Letter to the Editor
Pseudopheochromocytoma caused by clozapine
Seudofeocromocitoma causado por clozapina
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It is thus a different diagnosis, without its typical clinical expression.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> The pathophysiology is unknown, although the main mechanism is believed to be the activation of the sympathetic nervous system (increase in secretion of dopamine and epinephrine and a certain hypersensitivity of the adrenoreceptors). A deregulation of the sympathetic nervous system or adrenal medulla in response to emotional factors are probably also involved, being more frequent in individuals with repressive emotional traits.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Several medications (acetaminophen, labetalol and levodopa) can cause elevation of catecholamine and/or plasma and urinary metanephrines. Clozapine (8-chloro-11-[4-methyl-piperazinyl]-5H-dibenzo [b,e] [1,4]diazepine) plays a key role in the treatment of refractory schizophrenia. Paradoxical hypertension has been reported as an adverse effect in response to increasing concentrations of catecholamines, although rarely and in combination with other anti-psychotic drugs.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> A case of pseudopheochromocytoma caused by clozapine is presented.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A 40-year-old woman previously diagnosed with paranoid schizophrenia, who was in remission with clozapine (100<span class="elsevierStyleHsp" style=""></span>mg for 11 months). She visited the consultation because of sudden onset headache episodes with no palpitations or sweating accompanied by high blood pressure (200/100<span class="elsevierStyleHsp" style=""></span>mmHg<span class="elsevierStyleMonospace">)</span> and increased heart rate (109<span class="elsevierStyleHsp" style=""></span>lpm), despite being treated with enalapril for a month. She did not have a history of endocrine disorders, diabetes mellitus or hypertension.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was in good general condition, with no evidence of virilisation or cushinoides stigmas. On physical examination, blood pressure was 230/100<span class="elsevierStyleHsp" style=""></span>mmHg, heart rate was 91<span class="elsevierStyleHsp" style=""></span>bpm and temperature was 37.3<span class="elsevierStyleHsp" style=""></span>°C. Fundus examination, electrocardiogram and chest radiograph were normal. Liver, kidney, thyroid, serum electrolytes, haematology, lipid profile and coagulation tests were all within normal limits. In the identification of fractionated catecholamines and their metabolites in 24<span class="elsevierStyleHsp" style=""></span>h urine an increase of urinary concentrations of noradrenaline (910<span class="elsevierStyleHsp" style=""></span>nmol/l; normal value: 75–560<span class="elsevierStyleHsp" style=""></span>nmol/l) was observed. Concentrations of the following hormones in 24<span class="elsevierStyleHsp" style=""></span>h urine were normal: vanillylmandelic acid 5.8<span class="elsevierStyleHsp" style=""></span>mg/l (0–6<span class="elsevierStyleHsp" style=""></span>mg/l); cortisole 210<span class="elsevierStyleHsp" style=""></span>nmol/l (<300<span class="elsevierStyleHsp" style=""></span>nmol/l); adrenaline 26<span class="elsevierStyleHsp" style=""></span>nmol/l (10–85<span class="elsevierStyleHsp" style=""></span>nmol/l); dopamine 2400<span class="elsevierStyleHsp" style=""></span>nmol/l (370–2900<span class="elsevierStyleHsp" style=""></span>nmol/l) and metadrenaline 0.9<span class="elsevierStyleHsp" style=""></span>nmol/l (0–2.0<span class="elsevierStyleHsp" style=""></span>nmol/l).</p><p id="par0025" class="elsevierStylePara elsevierViewall">MRIs showed adrenal glands of normal size. Scintigraphic tracking with <span class="elsevierStyleSup">131</span>I-metaiodobenzylguanidine showed no pathological uptake of the radiotracer. Based on these findings a diagnosis of pseudopheochromocytoma possibly caused by clozapine was given. Treatment was administered with phenoxybenzamine (50<span class="elsevierStyleHsp" style=""></span>mg) and propranolol (40<span class="elsevierStyleHsp" style=""></span>mg) to control blood pressure and heart rate. The patient was referred for psychiatric consultation where clozapine was replaced by olanzapine. Two weeks later, without antihypertensive drug treatment, the patient had normal pressure values and an analytical control observed that urinary concentrations of norepinephrine (291<span class="elsevierStyleHsp" style=""></span>nmol/l) were within normal limits.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Pseudopheochromocytoma is a disease that has few reported cases. The first cases are repeated clinical episodes of adrenergic crisis, without macroscopic adrenal disease and where the diagnosis depended on other processes. These are atypical presentations similar to pheochromocytoma, but with different causes, in which the study results may not match with the disease.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Hypertensive episodes have the following characteristics: sharp increase in blood pressure and sudden onset of other symptoms such as headache, chest pain, nausea, palpitations and sweating.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Only 9 cases of pseudochromocytoma in patients using clozapine have been reported. Neuropharmacological clozapine actions are complex and include a tendency for 5-HT2 receptors and in vitro adrenergic.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> Its side effects include paradoxical hypertension with elevated concentrations of catecholamines. Different studies have reported increased plasma concentrations of plasma norepinephrine in patients treated with clozapine.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5–8</span></a> Different mechanisms have been suggested to be the cause of increased plasma norepinephrine concentrations, include inhibition of synaptic reuptake, blockage of alpha-2-adrenoreceptor or a combination of these. An increase of vesicle fusion of noradrenaline storage in the nerve axon has also been suggested.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The association between treatment with clozapine and the onset of hypertension is controversial. This has been reported in between 4 and 16% of clozapine users, which may be due directly to blockage of the alpha-2-adrenoreceptor.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6,7</span></a> Breier et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> compared clozapine with haloperidol and fluphenazine and found that patients treated with clozapine had 5 times higher plasma noradrenaline concentrations. Elman et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">8</span></a> found that clozapine produced a 3-fold increase in plasma norepinephrine levels compared with fluphenazine or placebo. It has been reported that elevated circulating levels of norepinephrine is a normal part of the clozapine treatment. Norepinephrine can pass through central nervous system to the plasma, and in turn through urine, leading to the clinical and biochemical abnormalities observed in this case.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Due to poor knowledge of pseudopheochromocytoma, treatment is complex and based on 3 elements: antihypertensive therapy (beta and alpha blockers are often used), psychopharmacological (antidepressants and benzodiazepines) and psychotherapeutic, although this treatment is not effective in up to 40% of patients.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">9</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: López-Sánchez G, Reyna-Villasmil E. Seudofeocromocitoma causado por clozapina. 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