History Of Pheochromocytoma

In 1886, Frankel described bilateral adrenal tumors discovered at the autopsy of an 18-year-old woman who died suddenly following a year of retinitis and episodic palpitations, pounding heart, pallor, headaches, and vomiting. Her postmortem examination also revealed nephrosclerosis and myocardial hypertrophy.1

In 1896, Manasse demonstrated that such a tumor turned dark brown when exposed to chromium salts (the chromaffin reaction), a characteristic of adrenal medullary tissue; these tumors were subsequently termed "chromaffin" tumors. In 1901, the substance causing the chromaffin reaction was chemically identified as 3,4-dihydroxyphenyl-2-methylaminoethanol by two different researchers: Takamine, publishing in the Journal of Physiology in London, called the substance "adrenaline"; Aldrich, publishing in the American Journal of Physiology, coined the term "epinephrine."2 In 1908, Alezais and Peyronin described chromaffin tumors of the paraganglia as "paragangliomas." In 1912, Pick introduced the term "pheochromocy-toma," derived from the Greek words phaios (dark), chromo (color), and kytos (cell). It refers to the his-tologic color change that characterizes most such tumors: dichromate fixatives (eg, Zenker's, Orth's, or Helly's) produce a yellowish-brown coloration of cells with neurosecretory granules. Cells containing epinephrine turn dark brown, whereas cells containing norepinephrine turn pale yellow.3 A dilute Giemsa-Schmorl stain turns these cells green. Pheochromocytomas frequently become cystic and hemorrhagic (Figures 9-1 and 9-2).

Pheochromocytomas were first resected successfully in 1926 by Roux in Switzerland and by Mayo at the Mayo Clinic. In 1929, Rabin discovered a pressor substance in pheochromocytomas that could explain the clinical syndrome. In 1939, a patient with a pheochromocytoma was documented to have high blood levels of epinephrine.4

Ulf Svante von Euler, a pioneer in catecholamine research, discovered norepinephrine in the heart in 1946 and found that it was the neurotransmitter for the sympathetic nervous system. By 1950, von Euler and Engel reported the diagnostic usefulness of urinary epinephrine and norepinephrine in the diagnosis of pheochromocytoma. (In 1970, von Euler was awarded the Nobel Prize for Physiology.) In 1957, Armstrong reported the urinary excretion of vanil-lylmandelic acid (VMA), a urinary metabolite of catecholamines. LaBrosse described urinary

Figure 9-1. A 55-year-old man with chronically controlled hypertension suddenly developed multisystem failure ("pheocrisis") and was found to have a 9 cm right adrenal pheochromocytoma. Laparoscopic adrenalectomy was attempted but was converted to open because the tumor was too large. Courtesy of Quan-Yang Duh, MD.

Figure 9-1. A 55-year-old man with chronically controlled hypertension suddenly developed multisystem failure ("pheocrisis") and was found to have a 9 cm right adrenal pheochromocytoma. Laparoscopic adrenalectomy was attempted but was converted to open because the tumor was too large. Courtesy of Quan-Yang Duh, MD.

35% VMA, 10% conjugated catecholamines and other metabolites, and < 5% free catecholamines.

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