Phaeochromocytoma Flashcards
Phaeochromocytoma refers to a …-secreting tumour of chromaffin cells.
Phaeochromocytoma refers to a catecholamine-secreting tumour of chromaffin cells.
Chromaffin cells are predominantly found in the …, but also in the sympathetic paravertebral ganglia of the thorax, abdomen, and pelvis.
Chromaffin cells are predominantly found in the adrenal medulla, but also in the sympathetic paravertebral ganglia of the thorax, abdomen, and pelvis.
Catecholamine-secreting tumours may arise from the adrenal medulla or from the sympathetic ganglia and are known as phaeochromocytomas and paragangliomas respectively:
Phaechromocytoma: arising from the adrenal medulla, accounts for 80-85% of such tumours.
Catecholamine-secreting paraganglioma: arising from the sympathetic ganglia, accounts for 15-20% of such tumours. Sometimes referred to as ‘extra-adrenal phaeochromocytomas’.
Paragangliomas
Paragangliomas may arise from both parasympathetic and sympathetic ganglia. Paragangliomas affecting parasympathetic ganglia are commonly referred to as head and neck paragangliomas. They are usually non-secretory, derived from non-chromaffin cells and named after the tumour location (e.g. carotid body, glomus tympanicum, glomus jugulare).
Phaeochromocytomas and paragangliomas are … tumours.
Phaeochromocytomas and paragangliomas are rare tumours.
Phaeochromocytomas account for < …% of patients with hypertension. They most commonly present in the 4th or 5th decade, but at a younger age in hereditary cases. Around 10% of cases occur in children.
The majority of tumours are sporadic, but up to 40% have a hereditary component.
Phaeochromocytomas account for < 0.2% of patients with hypertension. They most commonly present in the 4th or 5th decade, but at a younger age in hereditary cases. Around 10% of cases occur in children.
The majority of tumours are sporadic, but up to 40% have a hereditary component.
Patients with … phaechromocytoma are more likely to be older and present with classic features. This is because screening for phaeochromocytoma is more well established in hereditary cases. Several susceptibility genes have been identified in phaeochromocytoma. As such, genetic testing should be considered in all patients, usually following resection.
Patients with sporadic phaechromocytoma are more likely to be older and present with classic features. This is because screening for phaeochromocytoma is more well established in hereditary cases. Several susceptibility genes have been identified in phaeochromocytoma. As such, genetic testing should be considered in all patients, usually following resection.
Up to 40% of phaeochromocytomas may have a hereditary component. Three familial syndromes are strongly associated with these catecholamine-secreting tumours:
Multiple endocrine neoplasia (MEN) type 2: autosomal dominant disorder due to a RET proto-oncogene mutation characterised by medullary thyroid cancer, phaechromocytoma and primary hyperparathyroidism. Phaechromocytoma is seen in 50% of cases. See our MEN syndromes notes for more details.
Von Hippel-Lindau (VHL) syndrome: autosomal dominant disorder due to VHL genetic mutation. Characterised by multiple tumours types including phaeochromocytoma, paraganglioma, hemangioblastoma (often involving cerebellum), renal cell carcinoma and many others. Phaeochromocytoma is seen in 10-20% of cases and frequently bilateral.
Neurofibromatosis (NF) type 1: autosomal dominant disorder due to a mutation in the NF1 gene. Characterised by multiple neurofibromas, cafe au lait spots, axillary and inguinal freckling, central nervous system gliomas and phaeochromocytomas in around 3% of cases.
Phaeochromocytomas are neuroendocrine tumours arising from … cells.
Phaeochromocytomas are neuroendocrine tumours arising from chromaffin cells.
The clinical manifestations of phaeochromocytomas are due to excess secretion of catecholamines from tumours leading to either paroxysmal or continuous symptoms. Catecholamines have wide-ranging effects as part of the normal sympathetic nervous system through activation of alpha and beta-adrenergic receptors. These effects include:
Alpha-adrenergic: elevated bloods pressure, increased cardiac contractility, increased glucose utilisation (glycogenolysis/gluconeogenesis).
Beta-adrenergic: increased heart rate, increased cardiac contractility.
Precipitants of hypertensive crisis
Drugs: opiates, dopamine antagonists, beta-blockers, cocaine, tricyclic antidepressants
Physical: direct pressure or handling during surgery
Anaesthesia: endotracheal intubation
Tumour characteristics
There are some key characteristics about phaeochromocytomas and paragangliomas.
Locations: >95% are located within the abdomen with up to 90% of these are intra-adrenal (i.e. phaeochromocytomas)
Laterality: multiple tumours are seen in 5-10% of cases and hereditary cases are more likely to be bilateral
Malignant potential: ~10% of cases are malignant. Malignant spread may occur a long-time following resection.
Phaeochromocytomas are characterised by a triad of…
Phaeochromocytomas are characterised by a triad of episodic headache, sweating and tachycardia.
Classically, clinical features of phaeochromocytoma are ….
Classically, clinical features of phaeochromocytoma are paroxysmal. However, some patients may have more persistent symptoms, while others are asymptomatic. Important to remember that even patients with essential hypertension may have paroxysmal symptoms.
Symptoms of phaeochromocytoma
Asymptomatic (50%): may be found incidentally on imaging or at autopsy Headache (90% in symptomatic): variable in duration and intensity Sweating (60-70% in symptomatic) Tachycardia Palpitations Dyspnoea Weakness Tremor Nausea
Signs of phaeochromocytoma
Hypertension (paroxysmal in 50%) Posturla hypotension Weight loss Pallor Arrhythmias Pulmonary oedema: crackles at both lung bases Fever Tremor
Patients may develop severe symptoms relating to a hypertensive crisis, also known as a phaeochromocytoma crisis. If severe, it may lead to circulatory collapse.
Patients may develop severe symptoms relating to a hypertensive crisis, also known as a phaeochromocytoma crisis. If severe, it may lead to circulatory collapse.
Hypertension Hyperthermia Confusion End-organ dysfunction (e.g. cardiomyopathy, pulmonary oedema) Hypotension (if circulatory collapse)
The following features warrant testing/screening for phaeochromocytoma:
Classic triad (episodic headache, sweating and tachycardia)
Hyperadrenergic spells (paroxysmal palpitations, sweating, headache, tremor, pallor)
Atypical hypertension (e.g. early-onset, resistant to treatment)
Associated familial syndrome
Family history of phaeochrocytoma
Typical adrenal adenoma on imaging
Other
… are a metabolite of adrenaline that may be measured in the urine or plasma. The choice between measuring plasma levels or urine levels depends on the centre and pre-test probability. Urinary measurements are generally used for low risk patients and plasma measurements for those at high-risk.
Metanephrines are a metabolite of adrenaline that may be measured in the urine or plasma. The choice between measuring plasma levels or urine levels depends on the centre and pre-test probability. Urinary measurements are generally used for low risk patients and plasma measurements for those at high-risk.
Urinary fractionated metanephrines
A 24-hour urinary collection for urinary metanephrines is an appropriate investigation for those with possible sporadic disease based on clinical suspicion. It may be completed twice on non-consecutive days.
Plasma free metanephrines
Patients considered high risk of phaeochromocytoma can have plasma levels of metanephrines. This is usually reserved for patients with a personal or family history of phaeochromocytoma, known genetic syndrome or suspected adenoma on imaging.
Plasma metanephrines and catecholamines have a high negative predictive value. This means patients without raised levels are high unlikely to have a phaechromocytoma. However, it does result in false positives. As such, to prevent unnecessary investigations and potential surgery, the test is reserved for …
Plasma metanephrines and catecholamines have a high negative predictive value. This means patients without raised levels are high unlikely to have a phaechromocytoma. However, it does result in false positives. As such, to prevent unnecessary investigations and potential surgery, the test is reserved for high risk patients.
Following confirmation of elevated catecholamines, … investigations are used to locate the tumour.
Following confirmation of elevated catecholamines, radiological investigations are used to locate the tumour.
Cross-sectional imaging = phaeochromocytoma
Computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis can both be completed as part of initial radiological investigations.
Both imaging modalities are highly sensitive (up to 100%) but only 70% specific due to the high rate of incidentalomas. An incidentaloma refers to an adrenal lesion >1 cm that is discovered incidentally on imaging. The problem with these lesions is that it is unclear whether they are malignant, functioning or the cause of symptoms. Further tests are usually required.
