ESPE Abstracts

Background: Von Hippel-Lindau (VHL) syndrome is a rare autosomal dominant genetic disorder characterized by retinal and central nervous system hemangioblastomas, pheochromocytomas and multiple cysts in the pancreas and kidneys, with increased risk of malignant degeneration.

Case presentation: A 9-year-old boy with uncomplicated premorbid and family history presented with ice-cold hands and profuse night sweating on the head and chest since 1 month. The only pathological findings from the physical status were sinus tachycardia and persistent arterial hypertension up to 160/100 mmHg. The FBC and all biochemical and hormonal tests (TFT, Cortisol, Aldosterone and PTH) were within reference ranges except for elevated plasma Dopamine: 78.8 pg/ml (0-50 pg/ml) and 24-hour urinary Normetanephrines: 16 922 µg/24h (n< 600 µg/24h). The CT scan revealed a well-demarcated, rounded, inhomogeneous tumor formation 47/38 mm in the right adrenal gland and an irregular oval nodular lesion 14/17 mm in the left adrenal gland. A small-sized, 3 mm, low-density round nodule was found in the thyroid gland. The patient underwent laparoscopic radical right adrenalectomy without surgical intervention on the left adrenal gland. The histological analysis showed alveolar pheochromocytoma with slightly expressed polymorphism and extensive necrosis. The differential diagnosis included: Multiple еndocrine neoplasia type 2A or 2B; Von Hippel-Lindau syndrome; Familial paraganglioma syndrome; Neurofibromatosis type 1 and sporadic PHEOs. The analysis of 19 genes, associated with hereditary syndromes with CNS and PNS tumors, detected a rare heterozygous pathogenic variant: c.340G>A (p.Gly114Ser) in exon 1 of the VHL gene, encoding the tumor-suppressor protein VHL. During the first six postoperative months the urinary Normetanephrines remained in the upper part of the normal range, after which they started to rise gradually. At the last visit, one year after the operation, the patient was asymptomatic, normotonic, with normal growth. The 24-hour urinary Normetanephrines were elevated - 1 250 µg/24 (n< 600 µg/24h). The abdominal MRI revealed that the tumor in left adrenal gland had increased to 20/27 mm. MRI suggested that it might be malignant. No renal or pancreatic lesions were detected. Ocular involvement was excluded by fundoscopy. Due to the lack of focal neurologic symptoms CNS imaging was not required. A left adrenalectomy was planned.

Conclusion: The early identification of VHL is important in view of the increased risk of malignancy. The pleiotropic clinical manifestations require a close, lifelong surveillance (especially of the renal, ocular and nervous systems) in order to timely detect and treat the complications.