Endocrine Hypertension Still Awaiting Improved Diagnosis, Management

A variety of rapid and reliable tests now exist to diagnose and facilitate the management of pheochromocytoma and primary aldosteronism, but more are needed.

A variety of rapid and reliable tests now exist to diagnose and facilitate the management of pheochromocytoma and primary aldosteronism, but more are needed, and hopefully will be developed in the next decade, William F. Young, Jr. MD, said at a general session at the American Association of Clinical Endocrinologists 19th Annual Meeting and Clinical Congress.

“The evolution and treatment of pheochromocytoma and primary aldosteronism have evolved dramatically since these two forms of endocrine hypertension were first detected and successfully treated in 1926 and 1954, respectively,” Young, Professor of Medicine at the Mayo Clinic in Rochester, Minnesota, told meeting attendees.

However, the initial treatment of pheochromocytoma has not changed, he said. “Surgery in 1926, surgery in 2010. Cesar Roux, in Lausanne, Switzerland, was the first in the world to successfully remove a pheochromocytoma, and Charlie Mayo was the first on the North American Content.”

The first endocrine test developed by endocrinologists was the histamine stimulation test, and it was discovered by serendipity.

Young recounted its discovery: “It was performed June 9, 1943 in Rochester, Minnesota, and at the time, it was thought that histamine might treat the hypertension associated with pheochromocytoma. A patient with pheochromocytoma was given 50 micrograms of histamine, and over the next several minutes, had a hypertensive crisis. This was exactly the opposite of what the clinicians were expecting to happen. The hypertension slowly abated over the next 20 minutes, the patient went to surgery a few days later, and her pheochromocytoma was resected. The patient was given 50 micrograms of histamine again. This time, there was no hypertension crisis, and the histamine stimulation test was found — by accident.”

From histamine-stimulation tests, biochemical testing for pheochromocytomas has progressed to phentolamine suppression tests, radioenzymatic assays for catecholamines, clonidine suppression tests, fluorometric assays for total metanephrines and vanillymandelic acid, high pressure liquid chromatography for fractionated catecholamines and metanephrines, and, most recently, tandem mass spectrometry assays for plasma and urine-fractionated metanephrines.

The biochemical testing for primary aldosteronism has progressed from bioassays to detect mineralocorticoid effect to radioimmunoassay for aldosterone, enzyme assays for plasma rennin activity, rennin mass measurement assays, and tandem mass spectrometry assays for aldosterone, Dr. Young said.

Localization of aldosterone-producing adenomas has progressed from adrtenal venous sampling to iodocholesterol scintigraphy to posture stimulation test, body computed tomography, measurement of aldosterone precursors such as 18-hydroxycorticosterone, and back to venous sampling, he said.

“For primary aldosterone we are somewhere in the midst of a 56-year evolution in diagnosis and management. What’s driving these adrenal glands, why do they get hyperplastic? Why do they make aldosterone? Despite 56 years of work on this, we don’t know. This is a major area that we need to sort out. We also need to determine where low rennin hypertension stops and primary aldosterone starts. We honestly don’t know where to draw that line.”

He continued: “We also need to sort out the impact of genetic and environmental factors on aldosterone secretion in patients with and without primary aldosteronism. We can only wonder what medical advances await this field in the coming years.”