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      Puberdade precoce: dilemas no diagnóstico e tratamento

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          Abstract

          Novos critérios para o diagnóstico e tratamento da puberdade precoce (PP) central (GnRH-dependente) têm sido propostos. Frente a uma menina com desenvolvimento sexual precoce o médico deve considerar: 1) O que é o desenvolvimento puberal normal e quando ele se inicia? O início puberal em meninas normais aparentemente tem ocorrido cada vez mais cedo. A idade limite para o desenvolvimento puberal normal é de 9 anos nos meninos e 8 anos nas meninas. Entre 6 e 8 anos, muitas meninas apresentam sinais puberais isolados, associados apenas a discreto avanço da velocidade de crescimento (VC) e da idade óssea (IO). O quadro representa uma aceleração constitucional do crescimento e puberdade e não necessita tratamento. A puberdade precoce GnRH-dependente patológica cursa com progressão dos caracteres puberais, aumento significante da VC e avanço desproporcional da IO, determinando redução da estatura final prevista. 2) Quais os valores normais de LH e FSH? Com o advento de novas técnicas os valores do normal devem ser cuidadosamente interpretados. 3) Por que devemos tratar a PP? Devido à perda estatural e comprometimento psicossocial. 4) Todas as crianças com PP necessitam tratamento? Quem deve ser tratado? Apenas as crianças com PP que apresentam avanço significante da IO e da VC com previsão de perda da estatura final e resposta puberal do LH. A etiologia do processo é investigada com a RM de crânio. Deve ser tratada com agonistas hiperativos do GnRH. Pode-se utilizar leuprolide ou triptorelina, na dose de 3,75mg IM, uma vez a cada 4 semanas. Habitualmente, obtem-se bom controle dos caracteres puberais. 5) Quais são os resultados do tratamento? Os resultados sobre a estatura final dependem do diagnóstico e tratamento precoces, preferencialmente antes dos 6 anos, e praticamente não existem efeitos colaterais importantes. 6) Quando associar o GH? Durante o tratamento com GnRHa, parte dos pacientes apresenta grande redução da VC e intenso comprometimento da previsão estatural. Nesta situação, a associação com GH pode ser considerada.

          Translated abstract

          New criteria have been proposed for the diagnosis and treatment of patients with central precocious puberty (PP) (GnRH-dependent). In girls, breast and pubic hair development are occurring significantly earlier than previously suggested. Usually, the age limit to consider puberty as normal is 9 years for boys and 8 years for girls. Between ages 6 and 8 years, some girls show isolated telarche or pubarche with absent or slightly elevated growth velocity (GV) and bone age (BA). This represents a constitutional acceleration of growth and puberty, and when compared to familial target, it presents no influence on predicted final height. Long-term clinical follow-up is recommended, but usually no treatment is required. On the other hand, pathologic GnRH-dependent PP is associated to progressive pubertal manifestation, increased GV and accelerated bone maturation, with consequent negative impact on the final height. The age of clinical manifestation is variable, and in part dependent on the etiology. When starting between the ages 6 and 8 the puberty is rapidly progressive. The cause for early hypothalamic-pituitary activation should be investigated by cranial MR. GnRH-dependent PP is best treated with slow-release GnRH analogues (leuprolide or tryptorelin). The initial recommended dose is 3.75mg IM, every four weeks. With this schedule, pubertal characteristics are efficiently controlled. The results on final height are influenced by the age of diagnosis and therapy, and the best outcome is observed when treatment begins before the age of 6. During GnRHa therapy, some patients show intense decrease in GV and substantial reduction in predicted final height. In this condition, additional use of growth hormone should be considered.

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          Most cited references46

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          Secondary Sexual Characteristics and Menses in Young Girls Seen in Office Practice: A Study from the Pediatric Research in Office Settings Network

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            Reexamination of the Age Limit for Defining When Puberty Is Precocious in Girls in the United States: Implications for Evaluation and Treatment

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              Diagnostic value of fluorometric assays in the evaluation of precocious puberty.

              To establish normative data and determine the value of fluorometric AutoDELFIA assays (Wallac Oy) in the investigation of precocious puberty, we determined serum levels of LH, FSH, testosterone, and estradiol under basal and GnRH-stimulated conditions in 277 normal subjects at various pubertal stages and in 77 patients with precocious puberty. A substantial overlap was observed in basal and GnRH-stimulated gonadotropin levels in normal individuals of both sexes with pubertal Tanner stages 1 and 2. The 95th percentile of the normal prepubertal population was the cut-off limit between prepubertal and pubertal levels. These limits were 0.6 IU/L in both sexes for basal LH, 9.6 IU/L in boys and 6.9 IU/L in girls for peak LH after GnRH stimulation, 19 ng/dL in boys for basal testosterone, and 13.6 pg/mL in girls for basal estradiol. Basal and peak LH exceeding these limits were considered positive tests for the diagnosis of gonadotropin-dependent precocious puberty. According to these criteria, the sensitivities of basal and peak LH for the latter diagnosis were 71.4% and 100% in boys, and 62.7% and 92.2% in girls. The specificity and positive predicted value were 100% in both sexes for basal and peak LH levels. The negative predicted values for basal and peak LH were 62.5% and 100% in boys, and 40.6% and 76.5% in girls. Basal and GnRH-stimulated FSH levels overlapped among the various pubertal stages in normal subjects and were, in general, not helpful in the differential diagnosis of precocious puberty. In conclusion, basal LH levels were sufficient to establish the diagnosis of gonadotropin-dependent precocious puberty in 71.4% of boys and 62.7% of girls. In the remaining patients, a GnRH stimulation test was still necessary to confirm this diagnosis. Finally, suppressed LH and FSH levels after GnRH stimulation indicate gonadotropin-independent sexual steroid production.
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                Author and article information

                Journal
                abem
                Arquivos Brasileiros de Endocrinologia & Metabologia
                Arq Bras Endocrinol Metab
                Sociedade Brasileira de Endocrinologia e Metabologia (São Paulo, SP, Brazil )
                1677-9487
                August 2001
                : 45
                : 4
                : 321-330
                Affiliations
                [01] São Paulo SP orgnameIrmandade da Santa Casa de Misericórdia de São Paulo orgdiv1Departamento de Pediatria orgdiv2Unidade de Endocrinologia Pediátrica
                Article
                S0004-27302001000400003 S0004-2730(01)04500403
                10.1590/S0004-27302001000400003
                d0c8776f-5b99-42e8-8dbc-dd26289a4754

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 20 March 2001
                : 13 March 2001
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 46, Pages: 10
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                SciELO Brazil

                Categories
                Artigos Originais, Revisões e Atualizações

                GnRH agonists,Puberdade precoce,Diagnóstico e tratamento,GnRH agonistas,Precocious puberty,Diagnosis and treatment

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