Phaeochromocytoma—views on current management

Abstract

Aims: To evaluate the current investigation and management of phaeochromocytoma.

Methods: Retrospective analysis of patients who underwent surgical excision of phaeochromocytoma in the Department of Endocrine Surgery at the University Hospital of Wales, Cardiff.

Forty-seven patients (24 female and 23 males) were studied. Preoperative diagnosis was established by measurement of urinary catecholamines (HMMA, metadrenalines, and fractionated catecholamines). Tumour localisation was achieved by using ultrasound, CT, MRI and MIBG scintigraphy.

Preoperative medical preparation and control of hypertension was achieved in the majority of cases by alpha adrenergic blockade with phenoxybenzamine and the beta blocker propranol.

Surgery was performed by a variety of approaches which included laparotomy, posterior extraperitoneal and laparoscopic methods.

All patients were followed up post-operatively in a surgical endocrine clinic.

Results: Seventy percent of patients presented with hypertension but only 21.3% gave a history of paroxsmal hypertension.

CT scanning and MRI proved to be the most sensitive localisation investigations.

Excellent preoperative control of hypertension was achieved with alpha adrenergic blockade but induction of anaesthesia, rather than tumour handling was noted to be associated with most hypertensive surges of blood pressure.

There was a zero 30 day post-operative mortality but 10 complications of surgery occurred in 8 patients (21.3%).

Cure of hypertension was achieved in 80% of patients.

Attempts to perform cortex sparing procedures in patients with familial disease and multiple tumours was not successful in the long term.

Conclusions: Surgical excision of phaeochromocytoma is a procedure, which can be performed with zero mortality and a low morbidity resulting in a high cure rate for hypertension. Adequate preoperative pharmacological control of hypertension is mandatory. Localisation techniques permit a focussed approach with increasing use of laparoscopy.

Those patients with familial disease and those with multiple tumours pose particular management challenges.

For an optimum and satisfactory outcome a planned multidisciplinary approach is required.

Introduction

A phaeochromocytoma (Ph) is a functioning tumour composed of chromaffin cells. They produce catecholamines and most (80–90%) occur in the adrenal medulla. The remainder occur in the extra-adrenal paraganglionic system, which extends from the pelvis to the base of the skull. The majority of extra-adrenal tumours (paraganglionomas) are intra-abdominal and retro-peritoneal arising most commonly arise from the organ of Zuckerkandl, paraspinal ganglia and bladder. About 2% of extra-adrenal tumours are situated in the neck and thorax, even including the myocardium. In 5–8% of adult sporadic cases, the tumours are bilateral or multiple.1., 2. Multiple, bilateral and extra-adrenal tumours are more common in children.³ Phaeochromocytomas are also found in familial settings, in association with multiple endocrine neoplasia (MEN) types IIa or IIb and neuroectodermal disorders such as multiple neurofibromatosis, von Hippel–Lindau syndrome, Sturge–Weber syndrome and tuberose sclerosis. The incidence of multiple tumours in hereditary syndromes is reported as 50–70%.⁴ Malignant phaeochromocytoma is reported to occur in 2.4–30%, with extra-adrenal tumours being more likely to exhibit malignant features.⁵ Phaeochromocytomas produce a wide spectrum of clinical and biochemical manifestations, the majority of which are related to catecholamine excess. Hypertension is the cardinal feature of this condition and may be either sustained or paroxysmal. Three quarters of patients will have the classical ‘attacks’ characterised by headaches, pallor sweating, palpatations and a feeling of impending dom. The condition may pose a major threat to life primarily because of these cardiovascular manifestations which also include arrythmias, cardiomyopathy and cerebral vascular accidents.

Frankel in 1886 was probably the first to describe a phaeochromocytoma in the adrenal gland and tumours of extra-adrenal chromaffin tissue were reported by Alezais and Peyron6., 7. in 1908. The term ‘Phaeochromocytoma’ was introduced by Pick in 1912.⁸ The important association with paroxysmal hypertension and phaeochromocytoma was described by L'Abbe, Tinel, and Doumer in 1922.⁹ In 1926, Vaquez and Donzelot recognised the condition in living patients and in the same year Ceser Roux working in Lausanne, France described the first successful surgical excision of a phaeochromocytoma.10., 11. The following year Dr Charles Mayo at the Mayo Clinic also successfully removed a tumour.¹² The first large senses of successful excisions was reported by Priestley and colleagues in 1956 at the same institution, when 51 patients were treated for 61 phaeochromocytomas with no mortality.¹³ This was the first time, pharmacological agents were used to successfully control the dangerous and life threatening blood pressure variations so typical of the diseases.

The incidence of phaeochromocytoma at 15 934 consecutive autopsies performed at the Mayo Clinic was 0.1%.¹⁴ Graham and colleagues estimated that 800 people die every year in the United States from the complications of undiagnosed phaeochromocytoma.¹⁵ Of patients discovered to have phaeochromocytoma at post-mortem, 75% had died suddenly from myocardial infarction or a cerebrovascular accident and most significantly one third of the patients who suffered sudden death had undergone unrelated minor operations.¹⁶

In this paper, we present our experience of this condition, placing particular emphasis on the management of blood pressure, the influence of improving localising investigations on surgical strategy and on those patients with familial and multiple tumour disease who may be candidates for cortex sparing adrenalectomy.