Endocrine Abstracts

Introduction

Based on the evidence available back then, in 2015 we developed a provincial multicenter protocol for screening and follow up of no-index patients with SDHB and SDHC mutations.

Objectives

1. To evaluate the performance of the protocol designed for the follow-up of asymptomatic SDHB and C carriers. 2. To describe the penetrance of manifestations associated with hereditary PGL-FEO syndromes type 3 and 4 in a provincial cohort of non-index carriers.

Methods

prospective observational study (January 2015–March 2019). Non-index SDH B and C mutations carriers were included. Once a year we determined catecholamines in a 24-h urine sample. Imaging and functional studies were established depending on type of mutation and catecholamines results. For SDHB+ we initially performed PET/CT with ¹⁸F-DOPA and ¹⁸F-FDG. For SDHC+ patients a head and neck MRI was requested if catecholamines were normal and ¹⁸F-DOPA PET/CT if elevated. After the first negative screening, patients continued with imaging follow-up (MRI) every two years added to annual urine catecholamines. For quantitative variables, results are expressed as mean±S.D. for normally distributed data and as median [range] for nonparametric data.

Results

n = 65.

– SDHB (n = 50, 11 families). 54% men. Age at genetic diagnosis: 46.5 ± 17.7 years. Follow-up time 25.9 ± 16.7 months. Abnormal uptakes were detected in 14/40 cases with ¹⁸F-DOPA and/or ¹⁸F-FDG PET/CT (2 false positives for ¹⁸F-FDG PET/CT and 12 true positives). Ten patients showed 11 lesions related to the syndrome: 5 abdominal PGL, 3 cervical PGL, 1 thoracic PGL, 1 pheochromocytoma and 1 medullary hyperplasia (60% functioning; age at diagnosis 35.2 [11–72] years; size 4.5 [1.1–10] cm). One metastatic case. Histological confirmation was obtained in 8/10 cases. Unrelated neoplasms were found in 2 patients (one lung squamous cell carcinoma and one large cell neuroendocrine carcinoma). The sensitivity and specificity of PET/CT with ¹⁸F-FDG were 100% and 93.9% (87.5% and 100% with ¹⁸F-DOPA). The penetrance was 22%.

– SDHC (n = 15, 2 families). 53% women. Age at diagnosis 49.9 ± 13.1 years. Follow-up time 26.9 ± 16.4 months. Only 2 patients showed lesions (one pituitary macroadenoma and one benign lymph node – false positive of MRI). The penetrance was 13.3%.

Conclusions

The proposed protocol detected PGL/FEO in 20% of non-index SDHB mutation carriers and only 60% had elevated catecholamines. In addition, it allowed us to detect other unsuspected neoplasms. The penetrance in SDHC mutation carriers is low, as expected.