Essential hypertension with low conjugated catecholamines imitates pheochromocytoma.

Abstract

SUMMARYThe correlation between the degree of conjugation of plasma noreplnephrine (NE) and epinepbrine (E) and the clinical features of sympathetic hyperactivity was studied in 38 essential hypertensive patients from a referral population biased toward pheochromocytoma (19 of them suspected of this diagnosis on clinical grounds). The patients were separated into two groups: 15 with subnormal plasma conjugated NE + E, i.e., below 0.23 ng/ml (Group 1), and 23 patients above this limit (Group 2). Patients clinically suspected of pheochromocytoma represented 93% of the patients in Group 1 but only 21% in Group 2.Group 1 patients, compared to those of Group 2, had: 1) higher baseline plasma free NE + E (0.51 ± 0.07 ng/ml vs 0.30 ± 0.04 ng/ml,p < 0.02); 2) an increase in plasma free NE + E in response to stressful sampling (148% ± 59%, p < 0.05 vs 58% ± 30%), and a more pronounced response (p < 0.05) to glucagon administration; 3) higher free NE + E and DA in the regional samples received during catheterization while conjugated NE and/or E were usually absent; and 4) a higher spread between maximum and minimum blood pressure and a higher maximum pulse rate recorded as well as the index of sympathotonia. All patients combined had the 'maximum pulse rate correlated negatively (p < 0.005) with conjugated NE + E, but positively (p < 0.005) with free NE + E. The clinical and biochemical similarity to pheochromocytoma was particularly striking in some Group 1 patients who had a selective defect in E conjugation; some of them had a history of surgical exploration for the lesion, without result.The association of subnormal conjugated plasma NE and/or E with moderately elevated plasma NE + E and a more frequent pseudopheochromocytoma presentation may result from inadequate conjugation, and hence inactivation of NE and/or E. Excessive free catecholamines would account for the clinical symptoms and for tbe fact that the patients are well controlled by treatment with beta-adrenerglc blocking agents, either alone or in combination with a-blockers. Awareness of tbe existence of this variety of essential hypertension can obviate unnecessary surgery for wrongly suspected pheochromocytoma. (Hypertension 3: 347-355, 1981) KEY WORDS • hypertension • catecholamine conjugation defect • pseudopheochromocytomaA N important mechanism for the inactivation of catecholamines (CA) is conjugation, yet this mechanism is poorly explored. In man, conjugation is mainly to sulfates. Circulating norepinephrine (NE) and epinephrine (E) are 80% conjugated (although it is usually the free form that is determined); circulating dopamine (DA) is almost entirely in the conjugated form.

Unconjugated hyperepinephrinemia: a hallmark of hypertension imitating pheochromocytoma?

“…Plasma NE and E were determined in duplicate with internal standards by the radioenzymatic method using thin-layer chromatography (TLC) 11 to differentiate between NE and E. Conjugated CA were hydrolyzed by lyophilization in dilute perchloric acid as described before 6 and the liberated free CA were measured to give a value of total (unconjugated + conjugated) CA. Subtraction of the unconjugated from the total values provide the concentrations of the conjugated CA.…”

“…Forty patients with essential hypertension (18 men, 22 women, aged 17-56 years; nine of them included in the previous study; 6 all except three of them hospitalized) were screened for secondary forms of hypertension. Twelve normotensive subjects (two men and 10 women, aged 21-59) served as controls.…”

Peripheral dopamine in hypertension and associated conditions

“…30,35 In addition, most of the patients with high DA sulfate had a decreased NA and A sulfoconjugation. 61 Since phenolsulfotransferase activity and sulfate availability are limit-ing factors in sulfoconjugation, it is conceivable that the high affinity DA sulfoconjugation occurs at the expense of the lower affinity NA and A conjugation and affect the biological impact of both antagonistic systems; low sulfoconjugation may increase the availability of free NA and A and their prohypertensive action whereas high sulfoconjugation decreases the free DA availability and its antihypertensive action. 62 An alternative explanation of an altered dopamine NA relationship in hypertensives is that a defective dopaminergic control in the central nervous system 63 yields excessive central and peripheral noradrenergic discharge.…”

Genetic Determinants of Dopaminergic Activity: Potential Role in Blood Pressure Regulation

“…This may be the case in pseudopheochromocytoma patients with defective NE and E conjugation as well as free NE and E responses to stimulation higher than those seen in control subjects (59). On the other hand, clinically comparable patients at the same time, often have DA discharges, particularly in the sulfated form (11).…”

“…6) may be due to decreased PST gene expression, but still sufficient to accommodate high affinity DA sulfoconjugation at the expense of low affinity NE and E conjugation. It is not clear whether this may be a consequence of increased sympathetic tone which characterizes this form of hyperadrenergic hypertension (59). It will be important to distinguish to what degree this sulfoconjugation imbalance is one of the factors additional to increased NE spillover in this form of hypertension (60), permitting NE action unopposed by DA which is sequestrated as an inactive metabolite (DA sulfate).…”