al. 2019

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Background There are conflicting recommendations and possibly overuse of imaging for surveillance of second primary tumors for patients with a history of head and neck paraganglioma. Methods Retrospective cohort study of 234 adults with head and neck paragangliomas (1990‐2010) followed for a mean of 7.5 ± 8.4 years. Results The rate of second paraganglioma was 1.7% after 5 years and 5.1% after 10 years, yielding an incidence of 6.65 per 1000 person‐years. Only 1.3% of patients (2.59 per 1000 person‐years) ever had a second paraganglioma in the chest, abdomen, or pelvis. Patients with a hereditary paraganglioma (hazard ratio [HR] = 4.84, 95% confidence interval [CI]: 1.52‐15.43) or carotid body tumor (HR = 3.55, 95% CI: 1.15‐10.99) were at greater risk. Conclusions The incidence rate of a second primary paragangliomas is low but increases with hereditary disease. These results question the utility of repeated imaging outside of the neck to screen for second paragangliomas.

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Section: Discussionmentioning

confidence: 85%

Second primary tumors in patients with a head and neck paraganglioma

et al. 2019

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“…The importance of surveillance screening in asymptomatic relatives is highlighted when analysing studies that separate out the asymptomatic carriers/relatives from the index cases (Table ). These combined cohorts provide data on 1341 asymptomatic SDHB carriers and demonstrate a tumour detection rate of 15.4% (207 asymptomatic carriers with PPGLs identified on screening), when index cases are excluded (individual studies report a tumour detection rate ranging from 3.5% to 35%) . Penetrance estimates have fallen over time as more disease‐free asymptomatic carriers are identified.…”

Section: Surveillance Programmesmentioning

confidence: 99%

Can subunit‐specific phenotypes guide surveillance imaging decisions in asymptomatic SDH mutation carriers?

Tufton

Sahdev

Drake

et al. 2018

Clinical Endocrinology

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Objective: With the discovery that familial phaeochromocytoma and paraganglioma syndrome can be caused by mutations in each subunit of the succinate dehydrogenase enzyme (SDH), has come the recognition that mutations in the individual subunits have their own distinct natural histories. Increased genetic screening is leading to the identification of increasing numbers of, mostly asymptomatic, gene mutation carriers and the implementation of screening strategies for these individuals. Yet there is, to date, no international consensus regarding screening strategies for asymptomatic carriers.Design: A comprehensive PubMed search from 1/1/2000 to 28/2/2018 was undertaken using multiple search terms and subsequently a manual review of references in identified papers to identify all clinically relevant cases and cohorts. In this review, the accumulated, published experience of phenotype and malignancy risks of individual SDH subunits is analysed. Where possible screening results for asymptomatic SDH mutation carriers have been analysed separately to define the penetrance in asymptomatic carriers (asymptomatic penetrance). Results:The combined data confirms that "asymptomatic penetrance" is highest for SDHD and when there is penetrance, the most likely site to develop a PGL is head and neck (SDHD) and extra-adrenal abdominal (SDHB). However, the risk in SDHB carriers of developing HNPGL is also high (35.5%) and a PCC is low (15.1%), and in SDHD carriers there is a high risk of developing a PCC (35.8%) or abdominal PGL (9.4%) and a small, but significant risk at other sympathetic sites. The data suggest that the risk of malignant transformation is the same for both PCC and extra-adrenal abdominal PGLs (30%-35%) in SDHB carriers. In SDHD carriers, the risk of malignant transformation was highest in HNPGLs (7.5%) and similar for sympathetic sites (3.8%-5.2%). Conclusions:Using this data, we suggest surveillance screening of asymptomatic carriers can be tailored to the underlying SDH subunit and review possible surveillance programmes. K E Y W O R D S imaging, MRI, paraganglioma, phaeochromocytoma, screening, SDH, succinate dehydrogenase, surveillance S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Tufton N, Sahdev A, Drake WM, Akker SA. Can subunit-specific phenotypes guide surveillance imaging decisions in asymptomatic SDH mutation carriers?. Clin Endocrinol. 2019;90:31-46. https://doi.

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“…A review of the literature identified 13 manuscripts that attempted to address this issue. Eight studies argued for surveillance to start before or at 10 years including one expert opinion, three case series with less than five patients, three retrospective studies with 32, 92 and 116 patients, respectively), and one case‐control study with 241 patients . Three reports recommended starting from the second decade of life (one systematic review of 95 papers suggesting a start age between 11‐20 years, one retrospective study with 91 patients suggesting an age of 27.1 years based on HNPGL penetrance calculations and one case series of three families suggested a starting age of 18 years for HNPGL screening) .…”

Section: Methodsmentioning

confidence: 99%

“…However, 24‐hour urinary collections can be difficult to obtain in young children. Tufton et al replaced MRI imaging with ultrasound in children under 10 years of age if they were unable to tolerate MRI. In doing so, the patients could experience the potential benefits of earlier surveillance whilst minimizing the anxiety involved during surveillance.…”

Section: Methodsmentioning

confidence: 99%

Clinical Practice Guidance: Surveillance for phaeochromocytoma and paraganglioma in paediatric succinate dehydrogenase gene mutation carriers

Wong

Andrews

Challis

et al. 2019

Clinical Endocrinology

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SummaryThe succinate dehydrogenase (SDH) enzyme complex functions as a key enzyme coupling the oxidation of succinate to fumarate in the citric acid cycle. Inactivation of this enzyme complex results in the cellular accumulation of the oncometabolite succinate, which is postulated to be a key driver in tumorigenesis. Succinate accumulation inhibits 2‐oxoglutarate‐dependent dioxygenases, including DNA and histone demethylase enzymes and hypoxic gene response regulators. Biallelic inactivation (typically resulting from one inherited and one somatic event) at one of the four genes encoding the SDH complex (SDHA/B/C/D) is the most common cause for SDH deficient (dSDH) tumours. Germline mutations in the SDHx genes predispose to a spectrum of tumours including phaeochromocytoma and paraganglioma (PPGL), wild type gastrointestinal stromal tumours (wtGIST) and, less commonly, renal cell carcinoma and pituitary tumours. Furthermore, mutations in the SDHx genes, particularly SDHB, predispose to a higher risk of malignant PPGL, which is associated with a 5‐year mortality of 50%. There is general agreement that biochemical and imaging surveillance should be offered to asymptomatic carriers of SDHx gene mutations in the expectation that this will reduce the morbidity and mortality associated with dSDH tumours. However, there is no consensus on when and how surveillance should be performed in children and young adults. Here, we address the question: “What age should clinical, biochemical and radiological surveillance for PPGL be initiated in paediatric SDHx mutation carriers?”.

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Outcomes of annual surveillance imaging in an adult and paediatric cohort of succinate dehydrogenase B mutation carriers

Cited by 13 publications

References 0 publications

Second primary tumors in patients with a head and neck paraganglioma

Second primary tumors in patients with a head and neck paraganglioma

Can subunit‐specific phenotypes guide surveillance imaging decisions in asymptomatic SDH mutation carriers?

Clinical Practice Guidance: Surveillance for phaeochromocytoma and paraganglioma in paediatric succinate dehydrogenase gene mutation carriers

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