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CONTEXT: The pituitary gland is key for childhood growth, puberty, and metabolism. Pituitary dysfunction is associated with a spectrum of phenotypes, from mild to severe. Congenital Hypopituitarism (CH) is the most commonly reported pediatric endocrine dysfunction with an incidence of 1:4000, yet low rates of genetic diagnosis have been reported. OBJECTIVE: We aimed to unveil the genetic etiology of CH in a large cohort of patients from Argentina. METHODS: We performed whole exome sequencing of 137 unrelated cases of CH, the largest cohort examined with this method to date. RESULTS: Of the 137 cases, 19.1% and 16% carried pathogenic or likely pathogenic variants in known and new genes, respectively, while 28.2% carried variants of uncertain significance. This high yield was achieved through the integration of broad gene panels (genes described in animal models and/or other disorders), an unbiased candidate gene screen with a new bioinformatics pipeline (including genes high loss of function intolerance), and analysis of copy number variants. Three novel findings emerged. First, the most prevalent affected gene encodes the cell adhesion factor ROBO1. Affected children had a spectrum of phenotypes, consistent with a role beyond pituitary stalk interruption syndrome. Second, we found that CHD7 mutations also produce a phenotypic spectrum, not always associated with full CHARGE syndrome. Third, we add new evidence of pathogenicity in the genes PIBF1 and TBC1D32, and report 13 novel candidate genes associated with CH (e.g. PTPN6, ARID5B). CONCLUSION: Overall, these results provide an unprecedented insight into the diverse genetic etiology of hypopituitarism.
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Resumen Introducción : La hipofisitis es una enfermedad in frecuente que plantea un desafío en el diagnóstico y tratamiento. El objetivo de este estudio multicéntrico y retrospectivo fue describir: a) características de pa cientes con hipofisitis primaria (HP), b) métodos diag nósticos, y c) tratamientos realizados. Además, evaluar: a) presentación clínica, b) bioquímica, c) radiológica, d) oftalmológica al diagnóstico y evolución según el tratamiento recibido. Métodos : Estudio retrospectivo donde se estudiaron 28 pacientes (23 mujeres/5 varones) con HP, edad pro medio de 38±11.1 años. Resultados . Los síntomas fueron: cefalea: 68%, po liuria-polidipsia: 50% y alteraciones visuales: 48%. El examen de laboratorio inicial informó disfunción ade nohipofisaria en 71% de los pacientes, siendo el eje gonadal el más afectado. Los hallazgos radiológicos más frecuentes fueron: lesión simétrica:78.5%, aumento homogéneo post contraste: 78.5% y engrosamiento de tallo:70%. En 4/23 mujeres (17%) se relacionó con em barazos o puerperio La conducta inicial fue expectante (CE) en 14 pacientes, cirugía de resección/descompresión en 8 y tratamiento con inmunosupresores en 6. Quince pacientes tuvieron confirmación histológica, 9 resulta ron hipofisitis linfocitaria, 5 hipofisitis por IgG4 y una xantomatosa. Trece fueron diagnosticados por criterios clínicos establecidos. El tamaño de la lesión disminuyó en 43% de pacientes con CE, 62.5% con cirugía y 50% con inmunosupresores. Los síntomas compresivos mejora ron en los 3 grupos, con escaso efecto sobre la función adenohipofisaria, sin resolución de la diabetes insípida. Discusión : En pacientes sin síntomas compresivos adoptamos CE. En aquellos pacientes sin certeza diag nóstica o con síntomas compresivos graves, se optó por cirugía transesfenoidal.
Abstract Introduction : Primary hypophysitis (PH) is a rare disease that represents a challenge among differential diagnosis and management. Our aim was to describe clinical characteristics, diagnostic criteria and different treatment outcomes in patients with PH. Multicentric, retrospective study. Clinical presentation, endocrine function, magnetic resonance imaging findings, visual field defects at diagnosis and treatment outcomes were recorded. Methods : Twenty-eight patients (23 women), with PH were included. Median age: 37. Results : The most frequent symptoms: headache: 68%, polyuria-polydipsia: 50% and visual disturbances: 48%. At diagnosis, anterior pituitary deficiency was present in 71%, being hypogonadotrophic hypogonad ism the most frequent manifestation. The radiological findings: symmetric lesion: 78.5%, homogeneous en hancement: 78.5% and pituitary stalk thickening: 70%. Association with pregnancy or puerperium was found in 4/23 women (17%). Fourteen patients did not receive any treatment ("wait and see" group), 8 underwent surgery for mass reduction or resection and 6 were treated with immunosuppression therapy. Among 15 patients with histopathological diagnosis, 9 were lymphocytic hypophysitis, 5 IgG4 related hypophysitis and 1 xanthomatous hypophysitis. Thirteen were di agnosed by established clinical criteria. Mass reduction was observed in 43% of "wait and see group" patients, 62.5% of operated patients and 50% with immuno suppression therapy. Compressive symptoms showed improvement in the 3 groups, with modest effect on anterior pituitary function, diabetes insipidus did not resolve in any patients. Discussion : In patients without severe compressive symptoms, we adopted a "wait and see" approach. In patients with uncertain diagnosis of PH or severe com pressive symptoms, transsphenoidal surgery was the best option.
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INTRODUCTION: Primary hypophysitis (PH) is a rare disease that represents a challenge among differential diagnosis and management. Our aim was to describe clinical characteristics, diagnostic criteria and different treatment outcomes in patients with PH. Multicentric, retrospective study. Clinical presentation, endocrine function, magnetic resonance imaging findings, visual field defects at diagnosis and treatment outcomes were recorded. METHODS: Twenty-eight patients (23 women), with PH were included. Median age: 37. RESULTS: The most frequent symptoms: headache: 68%, polyuria-polydipsia: 50% and visual disturbances: 48%. At diagnosis, anterior pituitary deficiency was present in 71%, being hypogonadotrophic hypogonadism the most frequent manifestation. The radiological findings: symmetric lesion: 78.5%, homogeneous enhancement: 78.5% and pituitary stalk thickening: 70%. Association with pregnancy or puerperium was found in 4/23 women (17%). Fourteen patients did not receive any treatment ("wait and see" group), 8 underwent surgery for mass reduction or resection and 6 were treated with immunosuppression therapy. Among 15 patients with histopathological diagnosis, 9 were lymphocytic hypophysitis, 5 IgG4 related hypophysitis and 1 xanthomatous hypophysitis. Thirteen were diagnosed by established clinical criteria. Mass reduction was observed in 43% of "wait and see group" patients, 62.5% of operated patients and 50% with immunosuppression therapy. Compressive symptoms showed improvement in the 3 groups, with modest effect on anterior pituitary function, diabetes insipidus did not resolve in any patients. DISCUSSION: In patients without severe compressive symptoms, we adopted a "wait and see" approach. In patients with uncertain diagnosis of PH or severe compressive symptoms, transsphenoidal surgery was the best option.
Introducción: La hipofisitis es una enfermedad infrecuente que plantea un desafío en el diagnóstico y tratamiento. El objetivo de este estudio multicéntrico y retrospectivo fue describir: a) características de pacientes con hipofisitis primaria (HP), b) métodos diagnósticos, y c) tratamientos realizados. Además, evaluar: a) presentación clínica, b) bioquímica, c) radiológica, d) oftalmológica al diagnóstico y evolución según el tratamiento recibido. Métodos: Estudio retrospectivo donde se estudiaron 28 pacientes (23 mujeres/5 varones) con HP, edad promedio de 38±11.1 años. Resultados. Los síntomas fueron: cefalea: 68%, poliuria- polidipsia: 50% y alteraciones visuales: 48%. El examen de laboratorio inicial informó disfunción adenohipofisaria en 71% de los pacientes, siendo el eje gonadal el más afectado. Los hallazgos radiológicos más frecuentes fueron: lesión simétrica:78.5%, aumento homogéneo post contraste: 78.5% y engrosamiento de tallo:70%. En 4/23 mujeres (17%) se relacionó con embarazos o puerperio La conducta inicial fue expectante (CE) en 14 pacientes, cirugía de resección/descompresión en 8 y tratamiento con inmunosupresores en 6. Quince pacientes tuvieron confirmación histológica, 9 resultaron hipofisitis linfocitaria, 5 hipofisitis por IgG4 y una xantomatosa. Trece fueron diagnosticados por criterios clínicos establecidos. El tamaño de la lesión disminuyó en 43% de pacientes con CE, 62.5% con cirugía y 50% con inmunosupresores. Los síntomas compresivos mejoraron en los 3 grupos, con escaso efecto sobre la función adenohipofisaria, sin resolución de la diabetes insípida. Discusión: En pacientes sin síntomas compresivos adoptamos CE. En aquellos pacientes sin certeza diagnóstica o con síntomas compresivos graves, se optó por cirugía transesfenoidal.
Assuntos
Hipofisite Autoimune , Hipofisite , Hipopituitarismo , Gravidez , Humanos , Feminino , Adulto , Estudos Retrospectivos , Hipofisite/diagnóstico , Hipofisite/terapia , Hipofisite/patologia , Hipófise/patologia , Hipopituitarismo/diagnóstico , Hipofisite Autoimune/diagnóstico , Hipofisite Autoimune/terapia , Hipofisite Autoimune/patologia , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. SUBJECTS AND METHODS: We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. RESULTS: Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). CONCLUSION: this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7.
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Acromegalia/tratamento farmacológico , Cabergolina/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Somatostatina/análogos & derivados , Adulto , Idoso , Argentina , Cabergolina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Quimioterapia Combinada , Feminino , Seguimentos , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Somatostatina/administração & dosagem , Somatostatina/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
ABSTRACT Objective To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. Subjects and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. Results Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). Conclusion this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Acromegalia/tratamento farmacológico , Somatostatina/análogos & derivados , Agonistas de Dopamina/uso terapêutico , Hormônio do Crescimento Humano/análogos & derivados , Cabergolina/uso terapêutico , Argentina , Fator de Crescimento Insulin-Like I/análise , Valor Preditivo dos Testes , Estudos Retrospectivos , Seguimentos , Resultado do Tratamento , Agonistas de Dopamina/administração & dosagem , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/uso terapêutico , Quimioterapia Combinada , Cabergolina/administração & dosagemRESUMO
Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenoma. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57% respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenoma and normal visual field were periodically controlled and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.0 months). We did not observe tumor progression in elderly patients with non-functioning adenoma and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.
Se evaluó la presentación clínica, tratamiento y sus resultados durante el seguimiento prolongado de 37 pacientes mayores de 65 años con adenomas hipofisarios, y sus causas de muerte. El estudio fue retrospectivo y transversal. La prevalencia de incidentalomas fue 43% (16), macroadenomas 70.3% (26) y adenomas gigantes 16.2% (6). El fenotipo tumoral más frecuente fue el adenoma no funcionante (76%). La prevalencia de alteraciones en el campo visual y síntomas neurológicos fue 56% y 57% respectivamente. El 54% tuvo función hipofisaria normal, deficiencia parcial el 30% y panhipopituitarismo el 16%. Fueron tratados 32, 5 se perdieron en el seguimiento sin recibir tratamiento. Indicamos cirugía en 18. De los operados por vía transesfenoidal, el 23% tuvo complicaciones postquirúrgicas y el 54% mejoría del campo visual. Por vía transcraneal el 50% sufrió complicaciones post quirúrgicas y el 33% mejoró el campo visual. Durante el seguimiento (55.1 ± 48.7 meses) no observamos recrecimiento tumoral, excepto en un adenoma gigante. Cuatro pacientes operados murieron, dos por causas al tumor. Catorce no fueron operados, 11 con adenomas no funcionantes y campo visual normal fueron controlados periódicamente y 3 con adenomas funcionantes recibieron tratamiento médico. No observamos crecimiento tumoral durante el seguimiento (43.7 ± 38.1 meses). No observamos crecimiento tumoral en adenomas no funcionantes y campo visual normal, por lo que sugerimos conducta expectante y control periódico. Cuando existe alteración del campo visual, la cirugía transesfenoidal es segura y efectiva. En los adenomas secretantes y dependiendo de las comorbilidades, sería apropiado optar por tratamiento médico.
Assuntos
Adenoma/terapia , Neoplasias Hipofisárias/terapia , Adenoma/diagnóstico , Adenoma/mortalidade , Adenoma/cirurgia , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Estudos Transversais , Feminino , Humanos , Masculino , Hormônios Hipofisários , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/mortalidade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Se evaluó la presentación clínica, tratamiento y sus resultados durante el seguimiento prolongado de 37 pacientes mayores de 65 años con adenomas hipofisarios, y sus causas de muerte. El estudio fue retrospectivo y transversal. La prevalencia de incidentalomas fue 43% (16), macroadenomas 70.3% (26) y adenomas gigantes 16.2% (6). El fenotipo tumoral más frecuente fue el adenoma no funcionante (76%). La prevalencia de alteraciones en el campo visual y síntomas neurológicos fue 56% y 57% respectivamente. El 54% tuvo función hipofisaria normal, deficiencia parcial el 30% y panhipopituitarismo el 16%. Fueron tratados 32, 5 se perdieron en el seguimiento sin recibir tratamiento. Indicamos cirugía en 18. De los operados por vía transesfenoidal, el 23% tuvo complicaciones postquirúrgicas y el 54% mejoría del campo visual. Por vía transcraneal el 50% sufrió complicaciones post quirúrgicas y el 33% mejoró el campo visual. Durante el seguimiento (55.1 ± 48.7 meses) no observamos recrecimiento tumoral, excepto en un adenoma gigante. Cuatro pacientes operados murieron, dos por causas al tumor. Catorce no fueron operados, 11 con adenomas no funcionantes y campo visual normal fueron controlados periódicamente y 3 con adenomas funcionantes recibieron tratamiento médico. No observamos crecimiento tumoral durante el seguimiento (43.7 ± 38.1 meses). No observamos crecimiento tumoral en adenomas no funcionantes y campo visual normal, por lo que sugerimos conducta expectante y control periódico. Cuando existe alteración del campo visual, la cirugía transesfenoidal es segura y efectiva. En los adenomas secretantes y dependiendo de las comorbilidades, sería apropiado optar por tratamiento médico.
Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenoma. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57% respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenoma and normal visual field were periodically controlled and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.0 months). We did not observe tumor progression in elderly patients with non-functioning adenoma and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Neoplasias Hipofisárias/terapia , Adenoma/terapia , Hormônios Hipofisários , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/mortalidade , Adenoma/cirurgia , Adenoma/diagnóstico , Adenoma/mortalidade , Estudos Transversais , Estudos Retrospectivos , Causas de Morte , Resultado do TratamentoRESUMO
Clinical presentation, treatment and its results were evaluated during long-term follow-up of 37 patients older than 65 years with pituitary adenomas. Causes of death were also evaluated. It was a retrospective and cross-sectional study. Prevalence of incidentalomas was 43% (16), macroadenomas 70.3% (26) and giant adenomas 16.2% (6). The most frequent tumor phenotype was the non-functioning adenoma (76%). The prevalence of visual field defects and neurological symptoms was 56% and 57%, respectively. We found normal pituitary function in 54%, partial deficiency in 30% and panhypopituitarism in 16%. Thirty-two patients were treated, 5 were lost to follow-up without receiving treatment. Surgery was indicated in 18. Of those operated by trans-sphenoidal approach, 23% had postsurgical complications and 54% improved the visual field. By trans-craneal approach, 50% had post-surgical complications and 33% visual field improvement. During follow-up (55.1 ± 48.7 months) no tumor regrowth was observed, except in a giant adenoma. Four operated patients died, two due to causes related to tumor. Fourteen were not operated, 11 with non-functioning adenomas and normal visual field were periodically controlled, and 3 with secreting adenomas received medical treatment. No tumor growth was observed during follow-up (43.7 ± 38.1 months). We did not observe tumor progression in elderly patients with non-functioning adenomas and normal visual field, so we suggest watchful approach and periodic control. When there are visual field defects, trans-sphenoidal surgery can be considered safe and effective. In secreting adenomas and depending on the associated comorbidities, medical treatment would be the appropriate approach.
Se evaluó la presentación clínica, tratamiento y sus resultados durante el seguimiento prolongado de 37 pacientes mayores de 65 años con adenomas hipofisarios, y sus causas de muerte. El estudio fue retrospecti vo y transversal. La prevalencia de incidentalomas fue 43% (16), macroadenomas 70.3% (26) y adenomas gigantes 16.2% (6). El fenotipo tumoral más frecuente fue el adenoma no funcionante (76%). La prevalencia de alteraciones en el campo visual y síntomas neurológicos fue 56% y 57% respectivamente. El 54% tuvo función hipofisaria normal, deficiencia parcial el 30% y panhipopituitarismo el 16%. Fueron tratados 32, 5 se perdieron en el seguimiento sin recibir tratamiento. Indicamos cirugía en 18. De los operados por vía transesfenoidal, el 23% tuvo complicaciones postquirúrgicas y el 54% mejoría del campo visual. Por vía transcraneal el 50% sufrió complicaciones post quirúrgicas y el 33% mejoró el campo visual. Durante el seguimiento (55.1 ± 48.7 meses) no observamos recrecimiento tumoral, excepto en un adenoma gigante. Cuatro pacientes operados murieron, dos por causas al tumor. Catorce no fueron operados, 11 con adenomas no funcionantes y campo visual normal fueron controlados periódicamente y 3 con adenomas funcionantes recibieron tratamiento médico. No observamos crecimiento tumoral durante el seguimiento (43.7 ± 38.1 meses). No observamos crecimiento tumoral en adenomas no funcionantes y campo visual normal, por lo que sugerimos conducta expectante y control periódico. Cuando existe alteración del campo visual, la cirugía transesfenoidal es segura y efectiva. En los adenomas secretantes y dependiendo de las comorbilidades, sería apropiado optar por tratamiento médico.
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Neoplasias Hipofisárias/terapia , Adenoma/terapia , Hormônios Hipofisários , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/mortalidade , Adenoma/cirurgia , Adenoma/diagnóstico , Adenoma/mortalidade , Estudos Transversais , Estudos Retrospectivos , Causas de Morte , Resultado do TratamentoRESUMO
RESUMEN Objetivo El objetivo de esta guía es formular pautas para el diagnóstico de acromegalia adecuadas a los parámetros internacionales y a los recursos disponibles en Argentina. Participantes El grupo de trabajo propuesto por la Federación Argentina de Sociedades de Endocrinología (FASEN) incluyó un equipo multidisciplinario compuesto por 5 médicos endocrinólogos (4 especialistas y una profesional joven), un neurocirujano y una bioquímica, expertos en el tema. Evidencia Esta guía basada en la evidencia se desarrolló utilizando la metodología AGREE para describir tanto las recomendaciones como la calidad de las pruebas. Los borradores de esta guía fueron revisados por un grupo multidisciplinario de especialistas reconocidos en acromegalia. Conclusiones Utilizando un enfoque basado en la evidencia, esta guía aborda la evaluación diagnóstica de la acromegalia en Argentina.
ABSTRACT Objective The aim is to formulate guidelines for the clinical, biochemical and imaging diagnosis of acromegaly in accordance with international criteria and resources available in Argentina. Participants The task force selected by FASEN included a multidisciplinary team of 5 endocrinologists (4 senior and 1 junior), a neurosurgeon and a biochemist, experts in the field. Evidence This evidence-based guidelines were developed using the AGREE methodology to describe both the recommendations and the quality of evidence. The draft of these guidelines was reviewed by endocrinologists, biochemists and neurosurgeons experts in the field. Conclusions Using an approach based on evidence, these guidelines address the diagnosis of acromegaly in Argentina.
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Acromegalia/diagnóstico , Acromegalia/sangue , Acromegalia/diagnóstico por imagem , Fator de Crescimento Insulin-Like I/efeitos adversos , Diagnóstico Clínico , Hormônio do Crescimento Humano/efeitos adversosRESUMO
Pegvisomant (PEGv) is a growth hormone receptor antagonist approved for the treatment of acromegaly; one of its documented adverse effects is reversible elevation of hepatic enzymes. We report a 39-year-old male acromegalic patient with a pituitary macroadenoma who underwent transsphenoidal surgery. The patient's condition improved but GH and IGF-I levels did not normalize; as a consequence, we first administered dopamine agonists and then somatostatin receptor ligands (SRLs) with poor response. PEGv 15 mg every other day was added to lanreotide 120 mg monthly. The patient developed a severe hepatitis five months after starting the combination therapy. Elevated ferritin, iron, and transferrin saturation suggested probable hepatitis due to haemochromatosis. We performed a liver biopsy which showed an acute cholestatic hepatitis consistent with toxic etiology. A heterozygous genotype UGT1A1 (â) 28 polymorphism associated with Gilbert's syndrome was also found in this Argentine patient. The predominant clinical presentation resembled an acute cholestatic hepatitis associated with severe hemosiderosis, a different and new pattern of PEGv hepatotoxicity.