ABSTRACT
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.
ABSTRACT
E prostaglandins are formed in seminal vesicles and can be oxygenated by (omega-1)-hydroxylation catalysed by cytochrome P450 to 19(R)-hydroxy metabolites. The latter are not further metabolized. Prostaglandin E1 (PGE1), PGE2, 19-hydroxy-PGE1 and 19-hydroxy-PGE2 were measured in seminal fluid of 95 men, who attended the clinic for infertility. After extractive isolation, the E prostaglandins were converted to B prostaglandins by alkali treatment and analysed by high performance liquid chromatography on beta-cyclodextrin silica with 17-phenyl-PGE2 as an internal standard. The relative amount of 19-hydroxy E-prostaglandins varied between 26% and 97%. Most (86%) of the men were classified as rapid or normal hydroxylators with PGE/19-hydroxy PGE ratios below 0.75, while 14% were slow hydroxylators. The relative amount of 19-hydroxy E1 and 19-hydroxy E2 showed a 96% covariation, which supports that a common enzymatic mechanism is operating on both E1 and E2 prostaglandins and that this mechanism is the major determinant for formation of 19-hydroxy compounds. We conclude that the relative amounts of PGE1, PGE2, 19-hydroxy-PGE1 and 19-hydroxy-PGE2 in seminal fluid vary, possibly due to polymorphic expression of this enzymatic mechanism. Total output of 19-hydroxy-PGE compounds, but not the primary PGE compounds was correlated with the output of seminal fructose, supporting that the 19-hydroxy prostaglandins are the normal end products of the seminal vesicles. Low sperm concentration found among men with high output of E prostaglandins could here simply be explained by dilution of spermatozoa by a high output of seminal vesicular fluid.(ABSTRACT TRUNCATED AT 250 WORDS)