Increased urinary dopamine excretion in association with bilateral carotid body tumours - clinical, biochemical and genetic findings

Abstract

This report describes a rare case of a patient with increased urinary dopamine excretion in association with bilateral carotid body tumours. Excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and 4-hydroxy-3-methoxymandelic acid (HMMA) were within the reference ranges, and an 123 I-meta-iodobenzylguanidine (MIBG) scan showed uptake in the neck masses, with no other abnormal uptake anywhere else in the body. The patient is being managed conservatively as the tumours are not amenable to resection on account of their size and vascularity. There are only four previous case reports of dopamine-secreting tumours of the carotid body described in the literature, all of whom were women. The tumours were unilateral in three cases and bilateral in the fourth case. Familial cases of carotid body tumours have a higher prevalence of bilateral tumours than nonfamilial cases. Recent reports in the literature have suggested that a significant number of patients with extra-adrenal catecholamine-secreting paragangliomas have a genetic mutation in one of the identified susceptibility genes for catecholamine-secreting tumours, despite having no other affected family members, and a mutation has been found in the succinate dehydrogenase gene for this patient. 2006; 43: 156-160 Case report Ann Clin BiochemA 61-year-old gentleman with a long-standing history of hypertension presented with syncopal episodes to the casualty department in December 1999. The initial diagnosis was thought to be recurrent transient ischaemic attacks in association with bilateral carotid bruits. Following a neck ultrasound scan, carotid angiography revealed bilateral large carotid body tumours encircling each common carotid artery with splaying of the internal and external carotid arteries; a characteristic benign tumour blush was seen (Figure1). The masses in the neck (Figure 2) were ¢rst commented on by an Ear, Nose and Throat (ENT) surgeon when the patient underwent a tonsillectomy 20 years ago to alleviate sleep apnoea. Due to recurrence of this problem, a trachaeostomy was carried out, and due to episodes of collapse ascribed to asystole as a result of carotid sinus baroreceptor hypersensitivity secondary to his carotid body tumours, a permanent pacemaker was inserted. 1 Although these interventions brought about signi¢-cant improvement in the clinical condition of the patient, his blood pressure and heart rate showed large variations on 24 h monitoring (70/41--219/102 mmHg, 14--98 bpm). The patient is not currently receiving any medical management for his labile hypertension.Baseline laboratory investigations were normal (urea. As his blood pressure remained labile, urinary catecholamines were requested. Dopamine excretion was signi¢cantly elevated at 20,679 nmol/24 h (upper limit of reference range 4440 nmol/24 h); excretion of the dopamine metabolite homovanillic acid (HVA) was also increased at 13.1mmol/mol creatinine (upper limit of reference range 5 mmol/mol creatinine). Excretion of noradrenaline, adrenaline, normetadrenalin...

Impact of preoperative embolization on outcomes of carotid body tumor resections

“…Biochemical testing for catecholamine-secreting tumors should be performed in symptomatic patients and those with a family history of CBT or other paragangliomas. 27 The imaging studies we most often use in these circumstances are 123 I-metaiodobenzylguanidine scin- tigraphy and CT or magnetic resonance of the chest and abdomen. CT angiography of the head and neck also provides excellent tumor characterization, defines the superior and medial extent of the tumor, identifies concomitant paragangliomas, and allows for tumor volume assessment.…”

Pheochromocytomas and extra-adrenal paragangliomas detected by screening in patients with SDHD-associated head-and-neck paragangliomas

“…The urinary excretion of the O-methylated metabolite of dopamine, 3-methoxytyramine, was increased in 10 out of the 28 patients, but could be present in a variety of patients with or without pheochromocytomas, extra-adrenal paragangliomas, malignant disease, and producing glomus tumors. Interestingly, the elevated levels of 3-methoxytyramine in our study could be a reflection of the fact that we used the presence of HNP as an inclusion criterion, because carotid bodies are known to use dopamine as a neurotransmitter (Koch et al 2003, Jeffery et al 2006, Minguez-Castellanos et al 2007). We suspect HNP might continuously O-methylate dopamine and subsequently release methoxytyramine into the circulation, even in the absence of overt dopamine secretion.…”

SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma–paraganglioma syndromes

“…For the purpose of this study, 95 papers were reviewed. All papers were dealing with SDH germline mutations (57 in SDHD , 54 in SDHB and 13 in SDHC ) in patients affected by tumours related with the ‘PGL/PHEO syndromes’ [23–25, 31, 33, 35, 44–134]. These included all published reports cited in the Leiden Open Variation Database (LOVD) SDH gene databases at July 2008 (SDHB 080626: June 26, 2008; SDHC 080520: May 20, 2008; SDHD 080703: July 03, 2008) [135] and 13 recent publications.…”