Diagnosis of PPGLs using plasma or urinary free metabolites provides advantages of fewer false-positive results compared with commonly measured deconjugated metabolites. The plasma panel offers better diagnostic performance than either urinary panel for patients at high risk of disease and, with appropriate preanalytics, provides the test of choice. Measurements of methoxytyramine in urine show limited diagnostic utility compared with plasma.

BackgroundMass spectrometric-based measurements of the steroid metabolome have been introduced to diagnose disorders featuring abnormal steroidogenesis. Defined reference intervals are important for interpreting such data.MethodsLiquid chromatography–tandem mass spectrometry was used to establish reference intervals for 16 steroids (pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, aldosterone, 18-oxocortisol, 18-hydroxycortisol, 17-hydroxyprogesterone, 21-deoxycortisol, 11-deoxycortisol, cortisol, cortisone, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androstenedione, testosterone) measured in plasma from 525 volunteers with (n = 227) and without (n = 298) hypertension, including 68 women on oral contraceptives.ResultsWomen showed variable plasma concentrations of several steroids associated with menstrual cycle phase, menopause and oral contraceptive use. Progesterone was higher in females than males, but most other steroids were higher in males than females and almost all declined with advancing age. Using models that corrected for age and gender, body mass index showed weak negative relationships with corticosterone, 21-deoxycortisol, cortisol, cortisone, testosterone, progesterone, 17-hydroxyprogesterone and 11-deoxycorticosterone, but a positive relationship with 18-hydroxycortisol. Hypertensives and normotensives showed negligible differences in plasma concentrations of steroids.ConclusionAge and gender are the most important variables for plasma steroid reference intervals, which have been established here according to those variables for a panel of 16 steroids primarily useful for diagnosis and subtyping of patients with endocrine hypertension.

Objective Hypertension and symptoms of catecholamine excess are features of pheochromocytomas and paragangliomas (PPGLs). This prospective observational cohort study assessed whether differences in presenting features in patients tested for PPGLs might assist establishing likelihood of disease. Design and methods Patients were tested for PPGLs because of signs and symptoms, an incidental mass on imaging or routine surveillance due to previous history or hereditary risk. Patients with (n = 245) compared to without (n = 1820) PPGLs were identified on follow-up. Differences in presenting features were then examined to assess the probability of disease and relationships to catecholamine excess. Results Hyperhidrosis, palpitations, pallor, tremor and nausea were 30–90% more prevalent (P < 0.001) among patients with than without PPGLs, whereas headache, flushing and other symptoms showed little or no differences. Although heart rates were higher (P < 0.0001) in patients with than without PPGLs, blood pressures were not higher and were positively correlated to BMI, which was lower (P < 0.0001) in patients with than without PPGLs. From these differences in clinical features, a score system was established that indicated a 5.8-fold higher probability of PPGLs in patients with high than low scores. Higher scores among patients with PPGLs were associated, independently of tumor size, with higher biochemical indices of catecholamine excess. Conclusions This study identifies a complex of five signs and symptoms combined with lower BMI and elevated heart rate as key features in patients with PPGLs. Prevalences of these features, which reflect variable tumoral catecholamine production, may be used to triage patients according to likelihood of disease.