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Panminerva Medica 1998 June;40(2):103-6


lingua: Inglese

IGF-1 and IGFBP-3 in congenital and acquired hypothyroidism after long term replacement treatment

Bona G., Rapa A., Boccardo G.*, Silvestro L.*, Chiorboli E.

From the Department of Medical Sciences Pediatric Section of Novara, University of Turin, Italy * Department of Pediatric and Adolescent Sciences University of Turin, Turin, Italy


Background. Thyroid hor­mones are ­involved in the reg­u­la­tion of the GH/IGF ­axis. Hypothyroidism is asso­ciat­ed ­with a reduc­tion in GH pul­sa­til­ity and in GH-­response to stim­u­la­to­ry ­tests. In hypo­thy­roid­ism, ser­um lev­els of IGF-1 and ­IGFBP-3 ­fall and ­these chang­es are ­reversed ­after ­short ­term replace­ment ­with L-T4. This ­study was under­tak­en to deter­mine the ­effect of ­long ­term replace­ment ther­a­py ­with T4 in IGF-1 and ­IGFBP-3 ser­um lev­els.
­Methods. The ­study includ­ed 12 ­patients affect­ed ­with hypo­thy­roid­ism and in replace­ment treat­ment ­with T4. They ­were divid­ed into 3 ­groups accord­ing to age at the begin­ning of treat­ment. Group A con­sist­ed of 4 pre-puber­tal sub­jects ­with Congenital Hypothyroidism (CH) diag­nosed ­with neo­na­tal screen­ing, ­where T4 treat­ment was start­ed with­in 15 ­days of ­life. Group B con­sist­ed of 5 ­young ­adults ­where CH was clin­i­cal­ly diag­nosed at the ­median age of 6 ­months and replace­ment ther­a­py start­ed at ­this age. Group C con­sist­ed of 3 sub­jects affect­ed ­with hypo­thy­roid­ism sec­on­dary to thyr­oid­itis ­where diag­no­sis and replace­ment treat­ment ­were ­delayed at age 11,12 and 14 respec­tive­ly. All sub­jects ­were ­matched ­with a con­trol of the ­same age, sex, ­weight and puber­tal ­stage.
­Results. FT3, FT4 and TSH ­were in the nor­mal ­range ­both in ­patients and in con­trols. No cor­re­la­tion was ­found ­between FT3 or FT4 and IGF-1 or ­IGFBP-3 ser­um lev­els. IGF-1 ser­um lev­els in ­group A (198±122 ng/ml) ­were sig­nif­i­cant­ly low­er ­than ­that in ­group B (624±105, p<0.001) and in ­group C (649±98, p=0.003). ­IGFBP-3 ser­um lev­els in ­group A (1.98±0.56 µg/ml) ­were sig­nif­i­cant­ly low­er ­than in ­group B (3.65±1.10, p=0.03) and in ­group C (4.13±0.49, p=0.003). The ­increase in IGF-1 and ­IGFBP-3 lev­els was ­seen ­also in con­trol ­groups B and C ­when com­pared ­with con­trol ­group A. IGF-1 and ­IGFBP-3 ­were pos­i­tive­ly cor­re­lat­ed ­with age ­both in ­patients and in con­trols. A lin­e­ar cor­re­la­tion was ­found ­between IGF-1 and ­IGFBP-3 ­which was pos­i­tive for con­trols (r=0.946, p<0.001) and ­patient ­group A and B (r=0.839, p=0.005) but tend­ed to be neg­a­tive for ­patient ­group C (r=-0.65, n.s.).
Conclusions. Our ­data dem­on­strate ­that ­long ­term replace­ment ther­a­py in chil­dren ­with hypo­thy­roid­ism is asso­ciat­ed ­with a phys­io­log­i­cal ­increase in IGF-1 and ­IGFBP-3. The pos­i­tive cor­re­la­tion ­between IGF-1 and ­IGFBP-3 lev­els in ­group A and B con­firm the effi­ca­cy of ­long ­term replace­ment treat­ment on the IGF-1/BP-3 ­axis in pre-and ­post-puber­tal ­patients treat­ed for CH. However, ­this cor­re­la­tion tend­ed to be neg­a­tive in ­patients ­with hypo­thy­roid­ism sec­on­dary to thyr­oid­itis, sug­gest­ing ­that the ­cause of thy­roid insuf­fi­cien­cy and/or the age at the begin­ning of replace­ment ther­a­py may ­have a ­role in the ­post-puber­tal hor­mo­nal stat­us in IGF-1 and ­IGFBP-3 bal­ance.

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