526 Continuing Medical Education Article Anaesthesia for John Pullerits ~D eacr'c, Sigmund Ein MD FRCSC, J. Wi~liamson Belle MD r~cvc phaeochromocytoma Phaeochromocytomas are functionally active cate- Type II-b (characterized by medullary carcinoma of the eholamine-seereting tumours of chromaffin tissue. These thyroid, Marf~oid appearance, mucosal adenomas and tumours are usually found in the adrenal medullae but phaeochromoeytoma). They can also be found as part of may occur anywhere where chromaffln tissue exists. von Hippel-Lindau syndrome which includes multiple Chromaffin tissue occurs in association with the celiac, phaeochromocytomas in association with haemangioblas- mesenteric, renal, adrenal, hypogastric, testicular and lomas of the retinae, cerebellum and other arcas of the paravertehral sympathetic nervous plexuses. Although central nervous system) most phaeochromocytomas are found in the adrenal Although most phaeochromocytoma8 are unilateral, medulla (in 90 per cent of cases), they can occur anywhere about nine per cent occur bilaterally. Bilateral tumours in the body where paraganglion ceils of the sympathetic also tend to be familial. Phaeochromocytomas may occur nervous system are found. Multiple and extra-adrenal at any age, but occur with the greatest frequency in the tumours are far more common in children (35 per cent) fourth and fifth decades of life. Ten per cent of these than in adults (eight per cent).t Although about 90 per tumours are found in children. In adults, the sex distribu- cent are benign and surgically curable, they are of special tion of the patient population shows a slightly higher interest because of the profound physiological effects female preponderance (55-60 per cent). In children, the produced by the release of large quantities of catechnla- sex ratio is reversed since approximately 70 per cent of mines. Phaeochromocytomas can also contain a variety of phaeochromocytomas occur in boys,t peptides including enkephalins, somatostatin, calcitonin, Phaeochromocytomas can vary markedly in size, rang- oxytocin and vasopressin and, rarely, can be a source of ing in weight from 1 to 4000 g but average about 100 g in clinically important ectopic hormone production. 2 the adult population and 30 g in the paediatric population. Although these turnouts account for elevated arterial The average size adult phaeochromocytoma is said to pressure in only 0.1 per cent of the population with contain, however, the equivalent of nne thousand am- diastolic hypertension, the diagnosis should be suspected poules of norepinephnne! t in any patient who develops hypertension at an early age, who has hypertension resistant to conventional therapy, or in anyone with a history of paroxysmal headaches, Pathophysielogy Since a phaeoctu-omocytoma is a tumour of the syrnpa- palpitations, sweating and pallor. Phaeochromocytomas can also be part of an autosomal- dominant multiglandular neoplastic syndrome known as TABLE Medicalsyndromes of which phaeochromocytomais a part Multiple Endocrine Adenomatosis (Table). This syn- Multiple endocrine adc:nomatosis Parathyroid adenoma/hyperplaaia drome can be categorized as Type ll-a (SippLe's syndrome -Type Ii a (Sippte'ssyndrome) Medullary carcinomaof thyroid comprising medullary carcinoma of the thyroid, parathy- Phacochromocytoma roid adenoma/hyperplasia and phaeochromocytoma) or Multiple endocrine adenomatosis Medullary carcinomaof thyroid -Type I] b Mucosal adenomas Maffanoid appearance From the Departments of Anaesthesia, Surgery (SE) and Phaeochromocytomu Paediatrics (JWB), the Hospital for Sick Children, University of Toronto, Toronto, Ontario. yon Hippel Lindau Syndrome Haemangioblastomaof the retina, Address corresporwlence to: Dr. John Pullerits, Department cerebellum or other parts of the C3/S of Anesthesin, The Children's Hospital, Boston, Phaeochromocytoma Massachusetts 02115. CAN J ANAESTH 1988 / 3.5: S t pp526-34 Pullerits etal.: ANAESTHESIA FOR PHAEOCHROMOCYTOMA 527 Tyroslne Tyrosinehydroxylase DOPA l Oopad~ad)o1ylase Dopamlna I DopamineB-hydroxylase Phenylethanolamine N-melhynransferase Noreplnephrine Glucocofliooids Epinephrine Dihydroxymandellc acid Metenephrlne Normetanephrineo'-. l-f Vanlllylmandellc acid FIGURE The pathways for synthesis and breakdown ol catecholarni.es. The rate-limiting step in catechola- mine synthesis is mediated by the enzyme tyrosine hydroxylase~ thetic nervous system, a brief review of the latter is The sympathetic neuron manufactures neurotransmit- appropriate. ters from either phenylalanine or tyrosine as is shown in This system comprises two neuroendocrine systems the Figure. In the neuronal cytoplasm, the rate-limiting linked together by a common group of low molecular enzyme, tyrosine hydroxylase, converts tyrosine to di- weight substances c',dled catecholamines which include hydroxyphenylalanine or dopa. This is then decarboxylat- dopamine, norepinephrine and epinephrine. Only norepi- ed to dopamine which is transported from the neuronal nephrine is released from post-ganglionic sympathetic cytoplasm to storage granules in the axon where it is either neurons, while both nor'epinephrine and epinephrine are stored unchanged or converted by another enzyme to synthesized in the chromaffin cells of the adrenal medulla norepinephrine. In the functional cell of the adrenal and parts of the brain. Sympathetic neurons are also medulla, the phaeochromocyte, norepinephrine leaves known as "adrenergic" neurons and the targets of their the axonal granules to be methylated in the cytoplasm by transmitters are called sympathetic or adrenergie recep- an adrenal-specific enzyme called phenylethauolamine- tors. The three general classes of these receptors include N-methyltransferase. This forms epinephrine which is the alpha-adrenergie, beta-adrenergic and the dopaminer- then stored in a different group of axoplasmic granules. gic receptors with subtypes for the alpha and beta This transformation to epinephrine requires no~ only this receptors having been ~dentified. specific enzyme bat also the high ambient concentration 528 CANADIAN JOURNAL OF ANAESTHESIA of adrenal glucocorticoids found only in the adrenal that would probably pass as essential hypertension in gland. Hence, only adrena]ly derived phaeochromocy- older patients. Urinary excretion shows relatively more tomas are capable of secreting epinephrine. The catechola- inactive metabolites than the smaller turnouts produce. mines epinephrine, norepinephrine and dopamine exert Only about one-third of phaeochromocytomas present their physiologic effects by reversibly imeracting with with the secretory crisis pattern that is described as their appropriate receptors on target tissue. Stimulation of "typical" for phaeochromocytomas.4 Moreover, it is well alpha-I receptors on vascular smooth muscle causes documented that the concentration of free circulating vaseconstriction resulting in an increase in systemic catecholamines and associated haemodynamic conditions vascular resistance and elevation of blood pressure. often have no correlation whatsoever, s Normal blood Alpha-2 stimulation by high concentrations of catechola- pressures and heart rates have been observed when the mines inhibits insulin secretion of the pancreatic islet simultaneously determined plasma catecholamine levels cells. Stimulation of cardiac beta-I receptors causes the were many times higher than normal. The reason for this rate, contractility and automaticity of the heart to discordance is not fully understood but it has been increase. postulated that a chronic increase in circulating norepi- The termination of action of a catecholamine is mostly nephfi ne levels may cau~ a corresponding decrease in the by its active reuptake by the sympathetic nerve endings. concentration of alpha-2 receptors on resistance vessels In addition, two important enzyme systems, monoamine leading to diminished presser effects) nxidase (MAn) and catechoI-O-methyltrans ferase (COMT), Phaeochromocytomas occurring within the adrenal metabolically transform the cateeholarnine~ to inactive gland generally secrete both epinephrine and norepineph- metabolites which are excreted by the kidney. Released fine but norepinephrine is the predominant catecholamine norepinephrine that has interacted with its receptors can liberated. Extra-adrenal tumours, as a rule, secrete only be taken up again by adrenergic neurons to be stored in norepincphrine. In those rare cases where epinephrine is vesicles for reuse: any norepinephrine not retaken up can the main catecholamine produced, the patient may present enter the systemic circulation where it is metabolized by with hypotension. Only one case has been reported in the enzymes MAn and COMT to vanillylmandelic acid which dopamine was the major amine secreted. (VMA), the final common product of enzymatic break- Laboratory measurement of urinary catecholamines down. Approximately five per cent of released norepine- and their metabolites, normetanephrine, metanephrine phrine eventually appears unchanged in the urine while and VMA, is helpful in the diagnosis of this condition 95 per cent is converted to metabolic byproducts. Mea- but these laboratory tests require rigid dietary and drug surements of the urinary excretion of the rnetabolites of restriction on the part of the patient and can consequently epinephrine and norepinephrine (metanephfine, normeta- produce erroneous results. nephfine and VMA) reflect the amount of catecholamine Oral clonidine has been found to suppress plasma that has been released