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A Journal on Internal Medicine

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Panminerva Medica 1998 March;40(1):13-7

language: English

GH ­response to ­GHRH com­bined ­with pyri­dos­tig­mine or argi­nine in dif­fer­ent con­di­tions of ­low somat­o­trope secre­tion in adult­hood: obesity ­and Cushing’s syn­drome in com­par­i­son ­with hypo­pi­tui­tar­ism

Procopio M., Maccario M., Savio P., Valetto M. R., Aimaretti G., Grottoli S., Oleandri S. E., Baffoni C., Tassone F., Arvat E., Camanni F., Ghigo E.

From the Division of Endocrinology Department of Internal Medicine University of Turin, Italy


Background. Diagnosing GH defi­cien­cy in ­adults is dif­fi­cult ­due to ­the ­age-relat­ed vari­a­tions of GH/­IGF-I ­axis ­and ­the influ­ence of nutri­tion. Nowadays, GH replace­ment is ­allowed ­for ­patients ­with GH ­peak to pro­voc­a­tive stim­u­li <3 μg/L. Somatotrope insuf­fi­cien­cy is ­present in hypo­pi­tui­tar­ism ­but ­also in obes­ity ­and hyper­cor­ti­so­lism. However, to eval­u­ate GH insuf­fi­cien­cy in ­adults is dif­fi­cult ­due to vari­a­tions of GH ­and ­IGF-I lev­els as func­tion of ­age ­and nutri­tion stat­us.
Methods. We ­aimed to ver­i­fy ­the GH ­response to ­GHRH (1 μg/kg iv) com­bined ­with pyri­dos­tig­mine (PD, 120 mg po) or argi­nine (­ARG, 0.5 g/kg iv), in 26 hypo­pit­ui­tar­ic ­patients (GHD), in 11 ­obese wom­en (OB), in 8 wom­en ­with Cushing’s syn­drome (CS), ­and in 72 con­trol sub­jects (NS).
Results. ­IGF-l lev­els in ­GHD ­were low­er ­than ­those in OB (p<0.01) ­and in CS (p< 0.01) ­which, in ­turn, ­were low­er to ­those in NS (p<0.02). In NS, ­the GH ­peak respons­es to ­GHRH+PD ­and ­GHRH+­ARG ­were sim­i­lar ­and ­the min­i­mum nor­mal GH ­peak ­was 16.5 μg/L. ­GHD ­had GH respons­es sim­i­lar, low­er ­than ­those in NS (p<0.01) ­and ­always ­below ­the nor­mal lim­it. However, ­only 12/20 ­and 8/14 ­had ­peaks <3 μg/L; con­ven­tion­al­ly, ­below ­this lim­it ­severe GH defi­cien­cy is ­shown ­and rhGH replace­ment is ­allowed. In OB, ­the GH respons­es to ­GHRH+PD ­and ­GHRH+­ARG ­were sim­i­lar, low­er (p<0.01) ­and high­er (p<0.01) ­than ­those in NS ­and ­GHD, respec­tive­ly. Six ­out of 11 OB ­had GH ­peaks ­below ­the nor­mal lim­its ­but ­nobody <3 μg/L. In CS, ­the GH ­response to ­GHRH+PD ­was low­er ­than ­that to ­GHRH+­ARG (p<0.01); ­both ­these respons­es ­were low­er ­than ­those in NS (p<0.01) ­and ­even in OB (p<0.01) ­but high­er ­than ­those in ­GHD (p<0.01). All ­and 7/8 CS ­had GH ­peaks low­er ­than nor­mal lim­its ­after PD+­GHRH ­and ­ARG+­GHRH, respec­tive­ly ­while 6/8 ­showed GH ­peak <3 μg/L ­after PD+­GHRH ­but ­only 1 ­after ­ARG+­GHRH.
Conclusions. Present ­data dem­on­strate ­that ­the max­i­mal somat­o­trope secre­to­ry capac­ity is ­reduced in OB ­and ­even ­more in CS. From a diag­nos­tic ­point of ­view, PD+­GHRH ­and ­ARG+­GHRH ­tests dis­tin­guish OB ­from ­severe ­GHD. As hyper­cor­ti­so­lism ­impairs ­the activ­ity of chol­i­nes­te­rase inhib­i­tors, ­only ­ARG+­GHRH, ­but ­not PD+­GHRH is a reli­able ­test to ­explore ­the max­i­mal somat­o­trope secre­to­ry capac­ity in CS. Notably, ­even ­with ­the ­ARG+­GHRH ­test, in CS ­the max­i­mal somat­o­trope secre­to­ry capac­ity is some­times so ­reduced as to over­lap ­with ­that of ­severe ­GHD.

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