Generation of a mouse model of thyroid storm and preliminary investigation of the therapeutic effects of ghrelin.

BACKGROUND: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, has limited therapeutic options. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. We aimed to develop a TS mouse model by administration of triiodothyronine and lipopolysaccharide, and then to examine the effects of ghrelin on this model. METHODS: We evaluated the use of serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. To establish the mouse model, preliminary experiments were conducted to determine the non-lethal doses of triiodothyronine and lipopolysaccharide when administered individually. As a TS model, C57BL/6 mice were administered with triiodothyronine 1.0 mg/kg (subcutaneously, once daily for seven consecutive days) and lipopolysaccharide 0.5 mg/kg (intraperitoneally, on day 7) to develop a lethal model with approximately 30% survival on day 8. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin 300 µg/kg on these parameters in TS model. RESULTS: Serum IL-6 was increased in patients with TS compared with those with Graves' disease as the diseased control (18.2 vs. 2.85 pg/mL, P < .05, n = 4 each). The dosage for the murine TS model was triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg. The TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin improved the survival rate to 66.7% (P < .01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. CONCLUSION: We established an animal model of TS that exhibits pathophysiological states similar to human TS with induction of serum IL-6 and other biomarkers by administration of T3 and LPS. The results suggest the potential effectiveness of ghrelin for TS in humans.

Evaluation of bone mineral density (BMD) and trabecular bone score (TBS) in pheochromocytoma and paraganglioma; a multi-centric case-control study from India.

Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) due to excess sympathetic system stimulation. Our study revealed low BMD and TBS (trabecular bone score) in cases compared to matched controls. Plasma-free nor-metanephrine and hypertension duration found to be most consistent predictive factors. PURPOSE: Pheochromocytoma and paraganglioma (PPGL) have been associated with low bone mineral density (BMD) and increased fracture risks. Sympathetic nervous system stimulation has been shown to increase bone resorption and decrease bone formation via ß2 receptors. Chronic inflammation and increased cytokine production add to more bone loss. TBS (trabecular bone score) is an established surrogate marker for bone histomorphometry. BMD and TBS data in pheochromocytoma and PPGL are scarce. The aim was to assess the BMD and TBS in pheochromocytoma and PPGL and look for clinical and biochemical predictors. METHODS: This case-control study had sample size of 58 (29 cases and controls each). BMI-, age-, and sex-matched controls were taken for comparison. Both cases and controls had undergone DXA scan and BMD {Z-scores and bone mineral concentration (BMC) in g/cm2} and TBS were analyzed. Detailed clinical histories and relevant biochemistry values were noted. RESULTS: The mean age of our case population was 29.5 ± 9.4 years with a mean age of HTN onset at 26.86 ± 6.6 years. Lumbar spine BMC (0.86 ± 0.14 vs 0.96 ± 0.15; p = 0.036), femoral neck Z-score (- 1.23 ± 1.07 vs - 0.75 ± 0.97; p = 0.003), and whole body BMC (0.91 ± 0.14 vs 1.07 ± 0.11; p = 0.000) were significantly low in cases compared to controls. Similarly, TBS was significantly lower in cases compared to controls (1.306 ± 0.113 vs 1.376 ± 0.083; p = 0.001). CONCLUSION: This study establishes both low bone mass and poor bone quality in an Indian pheochromocytoma and PPGL patient's cohort. Plasma-free nor-metanephrine and duration of hypertension were found to be most consistent predictive factors in multivariate regression analysis.

Pancreas-sparing tumor resection for peripancreatic paraganglioma: a case series of six patients.

Paragangliomas (PGLs) located around the pancreas are rare and challenging to diagnose preoperatively. Tumor resection with pancreatectomy is often performed for peripancreatic PGL. However, pancreas-sparing tumor resection can be indicated with an accurate preoperative diagnosis. Six patients with pathologically diagnosed peripancreatic PGL were included. The clinical data were retrospectively collected from medical records. Five of them were suspected of peripancreatic PGL on imaging studies due to the fat plane identified between the tumor and pancreas, and subsequently diagnosed with PGL preoperatively based on elevated urinary catecholamine levels and/or metaiodobenzylguanidine scintigraphy without biopsy. All patients underwent pancreas-sparing tumor resection with negative surgical margins, and they did not develop postoperative complications related to potential damage to the pancreas. A fat plane between the tumor and pancreas on imaging studies and hormone levels are key findings for obtaining an accurate preoperative diagnosis of peripancreatic PGL, which can be managed with pancreas-sparing tumor resection.

Giant Cystic Pheochromocytoma Associated With Neurofibromatosis Type 1: A Case Report.

Pheochromocytomas are tumors that develop from the chromaffin cells of the adrenal medulla. More than 40% of cases of pheochromocytomas are associated with genetic conditions such as neurofibromatosis type 1 (NF1) or von Hippel-Lindau syndrome. Cystic pheochromocytomas are rare, generally asymptomatic, and thus of bigger size at the time of diagnosis. Surgical treatment is necessary to prevent cardiovascular morbidity and malignancy risk. We report the case of a 27-year-old patient admitted for further examination of a left adrenal mass that was discovered by an abdominal CT scan in the context of abdominal pain associated with hypertension evolving for three years. The clinical examination showed the presence of multiple café au lait spots, axillary and inguinal freckling with two dermal neurofibromas diagnosed clinically, as well as Lisch nodules on bilateral ophthalmic examination, thus meeting the clinical criteria for the diagnosis of NF1. The clinical laboratory investigation showed elevated urinary metanephrine and normetanephrine levels. CT scan examination showed a 10 cm left adrenal cystic mass on abdominal CT. This mass uptake of the radioligand in metaiodobenzylguanidine (MIBG) scintigraphy without secondary extra-adrenal localization allowed the diagnosis of a seemingly benign cystic pheochromocytoma to be made. The patient was put on presurgical drug preparation with volume expansion and then underwent left unilateral adrenalectomy. The histopathological study was in favor of a rather aggressive cystic pheochromocytoma with a pheochromocytoma of the adrenal gland scaled (PASS) score of 9. Blood pressure and urine catecholamines at seven days, three months, six months, and one year after surgery were normalized. Cystic pheochromocytoma is a rare tumor with a potentially poor prognosis. It is characterized by a more insidious evolution and a larger volume at diagnosis. It should be considered a diagnosis in patients with a cystic adrenal mass or an extra-adrenal mass with fluctuating blood pressure during surgery. This case illustrates the importance of both presurgical preparation and screening for pheochromocytoma in neurofibromatosis type 1.

Clinical Significance of Pheochromocytoma Size on the Timing and Extent of Surgery.

INTRODUCTION: Elevated metanephrine and catecholamine levels 3-fold upper limit of normal (ULN) are diagnostic for pheochromocytoma. We sought to determine whether size correlates with biochemical activity or symptoms which could guide timing of surgery. METHODS: Data from consecutive patients undergoing adrenalectomy for pheochromocytoma at our institution over a 10-year period were retrospectively collected. These included maximal lesion diameter on preoperative imaging, plasma/urine metanephrine and/or catecholamine levels, demographic variables and presence of typical paroxysmal symptoms. Receiver operating characteristic curves were used to assess predictive accuracy. RESULTS: Sixty-three patients were included in the analysis (41 females and 22 males). Median age was 56 (43, 69) years. Due to various referring practices, 31 patients had documented 24-h urine metanephrine, 26 had 24-h urine catecholamine, and 52 had fractionated plasma metanephrine levels available for review. Values were converted to fold change compared to ULN and the maximum of all measured values was used for logistic regression. Median tumor size was 3.40 (2.25, 4.55) cm in greatest dimension. Tumor size at which pheochromocytoma produced > 3-fold ULN was ≥2.3 cm (AUC of 0.84). Biochemical activity increased with doubling tumor size (odds ratio = 8, P = 0.0004) or ≥ 1 cm increase in tumor size (odds ratio = 3.03, P = 0.001). 40 patients had paroxysmal symptoms, but there was no significant correlation between tumor size/biochemical activity and symptoms. CONCLUSIONS: In our study, tumor size directly correlated with the degree of biochemical activity and pheochromocytomas ≥2.3 cm produced levels 3 times ULN. These findings may allow clinicians to adjust timing of operative intervention.

[Personalized treatment of pheochromocytoma]. / Personalisierte Therapie des Phäochromozytoms.

BACKGROUND: Pheochromocytoma is a rare but severe disease of the adrenal glands. The aim of this study is to present and discuss recent developments in the diagnosis and treatment of pheochromocytoma. MATERIAL AND METHODS: A narrative review article based on the most recent literature is presented. RESULTS AND DISCUSSION: The proportion of pheochromocytomas as tumors of adrenal origin is about 5% of incidentally discovered adrenal tumors. The classical symptomatic triad of headaches, sweating, and palpitations occurs in only about 20% of patients, while almost all patients show at least 1 of these symptoms. To diagnose pheochromocytoma, levels of free plasma metanephrines or alternatively, fractionated metanephrines in a 24­h urine collection is required in a first step. In the second step an imaging procedure, computed tomography (CT) or magnetic resonance imaging (MRI), is performed to localize the adrenal tumor. Functional imaging is also recommended to preoperatively detect potential metastases. Genetic testing should always be offered during the course of treatment as 30-40% of pheochromocytomas are associated with genetic mutations. The dogma of preoperative alpha blockade is increasingly being questioned and has been controversially discussed in recent years. Minimally invasive removal of the adrenal tumor is the standard surgical procedure to cure patients with pheochromocytoma. The transabdominal and retroperitoneal laparoscopic approaches are considered equivalent. The choice of the minimally invasive procedure depends on the expertise and experience of the surgeon and should be tailored accordingly. Individualized and regular follow-up care is important after surgery.

False-positive results for pheochromocytoma associated with norepinephrine reuptake blockade.

Measurements of plasma metanephrines and methoxytyramine provide a sensitive test for diagnosis of pheochromocytoma/paraganglioma. False-positive results remain a problem, particularly in patients taking norepinephrine reuptake-blocking drugs. Therefore, in this retrospective observational study, we measured plasma metanephrines and methoxytyramine in 61 patients taking norepinephrine reuptake blockers (tricyclic antidepressants or serotonin-norepinephrine reuptake inhibitors) and 17 others taking selective serotonin reuptake inhibitors, all without pheochromocytoma/paraganglioma. We highlight a singular case with strongly elevated plasma normetanephrine and methoxytyramine concentrations associated with norepinephrine reuptake blockade. Data were compared to results from 252 and 1804 respective patients with and without tumors. Plasma normetanephrine was 40% higher (P < 0.0001) in patients on norepinephrine reuptake blockers and methoxytyramine was 127% higher (P = 0.0062) in patients taking tricyclic antidepressants compared to patients not taking uptake blockers and without tumors. The corresponding false-positive rates rose (P < 0.0001) from 4.8% to 23.0% for normetanephrine and from 0.9% to 28.6% for methoxytyramine. Selective serotonin reuptake inhibitors did not increase plasma concentrations of metabolites. In the highlighted case, plasma normetanephrine and methoxytyramine were elevated more than six times above upper reference limits. A pheochromocytoma/paraganglioma, however, was excluded by functional imaging. All biochemical test results normalized after discontinuation of norepinephrine reuptake blockers. These findings clarify that norepinephrine reuptake blockers usually result in mild elevations of normetanephrine and methoxytyramine that, nevertheless, significantly increase the number of false-positive results. There can, however, be exceptions where increases in normetanephrine and methoxytyramine reach pathological levels. Such exceptions may reflect failure of centrally mediated sympathoinhibition that normally occurs with the norepinephrine reuptake blockade.

Malignant Pheochromocytoma With Intravascular Extension to the Heart.

Background: Malignant pheochromocytomas are rare and aggressive tumors that arise from the adrenal medulla and secrete catecholamines. Patients exhibit episodic symptoms of hypertension, headaches, sweating, and palpitations. The diagnosis is supported by elevated levels of urinary metanephrines, and imaging is used to determine the stage. Treatment involves surgical resection when possible. Case Report: A 57-year-old male presented with hematemesis and melena, and endoscopy revealed upper gastrointestinal bleeding. Imaging showed a malignant pheochromocytoma that had infiltrated the upper lobe of the right kidney and the right lobe of the liver, with a tumor thrombus extending into the hepatic inferior vena cava, the right atrium, and the right ventricle. The patient denied surgery and was treated with palliative medical therapy until he died 3 months later. Conclusion: Although rare, malignant pheochromocytomas may present with upper gastrointestinal bleeding. While metastasis to the liver is a typical manifestation of malignant pheochromocytomas, invasion of the inferior vena cava with infiltration to the right ventricle resulting in tricuspid valve malfunction is a rare finding.

Comparison of Perioperative Outcomes Between Laparoscopic and Robot-Assisted Adrenalectomy for Large Pheochromocytoma (≥ 5cm): A Retrospective Study.

Purpose: The objective of this study was to compare perioperative outcomes in patients with large (≥5cm) pheochromocytomas who underwent adrenalectomy. Patients and Methods: We retrospectively reviewed patients who underwent laparoscopic adrenalectomy (LA) and robot-assisted adrenalectomy (RA) for large pheochromocytoma (≥ 5cm) at our center between January 2015 to February 2023. We compared the perioperative outcomes between the two groups and investigated impact of high Nor-Metanephrine (NMN) levels on perioperative outcomes by analyzing this subgroup. Results: A total of 115 patients were included in the study, with 48 patients in the robotic group and 67 patients in the laparoscopic group. The following significant difference were identified in favor of RA: shorter operative (excluding docking time) time (190.0 vs 220.0 min, p=0.002), lower estimated blood loss (50.0 vs 120.0 mL, p=0.013), however, RA group has higher surgical expenses (37933.0 vs 7936.0 CNY, p< 0.001). This finding remained consistent when analyzing patients with high NMN levels. Conclusion: Patients with large pheochromocytoma may experience reduced blood loss and shorter operative time when undergoing robot-assisted adrenalectomy. However, it is important to note that the RA approach is associated with significantly higher costs.

A Sizeable Adrenal Ganglioneuroma: A Case Report.

Adrenal ganglioneuromas are mostly asymptomatic, although they may manifest with compressive local effects. We present a 27-year-old man with no medical history who was referred to the surgical oncology clinic due to the incidental finding of a left adrenal mass. The initial computed tomography (CT) abdomen revealed a large mass causing displacement of adjacent organs. A CT-guided biopsy was inconclusive, and further evaluation with an NM endo-adrenal (MIBG) medullary scan pointed to a possible diagnosis of pheochromocytoma. Laboratory tests showed normal levels of urinary metanephrine and normetanephrine. The patient's history revealed chronic abdominal pain, with no symptoms of hypertension, headache, palpitations, or sweating. Subsequently, the patient underwent a left adrenalectomy without complications. This case underscores the importance of a comprehensive approach in managing adrenal masses, particularly when dealing with non-specific symptoms, emphasizing the importance of timely diagnosis and appropriate treatment.

Treatment of recurrent hunting-associated respiratory distress episodes in 2 dogs.

Noncardiogenic pulmonary edema (NCPE) in hunting dogs is an uncommon and poorly described condition for which no preventive treatment is available. Two dogs were presented for recurrent respiratory distress strictly associated with hunting activities. Diagnosis was based on bilateral, symmetrical, interstitial-to-alveolar pattern in the caudodorsal lung fields on thoracic radiographs, exclusion of other causes, and spontaneous clinical and radiographic improvement. Considering that the pathogenesis of exercise-induced NCPE likely involves α- and ß-adrenergic overstimulation, treatment with sympathetic blockers was used in both dogs. The first dog no longer showed respiratory signs during hunting activities. However, treatment failed to prevent respiratory distress in the other dog. Based on the large number of red blood cells in the bronchoalveolar lavage fluid of the second dog, exercise-induced pulmonary hemorrhage was suspected, as described in racing horses. The loop diuretic furosemide successfully prevented further hunting-associated respiratory distress episodes in this dog.

Adrenal adenoma associated with raised metanephrine level: A case report.

INTRODUCTION AND IMPORTANCE: Adrenal adenomas are benign neoplasms of the adrenal cortex which can be functional or non-functional. The functional tumors manifest as Cushing syndrome. Rarely, they are associated with high levels of metanephrine due to pheochromocytoma. Here, we report an extremely rare case of adrenal adenoma associated with raised metanephrine, but no histopathological evidence of medullary changes. CASE PRESENTATION: A 30-year female with diabetes, hypothyroidism, and hypertension was admitted for resistant hypertension, severe refractory hypokalemia, decreased sleep, fearfulness, anxiety, and palpitation. Facial puffiness, ecchymoses on upper and lower limbs, and bilateral pedal edema were present. Laboratory investigation revealed raised 24-hour-urine cortisol (52.5 µmol/dL) and metanephrine (56.00 µmol/24 h), very low ACTH (<5.0 pg/mL), and negative dexamethasone suppression test. MRI brain findings were normal. CT scan of the abdomen revealed a well-defined soft tissue lesion in the right adrenal gland and diffuse osteopenia vertebrae. Hence, diagnosis of Cushing Syndrome secondary to adrenal adenoma, and pheochromocytoma was made, and laparoscopic adrenalectomy was done under pheochromocytoma protocol. The patient improved dramatically, thereafter. Histopathological findings showed adrenocortical adenoma only; no evidence of pheochromocytoma was found. CLINICAL DISCUSSION: We came across many articles reporting adrenal adenoma associated with high levels of metanephrine due to co-existing pheochromocytomas either in the ipsilateral or contralateral adrenal gland. But, in our case, the adrenal adenoma was associated with high metanephrine levels with no histopathologic features of pheochromocytoma. CONCLUSION: Cushing syndrome due to Cortisol secreting Adrenal adenoma can be associated with biochemical and clinical features suggestive of Pheochromocytoma which could resolve after adrenalectomy.

The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management

ABSTRACT Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.

Resection of a hormonally active carotid body tumor.

Treatment of carotid body tumors (CBTs) can be complicated by the presence of hormonal activity. This case describes the treatment of a 65-year-old woman that presented with an abnormally high blood pressure and was found to have a neck mass. Diagnostic imaging along with urine metanephrines revealed this mass to be a hormonally active CBT. Careful resection along with preoperative treatment with an alpha blockade allowed for a successful complete removal of the tumor without any complications. Although CBTs tend to be benign, and hormonally active tumors are rare, one must always maintain a level of suspicion of hormonal activity to prevent catastrophic operative events.

The Pheochromocytoma/Paraganglioma syndrome: an overview on mechanisms, diagnosis and management.

Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.

[Resistant hypertension - pheochromocytoma].

We report a case of a man with a 30-year history of treatment-resistant hypertension, hydropoiesis, tachycardic spells and dysgeusia. Despite repeated visits to the emergency department and work-up in an out-patient clinic, the diagnosis was unknown. Three years prior to remittance to an endocrinologist, the hypertension worsened, and he developed diabetes type-II. Further work-up revealed a 3 cm extra-adrenal pheochromocytoma, a paraganglioma. After surgical removal of the tumor, he is without medication and symptom free. Pheochromocytoma and paraganglioma are rare causes of hypertension, estimated to explain 0.1-0.6% of all cases, but nonetheless an important diagnosis to make, due to serious side effects.

Prevalence of Cortisol Cosecretion in Patients With Primary Aldosteronism: Role of Metanephrine in Adrenal Vein Sampling.

CONTEXT: Adrenal venous sampling (AVS) is the gold standard procedure for subtype diagnosis in patients with primary aldosteronism (PA). Cortisol is usually adopted for the normalization of aldosterone levels in peripheral and adrenal samples. However, asymmetrical cortisol secretion can potentially affect the lateralization index, leading to subtype misdiagnosis. OBJECTIVE: We aimed to assess the prevalence of asymmetrical cortisol secretion in patients undergoing AVS and whether variations in adrenal vein cortisol might influence AVS interpretations. We then evaluated the use of metanephrines for the normalization of aldosterone levels for lateralization index. METHODS: We retrospectively included 101 patients with PA who underwent AVS: 49 patients underwent unstimulated AVS, while 52 patients underwent both unstimulated and cosyntropin-stimulated AVS. Eighty-eight patients had bilateral successful AVS according to metanephrine ratio. We assessed the prevalence of asymmetrical cortisol secretion through the cortisol to metanephrine (C/M) lateralization index (LI). We then evaluated whether the use of aldosterone to metanephrine (A/M) LI can improve the diagnostic accuracy of AVS compared with aldosterone to cortisol (A/C) LI. RESULTS: Asymmetrical cortisol secretion is present in 18% of patients with PA. Diagnosis with A/M LI and A/C LI is discordant in 14% of patients: 9% had a diagnosis of unilateral PA with A/M LI instead of bilateral PA with A/C LI and 5% had a diagnosis of bilateral PA with A/M LI instead of unilateral PA. CONCLUSION: The assessment of metanephrine levels in AVS is useful for the determination of selectivity and lateralization, allowing an accurate diagnosis, especially in patients with asymmetrical cortisol secretion.

Erratum: Low number of neurosecretory vesicles in neuroblastoma impairs massive catecholamine release and prevents hypertension.

[This corrects the article DOI: 10.3389/fendo.2022.1027856.].

DESI-MSI-based technique to unravel spatial distribution of COMT inhibitor Tolcapone.

Ascertaining compound exposure and its spatial distribution are essential steps in the drug development process. Desorption electrospray ionization mass spectrometry (DESI-MSI) is a label-free imaging technique capable of simultaneously identify and visualize the distribution of a diverse range of biomolecules. In this study, DESI-MSI was employed to investigate spatial distribution of tolcapone in rat liver and brain coronal - frontal and striatal -sections after a single oral administration of 100 mg/Kg of tolcapone, brain-penetrant compound. Tolcapone was evenly distributed in liver tissue sections whereas in the brain it showed differential distribution across brain regions analyzed, being mainly located in the olfactory bulb, basal forebrain region, striatum, and pre-frontal cortex (PFC; cingulate, prelimbic and infralimbic area). Tolcapone concentration in tissues was compared using DESI-MSI and liquid-chromatography mass spectrometry (LC-MS/MS). DESI-MSI technique showed a higher specificity on detecting tolcapone in liver sections while in the brain samples DESI-MSI did not allow a feasible quantification. Indeed, DESI-MSI is a qualitative technique that allows to observe heterogeneity on distribution but more challenging regarding accurate measurements. Overall, tolcapone was successfully localized in liver and brain tissue sections using DESI-MSI, highlighting the added value that this technique could provide in assisting tissue-specific drug distribution studies.

Clinical, imaging and biochemical presentation of cystic pheochromocytomas.

OBJECTIVE: Cystic adrenal mass is a rare imaging presentation of pheochromocytoma. We aimed to describe the clinical, biochemical and imaging characteristics of patients with cystic pheochromocytoma. DESIGN: Single-centre, retrospective study, 2000-2020. PATIENTS: Consecutive patients with cystic pheochromocytoma were identified from our institutional pathology and adrenal tumour database. RESULTS: Of the 638 patients with pheochromocytomas, 21 (3.2%) had cystic pheochromocytomas (median age: 57 years, 57% women). Most pheochromocytomas were discovered incidentally (57%) or due to symptoms of catecholamine excess (24%). The median tumour size was 6.4 cm. On imaging, cystic pheochromocytomas were round or oval (90%), heterogeneous lesions (86%) with a thick solid rim (median rim thickness 13.9 mm, unenhanced computed tomography (CT) attenuation 40 Hounsfield units (HU), venous-phase CT attenuation 83 HU), and a median cystic component of 40% (unenhanced CT attenuation 17.6 HU, venous-phase CT attenuation 20.4 HU), and rarely with calcifications (15%). All 20 patients with biochemical testing had functioning tumours (adrenergic in 80%, noradrenergic in 20%). Total urinary metanephrine excretion correlated with the volume of the solid component (R2 = .75, p < .0001) but not the cystic component (R2 = .04, p = .4386). All patients underwent adrenalectomy (48% laparoscopic, 52% open), and the median duration of hospital stay was 4 days. CONCLUSIONS: Cystic pheochromocytomas are rare, large tumours with a phenotypic appearance that can masquerade as other adrenal cystic lesions. The degree of biochemical abnormality in cystic pheochromocytomas is associated with the volume of the solid component. All patients with adrenal cysts that have a solid component or an unenhanced attenuation >10 HU should undergo biochemical testing for pheochromocytoma.