Tumours of the adrenal medulla
Tumours of the adrenal medulla are classified
as follows:
•
neoplasms of the sympathetic neurons:
— ganglioneuroma,
— neuroblastoma
(sympatheticoblastoma);
•
neoplasm of chromaffin cells: phaeochromocytoma.
Those occurring
at any age
A ganglioneuroma is relatively benign. This
neoplasm is symptomless, grows to a large size and constitutes one of the
varieties of retroperitoneal ~sarcoma’ (Chapter 56). Only 15 per cent involve
the adrenal, the remainder occurring in any position along the sympathetic
chain. If removed completely at a comparatively early stage, a cure may be
expected.
Those occurring
in infants and children
Neuroblastoma
Neuroblastoma is a malignant tumour of neural
crest origin arising from sympathetic nervous tissue from the orbit to the
pelvis. Three-quarters arise in the abdomen and half of these from the adrenal
gland. It is the most common solid tumour of infancy and childhood, and by far
the most common in the newborn. The incidence is approximately 1 per 10 000 live
births. Ninety per cent of cases of neuroblastoma occur under the age of 8; over
half occur in children under 2 years.
Clinical
features. Three-quarters of patients present with an abdominal mass.
Metastatic
spread, via lymphatics and bloodstream, occurs at an early stage, and
approximately 70 per cent of cases have metastases at the time of initial
diagnosis (Fig. 45.12). Weight loss, failure to thrive, abdominal pain and
distension, fever and anaemia may be present. Excessive catecholamine production
may cause hypertension, flushing, sweating and general irritability. Some of
these tumours produce VIP, which results in watery diarrhoea and hypokalaemia.
Acute cerebellar ataxia characterised by opsomyoclonus and chaotic nystagmus or
the ‘dancing eye syndrome is an unusual manifestation of neuroblastoma of
unknown cause.
Diagnosis.
Over 80 per cent of patients excrete catecholamine metabolites in the urine.
The most common byproducts assayed in the urine are vanillylmandelic acid (VMA)
and homovanillic acid (HVA), and such measurements may be useful in monitoring
the course of the disease.
Plain
radiography shows fine, stippled calcification in 50 per cent of cases.
Abdominal ultrasound examination shows
the anatomical margins and extent of the
disease, and is particularly helpful in evaluating the results of treatment.
CT
demonstrates calcium in 80 per cent of cases and accurately evaluates
intraspinal extension as well as hepatic and renal metastatic disease. MRI is a
promising technique which may supersede CT in many patients. It will also
evaluate bone marrow metastases.
Meta-iodobenzyl-guanidine
(MIBG, see below) is metabolised by neuroblastoma cells and may be used for
imaging, especially in small residual tumours not evident on other conventional
imaging studies.
Bone-seeking
isotope (technerium-99m), as well as demonstrating bone involvement, is also
concentrated by 60 per cent of adrenal lesions.
Treatment.
Although surgical excision is the mainstay of cure in localised disease,
widespread disease at presentation often makes surgery inappropriate as the
primary form of treatment. Multi drug chemotherapy and radiotherapy are
instituted in advanced disease. Surgical excision is appropriate in disease
confined to one side of the midline, or as a delayed treatment following control
by chemotherapy and radiotherapy. However, the cure rare remains low with an
overall survival rare of 30—35 per cent. Age has an important favourable
influence on prognosis — the younger the patient the better the prognosis, and
children in the first year of life have a long-term survival rare of 70 per
cent.
Phaeochromocytoma
Phaeochromocytoma has been called the ‘10
per cent tumour’ because approximately 10 per cent are bilateral, malignant,
extra-adrenal, multiple, familial and occur in children. Although 90 per cent of
phaeochromocytoma arise in the adrenal medulla, they may be found anywhere
along the paraganglionic system. The most common extra-adrenal site is the organ
of Zuckerkandl at the aortic bifurcation and less common sires are the urinary
bladder, renal hilum, chest and neck. Extra-adrenal tumours have a higher
incidence of malignancy of 25—40 per cent. A phaeochromocytoma is a soft,
vascular tumour usually less than 5 cm
in diameter but occasionally very much larger. It is usually pink-tan in colour
and is composed of large, differentiated, sympathetic ganglion cells and a few
fibres, enclosed in a delicate capsule. It owes its name to the presence of
chromaffin granules. This tumour occurs in both sexes, usually during early
adult life or middle age. It produces, either intermittently or continuously,
an excess of adrenaline, and especially of nor-adrenaline: the ratio of the
latter to the former often being as high as 20:1 causing hypertension
which is either paroxysmal or persistent. The latter predominates statistically and probably
indicates a late stage of the disease. Consequently all patients under 60 years
of age who suffer from sustained arterial hypertension deserve routine tests to
confirm or exclude a phaeochromocytoma. Although not more than 0.5
per cent of cases of hypertension are caused
by a phaeochromocyroma, at the Mayo Clinic2, where routine diagnostic
procedures are undertaken to confirm or exclude the presence of this tumour in
all cases of hypertension, the percentage has been stated to be nearly 3 per
cent. Untreated, it progresses to a fatal termination from cardiac dysrhythmia
or cerebral haemorrhage.
The
importance of phaeochromocytoma as a component of the multiple endocrine
neoplasia syndromes MEN IIa and MEN IIb should be remembered (see earlier and
Chapter 44).
Clinical
features. A typical complaint is that of fear — ‘I thought I was going to
die’. The most common symptoms, in order of frequency, are: headache (55 per cent), palpitation, vomiting, swearing, dyspnoea, weakness
and pallor — i.e. the symptoms of adrenal overdosage. The paroxysmal attack
may vary from a few minutes to some hours. The blood pressure may be very high
and hyperglycaemia present. The symptoms may be mistaken for hyperthyroidism,
hypocalcaemia, an acute anxiety state, paroxysmal atrial tachycardia and
carcinoid syndrome. The main obstacle to the diagnosis of a phaeochromocytoma is
the failure to think of it as a cause of the observed symptoms.
Diagnostic
tests
The basis of the laboratory diagnosis is
measurement of elevated catecholamines and their metabolites in urine and
blood.
•
Urine studies. Confirmation of the diagnosis is usually readily made by
measurement of free catecholamines, VMA and metadrenalines (metanephrines) in
24-hour collections of - urine. Patients with phaeochrornocytoma usually excrete
free catecholamines in excess of 100 ag/24 hours, VMA in excess of 7 mg/24 hours
and metadrenalines in excess of 1.3 mg/24 hours. Laboratories vary in the
reliance they place on these various estimations; at the Mayo Clinic, for
example, most reliance is placed on urinary metadrenalines. False-positive
elevations of metadrenaline excretion may occur in patients taking monoamine
oxidase-inhihiting drugs, and in those who have recently had angiographic
contrast studies.
•
Plasma catecholamines. Sensitive assays are now available for plasma
catecholamines and patients with phaeochrornocytoma usually have total plasma
catecholamines in excess of 1000 pg/rn1. Such assays may be highly accurate in
confirming the diagnosis, but plasma catecholamines may not be continuously
elevated and many factors, including exercise, severe illness and the drug
methyldopa, may influence the levels.
Localisation
tests
•
Computerised tomography (Fig. 45.13) is the method of choice for
localisation with an accuracy of 90—95 per cent and has largely replaced more invasive and
hazardous techniques such as arteriography and selective venous sampling.
Because of their size, most adrenal phaeochromocytomas are also visible on
ultrasound scanning.
•
Radionuclide imaging. The development of a specific radionuclide for
catecholamine precursors, iodine-labelled MIBG, has been a
significant
recent advance in the localisation of adrenal and ectopic phaeochromocytomas.
Only abnormal areas of adrenergic tissue show uptake of MIBG and normal adrenals
do not visualise. MIBG scanning may be particularly valuable in locating an
ectopic phaeochromocytoma when CT shows normal adrenals (Fig.
45.14).
Preoperative
preparation
Catecholamine-secreting tumours are a
challenge to both the surgeon and anaesthetist. A patient with phaeochromocytoma
is hypovolaemic because of the contraction of the vascular bed by excess
circulating catecholamines. During surgery handling of the tumour may increase
circulating catecholamine levels up to 600-fold causing large swings in blood
pressure and cardiac arrhythmias. Severe hypotension may follow removal of the
tumour. These dangers may be minimised by careful preoperative preparation.
Effective blockade of the effects of high circulating catecholamines has
significantly reduced the operative mortality and is mandatory. The alpha-adrenergic
blocking drug
phenoxybenzamine in an initial dose of 20—40
mg/day is increased until hypertension is controlled and mild orthostatic
hypotension induced. Such preparation takes 1—3 weeks. In most centres a
beta-blocking drug such as propranolol is added for 3~7 days before operation to control tachycardia and arrythmias.
Extra fluids should be given iv. to occupy the sudden expansion of the vascular
bed when the tumour is removed, and a preoperative fluid ‘overload’ is
advisable.
Operation
During surgery, intravenous infusions of
alpha- and beta-blocking drugs are given, if required, as determined by the
blood pressure, pulse rate and central venous pressure. The hazardous phases in
the operation are during the induction of anesthesia, positioning of the
patient on the operating table, when the tumour is manipulated, and immediately
after removal of the tumour. Sodium nitroprusside, a direct peripheral
vasodilator, is the drug of choice for the management of significant
intraoperative hypertension.
Even
though preoperative localisation is highly accurate, the possible multiplicity
of tumours (intra- and extra-adrenal) and the need to avoid
excessive tumour manipulation necessitate a
generous transabdominal approach. The tumour should be manipulated as little as
possible and the main adrenal vein ligated as a first step. Inadvertent rupture
of the tumour should be avoided as this may result in local spread and
recurrence of even apparently benign tumours.