INSTRUCTIVE CASE
Paediatric bilateral adrenal phaeochromocytomas in association
with a novel mutation in the von Hippel Lindau gene
Leo Kim,
1
Andrew JA Holland,
1
Shubha Srinivasan,
2
Chris T Cowell,
2
Dindy E Benn
3
and Bruce G Robinson
3
1
Department of Academic Surgery and
2
The Institute of Endocrinology and Diabetes, The Children’s Hospital at Westmead and The University of Sydney, and
3
Cancer Genetics, Kolling Institute of Medical Research and Department of Endocrinology, Royal North Shore Hospital and The University of Sydney, Sydney,
Australia
Abstract: Functional phaeochromocytoma and paraganglioma are rare in children and adolescents. We report a 12-year-old male with
bilateral phaeochromocytoma in whom germ line testing identified a novel mutation in the von Hippel Lindau gene. Early age of onset, bilateral
phaeochromocytoma and other clinical features should prompt germ line DNA testing for mutations in genes associated with familial phaeo-
chromocytoma and paraganglioma syndromes.
Key words: paediatric; phaeochromocytoma; von Hippel Lindau syndrome.
Introduction
Phaeochromocytoma, a functional tumour of chromaffin tissue,
appears rarely but has been well described in children, with an
estimated incidence of one in 500 000
1
or 10–20% of all phaeo-
chromocytomas.
2
A third of children with phaeochromocytoma
will have multiple tumours
3
and up to 30% may report a rel-
evant family history. While 15–24% of adults with apparently
sporadic presentation of phaeochromocytoma will carry germ
line mutations indicating familial disease, for children the
proportion is higher.
We present a child with bilateral phaeochromocytomas in
association with a novel exon 1 mutation of the von Hippel
Lindau (VHL) gene.
Case Report
A 10-year-old Pacific Island boy was transferred to our institu-
tion for investigation of diagnosed hypertension following an
admission with septic shock. There was no relevant medical or
family history. His urinary catecholamines were elevated and an
abdominal computerised tomography (CT) scan revealed bilat-
eral adrenal masses. A presumptive diagnosis of bilateral phaeo-
chromocytomas was made and he was commenced on
nicardipine 40 mg three times a day.
On arrival, he appeared well with a lying blood pressure of
130/80 mm Hg. There were no stigmata suggestive of VHL
disease or evidence of hypertensive retinopathy. His body mass
index was 33 and no abdominal masses were palpable. A CT of
the chest and abdomen revealed bilateral discrete adrenal
masses: a 5.7 ¥ 3.7 cm mass in the right adrenal gland and a
2.6 ¥ 2 cm mass with some calcification in the left adrenal gland.
There were no other abnormalities or evidence of metastases.
Iodine-123 metaiodobenzylguanidine (MIBG) scanning indi-
cated focal areas of increased uptake in the upper abdomen
consistent with bilateral phaeochromocytoma (Fig. 1). Bio-
chemical screening for multiple endocrine neoplasia syndrome
found borderline high calcium of 2.7 mmol/L (2.1–2.65) with
normal parathyroid hormone at 1.8 pmol/L, calcitonin level at
5 pg/mL, and carcinoembryonic antigen was borderline high at
2.9 ug/L (0–2.5). Thyroid function was normal.
In view of the discrete nature of the tumours and the patient’s
isolated island location making post-operative monitoring and
endocrine care difficult, an adrenal gland sparing procedure was
performed. Alpha blockade with phenoxybenzamine was slowly
increased to 1.5 mg/kg/day. As the patient remained hyperten-
sive, amilodipine was also commenced. The tumours, which
were macroscopically discrete and well encapsulated, were
excised via a rooftop abdominal incision, preserving the remain-
ing adrenal glands. There was no evidence of local invasion or
regional lymphadenopathy. Histopathology was consistent with
phaeochromocytoma, but some nuclear atypia was present with
occasional mitotic figures and areas of stromal necrosis in both
tumours. The left tumour revealed several foci of capsular inva-
sion and in both glands, endothelial-lined vascular invasion was
observed.
Key Points
1 Suspect familial disease and screen for this in children with
phaeochromocytoma.
2 Adrenal sparing surgery may not be appropriate in this group of
patients.
3 Suspect residual or recurrent disease if patient remains
hypertensive.
Correspondence: Associate Professor Andrew JA Holland, Department
of Academic Surgery, The Children’s Hospital at Westmead, The University
of Sydney, Locked Bag 4001, Westmead, NSW 2145, Australia. Fax:
+612 9845 3346; email: andrewh3@chw.edu.au
Accepted for publication 24 January 2008.
doi:10.1111/j.1440-1754.2008.01360.x
Journal of Paediatrics and Child Health 44 (2008) 514–516
© 2008 The Authors
Journal compilation © 2008 Paediatrics and Child Health Division (Royal Australasian College of Physicians)
514