title: Circadian hypo- and hyper-amplitude-tension (CHAT) associated with putative pheochromocytoma and 12-hourly phenoxybenzamine treatment.
abstract: A 26-year-old white woman had an ablated sino-atrial node and ventricular pacemaker as an unusual feature of a pheochromocytoma-compatible history. Her status quo included, on three occasions, elevated 24-hour urinary epinephrine and metanephrine excretion. She monitored her blood pressure (BP) and heart rate (HR) at 15- to 60-minute intervals over several days, with interruptions, before and after the institution of 10 mg phenoxybenzamine per os every 12 hours (between 7:30 and 8:00 and between 19:30 and 20:00), with continued monitoring over several months. Her data were summarized for consecutive 3-day intervals by sphygmochron. Circadian parameters and original data are compared with gender- and age-specified reference values, yielding also non-parametric endpoints, such as the percentage time elevation, the extent of excess, and the timing of excess, that all can be acceptable for some days but unacceptable for other days. In her broader time structure, or chronome, cosinor analyses revealed a prominent and statistically significant circadian rhythm in BP and HR before and during the 12-hourly therapy. The 12-hour component of BP was more prominent during therapy than prior to it. A statistically significant decreasing trend occurred before therapy, and recurred during treatment. Chronomically interpreted monitoring revealed: 1) the persistence of a statistically significant circadian rhythm during 12-hourly phenoxybenzamine treatment; 2) days-long changes in BP MESOR, the duration of which could not be previously determined based on spotchecks; 3) changes in the circadian amplitude of BP, which can be either very small or very large, compatible with the diagnosis of intermittent circadian hyper-amplitude-tension (CHAT); and 4) a very wide range of BP and HR values, so that occasional (casual) measurements fail to convey the dynamics that may underlie this infrequently found clinical condition of an elevated catecholamine excretion compatible with a pheochromocytoma. All findings support the need for long-term monitoring of BP and HR that may account for controversy in earlier publications.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA. corne001@umn.edu
authors.forename: L D
authors.initials: LD
authors.lastname: Sabath
authors.forename: Germaine
authors.initials: G
authors.lastname: Cornélissen
authors.forename: Franz
authors.initials: F
authors.lastname: Halberg
authors.forename: Alexander
authors.initials: A
authors.lastname: Stoynev
authors.forename: Ognian
authors.initials: O
authors.lastname: Ikonomov
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Otsuka
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D001795:Blood Pressure Determination; D002940:Circadian Rhythm / Q000502:physiology*; D004334:Drug Administration Schedule; D004837:Epinephrine / Q000097:blood / Q000652:urine; D005188:False Negative Reactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008676:Metanephrine / Q000652:urine; D008722:Methods; D010643:Phenoxybenzamine / Q000008:administration & dosage / Q000627:therapeutic use*; D010673:Pheochromocytoma / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D013575:Syncope / Q000150:complications; D013610:Tachycardia / Q000150:complications; D013997:Time Factors
chemical_list: D010643:Phenoxybenzamine; D008676:Metanephrine; D004837:Epinephrine