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The urinary normetanephrine to creatinine ratio (uNMN/Cr) and urinary metanephrine to creatinine ratio (uMN/Cr) are commonly evaluated for the diagnosis of pheochromocytomas (PCC) in dogs. This study aimed to establish reference intervals for uNMN/Cr and uMN/Cr in 56 healthy dogs in Japan and to investigate the effect of urine collection methods on these measurements in 15 non-PCC dogs. The upper limits of reference intervals for uNMN/Cr and uMN/Cr were 124.4 nmol/mmol (90% confidence interval [CI] 107.7-137.0) and 121.1 nmol/mmol (90% CI 102.8-145.1), respectively. Both uNMN/Cr and uMN/Cr were significantly higher when urine was collected in the hospital compared to at home. Several factors, including the method of urine collection, should be considered when utilizing these reference intervals.

Pheochromocytomas are rare neuroendocrine tumors that derive from the chromaffin cells of the adrenal medulla and secrete catecholamines. The measurement of plasma or fractionated urine metanephrines is the hormonal determination of choice for the biochemical diagnosis. Once the biochemical diagnosis is confirmed, the next step is the localization study. It is recommended to request a genetic study in all patients with pheochromocytomas since 40% of cases are hereditary. Once the diagnostic study is completed, preoperative treatment with alpha blockers should be instituted at least 7-14 days before adrenalectomy. However, in low-risk patients, the omission of presurgical treatment could be considered if the surgery is performed in centers with experience and a strict monitoring of the patient is carried out during the perioperative period. This document offers a practical guide on the diagnosis and perioperative approach in patients with pheochromocytomas., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Background: The prevalence of metastatic pheochromocytoma and paraganglioma (PPGL) is approximately 15%-20%. Although there are indicators to assess metastatic risks, none of them predict metastasis reliably. Therefore, we aimed to develop and validate a scoring system using clinical, genetic, and biochemical risk factors to preoperatively predict the metastatic risk of PPGL., Methods: In the cross-sectional cohort (n = 180), clinical, genetic, and biochemical risk factors for metastasis were identified using multivariate logistic regression analysis, and a novel scoring system was developed. The scoring system was validated and compared with the age, size of tumor, extra-adrenal location, and secretory type (ASES) score in the longitudinal cohort (n = 114)., Results: In the cross-sectional cohort, pseudohypoxia group-related gene variants (SDHB, SDHD, or VHL), methoxytyramine >0.16 nmol/L, and tumor size >6.0 cm were independently associated with metastasis after multivariate logistic regression. Using them, the gene variant, methoxytyramine, and size of tumor (GMS) score were developed. In the longitudinal cohort, Harrell's concordance index of the GMS score (0.873, 95% confidence interval [CI]: 0.738-0.941) was higher than that of the ASES score (0.713, 95% CI: 0.567-0.814, p = 0.007). In the longitudinal cohort, a GMS score ≥2 was significantly associated with a higher risk of metastasis (hazard ratio = 25.07, 95% CI: 5.65-111.20). A GMS score ≥2 (p < 0.001), but not ASES score ≥2 (p = 0.090), was associated with shorter progression-free survival., Conclusion: The GMS scoring system, which integrates gene variant, methoxytyramine level, and tumor size, provides a valuable preoperative approach to assess metastatic risk in PPGL., (© 2024 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Introduction: Elevated metanephrine and catecholamine levels 3-fold upper limit of normal (ULN) are diagnostic for pheochromocytoma. We sought to determine whether size correlates with biochemical activity or symptoms which could guide timing of surgery., Methods: Data from consecutive patients undergoing adrenalectomy for pheochromocytoma at our institution over a 10-year period were retrospectively collected. These included maximal lesion diameter on preoperative imaging, plasma/urine metanephrine and/or catecholamine levels, demographic variables and presence of typical paroxysmal symptoms. Receiver operating characteristic curves were used to assess predictive accuracy., Results: Sixty-three patients were included in the analysis (41 females and 22 males). Median age was 56 (43, 69) years. Due to various referring practices, 31 patients had documented 24-h urine metanephrine, 26 had 24-h urine catecholamine, and 52 had fractionated plasma metanephrine levels available for review. Values were converted to fold change compared to ULN and the maximum of all measured values was used for logistic regression. Median tumor size was 3.40 (2.25, 4.55) cm in greatest dimension. Tumor size at which pheochromocytoma produced > 3-fold ULN was ≥2.3 cm (AUC of 0.84). Biochemical activity increased with doubling tumor size (odds ratio = 8, P = 0.0004) or ≥ 1 cm increase in tumor size (odds ratio = 3.03, P = 0.001). 40 patients had paroxysmal symptoms, but there was no significant correlation between tumor size/biochemical activity and symptoms., Conclusions: In our study, tumor size directly correlated with the degree of biochemical activity and pheochromocytomas ≥2.3 cm produced levels 3 times ULN. These findings may allow clinicians to adjust timing of operative intervention., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Urine metanephrines are used to screen for phaeochromocytoma or paraganglioma (PPGL). Current reference intervals (RI) derived in healthy individuals are not age or sex-stratified, and lower than in hypertensive patients, leading to high false positive rates. This study aims to determine age and sex-stratified RI from a contingent screening population., Methods: Patients with 24-h deconjugated urine metanephrines from 3/6/2010 to 27/8/2022 were included (2936 males, 5285 females), initially by liquid chromatography-electrochemical detection (LC-ECD) then liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bhattacharya analysis was used after log transformation to determine age and sex-stratified RI for metanephrine excretion, normetanephrine excretion, metanephrine/creatinine and normetanephrine/creatinine ratios., Results: Normetanephrine excretion increases with age (RI: males: 18-<30 years: <3.4 µmol/24 h, 30-<40 years: <3.7 µmol/24 h, 40+ years: <5.3 µmol/24 h; females: 18-<30 years: <2.7 µmol/24 h, 30-<40 years: <3.1 µmol/24 h, 40+ years: <3.7 µmol/24 h), while metanephrine excretion was consistent across adulthood (RI: males: 18+ years: <1.8 µmol/24 h; females: 18+ years: <1.2 µmol/24 h). However, normetanephrine/creatinine and metanephrine/creatinine increase steadily with age after early adulthood, likely due to a decrease in muscle mass, with females having higher normetanephrine/creatinine and metanephrine/creatinine ratios., Conclusions: Age and sex-stratified RI were derived for metanephrine excretion, normetanephrine excretion, metanephrine/creatinine and normetanephrine/creatinine ratios. This is expected to reduce false positives while flagging most PPGL., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Incidentaloma is an adrenal tumor detected during diagnostic imaging performed for extra‑adrenal causes. Evaluation of metanephrine concentrations in a 24‑hour urine collection can be a significant challenge in patients with multiple medications and comorbidities., Objectives: The aim of this study was to evaluate the effect of commonly used groups of drugs on metanephrine levels in the 24‑hour urine collection., Patients and Methods: A total of 1051 patients with adrenal mass below 10 Hounsfield units on unenhanced computed tomography were included in the study. Patients diagnosed with Cushing or Conn syndrome, adrenal carcinoma, pheochromocytoma, active extra‑adrenal malignant neoplasms, and exacerbation of severe illnesses were excluded. Metanephrine, normetanephrine, and 3‑methoxytyramine in the 24‑hour urine collection were measured by high‑performance liquid chromatography with electrochemical detection. Information on concomitant medication (β‑blockers, calcium channel blockers [CCBs], loop diuretics, thiazide diuretics, potassium‑sparing diuretics, α‑blockers, angiotensin‑converting enzyme inhibitors / angiotensin II receptor blockers, metformin, nonmetformin antidiabetic drugs [NMADs], lipid‑lowering drugs, proton pump inhibitors, levothyroxine, thyreostatics, antidepressants, neuroleptics, benzodiazepines, glucocorticosteroids, inhaled B‑receptor agonists, and ipratropium) was collected from each patient., Results: The urinary excretion of normetanephrine was significantly higher in the patients on β‑blockers, CCBs, loop diuretics, α‑blockers, NMADs, and neuroleptics. α‑Blockers increased urine metanephrine concentration, and NMADs, antidepressants, and glucocorticosteroids lowered it. There was no association between the analyzed drugs and urinary 3‑methoxytyramine level., Conclusions: Many drug groups interfere with the measurement of urinary fractionated metanephrines. These interactions should be taken into account during interpretation of a hormonal evaluation, as they can be crucial for further management, especially for making a decision on surgical treatment.