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Doctoral Thesis
DOI
https://doi.org/10.11606/T.5.2007.tde-24102007-112651
Document
Author
Full name
Maria Estela Justamante de Faria
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2007
Supervisor
Committee
Mendonça, Berenice Bilharinho de (President)
Bronstein, Marcello Delano
Carvalho, Deocleciano da Silva
Francesco, Renata Cantisani di
Siqueira, José Tadeu Tesseroli de
Title in Portuguese
Avaliação do crescimento craniofacial e das extremidades de pacientes com deficiência de hormônio de crescimento ou síndrome de Turner em tratamento prolongado com hormônio de crescimento
Keywords in Portuguese
Crânio/crescimento & desenvolvimento
Hipopituitarismo
Hormônio de crescimento/deficiência
Hormônio de crescimento/uso terapêutico
Síndrome de Turner
Abstract in Portuguese
INTRODUÇÃO: Pacientes com deficiência de GH e síndrome de Turner, associados a baixa estatura, são beneficiados com o tratamento com GH. Há controvérsias sobre a atuação deletéria do GH no crescimento craniofacial, porém a maioria dos trabalhos é retrospectiva. Nosso objetivo foi realizar estudo prospectivo para avaliar o crescimento craniofacial de pacientes em tratamento com GH e o possível desenvolvimento de traços acromegálicos. CASUÍSTICA: 30 pacientes com idade cronológica de 4,6 a 23 anos e idade óssea de 1,5 a 13 anos divididos em 3 grupos baseados no diagnóstico e uso de GH: grupo 1- pacientes virgem de tratamento com GH portadores de hipopituitarismo e deficiência isolada (n=6); grupo 2: pacientes já em tratamento com GH: portadores de hipopituitarismo e deficiência isolada (n=16); grupo 3: pacientes com síndrome de Turner em tratamento com GH (n=8). A dose do GH utilizada foi de 0.1 a 0.15 U/kg/dia, via subcutânea, à noite, por 2 a 11 anos. MÉTODOS: medidas antropométricas (altura, pés e mãos), radiografia panorâmica, telerradiografia seguida pela análise cefalométrica de Ricketts e medidas lineares da base do crânio, altura facial, terço inferior da face, mandíbula e maxila, e fotografia facial de frente e perfil anualmente, por no mínimo 3 anos. As medidas lineares citadas foram comparadas com a média da população brasileira e entre si para avaliar o desenvolvimento craniofacial individual. As medidas de mãos e pés foram comparadas com atlas de morfometria e consideradas alteradas quando >P97. Os níveis de IGF1 e IGFBP3 foram mensurados a cada 6 meses para adequação da dose de GH. Os resultados foram analisados estatisticamente tomando-se como significantes valores de p<0,05. RESULTADOS: grupos 1 e 2 (deficiência isolada de GH ou hipopituitarismo): 3 pacientes com perfil desarmonioso obtiveram harmonia, 2 pacientes devido ao crescimento mandibular e um paciente devido ao crescimento maxilar, nenhum paciente desenvolveu desarmonia facial; observamos aumento significante da base posterior do crânio, mandíbula e terço inferior da face (p<0,05). Grupo 3 (síndrome de Turner): 2 pacientes com face desarmoniosa obtiveram harmonia, devido ao crescimento mandibular e nenhuma paciente desenvolveu desarmonia facial. Todos os pacientes, quando comparadas a análise cefalométrica de Ricketts inicial e final, mantiveram o mesmo padrão de crescimento facial. Observamos aumento das mãos em 2 pacientes (1 do sexo masculino com deficiência de GH e outra com síndrome de Turner), enquanto que o aumento dos pés foi observado em 50% das pacientes com síndrome de Turner e em 32% dos pacientes com deficiência de GH. CONCLUSÕES: A comparação das medidas cefalométricas do grupo de pacientes com deficiência de GH, virgem de tratamento, demonstrou maior atuação do GH no crescimento da base posterior do crânio e mandíbula; todos os pacientes mantiveram o mesmo padrão de crescimento craniofacial durante o acompanhamento; não houve correlação estatisticamente significante entre as medidas cefalométricas e a harmonia da face, portanto a associação dos métodos de cefalometria e análise facial por fotografia é necessária para avaliar a atuação do GH no crescimento craniofacial, houve melhora da harmonia facial em 28% dos pacientes retrognatas, devido ao crescimento mandibular, portanto pacientes retrognatas podem ser beneficiados com o tratamento com GH; não observamos desenvolvimento de desproporções faciais e nenhum paciente desenvolveu desarmonia facial no decorrer do tratamento com doses padronizadas de GH. Observamos, no entanto, aumento das extremidades, principalmente dos pés.
Title in English
Craniofacial and extremities growth evaluation of patients with GH deficiency or Turner syndrome during long-term growth hormone treatment
Keywords in English
Growth hormone/deficiency
Growth hormone/therapeutic use
Hypopituitarism
Skull/growth & development
Turner syndrome
Abstract in English
INTRODUCTION: Patients with GH deficiency and Turner syndrome, associated to short stature can benefit from GH treatment. There are controversies on the deleterious effect of GH on craniofacial growth; however, most of the studies are retrospective. Our objective was to carry out a prospective study to evaluate the craniofacial growth of patients in treatment with GH and the possible development of acromegalic features. PATIENTS: 30 patients with chronological age of 4.6 to 23 years and bone age of 1.5 to 13 years divided in 3 groups based on the diagnosis and GH use: group 1- patients with hypopituitarism and isolated GH deficiency naïve to GH treatment (n=6); group 2: patients with hypopituitarism and isolated GH deficiency (n=16) and group 3: patients with Turner syndrome, both already on GH treatment (n=8). GH treatment (0.1 to 0.15 U/kg/day, subcutaneously) was carried out at the night for 2 to 11 years. METHODS: Anthropometrical (height, hands and feet) measurements, panoramic x-ray, teleradiography followed by cephalometric analysis according to Ricketts and linear measurements of the skull base, facial height, lower third of the face, lower jaw and maxilla, and frontal and profile analysis of face by photography were made annually, for at least 3 years. The mentioned linear measurements were compared with the average Brazilian population and among themselves to evaluate the individual craniofacial development. The hand and foot size measurements were compared with a morphometric atlas and were considered increased when >P97. The levels of IGF1 and IGFBP3 were measured each 6 months for GH dose adequacy. The results were analyzed statistically and p values < 0.05 were considered statistically significant. RESULTS: Group 1 and 2 with isolated GH deficiency or hypopituitarism: 3 patients with disharmonious profile attained harmony, 2 due to the mandibular growth and 1 patient due to maxillary growth; no patient developed facial disharmony; we observed a significant increase of the posterior skull base, inferior jaw and lower third of the face (P<0.05). Group 3 with Turner syndrome: 2 patients with facial disharmony obtained harmony due to the mandibular growth and no patient developed facial disharmony. All of the patients maintained the same pattern of facial growth when the initial and final cephalometric analyses according to Ricketts were compared. Hand size increase was observed in 2 patients (1 with GH deficiency and another with Turner syndrome); foot size increase was observed in 50% of the patients with Turner syndrome and in 32% of the patients with GH deficiency. CONCLUSIONS: The comparison of the cephalometric measurements of the group with GH deficiency naïve to GH treatment, demonstrated a greater GH effect on the growth of the posterior skull base and jaw; all of the patients had kept the same craniofacial growth pattern during the follow-up; there was no statistically significant correlation between the cephalometric measurements and facial harmony; therefore, the association of the methods of cephalometric and facial analysis through photography is mandatory to evaluate the effect of GH on craniofacial growth. There was an improvement in the facial harmony in 28% of the retrognathic patients due to mandibular growth; therefore, patients with mandibular retrognathism can benefit from GH treatment. None of the patients treated with standardized doses of GH developed facial disharmony during treatment. We observed however, an increase of the extremities, mainly of the feet.
 
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Publishing Date
2007-11-06
 
WARNING: The material described below relates to works resulting from this thesis or dissertation. The contents of these works are the author's responsibility.
  • CARVALHO, L. R. S., et al. Acromegalic features in growth hormone (GH) deficient patients after long-term GH therapy [doi:10.1046/j.1365-2265.2003.01899.x]. Clinical Endocrinology (Oxford) [online], 2003, vol. 59, nº 6, p. 788-792.
  • CARVALHO, L. R. S., FARIA, M. E. J., and MENDONCA BB. Craniofacial features with growth hormone treatment [doi:10.1016/j.jpeds.2004.08.032]. The Journal of Pediatrics [online], 2005, vol. 146, nº 2, p. 295-296.
  • FARIA, M. E. J., et al. Analysis of craniofacial and extremity growth in patients with growth hormone deficiency during growth hormone therapy [doi:10.1159/000197875]. Hormone Research [online], 2009, vol. 71, p. 173-177.
  • FARIA, M. E. J., et al. Analysis of craniofacial and extremity growth in GH deficient patients during growth hormone therapy. In The Endocrine Society´s 90th Annual Meeting, San Francisco, 2008. Program & Abstracts., 2008. Abstract.
  • FARIA, M. E. J., et al. Craniofacial and Extremity Growth Evaluation in Patients with Turner Syndrome during Growth Hormone Therapy. In The Endocrine Society 91st Annual Meeting - ENDO2009, Washington/DC, 2009. Abstracts 2 View - ENDO2009., 2009. Abstract.
  • FARIA, M. E. J., et al. Craniofacial growth of patients with Turner syndrome undergoing growth hormone (GH) treatment. In Proceedings of the 19th Congresso of the IADH, Santos, 2008. Journal of Disability and Oral Health., 2008. Abstract.
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