CONTEXT: Pheochromocytoma is a rare disease but with high mortality if it is not 
being diagnosed early. Several biochemical tests with high accuracy have been 
obtained, but the clinical threshold for request of these tests is not 
determined clearly.
OBJECTIVES: To determine the Likelihood Ratios of clinical symptoms and signs in 
diagnosing pheochromocytoma. And also meta-analysis of their sensitivity in this 
disease.
DATA SOURCES: MEDLINE was searched for relevant English-language articles dated 
1960 to February 2014. Bibliographies were searched to find additional articles.
STUDY SELECTION: We included original studies describing the sensitivity and/or 
likelihood ratios of signs and symptoms in clinical suspicion of 
pheochromocytoma. Their method of diagnosis should have been based on pathology. 
We excluded specific subtypes or syndromes related to pheochromocytoma, or 
specific ages or gender. Also we excluded studies before 1993 (JNC5) which no 
definition of hypertension was presented. 37 articles were chosen finally.
DATA EXTRACTION: Two authors reviewed data from articles independently and gave 
discrepancies to third author for decision. The aim was extraction of raw 
numbers of patients having defined signs or symptoms, and draw 2 × 2 tables if 
data available. We meta-analyzed sensitivities by Statsdirect and Likelihood 
Ratios by Meta-disc soft wares. Because our data was heterogeneous based on 
I(2) > 50 % (except negative Likelihood ratio of hypertension), we used random 
effect model for doing meta-analysis. We checked publication bias by drawing 
Funnel plot for each sign/symptom, and also Egger test.
DATA SYNTHESIS: The most prevalent signs and symptoms reported were hypertension 
(pooled sensitivity of 80.7 %), headache (pooled sensitivity of 60.4 %), 
palpitation (pooled sensitivity of 59.3 %) and diaphoresis (pooled sensitivity 
of 52.4 %). The definition of orthostatic hypotension was different among 
studies. The sensitivity was 23-50 %. Paroxysmal hypertension, chest pain, 
flushing, and weakness were the signs/symptoms which had publication bias based 
on Funnel plot and Egger test (P value < 0.05). Seven of the articles had 
control group, and could be used for calculating LR of signs/symptoms. 
Diaphoresis (LR+ 2.2, LR- 0.45), Palpitation (LR+ 1.9, LR- 0.52) and headache 
(LR+ 1.6, LR- 0.24) were significant symptoms in clinical diagnosis of 
pheochromocytoma. Other signs and symptoms had been reported in only one study 
and could not have been meta-analyzed. Classic triad of headache, palpitation 
and diaphoresis in hypertensive patients had the LR+ 6.312 (95 % CI 
0.217-183.217) and LR- 0.139 (95 % CI 0.059-0.331). Surprisingly, hypertension 
was not important in clinical suspicion of pheochromocytoma, and even 
normotension increased the probability of the disease.
CONCLUSIONS: By available data, there is no single clinical finding that has 
significant value in diagnosis or excluding pheochromocytoma. Combination of 
certain symptoms, signs and para-clinical exams is more valuable for physicians. 
Further studies should be done, to specify the value of clinical findings. Until 
that time the process of diagnosis will be based on clinical suspicion and lab 
tests followed by related imaging.