Avaliação auxológica e reavaliação do Eixo GH-IGF-1 em pacientes com deficiência de GH na infância, após o término do tratamento com hormônios de crescimento e recombinante

Abstract

Resumo: Pacientes com diagnostico de deficiencia de hormonio de crescimento na infancia (GHD) devem ser retestados apos o tratamento, pois nem todos persistem com GHD. Objetivos: Fazer avaliacao auxologica, reavaliar o eixo GH-IGF-1 e a presenca de outras deficiencias hormonais, em pacientes com GHD de inicio na infancia. Material e Metodos: Estudoretrospectivo e prospectivo de 47 pacientes (32 do sexo masculino) atendidos na UEP do HCUFPR, com diagnostico de GHD na infancia, apos o tratamento com RhGH. Realizada revisao dos prontuarios, avaliacao clinica e laboratorial (GH com ITT, IGF-1, TSH, T4T, LH, FSH, prolactina, cortisol, testosterona e estradiol). Resultados: Na infancia 57% dos pacientes apresentavam MPHD (deficiencia hipofisaria multipla), 43% GHD isolada e 91% GHD idiopatica. No inicio do tratamento a idade cronologica (IC) era de 12,68 } 3,03, escore-Z da estatura de -3,86 } 1,57, escore-Z da estatura alvo (EA) de -0,91 } 0,82, idade ossea (IO) de 9,58 } 3,6 (meninos) e de 9,31 } 3,48 (meninas); 60% eram pre-puberes. A duracao do tratamento foi de 4,51 } 2,42 anos e a dose de RhGH foi de 0,23 } 0,02 mg/kg/semana. Final do tratamento: IC foi de 17,34 } 2,17, IO foi de 14,92 } 1,12 (meninos) e de 13,75 } 1,06 (meninas) e escore-Z da estatura foi de -1,45 } 1,27. Avaliacao atual: IC foi de 20,6 } 3,13, escore-Z da estatura final foi de -1,23 } 1,24, diferenca entre escores-Z da estatura final e EA foi de -0,34 } 1,38. Em 44% dos pacientes o escore-Z da estatura final era . EA. Nao houve diferenca entre escores- Z da estatura final e da EA (p = 0,225).. Avaliacao laboratorial: pico de GH < 5 ng/ml no ITT em 35/47 pacientes (74%), IGF-1 baixo em 34/47 (72%), pico de GH < 5 ng/ml e IGF-1 baixo concomitantes em 33/47 (70%); MPHD ocorreu em 27/34 (79%) e GHD isolada em 7/34 (21%). Pacientes com persistencia de GHD tinham menor escore-Z da estatura no inicio do tratamento (p < 0,001) e maior velocidade de crescimento no primeiro ano de tratamento (p = 0,002), ganho de escore-Z de estatura no primeiro ano de ratamento (p = 0,024), diferenca entre escores-Z da estatura final e no inicio do tratamento (p = 0,002) que os sem GHD. Pacientes com MPHD apresentaram diferenca entre escores-Z da estatura final e no inicio do tratamento maior que os com GHD isolada (p = 0,038). Conclusoes: a) cerca de 50% dos pacientes atingiram seu potencial genetico de estatura; b) 72% dos pacientes persistem com GHD; c) valores de IGF-1 e icos de GH no ITT foram concordantes em 94% os pacientes.

Abstract: Patients with childhood onset growth hormone deficiency (GHD) must be re-evaluated after GH treatment to confirm GHD in adulthood. Aims: to evaluate auxological parameters, reevaluate GH-IGF-1 axis and presence of associated hormonal deficiencies, in patients with childhood onset GHD. Patients and Methods: evaluation of 47 patients (32 males) followed at the Pediatric Endocrinology Unit of the Federal University of Parana Clinics Hospital, with GHD, after the completion of RhGH treatment. Medical records, prospective medical history, physical exam, and auxological data were obtained. GH secretion on insulin tolerance test, IGF-1, TSH, TT4, cortisol, LH, FSH, prolactin, testosterone and estradiol were measured. Results: Most patients (91%) had idiopathic GHD; 57% had multiple pituitary hormonal deficiencies (MPHD) and 43% had isolated GHD diagnosed during infancy. At start of treatment chronological age (CA) was 12.68 } 3.03 yr, H-SDS -3.86 } 1.57, bone age (BA) was 9.58 } 3.6 yr (boys) and 9.31 } 3.48 (girls); 60% ere prepubertal. Duration of treatment was 4.51 } 2.42 yr and RhGH dose was 0.23 } 0.02 mg/kg/wk. At the end of treatment: CA was 17.34 } 2.17, BA 14.92 } 1.12 (boys) and 13.75 } 1.06 (girls) and H-SDS -1.45 } 1.27. Prospective data: CA was 20.6 } 3.13, final height (FH)-SDS was -1.23 } 1.24, difference between FH-SDS and TH-SDS was -0.34 } 1.38; 44% of patients achieved FH-SDS . TH-SDS. No significant difference was found between FH-SDS and TH-SDS (p = 0.225). Laboratory evaluation: GH peak < 5 ng/ml in 35/47 (74%) patients, low IGF-1 in 34/47 (72%) and concordant GH peak < 5 ng/ml and low IGF-1 33/47 (70%). At reevaluation, 79% of patients with confirmed GHD had MPHD and 21% had isolated GHD. Patients with persistent GHD had lower H-SDS at the start of treatment (p< 0,001) whereas HV during first yr of treatment (p = 0,002), H-SDS gain during first yr of treatment (p = 0.024), difference between FH-SDS and H-SDS at the start of treatment (p = 0,002) were significantly higher than those without GHD at retesting. Difference between FH-SDS and H-SDS at the start of treatment was higher in M HD patients than those with isolated GHD (p = 0.038). Conclusions: a) about 50% of patients achieved their genetic potential height; b) GHD was confirmed in 72% of patients at retesting and, c) IGF-1 and GH peak levels were concordant in 94% of patients.