Anorexia nervosa depends on adrenal sympathetic hyperactivity: opposite neuroautonomic profile of hyperinsulinism syndrome

Abstract

ObjectiveThe aim of our study was to determine the central and peripheral autonomic nervous system profiles underlying anorexia nervosa (AN) syndrome, given that affected patients present with the opposite clinical profile to that seen in the hyperinsulinism syndrome.DesignWe measured blood pressure and heart rate, as well as circulating neurotransmitters (noradrenaline, adrenaline, dopamine, plasma serotonin, and platelet serotonin), using high-performance liquid chromatography with electrochemical detection, during supine resting, one minute of orthostasis, and after five minutes of exercise. In total, 22 AN patients (12 binge-eating/purging type and 10 restricting type) and age-, gender-, and race-matched controls (70 ± 10.1% versus 98 ± 3.0% of ideal body weight) were recruited.ResultsWe found that patients with AN had adrenal sympathetic overactivity and neural sympathetic underactivity, demonstrated by a predominance of circulating adrenaline over noradrenaline levels, not only during the supine resting state (52 ± 2 versus 29 ± 1 pg/mL) but also during orthostasis (67 ± 3 versus 32 ± 2 pg/mL, P < 0.05) and after exercise challenge (84 ± 4 versus 30 ± 3 pg/mL, P < 0.01).ConclusionConsidering that this peripheral autonomic nervous system disorder depends on the absolute predominance of adrenomedullary C1 adrenergic nuclei over A5 noradrenergic pontine nucleus, let us ratify the abovementioned findings. The AN syndrome depends on the predominance of overwhelming adrenal sympathetic activity over neural sympathetic activity. This combined central and autonomic nervous system profile contrasts with that registered in patients affected by hyperinsulinism, hypoglycemia, and bulimia syndrome which depends on the absolute predominance of neural sympathetic activity.

RETRACTED: Anorexia Nervosa Versus Hyperinsulinism: The Two Opposite Faces of the Coin——Therapeutic Effects of Neuropharmacological Manipulations

“…We previously demonstrated that there are not significant neuroendocrine + neuroautonomic differences between the two clinical types of AN (restricted and binge-eating type) [9]. The results presented in this therapeutical trial showed that a low dose of amantadine (100 mg/daily), a drug which abruptly suppresses adrenal sympathetic ac-tivity [9,11], was able to annul AN symptoms when it is administered 45 minutes before the main meal, and in addition, when it is administered 45 minutes before the oral glucose tolerance test (manuscript in preparation).…”

“…The understanding of the pathophysiology of the AN syndrome requires the information dealing with the hyperactivity of the adrenal sympathetic branch [9,12,13] which Table 1. Systolic, diastolic blood pressure (SBP, DBP), heart rate (HR), noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet-serotonin (p5-HT) and free serotonin (f5-HT) blood values, at 0 min (resting), 1 min (orthostasis) and 5 min (post-exercise) in 22 patients with anorexia nervosa during symptomatic (pre-treatment period = ANs) and during asymptomatic period (three months after treatment with amantadine 100 mg/daily = ANa).…”

“…The study included 22 female AN patients (10 restricted type and 12 binge-eating type) before treatment [9], and after three months of amantadine (100 mg daily) treatment. The diagnoses were made according to DSM-IV criteria.…”

“…According to the above and with our previous demonstration showing that the AN syndrome is underlain by maximal adrenal sympathetic overactivity [9], we decided to test the possible therapeutic effects of amantadine, a NMDA antagonist that interferes with the excitatory glutamate axons at the medullary C1(Ad) nuclei, in 22 patients affected by this pathophysiological disorder.…”

Calcium‐overloaded sympathetic preganglionic neurons in a case of severe sepsis with anorexia nervosa

“…Although her cardiac function was normal until the last admission, there is a possibility that her heart function reserve was reduced, for example, due to persisting AN. In patients with AN, several groups have reported that parasympathetic/sympathetic imbalance exists; there is a shift in cardiac autonomic function toward parasympathetic predominance, and adrenal sympathetic over‐activity with neural sympathetic underactivity …”