Pheochromocytoma as a catecholamine producing tumor: Implications for clinical practice

Figures & data

Table I.  Signs and symptoms in subjects with familial and sporadic pheochromocytoma.

Symptoms and signs	Multiple endocrine neoplasia 2 (n = 19, %)	Von Hippel–Lindau (n = 31, %)	Paraganglioma syndrome 4 (SDHB) (n = 33, %)	Sporadic (n = 37, %)
Hypertension	42	19	73	>90
Symptoms (overall)	53	32	88	>90
Headache	32	26	57	92
Sweating	32	23	52	70
Palpitation	37	19	63	73
Anxiety	21	16	54	60

SDH, succinate dehydrogenase complex. Modified from Pacak et al. (2005) and Timmers et al. (2007).

Table II.  Main clinical features of syndromes associated with pheochromocytoma and functional paraganglioma.

Von Hippel–Lindau

Type 1 (no pheochromocytomas):

Renal cysts and carcinomas

Retinal and central nervous system hemangioblastomas

Pancreatic neoplasms and cysts

Endolymphatic sac tumors

Epididymal cystadenomas

Type 2 (with pheochromocytomas):

2A: Retinal and central nervous system hemangioblastomas

Endolymphatic sac tumors

Epididymal cystadenomas

Pheochromocytoma

2B: Renal cysts and carcinomas

Retinal and central nervous system hemangioblastomas

Pancreatic neoplasms and cysts

Endolymphatic sac tumors

Epididymal cystadenomas

Pheochromocytoma

2C: Pheochromocytoma only

Multiple endocrine neoplasia 2

2A: Medullary thyroid carcinoma

Pheochromocytoma

Hyperparathyroidism

Cutaneus lichen amyloidosis

2B: Medullary thyroid carcinoma

Pheochromocytoma

Multiple neuromas

Marfanoid habitus

FMTC: Familial medullary carcinoma only

Neurofibromatosis 1

Multiple fibromas on skin and mucosae

Café au lait skin spots

Pheochromocytoma

Paraganglioma syndrome 1 (SDHD)

Head and neck paragangliomas (carotid body tumors, vagal, jugular and tympanic paragangliomas)

Pheochromocytoma

Abdominal, pelvic and thoracic paragangliomas

Paraganglioma syndrome 4 (SDHB)

Abdominal, pelvic and thoracic paragangliomas

Pheochromocytoma

Head and neck paragangliomas

SDHB, succinate dehydrogenase subunit B gene; SDHD, succinate dehydrogenase subunit D gene.

Table III.  Hereditary pheochromocytoma and paraganglioma: facts and figures.

Parameter	Von Hippel–Lindau	Multiple endocrine neoplasia 2	Neurofibromatosis 1	Paraganglioma syndrome 1 (SDHD)	Paraganglioma syndrome 4 (SDHB)
Gene	VHL	RET	NF 1	SDHD	SDHB
Chromosome	3p25–26	10q11.2	17q11.2	11q23	1p36.13
Protein	pVHL19 and pVHL30	Tyrosine-kinase receptor	Neurofibromin	Membrane- spanning subunit in the inner mitochondrial wall	Catalytic iron–sulfur protein
Frequency of germ-line mutations in an apparently sporadic pheochromocytoma/ functional paraganglioma (%)	2–13	< 5	3	0.5–7	3–10
Frequency of malignancy (%)	5	3	3–11	3	70
Tumor catecholamine phenotype*	NE	E	E	NE	NE, DA
Adrenal disease	++	++	++	+	+
Bilateral adrenal disease	++	++	+	+	−
Extra-adrenal disease	+	−	−	++	++
Multifocal disease	−	−	−	++	+

Adapted from Eisenhofer et al. (2004a); Lenders et al. (2005); Amar et al. (2005a); Bausch et al. (2006) and Timmers et al. (2007); SDHB, succinate dehydrogenase subunit B gene; SDHD, succinate dehydrogenase subunit D gene; ++;+; − , relative likelihoods of adrenal or extra-adrenal disease from high to low

* Tumor catecholamine phenotypes are designated as either predominantly epinephrine-producing (E) or predominantly norepinephrine-producing (NE) with possible dopamine (DA) co-secretion.

Figure 1 Algorithm for genetic testing for genes associated with pheochromocytoma or paraganglioma. Abbreviations: RET, rearranged during transfection; SDHB, succinate dehydrogenase subunit B gene; SDHD, succinate dehydrogenase subunit D gene; VHL, Von Hippel–Lindau gene; NF 1, neurofibromatosis 1. Genes in parenthesis: second choice testing. Adapted from Bornstein and Gimenez-Roqueplo (2006) and Gimenez-Roqueplo et al. (2006).

Table IV.  Sensitivity and specificity of biochemical tests for diagnosis of pheochromocytoma.

Parameter	Sensitivity (%)	Specificity (%)
Plasma metanephrines	99	89
Plasma catecholamines	84	81
Urinary catecholamines	86	88
Urinary fractionated metanephrines	97	69
Urinary total metanephrines	77	93
Urinary vanillylmandelic acid (VMA)	64	95

Sensitivity values of all tests for familial pheochromocytoma are lower than for sporadic pheochromocytoma. The reverse is the case for the specificity values. Adapted from Lenders et al. (2002).

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