Phaeochromocytomas are rare neuroendocrine tumours that produce catecholamines. The name phios – dusky, chroma – colour, and cytoma – tumour refers to the colour of the tumour cells when stained with chromium salts. Catecholamine-producing neuroendocrine cells are consequently known as chromaffin cells and are usually found in the adrenal medulla and other ganglia of the sympathetic nervous system.1
Some authors restrict the use of phaeochromocytoma to tumours of the adrenal medulla, while others use the term more broadly to include paragangliomas. The defining characteristic of phaeochromocytoma in clinical practice is the autonomous production of catecholamines.2
Felix Frankel is credited with the first clinical description of phaeochromocytoma.3,4
This case has been made more interesting by a subsequent study tracing descendants of the original patient and undertaking genetic testing.5
The investigators demonstrated a RET
gene germ-line mutation in the kindred, thus diagnosing multiple endocrine neoplasia type 2 (MEN-2) 121 years after the original presentation. This study elegantly illustrates the importance of germ-line mutations in patients with phaeochromocytoma and this possibility should always be considered.
Phaeochromocytoma may cause problems for patients in two ways: firstly, due to adverse effects caused by the autonomous production of catecholamines and secondly, due to malignancy and metastatic spread. Case series report 5–20% of phaeochromocytomas as malignant.6–8
The five-year survival of malignant phaeochromocytoma is <50% and first-line treatment is surgery.9–11
Chemotherapy and radionuclide treatments are also used, but data is limited due to the rarity of the condition and the reported experience has been disappointing.10,11
Trials are underway of potentially more effective treatments, particularly using new radioisotope therapies, but currently surgery remains the mainstay of treatment.12
The consequences of catecholamine excess are many and varied. The classical clinical triad of hypertension, headache and sweating is of limited clinical utility, as it is neither sensitive nor specific for phaeochromocytoma.13–16
Patients may have symptoms related to any adrenoreceptor agonist effect or may have no symptoms at all. In the past, patients were most often diagnosed during investigation of hypertension or unexplained spells. More recently, with the widespread use of CT and MRI scanning, phaeochromocytoma is increasingly diagnosed during investigation of adrenal mass lesions identified incidentally by abdominal imaging studies carried out for other reasons.15–20
Patients thus come to attention in three main ways: “dif cult” hypertension, unexplained spells, or by incidental radiological identification of an adrenal mass. A fourth, familial screening, may soon be added to this list.21,22
For patients with hypertension or spells, the presence of additional features suggestive of catecholamine excess should be considered prior to biochemical investigation.23–26
For those with adrenal mass lesions, biochemical investigation is nearly always indicated.15–20,27
Biochemical testing for possible phaeochromocytoma is the primary focus of this review.
Genetic Syndromes of Phaeochromocytoma
The genetic syndromes commonly associated with phaeochromocytoma are shown in .8,21,22,28–32
These vary in age of onset, location, secretory product and propensity for malignancy. The mean age of diagnosis of phaeochromocytoma in Von Hippel Lindau syndrome is about 20 years, whereas in Neuro bromatosis Type 1 it is about 42 years, similar to sporadic cases.28,29
The incidence of malignancy in phaeochromocytoma associated with succinate dehydrogenase complex, subunit B (SDH-B)
mutations is about 1 in 3, whereas with SDH-D
they are nearly all benign.30–32
Genetic testing is not considered further in this discussion and for more information readers can refer to recent reviews.33–36
Selected characteristics of genetic syndromes associated with phaeochromocytoma.