Clinical presentation and diagnostic evaluation of pheochromocytoma: case series and literature review

ABSTRACT

Background

Pheochromocytoma is a rare tumor frequently overlooked mainly due to the wide range of its clinical presentation, which may vary from entirely untypical signs and symptoms to life-threatening complications.

Methods

The present study aims to present a case series recently treated in our center, with emphasis placed on patients’ specific characteristics, clinical presentation and diagnostic evaluation. Relevant literature and current guidelines are being briefly reviewed to summarize screening for pheochromocytoma and appropriate diagnostic procedures.

Results

While the classic symptoms include headache, palpitations and sweating with permanent or paroxysmal hypertension, a wide range of clinical manifestations may be attributed to pheochromocytoma. The initial screening test is measurement of plasma or 24-hour urine metanephrine levels. Abdominal computerized tomography with intravenous contrast infusion is suggested as the imaging examination of choice, whereas magnetic resonance imaging should be preferred over CT in exceptional cases. 123I-metaiodobenzylguanidine scintigraphy is particularly useful for establishing the diagnosis of pheochromocytoma and should be further applied to detect or exclude possible metastatic lesions.

Conclusion

Early diagnosis of pheochromocytoma is of great significance not only because it represents a curable form of secondary hypertension, but also because it is often related to familial syndromes, malignancy or metastatic disease. Physicians need to be familiar with relevant clinical manifestations and diagnostic steps to raise clinical suspiction of pheochromocytoma and establish a timely diagnosis.

KEYWORDS:

• Pheochromocytoma
• hypertension
• case series
• clinical presentation
• diagnostic evaluation

Introduction

Pheochromocytomas are neuroendocrine tumors producing catecholamines that derive from the chromaffin cells and develop within the adrenal medulla and autonomic nerve ganglia. Neoplasms that develop from chromaffin tissue outside the adrenal gland are called extra-adrenal pheochromocytomas or paragangliomas. The same term is used to describe tumors deriving from head or neck parasympathetic tissue, which, usually, don’t produce catecholamines. Almost 80–85% of pheochromocytomas develop within the adrenal gland medulla and only 10–15% derive from extra-adrenal tissue. The tumor is rare, with an estimated incidence of 2–8 cases for every million people and prevalence ranging from 0.2–0.6% of the general hypertensive population (1,2). Mean age of diagnosis is 40–50 years, although it can occur from childhood to late in adulthood (3,4). In around one-third (25–33%) of cases, pheochromocytoma occurs in the context of familial syndromes such as multiple endocrine neoplasia syndromes (MEN 2A, MEN 2B), type I neurofibromatosis, von Hippel-Lindau disease, Sturge-Webber syndrome and other paraganglioma syndromes. In these cases, the diagnosis is usually made at a younger age, typically before the 4th decade of life (5).

Early diagnosis of pheochromocytoma is of great significance for the following reasons. First, this neoplasia is a potentially curable cause of secondary hypertension. Secondly, its clinical manifestations can be dramatic and life-threatening. Third, it may occur as a malignancy with or without metastasis in around 10% of cases, which may rise up to 40% or even higher in extra-adrenal tumors and in patients with specific mutations in the context of familial syndromes (6). Finally, early diagnosis of pheochromocytoma may reveal underlying familial syndromes, thus leading to appropriate follow-up and management. However, the relatively high incidence of pheochromocytomas in autopsy series (0,05%), in association with the relatively high rates of histopathological documentation of the tumor in cases of adrenal incidentalomas (4–7%), demonstrates that this clinical entity is still underdiagnosed, often leading to premature mortality (7,8). Despite the improved modern diagnostic techniques, it has been found that it takes about 3 years from the first manifestations to the definitive diagnosis of pheochrmocytoma (9,10). The delay, or even omission, of diagnosis is at least partially attributed to the great diversity of clinical manifestations of the disease. For this reason, pheochromocytoma has been characterized as “the great mimic” (11,12). In addition, physicians need to be familiar with the diagnostic procedures to diagnose or exclude pheochromocytoma upon clinical suspicion (1). Therefore, the purpose of this study was to present the clinical manifestations and diagnostic approach of pheochromocytoma based on a literature review and current international guidelines. For this purpose, a PubMed search was performed to identify relevant articles published in English, using the following medical terms: “pheochromocytoma”; “hypertension”; “clinical presentation”; “diagnosis,” and “familial syndromes.” A number of recent interesting cases treated at our center will be additionally presented, with emphasis placed on clinical presentation and diagnostic steps. Patients’ divergent characteristics, clinical presentation, and relevant medical and family history are further summarized in Table 1.

Table 1. Summary of patients’ characteristics, clinical presentation, and relevant medical and family history.

Case Nr	Sex	Age	Clinical Presentation	Duration of symptoms	Medical History	Family History
1	Female	33	Diffuse abdominal pain Vomiting	48 hours	MEN2A syndrome Thyroidectomy	Mother with history of pheochromocytoma and thyroid myeloid cancer in the context of MEN2A syndrome, experiencing sudden death during an adrenal crisis
2	Male	59	Multiple episodes of hypertensive crisis, accompanied by tachycardia	18 months	Diabetes mellitus	Hypertension, diabetes
3	Female	75	Multiple episodes of tachycardia Dyspnoia Fatigue	2 Months	Hypothyroidism Hypertension Pulmonary edema Von Recklinghausen syndrome	Unspecified
4	Male	30	Headache Acute coronary syndrome Hypertension	6 Months	Frequent episodes of headache and tachycardia (1–2 per week)	Father with uncontrolled hypertension, experiencing sudden death following an ischemic stroke at the age of 48 years.
5	Female	58	Hypertension Tachycardia Orthostatic Hypotension	>6 months	Adrenalectomy due to pheochromocytoma 25 years ago	Hypertension

1^st case: A 33-year-old female attended the emergency department of our hospital due to multiple episodes of vomiting accompanied by diffuse abdominal pain, initiating around 48 hours ago. Medical history was remarkable for MEN 2A, for which the patient underwent total thyroidectomy 20 years ago. In her family history, her mother was diagnosed with thyroid myeloid cancer and pheochromocytoma in the context of MEN 2A syndrome and had died after an adrenal crisis. An abdominal computerized tomography (CT) scan was performed, which revealed bilateral large soft tissue lesions at the anatomic location of the two adrenal glands (left: 10 x 6.6 x 7.6 cm, right: 10 × 6 x 6 cm), which resembled hematomas with concomitant turbidity of the surrounding fat, as in acute bilateral adrenal gland hemorrhage. To investigate potential causes of adrenal hemorrhage, blood and urine cultures were obtained to rule out septic infection and testing for antiphospholipid syndrome was performed, with negative results. Acute adrenal insufficiency was ruled out with adrenal cortex stimulation test with corticosteroid hormone analogue (synacthen test). Biochemical testing for pheochromocytoma was performed that showed increased levels of urine metanephrines and vanilmandelic acid (VMA) in 24-hour urine collection (urine metanephrines 1,93 μg/24 h, normal value <0,83; VMA 42 mg/24 h, normal value: 1–11 mg/24 h). An abdominal MRI was further performed, which diagnosed hemorrhaging pheochromocytomas on both sides (Figure 1A). The patient underwent further investigation with Iodine-123 meta-iodobenzylguanidine Single-Photon Emission Tomography/CT (¹²³Ι-ΜΙBG SPECT/CT), which confirmed the presence of bilateral pheochromocytomas without active hemorrhage or extra-adrenal localization (Figure 1B).

Figure 1. Α) Abdominal MRI in a 33-year-old patient with MEN 2A, indicative of bilateral hemorrhaging pheochromocytomas (arrows). Β) Further imaging of the tumors with ¹²³Ι-ΜΙBG scintigraphy revealed bilateral pheochromocytomas without active bleeding or extraadrenal localization (arrows).

2^nd case: A 59-year-old male patient attended the emergency department due to increased blood pressure (BP) levels (220/120 mmHg) and tachycardia (120 bpm). He referred several episodes with similar symptoms over the past one and a half year, for which he had sought medical advice and was prescribed combined antihypertensive medication. The patient had already undergone an abdominal CT scan which revealed a 4.2 cm tumor at the anatomic location of the right adrenal gland, but it was characterized as an incidentaloma and he did not undergo further investigation. During his current visit at the emergency department, raised BP and tachycardia had already subsided at the time of the examination, and a reexamination was scheduled at the Outpatient Hypertension Department. Because of increased suspicion of secondary hypertension, the patient underwent biochemical screening for adrenal causes of hypertension. Screening for primary aldosteronism was negative (serum aldosterone: 16ng/dl; plasma renin activity: 1,2 ng/ml/h; aldosterone-to-renin ratio: 13,3). However, 24 h urine collection showed increased levels of both metanephrines (metanephrines 1,2 mg/24 h; normal values <0,37) and normetanephrines (6,7 mg/24 h; normal values <0,83), which, in combination with the abdominal imaging, led to the diagnosis of pheochromocytoma. To exclude the presence extra-adrenal neoplasm, ¹²³Ι-ΜΙBG SPECT/CT was further performed, which confirmed the presence of unilateral pheochromocytoma in the right adrenal gland.

3^rd case: A 75-year-old female attended the emergency department due to dyspnoia and fatigue persisting and progressively worsening over the past two months. She additionally complained of multiple episodes of tachycardia despite receiving b-blocker treatment. Her medical history was remarkable for von Recklinghausen disease, hypothyroidism, and hypertension. She had been previously hospitalized for acute pulmonary edema with concomitant hypokalaemia and acute kidney injury during a hypertensive urgency (BP 250/120 mmHg), with an abdominal CT scan showing a large tumor of the right adrenal gland (4.5 x 3.3 cm). At that time, biochemical testing with serum cortisol and aldosterone had been performed with negative results. Nevertheless, biochemical testing for pheochromocytoma had not been ordered and the patient had been discharged with a change in her antihypertensive medication (discontinuation of irbesartan/hydrochlorothiazide and initiation of amlodipine, β-blocker and furosemide).

During her current hospitalization in our department, significant hypoxia was found and bilateral pleural effusions were diagnosed from chest radiograph attributed to decompensation of heart failure. Intravenous diuretic medication was initiated with improvement of symptoms. Transthoracic cardiac ultrasound showed normal dimensions and wall thickness of the left ventricle, with preserved contractility (ejection fraction 60–65%), type 2 diastolic dysfunction, mild mitral and tricuspid regurgitation and increased dimensions of the left atrium. 24-hour urine collection revealed elevated levels of VMA (11.5 mg/24 h; normal value 1–11), metanephrines (0.32 mg/24 h; normal value <0.37) and normetanephrines (2.08 mg/24 h; normal value <0.83). Findings of ¹²³Ι-ΜΙBG SPECT/CT were consistent with right adrenal pheochromocytoma.

4^th case: A 30-year-old male was referred to our Hypertension Unit from the Cardiology Department of another hospital for further investigation of probable secondary hypertension. The patient was being hospitalized in the Cardiology Department due to an acute coronary syndrome presenting with constrictive pain in the chest extending to the jaw, and vomiting. Symptoms of severe occipital headache lasting hours before his admission, sweating and paleness without palpitations were additionally reported. The patient complained of frequent episodes of headache (1–2 episodes weekly) in the past six months lasting approximately one hour, with concomitant tachycardia (around 110 bpm). His father had suffered of uncontrolled hypertension and died at a relatively young age (48 years) after an ischemic stroke. During his hospitalization in the Cardiology Department, BP was repeatedly measured at consistently high levels (up to 240/130 mmHg). However, cardiac ultrasound, retinoscopy and 24-hour urine albumin measurement were not indicative of advanced hypertension modified organ damage. Abdominal ultrasound revealed a tumor of the right adrenal gland with mildly heterogeneous composition and peripheral calcification, and the patient was thereafter referred to our hospital.

At the time of his admission to our department, BP was 130/80 mmHg and heart rate 85 bpm with no signs of orthostatic hypotension. The patient was treated with amlodipine, carvedilol and spironolactone that had been initiated by cardiologists in his former hospitalization. However, 24-hour ambulatory blood pressure recording revealed increased 24 h BP of 173/95 mmHg, with daytime BP 168/95 mmHg and nocturnal BP 186/93 mmHg. Following a 2-week wash-out of carvedilol, 24-hour urine collection revealed increased levels of VMA (19.5 mg/24 h, normal values 1–11) and metanephrines (6,312 mg/24 h, normal values 341). Those results were consistent with the biochemical diagnosis of pheochromocytoma. Abdominal CT scan was subsequently performed, which showed a large nodule of 4.5 cm in the anatomical position of the right adrenal gland with heterogeneous enrichment compatible with pheochromocytoma. Diagnosis of pheochromocytoma was confirmed with ¹²³Ι-ΜΙBG scintigraphy (Figure 2). Considering the patient’s young age and family history, genetic testing was performed that was negative for endocrine neoplasia syndrome.

Figure 2. ¹²³Ι-ΜΙBG SPECT/CT scan in a 30-year-old male, showing increased radiotracer uptake in the anatomical location of the right adrenal gland representative of pheochromocytoma (arrows).

5^th case: A 58-year-old female was admitted to our department following the findings of a CT scan that was ordered for further investigation of iron deficiency anemia. She had a history of an open right adrenalectomy for the resection of an ipsilateral pheochromocytoma 25 years ago and postsurgical follow-up had ceased several years ago. CT scan revealed a 4x4x2 cm tumor-like lesion in the anatomical region of the right adrenal gland that dislocated the kidney and extended retroperitoneally behind the inferior vena cava. She complained of palpitation and tinnitus. Upon admission, she presented increased blood pressure (155/70 mmHg), tachycardia (98 bpm) and orthostatic hypotension. Based on clinical and imaging findings, a relapse of the patient’s pheochromocytoma was suspected. 24 h urine VMA was elevated (15.6 mg/24 h, normal values 1–11), although metanephrine levels were within normal range. ¹²³Ι-ΜΙBG SPECT/CT showed increased tracer uptake in the anatomical region of the right adrenal gland (Figure 3B), compatible with local recurrence of pheochromocytoma, without evidence of metastasis at non-chromaffin sites distant from the primary tumor. Due to the late recurrence of pheochromocytoma in combination with the patient’s young age at first presentation, genetic testing was ordered to rule out the presence of a familial syndrome, which came back negative.

Figure 3. Α) Abdominal CT in a 58-year-old female showing a 4x4x2 cm tumor-like lesion in the anatomical region of the right adrenal gland, with kidney dislocation and retroperitoneal extension behind the inferior vena cava. Β) Anterior and posterior planar views of ¹²³Ι-ΜΙBG-SPECT/CT scintigraphy showing a soft tissue mass with increased tracer uptake (arrow) in the anatomical area of the excised right adrenal gland extending to the retroperitoneal space. Findings compatible with local recurrence of pheochromocytoma.

Discussion

The increased production and release of catecholamines (adrenaline, noradrenaline and dopamine) from the tumor to the systemic circulation induces the clinical manifestations of pheochromocytoma. Catecholamines cause peripheral vasoconstriction and increase BP through their binding to vascular α-adrenergic receptors, along with tachycardia and sweating through β-adrenergic receptors stimulation (3). Thus, the classic clinical triad of symptoms includes headache, palpitations and sweating. Hypertension can be permanent or paroxysmal (13). Orthostatic hypotension, which may be severe and even result in syncope, is often seen in hypertensive patients with pheochromocytoma. It is associated with a reduction in intravascular volume secondary to prolonged vasoconstriction and desensitization of adrenergic receptors (3). Due to the paroxysmal catecholamine excretion by the tumor, symptoms may manifest as episodes with varying duration (from minutes to hours) and long asymptomatic intervals. Episodes may be triggered by the sudden release of catecholamines (adrenal crisis) from stimuli such as introduction into anesthesia, urination in cases of bladder pheochromocytoma, administration of drugs (glucagon, metoclopropamide, tricyclic antidepressants), intravenous injection of contrast agents, manual handling of the tumor or consumption of foods containing tyramine (14,15).

The afore-mentioned signs and symptoms, although not specific, are common in cases of pheochromocytoma and should be sought upon clinical suspicion. However, it needs to be emphasized that its clinical presentation ranges widely, from completely atypical manifestations to life-threatening complications, fully justifying the term of ‘the great mimic.’ As described in our 3^rd and 4^th case, the surge of excess catecholamines in the systemic circulation can even cause the so-called catecholaminergic cardiomyopathy. This clinical entity may present as an acute coronary syndrome with usually transient electrocardiographic disorders of ischemia, or as chronic heart failure. Hypertensive emergency and malignant hypertension with acute target organ damage (kidneys, heart, brain) is another potentially life-threatening clinical manifestation accompanied by significant morbidity and mortality (16,17). Notably, a wide range of atypical symptoms may occur that are most commonly attributed to various other causes. These include fatigue, nausea and vomiting, constipation, weight loss, fever, tremor, chest or abdominal pain, blurred vision or even papilledema, and heat intolerance (11,18). The insulin-antagonistic effects of catecholamines commonly cause hyperglycemia, which may evolve to diabetes mellitus with overt polyurea and thirst (19). During paroxysmal episodes, paleness and less often flushing may be observed. Several other unusual but severe clinical conditions have been described as atypical first clinical manifestations of pheochromocytoma, including cardiogenic shock, psychosis, preeclampsia, cerebral hemorrhage, chronic diarrheal syndrome, insulin-depended diabetes mellitus and diabetic ketoacidosis. However, these extreme manifestations may in fact represent progressively evolving signs and symptoms overlooked by physicians or patients. In any case, the differential diagnosis is broad and includes a wide range of more or less common clinical conditions, such as heart failure, arrhythmias and coronary syndrome, abrupt discontinuation of β-blockers and clonidine, thyrotoxicosis, hyperadrenergic hypertension, carcinoid syndrome, treatment with sympathomimetic drugs or monoaminoxidase inhibitors, hyperventilation syndrome, alcohol withdrawal syndrome, migraine, anxiety disorder and postmenopausal syndrome (1,20).

As described in our first and second case, pheochromocytoma may appear in the context of familial syndromes. From 1990 to date, a total of 14 predisposing genes have been identified which are present in approximately 1/3 of patients with pheochromocytomas and paragangliomas (6,21). According to the current international endocrinology guidelines and the hypertension guidelines from the European Society of Hypertension and the European Society of Cardiology (ESH/ESC), genetic testing is recommended in all patients diagnosed with pheochromocytoma and paraganglioma (6,22). The most common familial syndromes that include pheochromocytoma are as follows: 1) von Hippel-Lindau syndrome, associated with a variety of malignant and benign neoplasms, most commonly affecting the retina, cerebellum, hemangioma of the central nervous system (spinal cord, cerebellum) and renal cell carcinoma (23), 2) type 1 neurofibromatosis or von Recklinghausen disease, characterized by café au lait spots on the skin appearing in childhood and increasing in size and number over time, and neurofibromas that develop in adulthood, mainly of the skin, brain and the spinal cord (24), and 3) familial pheochromocytomas and paragangliomas due to mutations in the B and D subunits of mitochondrial succinate dehydrogenase (25,26). These syndromes usually have already been diagnosed before the clinical presentation of pheochromocytoma. However, in MEN 2 syndrome pheochromocytoma may be the first clinical manifestation in 10–30% of patients, encountered in as many as approximately half of patients during their lifetime (27). In particular, the MEN2A type, which constitutes the majority of MEN2 cases, may present with myeloid carcinoma of the thyroid gland, pheochromocytoma, and primary hyperparathyroidism due to multiple parathyroid gland neoplasms, while the MEN2B type includes myeloid thyroid carcinoma and pheochromocytoma, but not hyperparathyroidism.

Overall, the divergent individual characteristics of our cases highlight the diversity of clinical presentation of pheochromocytoma. In our first case, the initial symptomatology of persistent multiple episodes of vomiting in combination with diffuse abdominal pain would not have been directly linked to pheochromocytoma, but an underlying pheochromocytoma with an untypical presentation should be ruled out based on medical and family history of MEN 2A. By contrast, our 2^nd patient presented with pronounced BP elevation and tachycardia with unremarkable medical and family history, which are characteristic of catecholamine excess in pheochromocytoma. Notwithstandingly, the diagnosis had not been established for several months probably owing to clinical inertia or unawareness, and the presence of a large adrenal tumor warranting biochemical testing was overlooked. As presented in our 3^rd case, an underlying pheochromocytoma is an extremely rare cause of heart failure with preserved ejection fraction but may present as such in neglected cases. Again, the key lies to a thorough medical history, as relevant alarming signs and symptoms are often underestimated until the establishment of overt clinical manifestations of catecholaminergic cardiomyopathy. For instance, this patient had been previously hospitalized for a hypertensive emergency warranting the investigation of secondary hypertension, suffered from persistent tachycardia despite treatment with b-blocker, and most importantly, a large adrenal tumor had already been detected in this patient with a direct predisposition for pheochromocytoma related to von Recklinghausen disease. Likewise, despite the recurrent episodes of headache and tachycardia and the alarming family history in a young male as presented in our 4^th case, diagnosis was only established several months later following a life-threatening complication (acute coronary syndrome). These cases further indicate that although pheochromocytoma has been known for years among hypertension specialists, it still remains largely unknown within the general medical community.

Finally, our 5^th patient is a case of recurrent pheochromocytoma presenting 25 years post adrenalectomy. To our knowledge, this is the largest reported period until recurrence of a pheochromocytoma with a benign, non-syndromic appearance (28). Even though this is an exceptional case of very late recurrence, it underscores that recurrent disease remains possible even after a very long and uneventful postsurgical period of time. Considering the potentially catastrophic complications of an unrecognized relapse, our case raises awareness that an apparently successful resection of a pheochromocytoma does not necessarily entail complete cure. Careful and consistent follow-up is hence warranted for the timely detection of recurrent or metastatic disease, as will be analyzed below.

Diagnostic procedure

According to the international guidelines for the diagnosis and treatment of pheochromocytoma, the initial screening test is measurement of plasma or 24-hour urine metanephrine levels, whose diagnostic value is higher compared to the previously used urinary catecholamines or VMA (6,29). More specifically, measurement of urine metanephrines provides excellent sensitivity and specificity for the diagnosis of pheochromocytoma, reaching 97% and 91%, respectively (30). A positive biochemical screening test must be followed by imaging in order to locate the tumor. Abdominal CT with intravenous contrast infusion is suggested as the imaging examination of choice and is considered superior to magnetic resonance imaging (MRI) (6), owing to its excellent spatial analysis for the chest, abdomen and pelvis, with excellent sensitivity for tumor localization varying from 88% to 100% (31–34). MRI should be preferred over CT in exceptional cases such as patients with known allergy to intravenous contrast agents or patients whose exposure to ionizing radiation should be avoided (pregnancy, children, presence of surgical clips, need for repeated imaging as in familial syndromes) (6). However, it needs to be highlighted that both CT and MRI lack specificity for pheochromocytoma, which may present either as a homogeneous or heterogeneous mass, a necrotic mass with calcifications, or a solid or cystic tumor (3,35).

The imaging method that confirms the diagnosis is the ¹²³Ι-ΜΙBG scintigraphy (6). The method is based on detecting the pheochromocytoma’s activity, with excellent specificity for both pheochromocytomas (70–100%) and paragangliomas (84–100%) (36–38). ¹²³Ι-ΜΙBG SPECT/CT scan is particularly useful for establishing the diagnosis of pheochromocytoma and should be further applied to detect or exclude possible metastatic lesions. However, in patients with known metastatic disease, an (18)F-FDG PET/CT imaging should be performed (6).

It needs to be highlighted that, although pheochromocytoma is considered cured in the vast majority of patients who have undergone successful surgical removal, there is still a residual risk of local recurrence, as in our last case, metastatic disease or de novo development of a new tumor. This risk is about 5% for the next five years and is essentially eliminated within the next 15 years (39). However, as in our patient, very late relapses have been reported, up to 25 years later (28). Younger patients (<20 years), patients with syndromic paragangliomas or patients with large tumors are at higher risk for pheochromocytoma relapse (40). Therefore, the International Endocrinology Guidelines for Pheochromocytomas/Paragangliomas suggest annual reassessment of all patients that successfully underwent surgical resection for at least a decade or even lifetime-long in high-risk patients (those with young age at diagnosis, with known gene mutations and with large or an extra-adrenal tumors) (6,40). Annual postoperative follow-up examination should include careful medical history with emphasis on signs and symptoms of relapse, blood pressure measurement and biochemical testing as previously described (urinary or plasma metanephrines) (6,40).

Conclusions

A thorough medical history combined with clinical examination are essential in order to raise the clinical suspicion of pheochromocytoma. The classic triad of symptoms that should be sought include headache, palpitations and sweating. Hypertension may be permanent or paroxysmal and usually coexists with orthostatic hypotension, sometimes severe with syncope. However, the range of signs and symptoms associated with the tumor is wide and may vary from completely atypical manifestations to life-threatening complications, fully justifying the term of “the great mimic” attributed to pheochromocytoma. The initial screening test for the diagnosis of pheochromocytoma is measurement of plasma or 24 h urinary metanephrines, while CT scan is the imaging test of choice in order to locate the tumor. ¹²³Ι-ΜΙBG scintigraphy confirms the diagnosis and is particularly important for the detection of metastatic lesions. Increased awareness of clinically suspicious signs and symptoms and basic diagnostic steps is essential for the early diagnosis of pheochromocytoma.

Disclosure statement

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Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.