Circadian profiles of free plasma metanephrines in anorexia nervosa and constitutional thinness

Catecholamine metabolism contributes to energy homeostasis and may differ in low-weight conditions of various origins. Free plasma metanephrines, 3-methoxytyramine (3-MT), normetanephrine (NM), and metanephrine (M), are stable end-products of dopamine, noradrenaline, and adrenaline metabolism, respectively, with potential circadian rhythmicity. However, their 24-hour profiles remain unknown in anorexia nervosa (AN) and constitutional thinness (CT).

This exploratory study aimed to assess 24-hour variations of plasma free metanephrines in women with acute AN (n = 10), recovering AN (AN-Rec, n = 11), CT (n = 10), and healthy controls (n = 10), and to explore their association with biomarkers of undernutrition severity and weight regulation. Participants underwent 24-hour in-patient evaluation, including standardized meals and activity, and twelve time-point plasma sampling. Free metanephrines were measured by LC-MS/MS. 24-hour rhythmicity was analyzed using cosinor regression.

AN and CT showed higher mean 24-hour levels for 3-MT, NM, and M than controls, with variable patterns depending on metabolites. AN-Rec displayed higher 3-MT levels than controls only. Cosinor analysis revealed a significant 24-hour variation consistent with a circadian pattern for 3-MT with an acrophase around 13:00 in AN, AN-Rec, and CT. NM showed a circadian pattern in AN, CT, and controls. Mean 3-MT, NM and M correlated negatively with BMI and IGF-1, and positively with ALT and vitamin B12.

Midday elevations of free plasma metanephrines may reflect metabolic stress and hepatic alterations in AN. Their increase may may reflect distinct underlying physiological mechanisms in both AN and CT. Further studies are needed to confirm these exploratory findings.