General Medical Information

Metabolically Active Tumors

Jeffrey D. Bunn
Amy R. Coffey
George H. Petti, Jr.

Tumors that arise from cells within the endocrine glands may secrete normal hormones in abnormal amounts. These cells derive from neural crest, neural ectoderm, or placodal ectodermal tissue that secrete monoamine (e.g., serotonin) or polypeptide (e.g., insulin) substances. These tumors are referred to as APUDomas (i.e., amine precursor uptake and decarboxylation) or neurocrinopathies. Tumor types include islet cell tumors, medullary carcinoma from the thyroid C cells, pheochromocytomas from adrenal chromaffin cells, and carcinoid tumors from Kulschitsky or enterochromaffin cells found in almost every organ of the body.

Carcinoid tumors are the most common of the APUDomas. They occur most frequently in the ileum and bronchus and have a high incidence of synchronous and metachronous neoplasms, whether carcinoid or other types of neoplasms. The active tumors secrete serotonin, although other substances (e.g., histamine, dopamine, substance P) have been suggested. The carcinoid syndrome includes flushing, diarrhea, cardiac valve disease, and occasionally wheezing. The mainstay of diagnosis is the 24-hour urinalysis for 5-HIAA, the major metabolite of serotonin. Treatment is surgical removal or pharmacotherapy to control the diarrhea and flushing using serotonin antagonists (e.g., cyproheptadine, methasergide), parachlorophenylalanine, or natural or synthetic somatostatin.

Pheochromocytomas are associated with “spells” and hypertension, either episodic (50%) or sustained (50%), which is difficult to differentiate from essential hypertension. The spells include a variety of symptoms, such as headache and acute anxiety or panic attacks with sweating. The rule of 10s applies: 10% are malignant, 10% occur bilaterally, and 10% are extraadrenal, occurring anywhere along the sympathetic chain from the skull base to the gonads. These types of tumors are usually called paragangliomas. Active tumors secrete norepinephrine alone (i.e., paragangliomas) or norepinephrine combined with epinephrine (i.e., adrenal tumors).
Tumors are diagnosed using 24-hour urinalysis for vanillylmandelic acid, computed tomography, 131I-metaiodobenzylguanadine, or ultrasound. All patients must be prepared for surgical excision with 7 to 14 days of a-adrenergic blockers. Phenoxyabenzamine is used orally beginning at a dose of 10 mg given four times each day and gradually increased to 300 mg daily until postural hypotension develops. A b-adrenergic blocker may be added 48 hours before surgery if the patient has tachycardia or arrhythmia or if the catecholamine profile shows excess epinephrine secretion. Propranolol is given in doses of 10 mg four times a day. Both medications are given the morning of surgery, and large amounts of intravenous fluid are used intraoperatively after tumor removal to counteract the marked increase in intravascular capacity, which can cause an acute fall in blood pressure. This occurs because the adrenergic stimulation is precipitously removed as the secreting tumor is removed.