The carotid body and associated tumors: updated review with clinical/surgical significance.

Purpose: The carotid body functions as a chemoreceptor and receives richer blood supply, by weight, than any other organ in the body. We review the literature regarding the anatomy, histology, and function of the carotid body and the incidence, functionality, and clinical relevance of carotid body tumors and paragangliomas. These lesions are often nonfunctional but can be associated with catecholamine secretion. Most patients are asymptomatic or present initially with a cervical mass. As the tumors grow, they can impinge on nearby cranial nerves. Although there is some debate, the dominant clinical strategy is to surgically resect these tumors as early as possible. If they are resected early, the risk of postoperative neurovascular injury is minimized. Methods: Literature search was performed using the PubMed database with focus on articles including descriptions of the carotid body and associated tumors. Results: We reviewed recent literature that related to the anatomy of the carotid body while also including carotid pargangliomas and associated diagnosis with treatment interventions. Conclusion: As the carotid body serves as a vital modulator of cardiovascular and respiratory functions, illustrates the importance of identifying potential carotid paragangliomas due its ability to impede function of the carotid body. By understanding carotid paraganglioma's distinct etiologies while also understanding proper diagnosis of tumors allows for early detection and appropriate treatment options.

Metastatic brain carotid body paraganglioma with endocrine activity: a case report and literature review.

A woman with hypertension and hyperglycemia was diagnosed a metastatic brain carotid body paraganglioma. Her blood pressure, glucose, and norepinephrine were normal after craniotomy. Although most carotid body tumors are benign, a few show distant metastasis. This is the first reported case of intracerebral metastases from a carotid body tumor.

Intact blood pressure, but not sympathetic, responsiveness to sympathoexcitatory stimuli in a patient with unilateral carotid body resection.

Despite rapidly growing interest in the therapeutic resection of the carotid body (CB) chemoreceptors, few physiologic studies exist on the consequences of unilateral CB resection. We present a case of an otherwise healthy postmenopausal female who underwent unilateral CB resection for a paraganglioma. Approximately 4 years postoperatively, she underwent analysis of her sympathetic and hemodynamic responses to hypoxia, lower body negative pressure, cold pressor test (CPT), and ischemic hand grip exercise and postexercise ischemia (IHE/PEI). Hypoxic ventilatory response and baroreflex sensitivity were relatively normal. Hemodynamic responses to IHE/PEI and CPT showed characteristic increases in cardiac output (from 3.9 L/min to 5.2 L/min [IHE/PEI] and 4.9 L/min [CPT]) and blood pressure (from 126/72 mmHg to 161/87 mmHg [IHE/PEI] and 171/93 mmHg [CPT]). However, muscle sympathetic nerve activity (microneurography of the peroneal nerve) decreased from baseline during IHE/PEI and CPT (burst incidence nadir of 45% and 40% of baseline, respectively) and there was no observable change in total peripheral resistance (from 24 mmHg*min/L to 22 mmHg*min/L [IHE/PEI] and 25 mmHg*min/L [CPT]). These findings illustrate intact blood pressure responsiveness despite attenuated sympathoexcitation, possibly due to an increase in cardiac output and/or adaptive inhibitory effect of the baroreflex on peripheral sympathetic activity.

Effect of bilateral carotid body resection on the counterregulatory response to hypoglycaemia in humans.

NEW FINDINGS: What is the central question of this study? Hyperoxia blunts hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in carotid body-resected patients; and (ii) carotid body-resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. What is the main finding and its importance? Our data indicate that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, a relatively normal counterregulatory response to hypoglycaemia in carotid body-resected patients highlights: (i) the potential for long-term adaptations after carotid body resection; and (ii) the importance of redundant mechanisms in mediating hypoglycaemia counterregulation. Hyperoxia reduces hypoglycaemia counterregulation in healthy adults. We hypothesized that this effect is mediated by the carotid bodies and that: (i) hyperoxia would have no effect on hypoglycaemia counterregulation in patients with bilateral carotid body resection; and (ii) carotid body-resected patients would exhibit an impaired counterregulatory response to hypoglycaemia. Five patients (three male and two female) with bilateral carotid body resection for glomus tumours underwent two 180 min hyperinsulinaemic, hypoglycaemic (∼ 3.3 mmol l(-1)) clamps separated by a minimum of 1 week and randomized to either normoxia (21% fractional inspired O2 ) or hyperoxia (100% fractional inspired O2). Ten healthy adults (seven male and three female) served as control subjects. Hypoglycaemia counterregulation in carotid body-resected patients was not significantly altered by hyperoxia (area under the curve expressed as a percentage of the normoxic response: glucose infusion rate, 111 ± 10%; cortisol, 94 ± 6%; glucagon, 107 ± 7%; growth hormone, 92 ± 10%; adrenaline, 89 ± 26%; noradrenaline, 79 ± 15%; main effect of condition, P > 0.05). This is in contrast to previously published results from healthy adults. However, the counterregulatory responses to hypoglycaemia during normoxia were not impaired in carotid body-resected patients when compared with control subjects (main effect of group, P > 0.05). Our data provide further corroborative evidence that the effect of hyperoxia on hypoglycaemic counterregulation is mediated by the carotid bodies. However, relatively normal counterregulatory responses to hypoglycaemia in carotid body-resected patients highlight the importance of redundant mechanisms in mediating hypoglycaemia counterregulation.

Case report on carotid body tumor.

A 40 years old lady presented to us with the complaints of repeated attack of syncope with left sided neck swelling. Ultrasonography, Color Doppler study and arteriography were done which revealed a solid vascular mass in the carotid bifurcation. Mass was resected and histopathology was done. Histopathologic findings were typical of a carotid body tumour. As carotid body tumour is a rare disease. So, we are going to present this in this article.

[Hypoplasia of internal carotid artery associated with carotid paraganglioma. A case report and review of the literature]. / Hipoplasia de arteria carótida interna asociado con paraganglioma carotideo. Reporte de un caso y revisión de la bibliografía.

BACKGROUND: Hypoplasia of the internal carotid artery is a rare congenital malformation. It has been mainly associated with aneurysms and other pathologies but not in association with paraganglioma. The incidence is 0.01% of all the anomalies of carotid vessels. Although the exact cause is unknown, it is thought to represent a sequel to an insult due to mechanical causes or hemodynamic stress but perhaps also involves aspects of molecular biology of embryonic development. CLINICAL CASE: We describe the case of a 37 year-old female patient with paraganglioma associated with hypoplasia of the internal carotid artery, which was found incidentally during surgery. Previous angiographic studies as well as other analyses were carried out, but we failed to detect hypoplasia of the internal carotid artery. Tumor was removed along with ligation of the external carotid artery due to injury. The hypoplastic internal carotid artery was left intact. CONCLUSION: Angiographic studies of the base of the skull are important as well as hemodynamic analysis in order to not overlook these anomalies. The patient had a satisfactory evolution without sequelae.

Antecedentes: la hipoplasia de la arteria carótida interna es una rara malformación congénita. Se le ha relacionado principalmente con aneurismas y otros padecimientos, pero no con paraganglioma. Su incidencia es menor de 0.01% de todas las anomalías de los vasos carotídeos. Aunque su origen exacto no se conoce, se cree que es una secuela de una lesión provocada por causas mecánicas o por estrés hemodinámico; sin embargo, también pudieran estar implicados aspectos de biología molecular del desarrollo embrionario. Caso clínico: se describe un caso raro de una mujer de 37 años de edad con paraganglioma concomitante con hipoplasia de la arteria carótida interna. En estudios angiográficos y análisis rutinarios previos no se había detectado alteración de la arteria carótida interna. En la intervención se extirpó el tumor y se ligó la arteria carótida externa dado que estaba involucrada en la lesión; se dejó intacta la arteria carótida interna hipoplásica. Conclusión: es importante realizar estudios angiográficos de la base del cráneo, así como análisis hemodinámicos para no pasar por alto estas anomalías. La evolución fue satisfactoria y sin secuelas.

Implications of carotid sinus hypersensitivity following preoperative embolization of a carotid body tumor. An indication for prophylactic intraoperative cardiac pacing.

IMPORTANCE Carotid body tumors are rare neoplasms of neural crest origin that are both highly vascularized and locally invasive. Treatment options for these tumors often include surgery with preoperative embolization, which can pose major cardiovascular risk to patients. As demonstrated by this case report, hemodynamic instability following preoperative embolization of a carotid body tumor may indicate severe carotid sinus hypersensitivity and the need for temporary cardiac pacing. OBSERVATIONS This case report describes a man in his early 30s who presented for staged surgical resection of bilateral carotid body tumors with preoperative embolization. After embolization of the second tumor, the patient displayed transient episodes of bradycardia and hypotension, which resolved with medical management. Surgery commenced, and with minimal manipulation intraoperatively, the patient became asystolic and required resuscitation. Following a negative cardiac workup, a temporary pacemaker was implanted, and surgical resection of the tumor was successfully completed. CONCLUSIONS AND RELEVANCE Carotid sinus hypersensitivity is a rare but serious risk of preoperative embolization of carotid body tumors. Postembolization bradycardia or hypotension should be assessed as potential harbingers of carotid sinus hypersensitivity, and the need for temporary intraoperative cardiac pacing should be strongly considered.

Carotid body tumors are not associated with an increased risk for sleep-disordered breathing.

PURPOSE: Tumors in the carotid bodies may interfere with their function as peripheral chemoreceptors. An altered control of ventilation may predispose to sleep-disordered breathing. This study aimed to assess whether patients with unilateral or bilateral carotid body tumors (uCBT or bCBT, respectively) or bilateral CBT resection (bCBR) display sleep-disordered breathing and to evaluate the global contribution of the peripheral chemoreceptor to the hypercapnic ventilatory response. METHODS: Eight uCBT, eight bCBT, and nine bCBR patients and matched controls underwent polysomnography. The peripheral chemoreflex drive was assessed using euoxic and hyperoxic CO2 rebreathing tests. Daytime sleepiness and fatigue were assessed with the Epworth Sleepiness Scale and the Multidimensional Fatigue Index. RESULTS: All patient groups reported significant fatigue-related complaints, but no differences in excessive daytime sleepiness (EDS) were found. The apnea/hypopnea index (AHI) did not differ significantly between patient groups and controls. Only in bCBT patients, a trend towards a higher AHI was observed, but this did not reach significance (p=0.06). No differences in the peripheral chemoreflex drive were found between patients and controls. CONCLUSIONS: Patients with (resection of) CBTs have more complaints of fatigue but are not at risk for EDS. The presence or resection of CBTs is neither associated with an altered peripheral chemoreflex drive nor with sleep-disordered breathing.

Head-and-neck paragangliomas are associated with sleep-related complaints, especially in the presence of carotid body tumors.

OBJECTIVES: The carotid body functions as a chemoreceptor. We hypothesized that head-and-neck paragangliomas (HNP) may disturb the function of these peripheral chemoreceptors and play a role in sleep-disordered breathing. DESIGN: This is a case-control study. SETTING: This study was conducted in a tertiary referral center. PARTICIPANTS AND MAIN OUTCOME MEASURES: We assessed fatigue, sleep, and exercise capacity in 74 HNP patients using three questionnaires (Epworth Sleepiness Scale, St. George Respiratory Questionnaire, and a standard clinical sleep assessment questionnaire). Outcomes were compared to those of age- and sex-matched controls. RESULTS AND CONCLUSIONS: Activity, disturbance of psychosocial function, and total score were worse compared to controls (15.4 ± 18.5 vs. 7.2 ± 9.9, P = 0.007; 5.3 ± 10.5 vs. 1.2 ± 2.6, P = 0.008; and 10.4 ± 12.9 vs. 5.0 ± 4.8, P = 0.006, respectively). Patients reported more daytime fatigue, concentration difficulties, and depression (51% vs. 24%, P = 0.006; 31% vs. 10%, P = 0.010; and 19% vs. 2%, P = 0.012). Waking up was reported to be less refreshing in HNP patients (53% vs. 73%, P = 0.038). Dysphonia was a predictor of symptoms, activity, disturbance of psychosocial function, and total scores. Remarkably, the presence of a carotid body tumor was an independent predictor of increased daytime sleepiness (ß = 0.287, P = 0.029). In conclusion, patients with HNP have remarkable sleep-related complaints. Especially the presence of carotid body tumors appears to be associated with increased daytime somnolence.

Reversible cerebral vasoconstriction syndrome in two patients with a carotid glomus tumour.

We report two patients with reversible cerebral vasoconstriction syndrome (RCVS) and carotid glomus tumour. The first patient presented with multiple thunderclap headaches. Cervical and cerebral magnetic resonance imaging showed diffuse cerebral vasoconstriction on magnetic resonance angiogram (MRA) and a carotid glomus tumour. The second patient presented with a cervical mass and was diagnosed with a non-secreting paraganglioma of the carotid body. Surgery with pre-operative angiography was followed by thunderclap headaches and MRA showed segmental cerebral vasoconstriction. Both patients were treated with nimodipine and headaches stopped. Both had normal cerebral arteries on the control MRA at 3 months. These two cases suggest that a paraganglioma may increase the susceptibility to develop RCVS. As a consequence, patients with RCVS should be investigated for a carotid glomus tumour, and patients with paraganglioma reporting severe headaches should have a cerebral MRA in order to rule out cerebral vasoconstriction.

Plasticity of central chemoreceptors: effect of bilateral carotid body resection on central CO2 sensitivity.

BACKGROUND: Human breathing is regulated by feedback and feed-forward control mechanisms, allowing a strict matching between metabolic needs and the uptake of oxygen in the lungs. The most important control mechanism, the metabolic ventilatory control system, is fine-tuned by two sets of chemoreceptors, the peripheral chemoreceptors in the carotid bodies (located in the bifurcation of the common carotid arteries) and the central CO2 chemoreceptors in the ventral medulla. Animal data indicate that resection of the carotid bodies results, apart from the loss of the peripheral chemoreceptors, in reduced activity of the central CO2 sensors. We assessed the acute and chronic effect of carotid body resection in three humans who underwent bilateral carotid body resection (bCBR) after developing carotid body tumors. METHODS AND FINDINGS: The three patients (two men, one woman) were suffering from a hereditary form of carotid body tumors. They were studied prior to surgery and at regular intervals for 2-4 y following bCBR. We obtained inspired minute ventilation (Vi) responses to hypoxia and CO2. The Vi-CO2 responses were separated into a peripheral (fast) response and a central (slow) response with a two-compartment model of the ventilatory control system. Following surgery the ventilatory CO2 sensitivity of the peripheral chemoreceptors and the hypoxic responses were not different from zero or below 10% of preoperative values. The ventilatory CO2 sensitivity of the central chemoreceptors decreased by about 75% after surgery, with peak reduction occurring between 3 and 6 mo postoperatively. This was followed by a slow return to values close to preoperative values within 2 y. During this slow return, the Vi-CO2 response shifted slowly to the right by about 8 mm Hg. CONCLUSIONS: The reduction in central Vi-CO2 sensitivity after the loss of the carotid bodies suggests that the carotid bodies exert a tonic drive or tonic facilitation on the output of the central chemoreceptors that is lost upon their resection. The observed return of the central CO2 sensitivity is clear evidence for central plasticity within the ventilatory control system. Our data, although of limited sample size, indicate that the response mechanisms of the ventilatory control system are not static but depend on afferent input and exhibit a large degree of restoration or plasticity. In addition, the permanent absence of the breathing response to hypoxia after bCBR may aggravate the pathological consequences of sleep-disordered breathing.

Baroreflex control of muscle sympathetic nerve activity after carotid body tumor resection.

Bilateral carotid body tumor resection causes a permanent attenuation of vagal baroreflex sensitivity. We retrospectively examined the effects of bilateral carotid body tumor resection on the baroreflex control of sympathetic nerve traffic. Muscle sympathetic nerve activity was recorded in 5 patients after bilateral carotid body tumor resection (1 man and 4 women, 51+/-11 years) and 6 healthy control subjects (2 men and 4 women, 50+/-7 years). Baroreflex sensitivity was calculated from changes in R-R interval and muscle sympathetic nerve activity in response to bolus injections of phenylephrine and nitroprusside. In addition, sympathetic responses to the Valsalva maneuver and cold pressor test were measured. The integrated neurogram of patients and control subjects contained a similar pattern of pulse synchronous burst of nerve activity. Baroreflex control of both heart rate and sympathetic nerve activity were attenuated in patients as compared with control subjects [heart rate baroreflex sensitivity: 3.68+/-0.93 versus 11.61+/-4.72 ms/mm Hg (phenylephrine, P=0.011) and 2.53+/-1.36 versus 5.82+/-1.94 ms/mm Hg (nitroprusside, P=0.05); sympathetic baroreflex sensitivity: 3.70+/-2.90 versus 7.53+/-4.12 activity/100 beats/mm Hg (phenylephrine, P=0.10) and 3.93+/-4.43 versus 15.27+/-10.03 activity/100 beats/mm Hg (nitroprusside, P=0.028)]. The Valsalva maneuver elicited normal reflex changes in muscle sympathetic nerve activity, whereas heart rate responses were blunted in the patients with bilateral carotid body tumor resection. Maximal sympathetic responses to the cold pressor test did not differ between the two groups. Denervation of carotid sinus baroreceptors as the result of bilateral carotid body tumor resection produces chronic impairment of baroreflex control of both heart rate and sympathetic nerve activity. During the Valsalva maneuver, loss of carotid baroreflex control of heart rate is less well compensated for by the extra carotid baroreceptors than the control of muscle sympathetic nerve activity.

Baroreflex and chemoreflex function after bilateral carotid body tumor resection.

OBJECTIVE: To investigate whether bilateral carotid body tumor resection invariably and chronically affects arterial baroreflex or peripheral chemoreflex function. METHODS: We studied eight consecutive patients (two men and six women; ages 48.1 +/- 11.8 years), a median time of 3.4 years (range 1.3-20.6 years) after bilateral carotid body tumor resection, and 12 healthy control individuals (eight men and four women; ages 53.7 +/- 10.1 years). Baroreflex sensitivity (phenylephrine), blood pressure and its variability (24 h Spacelabs and 5 h Portapres recordings), responses to standard cardiovascular reflex tests and the ventilatory responses to normocapnic and hypercapnic hypoxia were assessed. RESULTS: Baroreflex sensitivity was lower in patients (6.4 +/- 7.2 ms/mmHg) than in controls (14.7 +/- 6.6 ms/mmHg; P +/- 0.011). Mean office blood pressure and heart rate were normal in patients (123.3 +/- 11.9/79.0 +/- 7.3 mmHg and 67.5 +/- 9.4 beats/min, respectively) and controls (117.8 +/- 10.6/74.0 +/- 6.8 mmHg and 61.1 +/- 9.2 beats/min, respectively). Blood pressure variability was increased during ambulatory measurements. Three patients exhibited orthostatic hypotension. The Valsalva ratio, an index of baroreflex-mediated cardiovagal innervation, was lower in patients (1.4 +/- 0.2) than in controls (1.8 +/- 0.5; P +/- 0.008). The normocapnic ventilatory response to hypoxia was absent in all patients, whereas a small residual response to hypoxia was observed under hypercapnic conditions in two patients. CONCLUSIONS: Bilateral carotid body tumor resection results in heterogeneous expression of arterial baroreflex dysfunction, whereas the normocapnic hypoxic drive is invariably abolished as a result of peripheral chemoreflex failure.

Etiopathogenesis and clinical presentation of carotid body tumors.

The carotid body (CB) is a highly specialized small organ located at the bifurcation of the common carotid artery in the neck and plays an important role in acute adaptation to hypoxia. The most common diseased state of the carotid body is its enlargement (i.e., the CB paraganglioma), which can be caused by a genetic predisposition (hereditary paraganglioma, PGL) and by chronic hypoxic stimulation. The CB is the most common tumor site in head and neck paragangliomas. Currently, inactivating germline mutations in the mitochondrial complex II subunits SDHB, SDHC, and SDHD have been identified as genetic risk factors for CB tumors (CBTs). Another locus at chromosome 11q13, identified by linkage analysis in a single family, may harbor a fourth susceptibility gene. Although CBTs are mostly slow-growing and benign, they can cause significant morbidity because of their proximity to major arteries and nerves in the head and neck. Here, we review the etiological factors implicated in the development of CBTs and provide information pertaining to their clinical presentation. Although CBTs are rare, they have the potential to provide unique insights for tumorigenesis and oxygen sensing and signaling mechanisms.

Paraglanglima de corpo carotídeo: apresentação de caso e revisão da bibliográfica / Carotid body tumor: a case report and literature review

Os paragangliomas são tumores que se desenvolvem a partir dos paragânglios. São raros, têm predominância familiar e malignizam-se em poucos casos. O mais comum é o de corpo carotídeo (0,012% de todos os tumores de cabeça e pescoço). A manifestação clínica mais comum é a presença de massa cervical lateral. Angiografia é o exame de escolha para o diagnóstico do tumor. O tratamento é cirúrgico. Apresentamos o caso de uma paciente com 67 anos de idade, com massa cervical bilateral, assintomática. São descritos a abordagem diagnóstica, os detalhes cirúrgicos e o resultado pós-operatório.

Paraganglioma are tumors that arise from paraganglia. They are rare, there is inheritability and malignancy is also rare. The most common one is carotid body paraganglioma (0,012% of all head and neck tumors). The most common feature is lateral cervical mass. Angiography is gold-standard for diagnoses. Surgical treatment is emphasised. We report the case of a 67 year-old woman with asimptomatic bilateral neck mass. Diagnostic and therapeutic approaches as outcome are described.