Influências da reposição de estrógenos e progestágenos na ação do hormônio de crescimento em mulheres com hipopituitarismo: [revisão] / The influence of estrogen and progestogen replacement on growth hormone activity in women with hypopituitarism: [review]

O tratamento do hipogonadismo hipogonadotrófico na mulher adulta com hipopituitarismo inclui diversas alternativas terapêuticas de estrógenos e progestágenos, sendo a via oral a de menor custo e a de maior comodidade à paciente. A rota estrogênica oral, entretanto, exerce marcada influência sobre o eixo hormônio de crescimento/fator de crescimento insulina-símile número 1 (GH/IGF-1) nessas mulheres. O tratamento com estrógenos orais, concomitante ao uso de GH em pacientes com hipopituitarismo, antagoniza as ações biológicas do GH e agrava as anormalidades de composição corporal e o metabolismo em geral. Presume-se que o estrógeno oral iniba a secreção/produção de IGF-1 por meio de efeito de primeira passagem hepática, causando aumento da secreção de GH por intermédio de inibição do feedback negativo de IGF-1 em mulheres normais. Isso é demonstrado clinicamente por redução da massa magra, aumento da massa gorda, perfil lipídico aterogênico e prejuízo do bem-estar psicológico. Alguns estudos apontam que os progestágenos com ação androgênica revertem o efeito de diminuição dos níveis séricos de IGF-1 induzida pelos estrógenos orais. Os progestágenos neutros não apresentam esse efeito, porém, quanto maior a potência androgênica, maior será a reversão do efeito de diminuição de IGF-1. Na presente revisão da literatura, serão abordados os aspectos clínicos da reposição com estrógenos e progestágenos nas mulheres com hipopituitarismo, suas interações nas outras deficiências hormonais, bem como o impacto do uso de estrógenos sobre as ações metabólicas do GH.

Treatment of hypogonadotropic hypogonadism in adult women with hypopituitarism can include a wide range of estrogen and progestogen treatment alternatives and oral administration is the route of least cost and greatest patient comfort. The oral estrogen route has a major impact on the growth hormone-insulin-like growth factor I (GH/IGF-1) axis. Oral estrogen therapy, when given concurrently with GH to patients with hypopituitarism, antagonizes the biological effects of GH treatment and aggravates the abnormalities of body composition and the metabolism in general. It is presumed that oral estrogen suppresses the secretion/production of IGF-1 by a hepatic first-pass mechanism, resulting in increased GH secretion by means of suppressing the IGF-1 negative feedback that is present in healthy women. This is clinically manifested in reduced lean body mass, increased fat mass, an atherogenic lipid profile and damage to psychological well-being. Some studies have indicated that progestogens with androgenic actions reverse the effect of reduced serum IGF-1 levels that is induced by the oral estrogens. Neutral progestogens do not exert this effect, however the stronger the androgenic potentialis, the more the effect of reduced IGF-1 will be reversed. This bibliographical review will deal with the clinical aspects of estrogen and progestogen replacement in women with hypopituitarism, their interactions with other hormone deficiencies and the impact of estrogen treatment on the metabolic actions of GH.

Respuesta glucémica e insulinémica y niveles de lípidos en pacientes con hipopituitarismo / Glucaemic and insulinaemic response and lipid levels in patients with hypopituitarism

Con el objetivo de identificar la respuesta glucémica e insulinémica y los niveles de lípidos en sangre de pacientes con hipopituitarismo, bajo tratamiento sustitutivo hormonal, según las causas de la insuficiencia hipofisaria, se evaluaron 51 pacientes de la consulta clínica de hipófisis de nuestra institución con ese diagnóstico, reclutados en un período de 6 meses. Al momento del estudio los pacientes estaban en tratamiento sustitutivo hormonal o habían recibido cirugía o radioterapia hipofisaria según causa de la hipofunción hipofisaria. Se excluyeron los pacientes con insuficiencia hipofisaria secundaria a enfermedad de Cushing o acromegalia. Se realizaron determinaciones de colesterol total, triglicéridos, HDL-colesterol y lipoproteína (a) y simultáneo a la extracción de sangre se insertó trocar para determinar glucemia e insulinemia basales y post-sobrecarga de 75 g de dextrosa oral. Se precisó el índice insulinemia/glucemia por cada grupo etiológico. Se realizó el cálculo del área bajo la curva y se compararon empleando el test de Wilcoxom y para someter a prueba la igualdad de las medias se empleó el análisis de varianza (ANOVA), con un nivel de significación estadística de p < 0,05. La media en años de duración del hipopituitarismo de los pacientes fue de 14,8 ± 9,9 y un promedio de edad al diagnóstico de 22,7 ± 12,6 años, con una talla media de 150,9 ± 11,3 cm. Se halló elevada proporción de pacientes con tratamiento de sustitución hormonal, pero ninguno había recibido tratamiento con hormona de crecimiento. Los valores de glucemia estuvieron en la normoglucemia baja con respuestas aplanadas, mientras que la insulinemia post-sobrecarga de glucosa estuvo elevada, con rangos amplios en todos los grupos etiológicos. El índice insulinémico glucémico medio más elevado lo presentó el grupo de pacientes con síndrome de Sheehan, que también manifestaron los niveles más altos de colesterol y triglicéridos. Se concluyó que la respuesta insulinémica ante una sobrecarga de glucosa oral está considerablemente elevada en los pacientes con diferentes causas de hipopituitarismo, pero que el síndrome de Sheehan presenta los valores más altos de hiperinsulinemia así como los trastornos lipídicos más manifiestos, como expresión de una mayor severidad del daño hipofisario.(AU)

In order to identify the glucaemic and insulinemic response and the levels of lipids in blood of patients with hypopituitarism under hormonal replacement treatment, according to the causes of hypophyseal insuficiency, 51patients with this diagnosis that were registered in a period of 6 months and were attended at the consulting room of hypophysis of our institution were evaluated. At the time of the study the patients were under hormonal replacement therapy or they have undergone surgery or hypophyseal radiotherapy according to the cause of hypophyseal hypofucntion. Patients with hypophyseal insuficiency secondary to Cushing disease or acromegaly were excluded. Total cholesterol, triglycerides, HDL-cholesterol and lipoprotein (a) were determined. Blood was extracted and at the same time a trocar was inserted to determine basal glucaemia and insulinaemia and post-overload of 75 g of oral dextrose. The insulinaemia/glucaemia index was found out for each etiologic group.The area under the curve was calculated and a comparison was made by using Wilconxom's test. To put to the test the equality of the means it was used the variance analysis (ANOVA) with a level of statistical signification of p < 0.05. The average duration of hypopituitarism among the patients was l4.8 ± 9.9 with an average age at the time of diagnosis of 22.7 ± 12.6, and an average height of 150.9 ±11.3 cm. The proportion of patients under hormonal replacement therapy was elevated, but none of them have received treatment with growth hormone. The values of glucaemia were within the low normoglucaemia with even responses, whereas insulinaemia after the overload of glucose was elevated with wide ranges in all the etiologic groups. The highest insulinaemic average index was observed in the group of patients witn Sheehan syndrome that also showed the highest levels of cholesterol and triglycerides. It was concluded that the insulinaemic response to an overload of oral glucose is considerably elevated in patients with different causes of hypopituitarism, but that the Sheehan syndrome presents the highest levels of hyperinsulinaemia as well as the most manifest lipid disorders, as an expression of a greater severity of the hypophyseal damage(AU)