Panhypopituitarism and bifid uvula / Journal of the ASEAN Federation of Endocrine Societies

@#A 20-year-old male was referred to the Endocrinology Clinic in view of abnormal thyroid function test result and poor development of secondary sexual characteristics. He was born out of non-consanguineous marriage and had a history of breech delivery at term. He had perinatal complications in the form of delayed cry and lower respiratory tract infection. Developmental delay was also present (delayed motor, speech and social milestones). His scholastic performance was below average and he reported being the shortest child in class from kindergarten.

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.

Sheehan’s Syndrome presenting as postpartum psychosis

@#Sheehan’s syndrome is characterized by hypopituitarism following ischemic necrosis of the pituitary gland caused by postpartum hemorrhage and impaired blood supply to the enlarged pituitary gland during pregnancy. The worldwide prevalence has since decreased due to improvements in obstetric care. Behavioral change is a rare presentation and is often misdiagnosed and managed as psychosis. We report a 42-year-old woman presenting with behavioral changes associated with postpartum failure of lactation and amenorrhea. Hormonal work-up revealed panhypopituitarism; serum cortisol, 98.93 (NV: 138–690 nmol/L); free T4, less than 5.15 (NV: 11.5–23.00 pmol/L); free T3, less than 2.30 (NV: 2.89–4.88 pmol/L); FSH, 3.63 (NV: 30–135 mIU/mL); LH, 3.88 (NV: 13–80 mIU/mL); serum estradiol, 3.89 (NV: 10.41–35.0 pg/mL); IGF-1, 13.13 (NV: 56–194 ng/mL); and serum prolactin, 1.8 (NV: 2.6–24.8 ng/mL). Cranial MRI with contrast revealed an atrophic pituitary gland consistent with Sheehan's syndrome. The symptoms improved substantially upon replacement with steroids and thyroid hormones and she was able to resume her routine activities. The psychiatric features of hypopituitarism can be attributed to a combination of hypothyroidism, hypoglycemia, and hypocortisolism and have been shown to reverse with adequate hormone replacement.

Treatment outcome of a β-hCG Secreting Intracranial Germ Cell Tumorin an adult Filipino using definitive Chemotherapy followed by Radiotherapy: A case report / Journal of the ASEAN Federation of Endocrine Societies

@#We report a case of a 24-year-old Filipino male who complained of general weakness, polydipsia, weight loss, bitemporal headaches, loss of libido and behavioral changes. Endocrine work-up revealed neurogenic diabetes insipidus and panhypopituitarism. Brain MRI showed multiple intracranial tumors in the left frontal lobe, pineal and suprasellar region with moderate non-communicating hydrocephalus. Intracranial mass biopsy with ventriculo-peritoneal shunting was done. Histopathology of the mass and CSF revealed a germinoma. He underwent chemoradiotherapy while on maintenance hormone replacement.

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases / 北京大学学报(医学版)

Pituitary immune-related adverse events induced by programmed cell death protein 1 inhibitors in advanced lung cancer patients: A report of 3 cases SUMMARY Programmed cell death protein 1 (PD-1) and its ligand 1 (PD-L1) have been widely used in lung cancer treatment, but their immune-related adverse events (irAEs) require intensive attention. Pituitary irAEs, including hypophysitis and hypopituitarism, are commonly induced by cytotoxic T lymphocyte antigen 4 inhibitors, but rarely by PD-1/PD-L1 inhibitors. Isolated adrenocorticotropic hormone(ACTH) deficiency (IAD) is a special subtype of pituitary irAEs, without any other pituitary hormone dysfunction, and with no enlargement of pituitary gland, either. Here, we described three patients with advanced lung cancer who developed IAD and other irAEs, after PD-1 inhibitor treatment. Case 1 was a 68-year-old male diagnosed with metastatic lung adenocarcinoma with high expression of PD-L1. He was treated with pembrolizumab monotherapy, and developed immune-related hepatitis, which was cured by high-dose methylprednisolone [0.5-1.0 mg/(kg·d)]. Eleven months later, the patient was diagnosed with primary gastric adenocarcinoma, and was treated with apatinib, in addition to pembrolizumab. After 17 doses of pembrolizumab, he developed severe nausea and asthenia, when methylprednisolone had been stopped for 10 months. His blood tests showed severe hyponatremia (121 mmol/L, reference 137-147 mmol/L, the same below), low levels of 8:00 a.m. cortisol (< 1 μg/dL, reference 5-25 μg/dL, the same below) and ACTH (2.2 ng/L, reference 7.2-63.3 ng/L, the same below), and normal thyroid function, sex hormone and prolactin. Meanwhile, both his lung cancer and gastric cancer remained under good control. Case 2 was a 66-year-old male with metastatic lung adenocarcinoma, who was treated with a new PD-1 inhibitor, HX008, combined with chemotherapy (clinical trial number: CTR20202387). After 5 months of treatment (7 doses in total), his cancer exhibited partial response, but his nausea and vomiting suddenly exacerbated, with mild dyspnea and weakness in his lower limbs. His blood tests showed mild hyponatremia (135 mmol/L), low levels of 8:00 a.m. cortisol (4.3 μg/dL) and ACTH (1.5 ng/L), and normal thyroid function. His thoracic computed tomography revealed moderate immune-related pneumonitis simultaneously. Case 3 was a 63-year-old male with locally advanced squamous cell carcinoma. He was treated with first-line sintilimab combined with chemotherapy, which resulted in partial response, with mild immune-related rash. His cancer progressed after 5 cycles of treatment, and sintilimab was discontinued. Six months later, he developed asymptomatic hypoadrenocorticism, with low level of cortisol (1.5 μg/dL) at 8:00 a.m. and unresponsive ACTH (8.0 ng/L). After being rechallenged with another PD-1 inhibitor, teslelizumab, combined with chemotherapy, he had pulmonary infection, persistent low-grade fever, moderate asthenia, and severe hyponatremia (116 mmol/L). Meanwhile, his blood levels of 8:00 a.m. cortisol and ACTH were 3.1 μg/dL and 7.2 ng/L, respectively, with normal thyroid function, sex hormone and prolactin. All of the three patients had no headache or visual disturbance. Their pituitary magnetic resonance image showed no pituitary enlargement or stalk thickening, and no dynamic changes. They were all on hormone replacement therapy (HRT) with prednisone (2.5-5.0 mg/d), and resumed the PD-1 inhibitor treatment when symptoms relieved. In particular, Case 2 started with high-dose prednisone [1 mg/(kg·d)] because of simultaneous immune-related pneumonitis, and then tapered it to the HRT dose. His cortisol and ACTH levels returned to and stayed normal. However, the other two patients' hypopituitarism did not recover. In summary, these cases demonstrated that the pituitary irAEs induced by PD-1 inhibitors could present as IAD, with a large time span of onset, non-specific clinical presentation, and different recovery patterns. Clinicians should monitor patients' pituitary hormone regularly, during and at least 6 months after PD-1 inhibitor treatment, especially in patients with good oncological response to the treatment.

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.

Cryptorchidism is a useful clue for Idiopathic Hypogonadotropic Hypogonadism in Pituitary Stalk Thickening / Journal of the ASEAN Federation of Endocrine Societies

@#Pituitary stalk lesions can represent a wide range of pathologies. The exact cause is often unknown due to hesitancy to proceed with biopsy. We present a 16-year-old adolescent who presented with delayed puberty, short stature and bilateral cryptorchidism. He was found to have a thickened pituitary stalk of uncertain etiology with partial hypopituitarism (gonadotrophin and growth hormone deficiency) on further assessment. The presence of bilateral cryptorchidism and micropenis represents lack of “mini puberty,” a phenomenon of activation of the hypothalamic-pituitary-gonadal (HPG) axis in-utero or within the first few months of life.1 These key clinical features have been useful to establish an early temporal relationship and suggest a congenital origin of disease. This enabled a more conservative approach of surveillance to be employed as opposed to invasive pathological examination with pituitary stalk biopsy.

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