Pituitary Metastasis Clinical Presentation of Diabetes Insipidus Six Years after Invasive Breast Carcinoma Diagnosis: Case Report / Apresentação Clínica de Metástase Hipofisária com Diabetes Insipidus Seis Anos após o Diagnóstico de Carcinoma Mamário Invasivo: Relato de Caso / Presentación Clínica de Metástasis Hipofisaria con Diabetes Insípida Seis Años después del Diagnóstico de Carcinoma Mamario Invasivo: Informe de Caso

Introduction: Breast carcinomas are the major cause of death in women with cancer worldwide, mainly in metastatic cases. The pituitary gland stands for only 6-8% of the secondary sites of distant metastasis and it is usually asymptomatic. When symptomatic, these lesions can mimic primary pituitary diseases. Case report: A 43-year-old woman underwent a left mastectomy with axillary lymph node dissection in April 2013 due to a luminal, invasive ductal carcinoma with nodal metastasis. Six years later, she started complaining of myalgia, bone pain, dizziness and decreased visual acuity, in addition to polydipsia and polyuria. Laboratory tests showed hyperprolactinemia and diabetes insipidus suggestive of panhypopituitarism. Magnetic resonance imaging of the brain showed a sellar tumor with extension to adjacent structures which was removed on November 2019. A pathology report of an epithelial neoplasm of unknown origin and an immunohistochemical study showed positivity for estrogen, progesterone receptors and GATA 3, and negativity for pituitary hormones. This set of findings and the histological morphology were consistent with a metastatic mucinous adenocarcinoma of mammary origin without HER-2 overexpression. The patient underwent ovarian ablation, central nervous system radiotherapy, chemotherapy and oncological follow-up. Conclusion: The patient's young age and clinical presentation of visual impairment and sudden development of diabetes insipidus diverges from the current data, since these findings are usually present in asymptomatic women over sixty-years-old. The varied clinical presentation can lead to a delay in diagnosis of pituitary metastasis, which reinforces the importance of reporting cases like this.

Introdução: O carcinoma mamário é a maior causa de morte por câncer em mulheres no mundo, majoritariamente nos casos metastáticos. A hipófise configura apenas 6-8% dos sítios metastáticos a distância, e geralmente são assintomáticos. Quando sintomáticos, podem mimetizar uma doença primária dessa glândula. Relato do caso: Mulher, 43 anos, submetida à mastectomia com esvaziamento axilar à esquerda em abril de 2013 por carcinoma mamário ductal invasivo, luminal, com metástase linfonodal. Seis anos depois, iniciou com queixa de mialgia, dor óssea, tontura e piora progressiva de acuidade visual, além de polidipsia e poliúria. Exames laboratoriais evidenciaram hiperprolactinemia e diabetes insipidus sugerindo pan-hipopituitarismo. A ressonância magnética de encéfalo demonstrou tumor selar com extensão a estruturas adjacentes que foi ressecado em novembro de 2019, com laudo de neoplasia epitelial de origem indeterminada, sendo necessário estudo imuno-histoquímico para elucidação diagnóstica. Houve positividade para o receptor de estrógeno, progesterona e GATA 3 e negatividade para hormônios hipofisários. Esse conjunto de achados e a morfologia histológica foram condizentes com adenocarcinoma mucinoso metastático de origem mamária, sem hiperexpressão de HER-2. A paciente foi submetida à ablação ovariana, radioterapia em sistema nervoso central, quimioterapia e a acompanhamento oncológico. Conclusão: A idade, a apresentação clínica de comprometimento visual e o desenvolvimento de diabetes insipidus repentino destoam dos dados da literatura, uma vez que estes costumam estar associados a mulheres acima dos 60 anos e assintomáticas. Essa apresentação clínica diversificada pode levar a um atraso no diagnóstico da metástase hipofisária, o que reforça a importância de relatar casos como este.

Introducción: Los carcinomas de mama son la principal causa de muerte en mujeres con cáncer en todo el mundo, principalmente en casos metastásicos. La glándula pituitaria representa solo el 6-8% de los sitios secundarios de metástasis a distancia y generalmente es asintomática. Cuando son sintomáticas, estas lesiones pueden imitar enfermedades pituitarias primarias. Informe de caso: Mujer, 43 años, se sometió a una mastectomía izquierda con disección de ganglios linfáticos axilares en abril de 2013 debido a un carcinoma de mama ductal invasivo luminal con metástasis ganglionar. Seis años después, comenzó a quejarse de mialgia, dolor óseo, mareos y disminución de la agudeza visual, además de polidipsia y poliuria. Los análisis de laboratorio revelaron hiperprolactinemia y diabetes insípida, lo que sugiere un cuadro de panhipopituitarismo. La resonancia magnética cerebral mostró un tumor de la silla turca con extensión a estructuras adyacentes, que se extirpó en noviembre de 2019. Un informe patológico indicó una neoplasia epitelial de origen desconocido, y ha sido necesario un estudio inmunohistoquímico para dilucidar, que se mostró positivo para los receptores de estrógeno, progesterona y GATA 3, y negativo para las hormonas pituitarias. Este conjunto de hallazgos y la morfología histológica fueron consistentes con un adenocarcinoma mucinoso metastásico de origen mamario sin superexpresión de HER-2. La paciente se sometió a ablación ovárica, radioterapia del sistema nervioso central, quimioterapia y seguimiento oncológico. Conclusión: La edad de la paciente y la presentación clínica de deterioro visual y desarrollo repentino de diabetes insípida difieren de los datos actuales, ya que estos hallazgos suelen estar presentes en mujeres asintomáticas mayores de 60 años. Una variada presentación clínica puede retrasar el diagnóstico de metástasis pituitaria, lo que refuerza la importancia de informar casos como este.

Pituitary Metastasis Clinical Presentation of Diabetes Insipidus Six Years after Invasive Breast Carcinoma Diagnosis: Case Report

Breast carcinomas are the major cause of death in women with cancer worldwide, mainly in metastatic cases. The pituitary gland stands for only 6-8% of the secondary sites of distant metastasis and it is usually asymptomatic. When symptomatic, these lesions can mimic primary pituitary diseases. Case report: A 43-year-old woman underwent a left mastectomy with axillary lymph node dissection in April 2013 due to a luminal, invasive ductal carcinoma with nodal metastasis. Six years later, she started complaining of myalgia, bone pain, dizziness and decreased visual acuity, in addition to polydipsia and polyuria. Laboratory tests showed hyperprolactinemia and diabetes insipidus suggestive of panhypopituitarism. Magnetic resonance imaging of the brain showed a sellar tumor with extension to adjacent structures which was removed on November 2019. A pathology report of an epithelial neoplasm of unknown origin and an immunohistochemical study showed positivity for estrogen, progesterone receptors and GATA 3, and negativity for pituitary hormones. This set of findings and the histological morphology were consistent with a metastatic mucinous adenocarcinoma of mammary origin without HER-2 overexpression. The patient underwent ovarian ablation, central nervous system radiotherapy, chemotherapy and oncological follow-up. Conclusion: The patient's young age and clinical presentation of visual impairment and sudden development of diabetes insipidus diverges from the current data, since these findings are usually present in asymptomatic women over sixty-years-old. The varied clinical presentation can lead to a delay in diagnosis of pituitary metastasis, which reinforces the importance of reporting cases like this

O carcinoma mamário é a maior causa de morte por câncer em mulheres no mundo, majoritariamente nos casos metastáticos. A hipófise configura apenas 6-8% dos sítios metastáticos a distância, e geralmente são assintomáticos. Quando sintomáticos, podem mimetizar uma doença primária dessa glândula. Relato do caso: Mulher, 43 anos, submetida à mastectomia com esvaziamento axilar à esquerda em abril de 2013 por carcinoma mamário ductal invasivo, luminal, com metástase linfonodal. Seis anos depois, iniciou com queixa de mialgia, dor óssea, tontura e piora progressiva de acuidade visual, além de polidipsia e poliúria. Exames laboratoriais evidenciaram hiperprolactinemia e diabetes insipidus sugerindo pan-hipopituitarismo. A ressonância magnética de encéfalo demonstrou tumor selar com extensão a estruturas adjacentes que foi ressecado em novembro de 2019, com laudo de neoplasia epitelial de origem indeterminada, sendo necessário estudo imuno-histoquímico para elucidação diagnóstica. Houve positividade para o receptor de estrógeno, progesterona e GATA 3 e negatividade para hormônios hipofisários. Esse conjunto de achados e a morfologia histológica foram condizentes com adenocarcinoma mucinoso metastático de origem mamária, sem hiperexpressão de HER-2. A paciente foi submetida à ablação ovariana, radioterapia em sistema nervoso central, quimioterapia e a acompanhamento oncológico. Conclusão: A idade, a apresentação clínica de comprometimento visual e o desenvolvimento de diabetes insipidus repentino destoam dos dados da literatura, uma vez que estes costumam estar associados a mulheres acima dos 60 anos e assintomáticas. Essa apresentação clínica diversificada pode levar a um atraso no diagnóstico da metástase hipofisária, o que reforça a importância de relatar casos como este.

Los carcinomas de mama son la principal causa de muerte en mujeres con cáncer en todo el mundo, principalmente en casos metastásicos. La glándula pituitaria representa solo el 6-8% de los sitios secundarios de metástasis a distancia y generalmente es asintomática. Cuando son sintomáticas, estas lesiones pueden imitar enfermedades pituitarias primarias. Informe de caso: Mujer, 43 años, se sometió a una mastectomía izquierda con disección de ganglios linfáticos axilares en abril de 2013 debido a un carcinoma de mama ductal invasivo luminal con metástasis ganglionar. Seis años después, comenzó a quejarse de mialgia, dolor óseo, mareos y disminución de la agudeza visual, además de polidipsia y poliuria. Los análisis de laboratorio revelaron hiperprolactinemia y diabetes insípida, lo que sugiere un cuadro de panhipopituitarismo. La resonancia magnética cerebral mostró un tumor de la silla turca con extensión a estructuras adyacentes, que se extirpó en noviembre de 2019. Un informe patológico indicó una neoplasia epitelial de origen desconocido, y ha sido necesario un estudio inmunohistoquímico para dilucidar, que se mostró positivo para los receptores de estrógeno, progesterona y GATA 3, y negativo para las hormonas pituitarias. Este conjunto de hallazgos y la morfología histológica fueron consistentes con un adenocarcinoma mucinoso metastásico de origen mamario sin superexpresión de HER-2. La paciente se sometió a ablación ovárica, radioterapia del sistema nervioso central, quimioterapia y seguimiento oncológico. Conclusión: La edad de la paciente y la presentación clínica de deterioro visual y desarrollo repentino de diabetes insípida difieren de los datos actuales, ya que estos hallazgos suelen estar presentes en mujeres asintomáticas mayores de 60 años. Una variada presentación clínica puede retrasar el diagnóstico de metástasis pituitaria, lo que refuerza la importancia de informar casos como este.

Embolia de líquido amniótico asociada a paro cardiorrespiratorio recuperado y síndrome de Sheehan / Amniotic fluid embolism associated with recovered cardiac arrest and postpartum Sheehan's syndrome

Resumen La embolia de líquido amniótico es una condición catastrófica propia del embarazo que ocurre típicamente durante el parto o justo posterior a este, cuyo sustrato fisiopatológico no ha sido aclarado por completo. Se ha estimado, según cifras de los Estados Unidos, que su incidencia rondaría 1 por cada 12.953 partos, y en el Reino Unido 1 por cada 50.000 partos; sin embargo, estas cifras pueden ser imprecisas debido a que no existen una referencia ni un consenso respecto a los criterios diagnósticos, además de que el cuadro clínico se puede confundir con otras emergencias obstétricas. Se presenta el caso de una paciente sin antecedentes mórbidos que presenta un cuadro de embolia de líquido amniótico no fatal, caracterizado por un estado fetal no tranquilizador durante la inducción del trabajo de parto, seguido de un paro cardiorrespiratorio durante la cesárea de urgencia y la rápida y catastrófica aparición de signos clínicos de una coagulopatía de consumo grave. Se describen además las complicaciones posoperatorias y su manejo, entre ellas un síndrome de Sheehan y la aparición de convulsiones tónico-clónicas generalizadas con alteración de neuroimágenes.

Abstract Amniotic fluid embolism is a catastrophic pregnancy condition that typically occurs during or inmediately after delivery, and whose pathophysiological background has not been fully clarified. According to US records the incidence of amniotic fluid embolism could been around 1 for every 12,953 births and in the United Kingdom 1 for every 50,000 births, however these numbers may be imprecise because there is no gold standard as well as no consensus regarding the diagnostic criteria, in addition that the clinical presentation can be misdiagnosis with other obstetric emergencies. We present the clinical case of a patient without a morbid history who presents with a non-fatal amniotic fluid embolism, characterized by an non-reassuring fetal status during labor induction, followed by cardiorespiratory arrest during emergency cesarean section and the rapid and catastrophic appearance of clinical signs of a severe consumptive coagulopathy. Postoperative complications and their management are also described, including Sheehans syndrome and the appearance of generalized tonic-clonic seizures with impaired neuroimaging.

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

Germinoma en un paciente con emaciación y retraso de crecimiento. A propósito de un caso / Germinoma in a patient with emaciation and growth retardation. Case report

Los tumores del sistema nervioso central representan la segunda enfermedad oncológica más habitual en niños y adolescentes. Entre los tumores intracraneales, los de células germinales son infrecuentes. Los síntomas que desencadenan son cefalea, náuseas, vómitos, déficits hormonales, alteraciones visuales, pérdida de peso, pobre crecimiento y pubertad precoz. Menos frecuentemente, producen trastornos del movimiento o psiquiátricos. Algunos de estos tumores pueden ser asintomáticos un largo período, lo que desencadena un diagnóstico tardío.Se presenta a una paciente femenina de 14 años con pérdida de peso y falla del crecimiento, con diagnóstico erróneo de trastorno de la conducta alimentaria. Tras estudios pertinentes, se arribó al diagnóstico de germinoma del sistema nervioso central. Al ser esta patología infrecuente y de presentación variable, requiere alto sentido de alerta por parte de la familia involucrada y del equipo de salud para evitar retrasos en el diagnóstico y el tratamiento

Central nervous system tumors are the second most frequent oncological disease among children and teenagers. Among the intracranial tumors, the germ cells ones are infrequent. The symptoms they cause are headaches, nausea and vomiting, hormonal deficits, visual disturbances, weight loss, poor growth and early puberty. Less frequently, they produce movement or psychiatric disorders. Some of these tumors can be asymptomatic for a long period leading to a late diagnosis.The case of a 14-year-old female patient is presented. She showed weight loss and growth failure, with wrong diagnosis of eating disorder. After proper study methods, we arrived to central nervous system germinoma diagnosis. Because this pathology is rare and has a variable form of presentation, it requires that the family involved and the health team to be alert, to avoid delays in diagnosis and treatment.

Pan-hipopituitarismo de surgimento na infância e diagnóstico diferencial de poliúria / Childhood-onset panhypopituitarism and differential diagnosis of polyuria

RESUMO: O hipopituitarismo é a deficiência de dois ou mais hormônios hipofisários, que se expressa por sintomas dependentes do tipo e grau de déficit hormonal. A adequada condução destes pacientes é de fundamental importância para que não acarrete atraso no crescimento e desenvolvimento, óbito ou mudanças na qualidade de vida dos indivíduos. Objetiva-se, neste estudo, relatar caso clínico de abordagem de paciente pediátrico com pan-hipopituitarismo e descrever o manejo adotado, bem como a importância do acompanhamento pelo endocrinologista pediátrico. Trata-se de paciente do sexo masculino, 14 anos, com pan-hipopituitarismo iniciado na infância, secundário ao surgimento de germinoma e ao tratamento realizado para o mesmo. A primeira deficiência hormonal apresentada foi diabetes insipidus, seguida, após a realização de quimioterapia e radioterapia, de múltiplas deficiências. O menor segue em acompanhamento especializado, e faz uso de levotiroxina, desmopressina, somatropina, testosterona e prednisolona. A partir do presente relato, percebe-se a importância do diagnóstico oportuno e da adequada abordagem da criança com pan-hipopituitarismo e de seu seguimento a fim de se manter uma qualidade de vida satisfatória. (AU)

ABSTRACT: Hypopituitarism is the deficiency of two or more pituitary hormones. Its symptoms depend on the type and degree of hormonal deficit. Proper care of these patients is of fundamental importance to avoid delay in growth and development, death, or changes in the quality of life. The objective of this study is to report a clinical case of a pediatric patient with pan-hypopituitarism and describe the care adopted, as well as the importance of monitoring by the pediatric endocrinologist. The patient was a 14-year-old boy, with pan-hypopituitarism beginning in childhood, secondary to the appearance of germinoma and the treatment performed for it. The first hormonal deficiency presented was diabetes insipidus, followed by multiple deficiencies after chemotherapy and radiotherapy. The patient is under specialized monitoring and takes levothyroxine, desmopressin, somatropin, testosterone, and prednisolone. From the present report, timely diagnosis and adequate approach to a child with pan-hypopituitarism and its follow-up are important to maintain a satisfactory quality of life. (AU)

Hipopituitarismo postraumatismo encefalocraneano: revisión de la literatura y algoritmo de estudio y abordaje terapéutico

Hypopituitarism after moderate or severe traumatic brain injury (TBI) is usually underdiagnosed and therefore undertreated. Its course can be divided in an acute phase during the first 14 days after TBI with 50 to 80% risk of hypopituitarism, and a chronic phase, beginning three months after the event, with a prevalence of hypopituitarism that ranges from 2 to 70%. Its pathophysiology has been addressed in several studies, suggesting that a vascular injury to the pituitary tissue is the most important mechanism during the acute phase, and an autoimmune one during chronic stages. In the acute phase, there are difficulties to correctly interpret pituitary axes. Hence, we propose a simple and cost-effective algorithm to detect and treat a potential hypothalamic-pituitary-adrenal axis impairment and alterations of sodium homeostasis, both of which can be life-threatening. In the chronic phase, post-concussion syndrome is the most important differential diagnosis. Given the high prevalence of hypopituitarism, we suggest that all pituitary axes should be assessed in all patients with moderate to severe TBI, between 3 to 6 months after the event, and then repeated at 12 months after trauma by a specialized team in pituitary disease.

Lipid profile and response to statin therapy in patients with hypopituitarism

ABSTRACT Objective: Dyslipidemia is prevalent among patients with hypopituitarism, especially in those with growth hormone (GH) deficiency. This study aimed to evaluate the response to statin therapy among adult patients with dyslipidemia and hypopituitarism. Subjects and methods: A total of 113 patients with hypopituitarism following up at a neuroendocrinology unit were evaluated for serum lipid levels. Dyslipidemia was diagnosed in 72 (63.7%) of these patients. A control group included 57 patients with dyslipidemia and normal pituitary function. The distribution of gender, age, weight, and dyslipidemia type was well balanced across both groups, and all participants were treated with simvastatin at doses adjusted to obtain normal lipid levels. Results: Patients with hypopituitarism and dyslipidemia presented deficiency of TSH (69%), gonadotropins (69%), ACTH (64%), and GH (55%) and had a similar number of deficient pituitary axes compared with patients with hypopituitarism but without dyslipidemia. All patients with dyslipidemia (with and without hypopituitarism) had lipid levels well controlled with doses of simvastatin ranging from 20-40 mg/day. The mean daily dose of simvastatin was not significantly different between patients with and without hypopituitarism (26.7 versus 23.5 mg, p = 0.10). Similarly, no significant variation in simvastatin dose was observed between patients with different causes of hypopituitarism, presence or absence of GH deficiency, number of deficient pituitary axes, prior pituitary radiation therapy or not, and presence or absence of obesity. Conclusions: Patients with GH deficiency without GH replacement showed good response to simvastatin at a mean dose equivalent to that used in individuals with dyslipidemia and normal pituitary function.

Non-functioning pituitary adenomas and pregnancy: one-center experience and review of the literature

SUMMARY The usual clinical presentation of non-functioning pituitary adenoma (NFPA) consists of symptoms of mass effect and hypopituitarism. NFPA is a rare condition in young women and an uncommon complication during pregnancy. We present the outcome of three patients with NFPA during pregnancy. Case 1: a 38-year-old woman was referred at 32nd week of spontaneous pregnancy because of diagnosis of a pituitary macroadenoma discovered in the context of progressive visual loss. Hormonal deficiency and hypersecretion were ruled out. Prolactin levels were high as expected. She developed diplopia and severe headache despite the use of dopamine agonists and corticosteroids, so pregnancy was interrupted at 34th week. After an uncomplicated delivery of a healthy newborn, transsphenoidal surgery was performed. The pathology was consistent with a gonadotroph adenoma. She recovered visual field, and remained with normal pituitary function. Postsurgical tumor remnant increased in size during the follow-up. Case 2: a 34-year-old woman was referred due to secondary amenorrhea and galactorrhea. A macroadenoma with suprasellar extension was discovered. Transsphenoidal surgery confirmed a gonadotroph adenoma. Two years after surgery she had a normal pregnancy. Six years after surgery a small tumor recurrence occurred. Case 3: a 23-year-old woman was referred due to a microincidental pituitary adenoma. Laboratory testing was normal. No findings on physical examination. A wait and see approach was decided. Two years after diagnosis, the patient got pregnant without complications. Image remained stable. This article may contribute new cases and provides an extensive review of NFPA during pregnancy.

Hipofisitis linfocitaria primaria. Caso clínico / Primary lymphocytic hypophysitis. Report of one case

Primary lymphocytic hypophysitis is an autoimmune disease characterized by lymphocytic infiltration of the pituitary gland, with a higher incidence during late pregnancy and the postpartum period. It causes glandular destruction, mass effect and symptoms such headache, visual field defects, ophthalmoplegia and symptoms of hypopituitarism. We report a 38-year-old postpartum woman who, after giving birth presented decreased left visual acuity associated with a non ictal headache. Magnetic resonance imaging demonstrated a sellar mass associated with decreased free thyroxine and cortisol levels. Suspecting a primary lymphocytic hypophysitis, she was treated with prednisone 60 mg/day and hormonal replacement therapy. One month later, size of the pituitary gland decreased, and the visual field defect improved. Steroidal treatment was maintained for 36 months and progressively tapered. After two years of follow-up, the imaging studies show a normal sized pituitary gland.

Diagnóstico precoce de craniofaringioma na infância - relato de caso / Early diagnosis of craniopharingioma in childhood - case report

OBJETIVO: Relatar um caso de craniofaringioma em um pré escolar com sintomatologia de início recente. RELATO DO CASO: Menino de cinco anos com cefaleia de início há 20 dias, acompanhada de vômitos. Na admissão foi realizada uma tomografia computadorizada (TC) de crânio que mostrou uma hidrocefalia com presença de uma massa sugestivo de craniofaringioma. Realizou a ressecção microcirúrgica em outro serviço, sendo que no pós-operatório paciente evoluiu com pan-hipopituitarismo, trombose assintomática do seio sagital superior e oscilações do sódio sérico. CONSIDERAÇÕES: A combinação clínica de cefaleia, deficiência visual, diminuição da taxa de crescimento e polidipsia/poliúria levar à suspeita de craniofaringioma como diagnóstico diferencial. O diagnóstico é realizado por exames de imagem como TC ou RM. O principal tratamento é a resseção cirúrgica. Algumas complicações como alteração no eixo hipotálamo-hipofisário, diabetes insipido e obesidade hipotalâmica são frequentes nesses pacientes

OBJECTIVE: To report a case of craniopharyngioma in a preschool with symptoms of recent onset. CASE REPORT: Five-year-old boy with headache starting 20 days ago, accompanied by vomiting. Upon admission, a computed tomography (CT) scan of the skull was performed, which showed hydrocephalus with the presence of a mass suggestive of craniopharyngioma. Microsurgical resection was performed in another service, and in the postoperative period the patient developed pan-hypopituitarism, asymptomatic thrombosis of the upper sagittal sinus and oscillations in serum sodium. CONSIDERATIONS: The clinical combination of headache, visual impairment, decreased growth rate and polydipsia / polyuria lead to the suspicion of craniopharyngioma as a differential diagnosis. The diagnosis is made by imaging exams such as CT or MRI. The main treatment is surgical resection. Some complications, such as changes in the hypothalamic-pituitary axis, diabetes insipidus and hypothalamic obesity are common in these patients

Hormona de crecimiento en sangre de papel filtro para el diagnóstico de deficiencia de hormona de crecimiento / Growth hormone of dried blood spot for the diagnosis of growth hormone deficiency

INTRODUCCIÓN: El diagnóstico de deficiencia de hormona de crecimiento (DHC) es difícil de establecer, y se puede asociar a serias complicaciones, especialmente en el período neonatal. La prueba de estímulo de secreción de hormona de crecimiento (HC) se considera de elección para el diagnóstico, pero presenta complicaciones metodológicas y se asocia a efectos adversos. Los neonatos presentan aumento de la secreción de HC de forma fisiológica, siendo una ventana diagnóstica. OBJETIVO: Evaluar si la muestra de sangre en papel filtro tomada en el período neonatal, en contexto del tamizaje neonatal de hipotiroidismo congénito y fenilcetonuria, permite diferenciar pacientes con DHC, de los que no la presentan. PACIENTES Y MÉTODO: Estudio de casos y controles mediante determinación de concentración de HC en sangre de papel filtro extraída en período neonatal, comparando controles con DHC con casos con deficiencia descartada. Se realizó extracción de la muestra del papel filtro, obteniendo dos discos de 0,125 pulgada por cada uno de los pacientes desde el centro de la mancha de sangre del papel, para un ELISA de HC humana altamente sensible basado en el uso de anticuerpos policlonales dirigidos contra la HC humana recombinante de 22kDa de peso molecular. RESULTADOS: Se obtuvo un total de 7 casos de DHC y 10 controles. La mediana de concentración de HC de papel filtro en los casos es 2,0 ng/ml (Rango intercuartil 3,6 ng/ml) y controles 2,05 ng/mL (RIC 2,0 ng/ml), U de Mann-Withney 30,5 (p = 0,68). Los dos casos con deficiencia de hormonas hipofisarias múltiples (DHHM) presentan concentraciones menores a 1 ng/ml. CONCLUSIÓN: La muestra de papel filtro no permitió diferenciar a los pacientes con DHC de los casos controles, aunque los casos con DHHM presentaron concentraciones mucho menores, en comparación a la deficiencia de hormona de crecimiento aislada (DHCA).

INTRODUCTION: The diagnosis of growth hormone deficiency (GHD) is difficult to determine, and could be associated with severe complications, especially in the neonatal period. The stimulation test of growth hormone (GH) secretion is considered the gold standard for diagnosis, but it has methodological complications and is associated with adverse effects. Neonates present physiological increased secretion of GH, representing a diagnostic window. OBJECTIVE: To evaluate if the dried blood spot on filter paper obtained in the neonatal period, as part of a neonatal screening for con genital hypothyroidism and phenylketonuria, allows differentiating patients with GHD from those who do not have it. PATIENTS AND METHOD: Study of cases and controls by measuring the GH concen tration in dried blood spot on filter paper obtained in the neonatal period, comparing controls with GHD with cases with discarded deficiency. The sample was extracted from the filter paper, obtaining two 0.125 inch discs per each patient from the center of the blood spot on the paper, for a highly sen sitive ELISA assay for human GH based on the use of polyclonal antibodies against 22 kDa recom binant human GH. RESULTS: Seven cases of GHD and ten controls were obtained. The median GH concentration of the dried blood spot in the cases is 2.0 ng/ml (Interquartile range 3.6 ng/ml) and 2.05 ng/ml (Interquartile range 2.0 ng/ml) in the controls, Mann-Whitney U test 30.5 (p = 0.68). The two cases with multiple pituitary-hormone deficiency (MPHD) present concentrations lower than 1 ng/ml. CONCLUSION: The dried blood spot sample did not differentiate GHD patients from control cases, although MPHD cases present much lower concentrations compared to isolated growth hor mone deficiency (IGHD).

Combined pituitary hormone deficiency caused by PROP1 mutations: update 20 years post-discovery

ABSTRACT The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and genetic characteristics of patients with PROP1 mutations and summarized the phenotypes of 14 patients with 7 different pathogenic PROP1 mutations followed at the Hospital das Clínicas of the University of Sao Paulo. In addition to deficiencies in GH, TSH, PRL and gonadotropins some patients develop late ACTH deficiency. Therefore, patients with PROP1 mutations require permanent surveillance. On magnetic resonance imaging, the pituitary stalk is normal, and the posterior lobe is in the normal position. The anterior lobe in patients with PROP1 mutations is usually hypoplastic but may be normal or even enlarged. Bi-allelic PROP1 mutations are currently the most frequently recognized genetic cause of CPHD worldwide. PROP1 defects occur more frequently among offspring of consanguineous parents and familial cases, but they also occur in sporadic cases, especially in countries in which the prevalence of PROP1 mutations is relatively high. We classified all reported PROP1 variants described to date according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines: 29 were pathogenic, 2 were likely pathogenic, and 2 were of unknown significance. An expansion of the phenotype of patients with PROP1 mutations was observed since the first description 20 years ago: variable anterior pituitary size, different pathogenic mutations, and late development of ACTH deficiency. PROP1 mutations are the most common cause of autosomal recessive CPHD with a topic posterior pituitary lobe. Arch Endocrinol Metab. 2019;63(2):167-74

Síndrome de Sheehan: Epidemiología, clínica, diagnóstico y manejo / Sheehan's syndrome: Epidemiology, clinical features, diagnosis and treatment

El síndrome de Sheehan es la necrosis de la hipófisis. Conduce a hipopituitarismo y es causado por vasoespasmo, trombosis e isquemia de las arterias hipofisiarias y se asocia con varios grados de disfunción de la glándula, Es más común en países en vías de desarrollo y poco frecuente en países desarrollados. En 1937 Sheehan describió una serie de autopsias con hallazgo de atrofia de la hipófisis con hemorragia postparto como causa común. La incidencia puede aproximarse a 5 casos por 100.000 nacidos vivos y el diagnóstico puede ser tardío entre 1 y 33 años luego del parto. El principal factor de riesgo es el embarazo. La disfunción endocrina es progresiva, sugiriendo que puede haber un trasfondo autoinmune asociado. Generalmente la primera manifestación es la agalactia seguida de amenorrea y otros signos de panhipopituitarismo pueden aparecer progresivamente. Los síntomas pueden ser escasos lo que dificulta el diagnóstico. La RNM es la imagen preferida para el diagnóstico y el tratamiento depende de las líneas hormonales comprometidas.

Sheehan´s syndrome is the necrosis of the hypophysis. It conducts to hypopituitarism and is caused by vasospasm, thrombosis and ischemic damage of hypophyseal arteries and is associated with various degrees of disfunction of the gland. It is more common in developing countries and unfrequent in developed ones. In 1937 Sheehan described a series of autopsies finding atrophy of the hypophysis with postpartum hemorrhage as a common cause. The incidence may be around 5 cases for 100.000 born alive, and the diagnosis can be done between 1 and 33 years after parturition. The basic risk factor is pregnancy. The endocrine disfunction is progressive, suggesting an autoimmune background associated. Usually the first clinical manifestation is agalactia followed by amenorrhea and later signs of panhypopituitarism may appear. Symptoms may be scarce and difficult diagnosis. MRI is the preferred imaging for diagnosis and treatment depends on endocrine deficiencies present.

Insuficiencia Hipofisaria Congénita / Congenital Pituitary Hormone Deficiency

La insuficiencia hipofisaria congénita es un trastorno originado en la alteración de la ontogenia de la glándula hipofisaria que determina la disminución o falta de trofinas hipofisarias: adrenocorticotropina, tirotropina, hormona de crecimiento, prolactina, gonadotrofinas y/u hormona antidiurética. Es una patología compleja e infrecuente que, debido a su signo sintomatología inespecífica, suele ser difícil de reconocer a edades tempranas, derivando en aumento de la morbilidad y eventualmente de la mortalidad. Durante el periodo neonatal, es característica la ictericia colestática asociada a hipoglucemias recurrentes. Puede formar parte de un cuadro sindrómico, siendo el más frecuente la displasia septoóptica, que asocia defectos de línea media y alteraciones oculares. La mayoría presenta anomalías anatómicas de la región selar y supraselar evidenciables en la Resonancia Magnética. El diagnóstico bioquímico tiene especificaciones particulares para la evaluación de cada trofina hipofisaria y de acuerdo a la edad del paciente. El tratamiento consiste en la terapia de reemplazo hormonal observándose buena respuesta en la mayoría de los pacientes. La detección precoz de los niños con insuficiencia hipofisaria permite la activación rápida y efectiva de una estrategia diagnóstica con la toma de muestras bioquímicas apropiadas, la consulta temprana al endocrinólogo infantil y la instauración del tratamiento específico

Congenital pituitary hormone deficiency is a disorder originated in pituitary gland ontogeny generating decrease or lack of pituitary hormones: adrenocorticotropin, thyrotropin, growth hormone, prolactin, gonadotropins and/or antidiuretic hormone. It is a complex and infrequent disease usually difficult to recognize at an early age due to its non-specific symptomatology, resulting in increased morbidity and eventual mortality. During the neonatal period, cholestatic jaundice associated with recurrent hypoglycaemia is frequent. Pituitary hormone deficiency can be part of a syndrome; the most frequent is septo-optic dysplasia, associating midline defects and ocular disorders. Most have anatomical anomalies of the sellar and suprasellar region seen in magnetic resonance imaging. Biochemical diagnosis has particular specifications for the evaluation of each pituitary hormone and varies according to patient´s age. The treatment consists in hormone replacement therapy and generally with good results. The early detection of children with pituitary hormone deficiency allows the rapid and effective activation of a diagnostic strategy, facilitates the appropriate biochemical samples, the early contact with the pediatric endocrinologist and the establishment of specific treatment

Hypopituitarism Secondary to an Arachnoid Cyst ­ Case Report

Arachnoid cysts (ACs) are a rare condition of mass effect injury and are usually found in the Sylvian fissure. However, rarely, they can appear in the sellar area, causing symptoms of compression. Due to the mass effect, the sellar arachnoid cyst (SAC) may cause headaches, visual disturbances, hypopituitarism, precocious puberty, and the "bobble-head doll" syndrome. We present the case of JNS, 61 years old, male. The patient presented with hypotestosteronism, hypothyroidism, hypocortisolism and bitemporal hemianopsia. The magnetic resonance imaging scans revealed a mass above the pituitary gland, compatible with a SAC. A surgical excision was performed with removal of the capsule and fenestration within the subarachnoid spaces for emptying the cyst. After the procedure, the patient presented great clinical improvement. The rarity of the case calls attention to the fact that SACs should be thought of as a differential diagnosis in cases of hypopituitarism.

Cistos aracnoides são uma condição rara de lesão de efeito de massa e que comumente aparecem na região da fissura silviana. No entanto, raramente, podem aparecer na região selar, ocasionando sintomas de compressão. Devido ao efeito de massa, podem causar dores de cabeça, distúrbios visuais, hipopituitarismo, puberdade precoce e síndrome da "bobble-head doll. " Apresentamos o caso de JNS, 61 anos, do sexo masculino. Paciente com hipotestosteronismo, hipotiroidismo, hipocortisolismo e hemianopsia bitemporal. As imagens de ressonância magnética (RM) revelaram uma massa acima da hipófise, mostrando um cisto aracnoide selar. O paciente foi submetido a excisão cirúrgica com fenestração dentro dos espaços subaracnoides para esvaziamento do cisto e apresentou grande melhora clínica após o procedimento. A raridade deste caso chama atenção para o fato de que o cisto aracnoide selar deve ser considerado como um diagnóstico diferencial em casos de hipopituitarismo.

Panhipopituitarismo secundario a metástasis del sistema nervioso central por un adenocarcinoma broncogénico / Panhypopituitarism secondary to metastasis of the central nervous system due to a bronchogenic adenocarcinoma

Resumen Mujer de 45 años de edad con antecedente de extabaquismo pesado, cursó con cuadro crónico de cefalea en región occipital irradiado a región temporal asociado a disminución de la agudeza visual de ojo izquierdo. El cuadro empeoró en los últimos seis meses y se asoció a polidipsia y poliuria. Presentó cuadro sincopal con amnesia retrógrada, para lo cual se realizó una tomografía axial computarizada (TAC) contrastada de cráneo que mostró múltiples lesiones parenquimatosas cerebrales y del cerebelo compatibles con metástasis. Se hizo estudio hormonal para evaluar la función hipofisiaria evidenciando un panhipopituitarismo secundario. Se detectó foco primario neoplásico mediante TAC contrastada de tórax, evidenciando una lesión espiculada en el lóbulo superior derecho sugestiva de carcinoma broncogénico, posteriormente se tomó biopsia por fibrobroncoscopia el cual confirmó por histopatología e inmunohistoquímica el diagnóstico de un adenocarcinoma broncogénico. (Acta Med Colomb 2018; 43: 115-118).

Abstract A 45-year-old woman with a history of heavy extabaquism presented with chronic headache in the occipital region irradiated to the temporal region associated with decreased visual acuity of the left eye. The picture worsened in the last six months and was associated with polydipsia and polyuria. She presented a syncopal picture with retrograde amnesia, for which a contrast computed tomography (CT) of the skull was performed, which showed multiple parenchymal brain and cerebellar lesions compatible with metastasis. Hormonal study was done to evaluate the hypophyseal function evidencing a secondary panhypopituitarism. A primary neoplastic focus was detected by a contrast chest CT scan, showing a spiculated lesion in the right upper lobe suggestive of bronchogenic carcinoma. A biopsy was subsequently taken by fibrobronchoscopy, which confirmed the diagnosis of a bronchogenic adenocarcinoma by histopathology and immunohistochemistry. (Acta Med Colomb 2018; 43: 115-118).

Panhipopituitarismo y escotoma perimacular como presentación de enfermedad relacionada a IgG4 / IgG4 related disease presenting as panhypopituitarism and perimacular scotoma

La enfermedad relacionada a IgG4 (IgG4-RD) constituye una entidad sistémica recientemente descrita, de causa desconocida. Afecta predominantemente a hombres mayores y presenta características histopatológicas distintivas, como fibrosis estoriforme, flebitis obliterante y denso infiltrado linfoplasmocitario con inmunomarcación para IgG4, pudiendo estar asociada a elevación sérica de dicha inmunoglobulina. Si bien cualquier órgano puede estar afectado, el compromiso de la hipófisis es infrecuente. Describimos el caso de un hombre de 36 años que se presentó con cefaleas, alteración del campo visual, panhipopituitarismo, diabetes insípida y una imagen que mostraba una lesión infiltrativa infundíbulo-panhipofisaria extendida. Arribamos al diagnóstico de IgG4-RD a través de biopsia hipofisaria. La respuesta al tratamiento con dosis inmunosupresoras de corticoides fue exitosa.

IgG4-related disease (IgG4-RD) is a recently described systemic entity of unknown origin. It predominantly affects older men and has distinctive histopathologic features as storiform fibrosis, obliterative phlebitis, dense lymphoplasmacytic infiltrate with immunostaining for IgG4, and it may be associated with elevated serum levels of IgG4. Although any organ can be affected, pituitary gland is rarely involved. We describe the case of a 36-year-old man who presented with headaches, impaired vision, panhypopituitarism with diabetes insipidus and an infiltrative lesion mainly of infundibulum and pituitary. We arrived at diagnosis of IgG4-RD by pituitary biopsy. A successful response to treatment with immunosuppressive doses of corticosteroids was achieved.