Humor

Libro de Visitas

Revision of Literature and other considerations on the nervous anorexy.

Porras Obeso, Salvador; Ortiz Díaz, Francisco; Gavilán Martín, Cristina; Ortuño Adán, Encarnación; Vidal Peracho, Concepción.
General hospital of Elda (Alicante, ESPAÑA-UE).

DISCUSSION:

The nutritional behavior is governed by numerous biological, psychological and sociological factors. The disturbances of the nutritional behavior have a volitivo beginning followed of a loss of control modulated by the undernourishment and the consequent biological changes.

The actions of monoamines on the nutritional behavior have been clarified in physiology animal (H. Saltiel 1989, Dark brown JF 1990), without it is possible to be extrapolated to the human pathology. It is known that receiving beta-adrene'rgicos and dopaminérgicos of the lateral hypothalamus reduce the food taking, mainly in damage of proteins. Receivers alpha-noradrene'rgicos and serotoninérgicos are antagonistic in the nucleus to paraventricular of the average hypothalamus, reducing or increasing, respectively the satiety, mainly in which it talks about carbon hydrates. In the last years it has been stated the presence of upheavals of the serotoninérgica neurotransmisión in a great variety of psychiatric pictures in which the depressive upheavals are included, the aggressive conduct, the suicidal conduct, the alcoholism, the alterations of the nourishing conduct and the upheavals of anguish among others from collected data so much in investigation animal as in clinical investigation with drugs that modify the serotoninérgica neurotransmisión. It is possible that in these upheavals a shared neurobiológica disfunción exists. Neuroanatómicas evidences exist that demonstrate as the located serotoninérgicas neurons in the nuclei of rafe have an inhibiting effect on the activity of diverse cerebral areas implied in the mediation of the anxiety like locus ceruleus, the tonsil and the seahorse. The anxiety is present in all the mentioned pictures.

The distribution of histamina (IT HAS) cerebral that is very similar in humans and rodents, with the Maxima located cerebral concentration in later hypothalamus (2-4 nmol/g), in where finds the producing neurons of the histaminérgico system (Cacabelos ET al.1989). In areas neuroendocrinas like average eminence (4-6 nmol/g) and neurohipófisis (3-7 nmol/g), the levels of HAVE exceed the hipotalámica concentration. Several explanations exist to justify the increase of HAS in the AN. One of the functions of IS it is the regulation of the rate dream-watch, in where it seems that THERE IS it exerts a modulador effect on the arousal answers. In the AN frequently there are upheavals of the dream. Also one has seen that THERE IS can it

to aggravate the depressive symptoms in the patients with affective upheavals. These effects could be in favor in relation to hipotálamo-hipocámpicas eferentes routes and hipotálamo-accumbeus, as well as of afferent fibers that coming from the infralímbica division of the prefrontal area (area 25 of Brodmann) arrive until the later hypothalamus to regulate to the histaminérgicas neurons. THERE IS hipotalámica would be increased in hypothalamus in the AN, similarly that is it in the terminal patients of disease of Alzheimer and what it would explain the malnutrición.

Evidences exist of which GRF and SS exert antagonistic effects on IS it neuronal (Cacabelos ET al.1988), being the GRF a estimulador factor and the SS an inhibiting factor. The growth hormone (GH) is less respondent to the stimulation with GRF (Growth Hormone-Releasing Factor) in old adults and who in young individuals of different species (Cacabelos 1986). This partial insensibilidad of GH to GRF could be in favor half-full of a hypertone of SS and a deficient activity adenilciclasa adenohipofisaria. One knows that the answer of GH to GRF in experimentation in hipófisis of chickens decreases when the concentrations are increased of diverse catecholamines (Donoghue 1990). The answer of GH to GRF very is diminished in our casuistry (Clubs 1998). After being dealt with antihistamine (H1) and to have gained a discreet weight there is hyperanswer of GH to GRF. These facts suggest in the AN the GRF is used fundamentally in producing HAS of selective form and noncGh. A hypertone of SS would block both routes, reason why it is very possible that the excess of histamina once blocked their postsinápticos receivers is the person in charge of feed back intrahipotalámico to compensate the GH deficit autolimitando the clinical picture. One considers to us if the natural evolution of the AN without intervention some will not be a picture limited by a hipersensibilización of histamínicos receivers that would end up causing the same mechanism compensating the GH deficit. This hypothesis seems to be in contradiction with the absence of communications on the spontaneous remission of the AN, but it does not go against treated cases of AN that they stay during years in situation limit, not autoperpetuando itself around a critical weight.

Of empirical form systematically they are used antihistamine in the psychogenic treatment of the AN. The antidepressant association does not demonstrate significant differences in the evolution and it even delays the menorrea, although they are continued using with a smaller frequency the use of ciproheptadina and in similar frequency that the sedative neurolépticos. These are not only active in several systems (noradrenérgico, dopaminérgico, colinérgico and serotoninérgico), but that also behave like antihistamine and antitriptaminérgicos. The therapeutic farmacológica seems to go oriented to interfere with concrete monoaminérgicas routes which would be correlated with precise conductales modifications to the time which they would favor hipo or hipersensibilización of sinápticos receivers to the rest of monoamines.

Interactions between monoamines and different peptides exist in addition, between which the galanina seems to have an important function that produces its greater action in the average portion of the knot

to paraventricular (Leibowitz 1989). The pathological saciamiento that occurs in the nervous anorexy could be associated to endogenous opiate peptides (Armstrong 1990, Baranowska 1990) and would be reversible by naloxona, which has not been verified.

At the moment the peripheral nervous control of the nourishing ingestion modulated by the vague nerve from esophagus to intestine, as well as the precocious sensible visual reconnaissances and orofaríngeas to the organolépticas properties of foods is being accepted (Jeanningros R.1989).

Between the biological aspects of the nervous anorexy an stimulation of the center of the satiety (ventromedial hypothalamus) triggers an inhibition of the appetite with an increase of catabolic answers, whereas an injury of the lateral hipotalámico center, related to the beginning of the ingestion triggers one hipofagia. The sensation of hunger and satiety is to explain by diverse theories in which they would be implied glucemia, protein imbalances (aminostática theory), sensorial temperature, stimuli, hour habits, affective upheavals, sociocultural atmosphere, etc.

Of the theories of the location of the injury in hypothalamus one has gone to the theory of the disfunción of systems of neurotransmisión in general and it is not chance that the hypothalamus is destination exit or passage of the routes of these systems.

At the present moment the hypotheses that they relate to the serotoninérgico system to the different processes that regulate the weight are based by a side on the finding on experimentation animal of

serotonin in the center of the satiety and by another one in the results of the serotoninérgicos drugs that selectively reduce the carbohydrate ingestion in the diet, as well as

the answer of gain of weight with ciproheptadina and metisergida, both antagonists of serotonin.

The answer of GH to GRF seems to be modulated by different factors (Ferrández To 1987). With object to value that systems are implied in the somatostatina production it has found that the tone of the somatostatina is regulated by the adrenérgico system beta, which it implies that the beta blockade inhibits the somatostatina production (Richardson SB 1990) and would increase the secretion of GH. In a brief bibliographical revision we found that the answer of GH to GRF in the AN is not blocked when pirenzepine is used (blocking selective of muscarínicos colinérgicos receivers), whereas control is blocked in the group (Breastcollar, M.1990, Breastcollar, M.1991, Tamai, H.1990) what suggests these receivers are implied in the GH secretion. The GH answer appears increased in the AN in relation to the group control, but it does not seem related to the weight (Lomeo, A.1989). The hyperanswer of GH to GRF is exaggerated in the AN, but hiperglucemia reduces the answer in normal subjects, while

hardly it diminishes it in the acute phase of mental anorexy (Breastcollar, M.1991, Tamai 1991). The hyperanswer of GH is significant in AN when it is stimulated with GRF and not with the clonidina stimulus which suggests a adrenorreceptor subsensitivity of alpha-2 (Brambilla, F.1989, Devesa J.1990, Nussbaum 1990). In a sample of 23 anoréxicas, single in 8 was hyperanswer of GH to GRF (44) (Masuda, A.1988). The answer of GH to GRF in AN is similar to the group control when receiving estrogénicos have been blocked (they tamoxifen) (Casanueva FF.1987). The nutricional state and the corporal weight influence in the answer of GH to GRF (Of Marinis 1988, Méndez 1989).

Our study sample that in the nervous anorexy, the studied population far below presented/displayed a GH answer after stimulus with GRF to the detected one in healthy population. We have not found similar results in the reviewed bibliography. Until these moments one has been to study as they are the different factors that modify the answer of GH to different

stimuli (saline serum, estrogen glucosado, levels, nutricional state, corporal, apomorfina, clonidina weight) between which include the selective agonists of the receivers alpha-2

power stations. The results are different even when the selective stimulation with GRF is used. Brambilla finds in 21 anoréxicas patients that the GH answer significantly more is elevated than in 10 cases of healthy population when the stimulation with GRF is made and the increase when stimulating with clonidina is not significant. All the anoréxicas presented/displayed smaller depressive sintomatología, which suggests it dose of used clonidina was low, or that the main diagnosis era of depression.

In our sample we have excluded the anoréxicas patients who presented/displayed an affective upheaval. This exclusion of the affective upheavals is forced because the bibliography on

answer of GH to GRF and clonidina in AN without considering the affective state in general is at least of hyperanswer in a third of the samples even when estimuladores of the liberation of GH different from the GRF are used. On the other hand in a retrospective study of the anoréxicos patients treated in our hospital (all women) we observed that they had been used antidepressing to average and high doses in the patients who presented/displayed hyperanswer of GH to the stimulation with GRF, reason why we both justified the exclusion in this work of cases with depression.

We concluded whereupon, although not yet we have sufficient casuistry on the upheavals of the feeding, in the case of the anorexy is to wait for an hipo-answer of GH to the stimulation with GRF whenever the following criteria are fulfilled: lost of a minimum weight, amenorrhoea in the woman of a minimum time, absence of the mental upheavals mentioned in DSM III-R and absence of a depressive upheaval. They would exist because critical values for the loss of weight and the definibles but hardly perhaps superposable time of amenorrhoea to the reflected ones as functional criteria of DSM III-R (15% of peso and minimum amenorrhoea of 3 months). If the diagnosis of nervous anorexy were present depressive sintomatología it would happen to occupy a secondary place.

We asked ourselves if a state marker cannot be the test of stimulation with GRF. By the results of our investigation with the obtaining of an hypoanswer of GH in

patients whose main diagnosis is the one of mental anorexy we think that it is a good marker. In order to confirm we studied it the phase of preanorexy, considering like so to all patient with criterion of anorexy including in the DSM III-R, that takes less than three months of evolution and that it does not have but of two amenorrhoeas. We found an answer of flattened GH to GRF what suggests lost it of weight by itself is not able to modify the GH answer, not needing a critical time evolution so that it is restored the hypoanswer.

That the test is a good marker of state it seems to be confirmed by the evolution of the patient. The hypoanswer of GH in the acute phase of the anorexy is standardized when it gains weight and long before which sends the amenorrhoea. The normalization of the GH answer very possibly happens with the gain of a critical weight still to define, thus at the moment we made the test in the acute phase at different moments with greater weights every time sending the hipo-answer when it has gained around a 10% what supposes a different nutricional state already.

Summarizing, all hyperanswer of GH to GRF in patient with clinic of nervous anorexy with all the criteria of DSM III-R and a doubtful sintomatología of affective upheaval must be included like such affective upheaval referred concretely the depression and therefore to be excluded from all casuistry that includes like main diagnosis the one of Nervous Anorexy, or to consider that two different types of anorexy exist: one hipo-responder and another hyperresponder, which is little probable.

The hipo-answer of GH to GRF in the acute anorexy we think that it is a biological criterion to make the diagnosis main of Nervous Anorexy. In opposite sense the hyperanswer of GH can be a biological criterion to simply make the diagnosis of a type different from anorexy or that the nutricional state has not passed a tactically important point from as there would be hipo-answer and not yet indicate a very severe state of undernourishment.

BIBLIOGRAPHY:

1. Henri Saltiel. Cerebral Monoaminas and nutritional behavior. Psychiatric Confrontations n.25-1989.

2. Dark brown JF; Olchovsky D; White JD; Leidy JW; Song J; Berelowitz M. Influence of food deprivation in the rat on hypothalamic expression of growth hormone-releasing factor and somatostatin. Endocrinology.1990 Nov;127 (5):2111-6.

3. Cacabelos R., Yamatodani To, Niigawa H., Hariguchi S., Tada K., Nishimura T., Wada H., Brandeis L., Pearson J.: Brain histamine in Alzheimer's disease. Meth Find Exp Clin Pharmacol 1989;11:353-360.

4. Cacabelos R., Niigawa H., Yamatodani To, Go'mez-Pan To, Nishimura T., Wada H.: Antagonistic effects of growth hormone-releasing factor and somatostanin on brain histamine. Endocrinology1988;122:1269-1276.

5. Cacabelos R., Niigawa H., Nishimura T.: Neuroendocrine system and aging brain. Gerontopsychiatry 1986;3:691-711.

6. Clubs S; Ortiz F; Sparrowhawk C; Ortuño E; Vidal C. preliminary Study on the answer of the hormone of growth to the stimulation with GRF (1-29)NH2 in the nervous anorexy. Papers of Jofré Father. http://www.medired.com/spcv/papeles/.

7. Donoghue DJ; Perez FM; Make shine like diamonds BS; Malamed S; Scanes Cg. Influence of catecholamines, prostaglandins and thyroid hormones on growth hormone secretion by chicken pituitary cells in vitro. Domest-Anim-Endocrinol. 1990 Jan;7 (1):35-42.

8. Leibowitz S.F.: Hipotalámicos neurotransmitters, hormones and nutritional behavior. Psychiatric Confrontations n.25-1989.

9. Armstrong JD; Esbenshade KL; Coffey TM; Heimer E; Campbell R; Mowles T. Opioid control of growth hormone in the suckled sow is primarily mediated thruogh growth hormone releasing factor. Domest-Anim-Endocrinol.1990 Apr; 7 (2):191-8.

10. Baranowska B: Plows disturbances in opioid and adrenergic systems involved in the hormonal dysfunction of nervosa anorexy? Psychoneuroendocrinology, 15 (5-6) 371-9/1990.

11. Jeanningros R.: Peripheral nervous control of the nourishing ingestion. Psychiatric Confrontations n.25-1989.

12. Ferrandez A; Arnal JM; Mayayo E; Vergara JM; Valdizan J; Advanced S; Guallar A; Phillips JA. Tests of study of the growth hormone secretion. Bring up to date. An. Esp. Pediatr., 27(1)41- 8/1987 Jul.

13. Richardson SB; Twente S. Inhibition of hypothalamic somatostatin release by beta-adrenergic antagonists. Endocrinology. 1990 Feb; 126 (2):1043-6.

14. It rolls M; Andreoni A; Belliti D; Ferdeghini M; Cristofani R; Mueller EE. Effects of cholinergic muscarinic antagonist pirenzepine on GH response to GHRH 1-40 in patients with nervosa anorexy. Endocrinol Exp, 24 (1-2) 195-204,1990 Sea.

15. It rolls M; Andreoni A; Belliti D; Cristofani R; Ferdeghini M; Mueller EE. Blockade of cholinergic muscarinic receptors by pirenzepine and GHRH-induced GH secretion in the acute and recovery phase of atypical nervosa anorexy and eating disorders.Biol.Psychiatry, 29 (11) 1079-91,1991 Jun 1.

16. Tamai H; Komaki G; Matsubayashi S; Kobayashi N; Mori K; Nakagawa T; Truong MP; Walter RM JR; Kumagai LF. Receiving Effect of cholinergic muscarinic blockade on human growth hormone (GH)-releasing hormone (1-44) induced GH secretion in nervous anorexy. J.Clin. Endocrinol.Metab, 70(3)738-41/1990 sea.

17. Lomeo A; Mazzocchi G; Sessarego P; Tower R; Delmonte P; Giusti M. Growth hormone and prolactin response to growth hormone releasing in nervosa anorexy. Recenti Prog.Med.80(11)569-73/1989 Nov.

18. It rolls M; Andreoni A; Belliti D; Ferdeghini M; Ferrannini And Failure of glucose infusion to suppress the exaggerated Gh response to GHRH in patients with nervosa anorexy. Biol.Psychiatry, 29 (11) 1079-91,1991 Jun 1.

19. Tamai H; Kiyohara K; Mukuta T; Kobayashi N; Komaki G; Nakagawa T; Kumagai LF; Aoki TT. Responses of growth hormone and cortisol to intravenous glucose loading test in patients with nervosa anorexy. Metabolism, 40 (1) 31-4,1991 Jan.

20. Brambilla F; Ferrari E; Cavagnini F; Zanoboni A; Massironi R; Catalano M; Cocchi D; Mueller EE. 2-adrenoceptor Alpha sensitivity in nervous anorexy: GH response to clonidine or GHRH stimulation.Biol Psychiatry, 25(3)256-64/1989 Feb 1.

21. Devesa J; Maple V; Lois N; Tresguerres JA; Lima L. Alpha 2-adrenergic agonism enhances the growth hormone (GH) response to GH-releasing hormone through an inhibition of hypothalamic somatostatin release in normal men. J-Clin-Endocrinol-Metab. 1990 Dec;71 (6): 1581-8.

22. Nussbaum MP; Blethen SL; Chasalow FI; Jacobson MS; Shenker TO GO. Blunted growth hormone responses to clonidine in adolescent girls with early for anorexy nervosa.Evidence an early hypothalamic defect. J.Adolesc.Health Care, 11 (2) 145-8,1990 Sea.

23. Masuda A; Shibasaki T; Hotta M; Suematsu H; Shizume K. abnormal Study on the mechanism of growth hormone (GH) secretion in anorexy nervosa:no evidence of involvement of to low somatomedin-C level in the abnormal GH secretion.J.Endocrinol Invest, 11(4) 297-302.

24. Casanueva FF; Flocks Cg; Burguera B; It files L; Muruais C; Tresguerres JA; Devesa J. Growth hormone and prolactin secretion to after growth hormone-releasing hormone administration, in nervous anorexy patients, normal controls and tamoxifen-pretreated volunteers. Clin. Endocrinol (Oxf), 27(5)517-23/1987 Nov.

25. Of Marinis L; Folli G; D'Amico C; Mancini A; Sambo P; Tofani A; Oradei A; Barbarino To Differential effects of feeding on the ultradian variatio of the growth hormone (GH) response to normal GH-releasing hormone in subjects and patients with obesity and nervosa anorexy. J.Clin.Endocrinol.Metab, 66(3)598-604/1988 Sea.

26. Mendez JP; Garcia E; Salt mines JL; Perez-Palaces G; Ulloa-Aguirre To nervosa Anorexia: endocrine function during the phases of body weight loss and recovery. Rev.Invest.Clin, 41 (4) 337-44,1989 Oct-DEC.