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Schofer J, Tews A
[The clonidine inhibition test: an aid in the diagnosis and postoperative therapeutic control in pheochromocytoma]
Dtsch Med Wochenschr 1985 Sep 13;110(37):1403-7
A clonidine-suppression test was carried out in 8 patients with arterial hypertension, raised urinary and plasma catecholamine levels and symptoms suggesting the presence of a pheochromocytoma. In 6 of the patients clonidine reduced the plasma catecholamine concentrations and no pathological findings were seen in the abdominal computed tomogram (CT). In 2 patients noradrenaline levels were excessively high and not lowered by clonidine; in one of these patients the plasma adrenaline concentration was also raised and this too could not be reduced with clonidine. A tumor was detectable in both patients using CT, in one case situated in the left adrenal, in the other extra-medullary. On operation both were found to be a pheochromocytoma. Peritoneal and intra-hepatic metastases were discovered during surgery in the case of the extramedullary localized tumor. The clonidine-suppression test was repeated postoperatively in both patients: it was normal in the case of the completely excised, intramedullarysituated tumor but still pathological in the other. Thus the clonidine-suppression test is useful in the diagnosis and post-surgical assessment of pheochromocytoma.
Grossman E, Goldstein DS, Hoffman A, Keiser HR
Glucagon and clonidine testing in the diagnosis of pheochromocytoma.
Hypertension 1991 Jun;17(6 Pt 1):733-41
We assessed the sensitivity and specificity of glucagon stimulation and clonidine suppression tests in the diagnosis of pheochromocytoma in 113 hypertensive patients, 39 with and 74 without the tumor. In the glucagon stimulation test, blood was sampled 2 minutes after intravenous injection of 0.28 mumol (1 mg) glucagon, and in the clonidine suppression test, blood was sampled 3 hours after administration of oral clonidine, 1.30 mumol (0.3 mg)/70 kg body wt. Baseline levels of catechols in antecubital venous blood were abnormal, with norepinephrine greater than 7.10 nmol/l (1,200 pg/m), epinephrine greater than 1.51 nmol/l (276 pg/ml), norepinephrine/dihydroxyphenylglycol (DHPG) ratio greater than 1.09, or dopa greater than 35.53 nmol/l (7,000 pg/ml), in 30 of 39 patients with pheochromocytoma (sensitivity 77%) and 1 of 74 patients without pheochromocytoma (specificity 99%). Results of the glucagon test were abnormal (norepinephrine greater than 11.83 nmol/l [2,000 pg/ml] or more than threefold increase from baseline) in 25 of 31 patients with pheochromocytoma (sensitivity 81%) and 0 of 72 patients without pheochromocytoma (specificity 100%). Results of the clonidine test were abnormal (after clonidine norepinephrine greater than 2.96 nmol/l [500 pg/ml] or less than 50% decrease from baseline) in 29 of 30 patients with pheochromocytoma (sensitivity 97%) and in 7 of 30 patients without pheochromocytoma (specificity 67%). Very high baseline levels of catechols therefore indicated the presence of pheochromocytoma, but there were several false-negative results when normal levels were obtained. The glucagon test alone was highly specific but not sensitive, and the clonidine test was highly sensitive but less specific.
Sjoberg RJ, Simcic KJ, Kidd GS
The clonidine suppression test for pheochromocytoma. A review of its utility and pitfalls.
Arch Intern Med 1992 Jun;152(6):1193-7
OBJECTIVE--The intent of this study is to retrospectively evaluate our experience, as well as all published information, regarding the clonidine suppression test to determine its utility, accuracy, and safety in the diagnosis of pheochromocytoma. PATIENTS AND METHODS--All 22 patients (including four with pheochromocytoma) evaluated at a major military referral hospital with the clonidine suppression test for suspected pheochromocytoma for more than 6 years were retrospectively reviewed. All published series of patients similarly evaluated were also critically reviewed. RESULTS--All studies confirm that a nonstressed plasma norepinephrine of more than 2000 pg/mL is diagnostic of pheochromocytoma. In those patients with a plasma norepinephrine of less than 2000 pg/mL, the clonidine suppression test is 92% accurate in diagnosing pheochromocytoma when the normal response to clonidine is defined as total plasma catecholamines of less than 500 pg/mL. Its accuracy diminishes in patients with low baseline plasma catecholamine levels, who may better be tested with a stimulatory test (ie, glucagon). The use of diuretics, beta-blockers, and antidepressants may cause false-positive results or severe hypotension during the clonidine suppression test. Those previously treated with clonidine or with baroreceptor dysfunction may also be prone to severe hypotension, but this complication is otherwise uncommon after acute clonidine ingestion. CONCLUSION--Although it is rarely necessary for the diagnosis of pheochromocytoma, the clonidine suppression test is an accurate and safe test in a select group of patients.
Manger WM, Gifford RW Jr
Pheochromocytoma: current diagnosis and management.
Cleve Clin J Med 1993 Sep-Oct;60(5):365-78
BACKGROUND: Pheochromocytoma is a catecholamine-secreting tumor of chromaffin cells that causes hypertension. OBJECTIVE: To reviewthe clinical presentation, diagnosis, and treatment of this disease. SUMMARY: Pheochromocytoma can mimic a number of other diseases, making recognition difficult. Hypertension may be paroxysmal or sustained. The signs and symptoms of pheochromocytoma are mostly due to hypercatecholaminemia, hypertension, complications, or coexisting diseases; however, measurements of catecholamines and their metabolites in the plasma and urine may be normal between "attacks", and other conditions can elevate these values. The clonidine suppression test confers specificity to the clinical and laboratory findings, and magnetic resonance imaging is the most reliable method of locating a tumor. Surgical resection is successful in 90% of patients; however, the disease is fatal if it is not detected and treated. CONCLUSIONS: Pheochromocytoma should be suspected in patients with paroxysmal or sustained hypertension, particularly if symptoms are present.
Brandstetter K, Krause U, Beyer J
Preliminary results with the clonidine suppression test in the diagnosis of pheochromocytoma.
Cardiology 1985;72 Suppl 1():157-9
23 patients presenting with symptoms of pheochromocytoma were subjected to the clonidine suppression test. In 6 patients, in whom a pheochromocytoma was surgically approved later on, norepinephrine was not suppressed by clonidine. 17 patients in whom a secondary form of hypertension could be excluded by other diagnostic measures showed a marked decrease of plasma norepinephrine. Apart from drowsiness, no adverse side effects were observed. In our hands, the clonidine test proved as a safe and specific test in the diagnosis of pheochromocytoma.
Taylor HC, Mayes D, Anton AH
Clonidine suppression test for pheochromocytoma: examples of misleading results.
J Clin Endocrinol Metab 1986 Jul;63(1):238-42
Baseline plasma norepinephrine (NE) and epinephrine (E) levels over 2000 pg/ml or failure to suppress to less than 500 pg/ml after oral clonidine have been considered diagnostic of the presence of a pheochromocytoma. We found a false negative clonidine suppression test in a patient with an asymptomatic ACTH-secreting pheochromocytoma who had minimally increased resting plasma NE and E values of 669 and 419 pg/ml, respectively. Clonidine suppression caused decreases at 2 and 3 h to 372 and 408 pg/ml, respectively. A positive test was found in a patient with repeatedly elevated baseline plasma NE and E concentrations; the two highest results were 2501 and 3022 pg/ml. Clonidine administration on five occasions failed to decrease plasma NE and E levels to less than 500 pg/ml. However, no pheochromocytoma was found by selective venous catheterization, two laparotomies, and, ultimately, postmortem examination. Diffuse infiltration of lymphoplasmacytic cells throughout sympathetic ganglia and adrenal medulla raise the possibility of a diffuse autoimmune disorder, resulting in excessive catecholamine production. These examples suggest that the clonidine suppression test does not always indicate the presence or absence of a pheochromocytoma.
Karlberg BE, Hedman L
Value of the clonidine suppression test in the diagnosis of pheochromocytoma.
Acta Med Scand Suppl 1986;714():15-21
The clinical value of a clonidine suppression test was assessed in three different groups: I. 14 normotensive, healthy people: II. 34 patients with "neurogenic" hypertension: III. 10 patients with pheochromocytoma confirmed at operation. After clonidine (300 mg by mouth) blood pressure (BP) and circulating plasma catecholamines (CA) were reduced in groups I and II. The maximum fall in mean BP was 25/9 mmHg in group I and 43/24 mmHg in group II; the corresponding fall in patients with pheochromocytoma was 19/0 mmHg. The mean concentrations of circulating noradrenaline (NA) were significantly reduced in groups I and II, maximum suppression occurring 2-3 h after giving clonidine. In group I the mean reductions in NA were from 1.3 (SEM 0.2) to 0.6 (0.06) nmol/l (p less than 0.01), and in group II from 2.6 (0.3) to 0.7 (0.05 nmol/l (p less than 0.2); plasma concentrations of A were very low (less than 0.01 nmol/l) in both groups, and remained unchanged throughout the test. In contrast, in the 10 patients with pheochromocytoma the mean basal plasma CA concentrations exceeded our upper reference limit NA 7.7 (2.2 and A 4.0 (1.7 nmol/l), and remained high or even rose during the test. Four patients in this group with only marginally elevated basal plasma CA showed the same pattern of response during clonidine administration. After successful removal of the catecholamine-secreting tumour all patients achieved a normal BP. The plasma CA was suppressed into the normal range when the clonidine test was repeated 1-2 weeks postoperatively. No serious adverse effects were observed.
Hui TP, Krakoff LR, Felton K, Yeager K
Diuretic treatment alters clonidine suppression of plasma norepinephrine.
Hypertension 1986 Apr;8(4):272-6
The effect of short-term diuretic treatment on the action of clonidine was evaluated in eight subjects with mild, uncomplicated hypertension. A single oral dose of clonidine (0.3 mg) was given before and after 1 week of therapy with hydrochlorothiazide, 50 mg, and amiloride, 5 mg, taken daily. Changes in mean arterial pressure, heart rate, plasma norepinephrine and epinephrine levels, and plasma renin activity were assessed. Diuretic treatment caused a significant weight loss, increased plasma renin activity, and reduced serum potassium concentration but did not significantly alter the absolute reduction in mean arterial pressure caused by clonidine. Absolute clonidine-induced reduction in plasma renin activity after diuretic treatment was three times greater than before treatment, although percent changes were similar. Before diuretic therapy, clonidine significantlyreduced the level of norepinephrine (absolute and percent change). After diuretic treatment, clonidine failed to suppress norepinephrine, and the difference from prediuretic changes was significant. The level of epinephrine was not altered significantly either by diuretic treatment or clonidine. These results indicate that diuretic therapy alters the clonidine-activated mechanism for reduction of arterial pressure through a shift from overall suppression of sympathetic tone to pathways that are more restricted to renal tone. This shift may be due to changes in fluid or electrolyte balance that alter the action of alpha 2-adrenergic receptor-mediated pathways. Use of the clonidine suppression test for the diagnosis of pheochromocytoma may give false-positive results in diuretic-treated patients.
Mulinari RA, Zanella MT, Guerra EM, Kohlmann O Jr, Saad CI, Andriollo A, Carvalho JG, Ribeiro AB
The clonidine test for the diagnosis of pheochromocytoma: the usefulness of urinary metanephrine measurements.
Braz J Med Biol Res 1987;20(1):43-6
1. The clonidine suppression of urinary metanephrines as a criterion for the diagnosis of pheochromocytoma is described. Twenty-four patients were divided into 3 groups: Group I, 10patients with pheochromocytoma (confirmed by tomography and surgery); Group II, 9 patients with suspected pheochromocytoma (clinical evidence plus one mildly elevated value of urinary metanephrines, but with negative tomography); Group III, 5 patients with proven essential hypertension. 2. Urinary metanephrine levels were determined in urine collected before (basal) and 3 h after a single oral dose of clonidine (0.4 or 0.8 mg). 3. Mean basal urinary metanephrine levels were above normal for group I (9.2 +/- 2.2 micrograms/mg creatinine) and group II (2.2 +/- 0.3micrograms/mg creatinine) but were within the normal range for group III (0.6 +/- 0.1 microgram/mg creatinine). After clonidine administration, urinary metanephrine levels remained elevated for all patients with pheochromocytoma but decreased to within the normal range for all but one patient in group II. The urinary metanephrine levels of group III were not significantly altered by clonidine. 4. These data demonstrate that, when monitored by the clonidine suppression test, urinary metanephrine levels are useful for the diagnosis of pheochromocytoma, permitting the differentiation of affected patients from those exhibiting essentialhypertension and increased sympathetic drive.
Mannelli M, De Feo ML, Maggi M, Pupilli C, Opocher G, Valenza T, Baldi E, Serio M
Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma.
J Endocrinol Invest 1987 Aug;10(4):377-82
In the present paper we report our experience on the utility of basal plasma catecholamine (CA) measurement and of the clonidine-suppression test in the diagnosis of pheochromocytoma. Basal noradrenaline (NA) and adrenaline (A) were assayed in plasma samples of 27 subjects affected by pheochromocytoma. When compared to basal values obtained in hypertensive patients without pheochromocytoma, one or both the CA resulted pathologically elevated inall patients except o one. The response to the clonidine-suppression test was evaluated in 41 hypertensive patients suspected of having a pheochromocytoma measuring plasma NA and A in basal conditions and 2 and 3 h after oral administration of 300 micrograms clonidine. Extensive laboratory and instrumental findings confirmed the presence of pheochromocytoma only in 12 patients. Among the other 29 patients basal plasma CA resulted higher than normal in 4 patients. In patients without pheochromocytoma clonidine induced a significant fall in both NA and A plasma levels. The decrease in NA was observed in each patient. The 12 patients with pheochromocytoma showed a pathological elevation of one or both the CA. In this group clonidine did not significantly suppress plasma CA. The individual responses were extremely variable. Our data confirm the validity of plasma CA measurement as a diagnostic tool for the diagnosis of pheochromocytoma. The results of the clonidine-suppression test were generally confirmatory of the basal CA plasma values but in the 4 hypertensive patients without pheochromocytoma who showed basal plasma CA higher than normal clonidine resulted a useful tool in excluding the presence of pheochromocytoma.
Stimpel M, Schurmeyer T, Ivens K, Wambach G, Volkmann HP, von zur Muhlen A
[Diagnostic significance of the clonidine suppression test in suspected pheochromocytoma]
Dtsch Med Wochenschr 1988 Jan 29;113(4):130-4
A clonidine suppression test and the measurement of the catecholamine (noradrenaline and adrenaline) concentration in 24-hour urine were undertaken on 13 patients with benign phaeochromocytoma (PCC), 30 patients with benign hypertension (BHT) and ten healthy, normotensive volunteers. In 11 patients with PCC (85%) the clonidine suppression test gave true-positive results (no significant suppression of initially raised plasma-catecholamine concentration after oral intake of 300 micrograms clonidine). Continuous fall in plasma-catecholamine level after clonidine occurred in two patients with PCC and only moderately elevated initial levels (false-negative results, 15%), as well as in all patients with BHT and all normal controls (true-positive, 100% each). A false-negative result for catecholamine concentration in 24-hour urine was obtained in only one patient (8%). In all others there were either true-positive results (urine concentration greater than 200 micrograms/24 h in 12 patients with PCC, 92%) or true-negative results (urine concentration less than 150 micrograms/24 h in all patients with BHT, 100% each). Compared with direct catecholamine measurement in 24-hour urine, the clonidine suppression test did not fulfil the criteria for further investigations in those patients who had moderately raised plasma-catecholamine levels.
Macdougall IC, Isles CG, Stewart H, Inglis GC, Finlayson J, Thomson I,
Lees KR, McMillan NC, Morley P, Ball SG
Overnight clonidine suppression test in the diagnosis and exclusion of pheochromocytoma.
Am J Med 1988 Jun;84(6):993-1000
In a prospective study designed to differentiate pheochromocytoma from other forms of hypertension, urinary catecholamines were measured after sleep and clonidine administration in 12 patients with pheochromocytoma, 19 hypertensive patients in whom pheochromocytoma was suspected but later excluded, and 31 hypertensive patients in whom pheochromocytoma was never suspected. The test correctly identified all 12 patients in whom pheochromocytoma was present. Four of these had equivocal plasma levels of both norepinephrine and epinephrine, suggesting that overnight clonidine suppression may be of particular value when tumor secretion is intermittent or low. When pheochromocytoma was not present, urinary norepinephrine and epinephrine levels were suppressed below 60 and 20 nmol/mmol creatinine, respectively, after sleep and clonidine, the two in combination giving better suppression than sleep alone. Since urinary catecholamines can be determined relatively easily by high-pressure liquid chromatography with electrochemical detection, this test may be more widely applicable than suppression tests based on plasma measurements.
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