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.Because free IGF-I is the biologically active form[265], its reduction would be consistent with the decreased sensitivity ofsymptomatic anorexics to GH.However, free IGF-I levels are reported to benormal in anorexia nervosa [266].The GH response to GH-releasing hormone (GHRH) is increased inanorexic patients [30,267,268] and the decrease in peripheral IGF-I may playa role in this phenomenon, because this somatomedin exerts a negativefeedback on GH secretion.It has been demonstrated recently that theadministration of recombinant human IGF-I in anorexic patients signifi-cantly reduces basal GH levels and decreases, but does not restore, the GHresponse to exogenous GHRH [269].This finding suggests that, besides thePHYSICAL COMPLICATIONS AND ABERRATIONS: A REVIEW ___________________ 159reduced negative feedback of peripheral IGF-I, a central dysregulation ofGH secretion also occurs in anorexia nervosa.In particular, the hyperre-sponsiveness of GH to GHRH is not inhibited by the cholinergic antagonistpirenzepine [270], nor is it increased by the cholinergic agonist pyrido-stigmine [271,272].Because acetylcholine has a stimulatory action onhypothalamic somatostatin, these findings support the idea that GHhypersecretion in anorexia nervosa is partially linked to a reducedsomatostatin tone because of an increased hypothalamic cholinergic activity[273].However, assessment of somatostatin secretion has providedconflicting results, because either low or normal levels of this hormonehave been found in symptomatic anorexic patients [274,275].Paradoxicalresponses of GH to both GnRH and thyrotrophin-releasing hormone (TRH)[276 278] and a lack of suppression of the GH response to GHRH by CRFadministration [279] occur in anorexia nervosa.Finally, GH responses toinsulin, clonidine, L-dopa and apomorphine are lower than normal inunderweight anorexics [30,280], suggesting a dysfunction in both thenoradrenergic and dopaminergic modulation of GH secretion.It seems evident that in underweight anorexics peripheral mechanisms,such as the decreased IGF-I production, resulting from both the reducedcalorie intake and concomitant receptor alterations, increase GH secretionbecause of impairment of the negative regulatory feedback.Concomitantly,primary or secondary hypothalamic or supra-hypothalamic changes mayfurther affect GH production.From a clinical point of view, the dysregulation of the hypothalamic GHIGF-I axis may be involved in the pathogenesis of osteopenia, because IGF-Ihas a trophic effect on the bone.Moreover, in prepubertal subjects, the  resistance  to GH may be responsible for a delay or a stop in the growth,with the possibility that when these alterations resolve the final height belower than that determined genetically [281].The recently availablerecombinant human IGF-I or GH could have therapeutic applications inanorexic patients in order to prevent bone loss or bone fractures and tofacilitate a more rapid metabolic recovery.In this regard, Grinspoon et al.[265,282] have reported recently that the administration of recombinanthuman IGF-I in severely osteopenic anorexic women increases the markersof bone turnover in the short term and ameliorates bone density in themedium term (9 months); the latter effect is potentiated by concomitant oralcontraceptive administration.Moreover, Hill et al.[283] have shown thatanorexic patients treated with recombinant human GH achieve medical/cardiovascular stability more rapidly.Both increased and normal baseline GH levels with a normal circadianrhythm are reported in individuals with bulimia nervosa [30,276,284,285].Circulating IGF-I, instead, is reduced [286,287].Growth hormone responsesto clonidine or apomorphine are blunted or normal [30,284,288] and, as with160 ___________________________________________________________________________ EATING DISORDERSanorexia nervosa, the administration of TRH induces an abnormal increasein GH secretion that persists after the normalization of eating behaviour[255,276,284].Hypothalamic Pituitary Thyroid AxisDecreased circulating levels of triiodothyronine (T3) with increasedconcentrations of reversed T3 (rT3), which is biologically inactive, andnormal thyroxine (T4) and thyroxine-stimulating hormone (TSH) levels arecommon in symptomatic anorexic patients [289,290] [ Pobierz całość w formacie PDF ]