Pheochromocytoma as a first manifestation of von Hippel-Lindau disease

A 28-year-old woman presented with a three-year history of intermittent hypertension, palpitations, tachycardia and headaches. The patient was otherwise healthy. Plasma levels of normetanephrines and metanephrines were increased.

Abdominal ultrasound revealed a right adrenal mass of about 35 mm diameter and inhomogeneous structure (Figure 1).
Computed tomography (CT) confirmed the right adrenal mass, characterised by a finely inhomogeneous structure with an intense and heterogeneous contrast enhancement in arterial contrast phase (Fig. 2), because of the presence of necrotic areas and cystic change.
Magnetic resonance imaging (MRI) was performed and the right adrenal mass showed low T1 signal intensity, high T2 signal intensity and intense, prolonged, heterogeneous paramagnetic contrast enhancement on T1-weighted images (Fig. 3).
An iodine-123 meta-iodobenzylguanidine (I123-MIBG) scintigraphy demonstrated a markedly increased tracer in the right adrenal mass (Fig. 4).
The lesion was completely excised and the diagnosis of pheochromocytoma was confirmed.
The genetic analysis found a missense mutation in the exon 3 of the VHL gene, compatible with von Hippel-Lindau (VHL) type 2C disease.
A craniospinal axis MRI, an ophthalmologic and audiologic examination excluded other tumours.

Von Hippel-Lindau disease (VHL) is a hereditary autosomal dominant condition caused by different mutations leading to loss of function of the VHL gene, a tumour suppressor gene located on chromosome 3p25–26.
Retinal and central nervous system haemangioblastomas, clear cell renal cell carcinomas (RCC), pancreatic neuroendocrine tumours, pheochromocytomas and endolymphatic sac tumours (ELSTs) [1] are the typical manifestations of the disease.
VHL can be classified into types 1 and 2, according to the probability of developing pheocromocytoma. Type 1 is at low-risk for pheochromocytoma, but higher risk for the other VHL-associated lesions. Type 2 is at high risk for pheochromocytoma and divided into three subtypes: A (low risk for RCC), B (high risk for RCC) and C (high risk for pheochromocytomas only).
Pheochromocytomas arise in 10–26% of VHL patients whose mean age at presentation is approximately 30 years [2].
Pheochromocytoma is a catecholamine-secreting tumour that arises from chromaffin cells of the adrenal medulla. The most common symptoms are headache, palpitations, sweating and elevated, paroxysmal hypertension [3].
On B-mode ultrasound and on unenhanced CT, the neoplasia can appear either homogeneously solid or characterised by necrotic areas and cystic changes. On contrast-enhanced CT, most cases show intense enhancement of the solid components. On MRI, pheochromocytomas have low T1 signal intensity, high T2 signal intensity ("light bulb sign") and avid paramagnetic contrast enhancement, keeping in mind that the possible presence of necrosis areas could alter the signal and the gadolinium enhancement [4]. Nuclear medicine investigations, performed with different functional ligands (such as I123-MIBG, which was reported to have a sensitivity of 83% 100% and specificity of 95%–100% for detecting PHEOs [5]), are useful in a whole-body evaluation in order to identify extra-adrenal pheochromocytomas, metastasis and tumour recurrence.
The standard treatment is surgical resection and preoperative medical management is essential in order to reduce the risk of intraoperative hypertensive crises.

Written informed patient consent for publication has been obtained.