Pheochromocytoma


Another potential cause of hypertension stemming from adrenal pathology is hypersecretion of the catecholamines by pheochromocytoma. Approximately 1-2 per 100,000 individuals are diagnosed with pheochromocytomas each year, and less than 1% of hypertension cases are due to this condition.48, 49

It is important to mention that up to a quarter of all sporadic pheochromocytoma cases are proven hereditary upon genetic evaluation.50 Pheochromocytoma accounts for approximately 5% of adrenal incidentalomas, and unlike aldosterone or cortisol-secreting adenomas, these tumors are lipid-poor on cross sectional imaging. As such, pheochromocytomas measure >10HU in attenuation on non-contrast CT scan, fail to washout contrast on CT-washout studies, and do not exhibit signal dropout on in and out of phase magnetic resonance imaging.1, 51, 52

The classic triad of headache, paroxysmal perspiration, and tachycardia is not reported by all patients, and up to 20% of individuals are entirely asymptomatic.53 Although pheochromocytoma classically is known as the “10% tumor,” some aspects of this rule no longer apply.


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As mentioned, up to 30% of cases are familial,54 as many as 25% are extra-adrenal,55 and only ~5% of adrenal pheochromocytomas are malignant (while as many as 30% of extra-adrenal pheochromocytomas, known as paragangliomas, demonstrate metastatic potential).49 Nevertheless, it is generally accepted that 10% of pheochromocytoma’s are bilateral and approximately 10% are found in children.55

Modern metabolic diagnosis of pheochromocytoma focuses on testing of catecholamine metabolites. Measurement of metanephrines—a collective term for metabolite of epinephrine (metanephrine) and metabolite of norepinephrine (normetanephrine)—in the serum or urine constitutes the most reliable method of biochemical diagnosis of pheochromocytoma. Because this conversion of catecholamines to metanephrines occurs in the adrenal medulla, elevation of metanephrine levels is a much more reliable metabolic perturbation than the short-lived paroxysmal rise in catecholamine levels themselves.56, 57

As such, measurement of plasma free metanephrines or total urinary metanephrines is mandatory in patients in whom diagnosis of pheochromocytoma must be ruled out. 


Treatment of pheochromocytoma is largely surgical. Adrenalectomy should be performed by experienced practitioners who understand the nuances of peri-operative management and catecholamine blockade.49, 58, 59. 
Importantly, recurrent pheochromocytoma has been documented up to 15 years following initial adrenalectomy and because of this, patients require life-long metabolic follow-up.49, 60-62

Metabolic evaluation of adrenal incidentalomas


All adrenal masses require metabolic testing, as some 10% of these will prove to be either: cortisol, aldosterone, or catecholamine-producing lesions.41 As stated, Conn syndrome work-up is only necessary for those with hypertension, while hypercortisolemia and pheochromocytoma work-up is recommended for all patients. Although only 2% of patients with small adrenal lesions are destined to develop metabolic activity following an initial negative work-up,64 guidelines indicate the metabolic evaluation should be repeated annually for 3 to 4 years.41

Conclusions


Diagnosing adrenal causes of hypertension requires a high level of clinical suspicion and a working knowledge of adrenal pathophysiology. Given the intimate anatomical and physiological relationship of the adrenals to the kidney, an understanding of adrenal disease is imperative for urologists and nephrologists alike.

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