Extra-pituitary midline structural abnormalities associated with ectopic posterior pituitary detected on a new rapid MRI protocol (FAST1.2)

ABSTRACT Objective: Test if the MRI FAST1.2 protocol can detect extra-pituitary midline structural brain abnormalities in patients with ectopic posterior pituitary (EPP), and highlighting their radiological-laboratory correlations. Subjects and methods: Cross-sectional study of patients with EPP and control group. All individuals were submitted to FAST1.2, which combines the FAST1 protocol developed by our group with 3D T2DRIVE imaging. Results: We evaluated 36 individuals with EPP and 78 as control group. Pituitary stalk (PS) was identified in 7/36 patients in EPP group by FAST1, and in 24/36 patients in FAST1.2 (p < 0.001). FAST1 failed to detect PS in one individual in the control group, while the FAST1.2 defined the PS in all individuals. In EPP group, eleven had interhypothalamic adhesion (IHA), three septo-optic dysplasia, and one cerebellar malformation. We didn't observe higher frequency of panhypopituitarism or developmental delay in patients with IHA. In control group, three had pars intermedia cysts, one hydrocephalus, and one hypothalamic hamartoma. Conclusions: FAST1.2 allows confident recognition of midline structural abnormalities, including the pituitary stalk and IHA, thereby making MRI acquisition faster and with no need for contrast administration. IHA could be associated with defects in neuronal migration, as occur in patients with EPP, with no clinical significance.

Sampling of the petrosal sinuses. Indications, results and usefulness / Muestreo de senos petrosos. Indicaciones, resultados y utilidad

Abstract Objectives: to analyze, evaluate and describe the usefulness of petrosal sinus sampling for diagnosing central Cushing's syndrome. Materials and methods: the technical aspects and results of bilateral venous sampling of the petrosal sinuses at the Hospital Universitario San Vicente de Paul in Medellín, Colombia, from January 1, 2012 to December 31, 2018, were analyzed. Results: the average age was 43.3 years, with a range from 19 to 69 years. Laterality could be shown in 68.2% of cases, with a tendency to be located on the left in 53.3%. The central source of ACTH production could be shown in 95.4% of cases, with a basal average central/peripheral ratio of 21.7, and 70.8 after stimulation. All samples at 3, 5 and 10 minutes were confirmatory following stimulation. Conclusion: in our retrospective study, petrosal sinus catheterization provided laboratory confirmation of the central source of ACTH production in a high percentage of patients, with no immediate complications.

Resumen Objetivos: analizar, evaluar y describir la utilidad del muestreo de senos petrosos para diagnóstico del síndrome de Cushing de origen central. Material y métodos: se analizaron los aspectos técnicos y resultados del muestreo bilateral venoso de senos petrosos, desde el 1° de enero de 2012 a 31 de diciembre de 2018 en el Hospital Universitario San Vicente de Paúl en Medellín, Colombia. Resultados: el promedio de edad fue 43.3 años con un rango de edad desde los 19 hasta los 69 años. La lateralidad pudo ser demostrada en 68.2% de los casos con una tendencia a la localización en el lado izquierdo en 53.3%. El origen central de producción de ACTH logró ser demostrado en 95.4% de los casos, con una relación central/periferia basal promedio de 21.7 y postestimulación de 70.8. Todas las muestras a los 3, 5 y 10 minutos fueron confirmatorias tras la estimulación. Conclusión: en nuestro estudio retrospectivo el cateterismo de senos petrosos confirmó la fuente central de producción de ACTH por laboratorio en un alto porcentaje de pacientes sin ninguna complicación inmediata.

As consequências irreversíveis do diagnóstico tardio de macroadenoma de hipófise em paciente jovem / The irreversible consequences of late diagnosis of pituitary macroadenoma in a young patient

Resumo Os tumores de hipófise representam aproximadamente 15% de todos os tumores cerebrais e dependendo do tamanho, pressionam o quiasma óptico, resultando em comprometimento da função visual que se manifesta como defeitos no campo visual, diminuição da acuidade visual e da visão das cores. O objetivo do presente estudo foi relatar um caso de macroadenoma de hipófise com compressão do quiasma óptico e defeito no campo visual, tratado inicialmente como glaucoma, levando a um diagnóstico e tratamento tardio.

Abstract Pituitary tumors represent approximately 15% of all brain tumors and depending on size, pressure optic chiasma, resulting in impaired visual func-tion that manifests itself as defective in the visual field, decreased acuity visual and color vision. The ob-jetive of the present study was to report a case of pitui-tary macroadenoma with compression of optical chiasma and visual field de-fect, initially treated as glaucoma, leading to a late diagnosis and treatment.

Pituitary gigantism: a case series from Hospital de San José (Bogotá, Colombia)

ABSTRACT Introduction Gigantism is a rare pediatric disease characterized by increased production of growth hormone (GH) before epiphyseal closure, that manifests clinically as tall stature, musculoskeletal abnormalities, and multiple comorbidities. Materials and methods Case series of 6 male patients with gigantism evaluated at the Endocrinology Service of Hospital de San José (Bogotá, Colombia) between 2010 and 2016. Results All patients had macroadenomas and their mean final height was 2.01 m. The mean age at diagnosis was 16 years, and the most common symptoms were headache (66%) and hyperhidrosis (66%). All patients had acral changes, and one had visual impairment secondary to compression of the optic chiasm. All patients underwent surgery, and 5 (83%) required additional therapy for biochemical control, including radiotherapy (n = 4, 66%), somatostatin analogues (n = 5, 83%), cabergoline (n = 3, 50%), and pegvisomant (n = 2, 33%). Three patients (50%) achieved complete biochemical control, while 2 patients showed IGF-1 normalization with pegvisomant. Two patients were genetically related and presented a mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene (pathogenic variant, c.504G>A in exon 4, p.Trp168*), fulfilling the diagnostic criteria of familial isolated pituitary adenoma. Conclusions This is the largest case series of patients with gigantism described to date in Colombia. Transsphenoidal surgery was the first-choice procedure, but additional pharmacological therapy was usually required. Mutations in the AIP gene should be considered in familial cases of GH-producing adenomas.

Pituitary stalk interruption syndrome in newborn: a case report / 中华围产医学杂志

This study reported a postterm female infant born at 43+2 weeks of gestation via cesarean section with a birth weight of 2 950 g.Cyanosis was presented around 14 h after birth.Laboratory test results showed that the blood glucose was 1.4 mmol/L and the levels of free triiodothyronine (FT3),free tetraiodothyronine (FT4),thyrotropin (TSH),growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were significantly reduced.Cranial MRI confirmed the diagnosis of pituitary stalk interruption syndrome.The baby girl was treated with hydrocortisone and levothyroxine and discharged following clinical symptoms improvement and blood glucose normalization.Follow-up data showed unstable blood glucose and hypothyroidism at six and 10 months after birth and growth retardation at 15 months.

Pituitary stalk interruption syndrome in newborn: a case report / 中华围产医学杂志

This study reported a postterm female infant born at 43+2 weeks of gestation via cesarean section with a birth weight of 2 950 g. Cyanosis was presented around 14 h after birth. Laboratory test results showed that the blood glucose was 1.4 mmol/L and the levels of free triiodothyronine (FT3), free tetraiodothyronine (FT4), thyrotropin (TSH), growth hormone (GH) and insulin-like growth factor-1 (IGF-1) were significantly reduced. Cranial MRI confirmed the diagnosis of pituitary stalk interruption syndrome. The baby girl was treated with hydrocortisone and levothyroxine and discharged following clinical symptoms improvement and blood glucose normalization. Follow-up data showed unstable blood glucose and hypothyroidism at six and 10 months after birth and growth retardation at 15 months.

Thickened pituitary stalk associated with a mass in the sphenoidal sinus: an alarm to suspect hypophysitis by immunoglobulin g4?

Introduction Hypophysitis is a chronic inflammation of the pituitary gland of complex and still incompletely defined pathogenesis. It belongs to the group of non-hormonesecreting sellar masses, sharing with them comparable clinical presentation and radiographic appearance. Objectives Describe the case of immunoglobulin G4 (IgG4)-related hypophysitis presenting as a mass in the sphenoid sinus. Resumed Report A 40-year-old Brazilian man had a diagnosis of central diabetes insipidus since 2001 associated with pituitary insufficiency. Pituitary magnetic resonance imaging revealed a centered pituitary stalk with focal nodular thickening and the presence of heterogeneous materials inside the sphenoid sinus. The patient was treated with testosterone replacement therapy. Laboratory results revealed increased IgG4 serum. Conclusion IgG4-related hypophysitis should be considered in patients with pituitary insufficiency associated with sellar mass and/or thickened pituitary stalk. IgG4 serum measurement for early diagnosis of IgG4-related hypophysitis should be performed.

Surgical treatment of non-functioning pituitary macroadenomas by the endoscopic endonasal approach in the elderly / Tratamento cirúrgico dos macroadenomas não secretores de hipófise por via endoscópica endonasal em idosos

Over the past three decades, surgical series of elderly patients treated for pituitary adenomas have been published, all of which used the microscopic transsphenoidal or transcranial approach. The objective of this study was to retrospectively analyze the surgical results of our first 25 elderly patients with non-functioning pituitary macroadenoma (NFPM) operated by the endoscopic endonasal approach (EEA). Preoperative visual loss was found in 92.8% of the cases, and 70.8% experienced visual improvement following surgery. Preoperative pituitary dysfunction was found in 69.2% of the cases and postoperative pituitary recovery occurred in 22.2% of them. Mean hospital stay was 6.7 days. The results of this study suggest that surgery remains the first line of treatment for NFPM in the elderly. Because age alone is not a barrier for surgery, patients should be selected for surgical treatment based on their symptoms and clinical condition, as defined by comorbidities.

Nas últimas três décadas, foram publicadas casuísticas de pacientes idosos operados por adenomas de hipófise, nas quais foram utilizadas as vias transcraniana ou transesfenoidal microcirúrgicas. O objetivo deste estudo foi analisar retrospectivamente os resultados dos nossos primeiros 25 pacientes idosos com macroadenomas não secretores de hipófise, operados pela via endoscópica endonasal. O déficit visual pré-operatório foi encontrado em 92,8% dos casos e 70,8% apresentaram melhora da visão depois da cirurgia. O hipopituitarismo pré-operatório foi encontrado em 69,2% dos casos e a sua recuperação ocorreu em 22,2% destes casos. A estadia hospitalar média foi de 6,7 dias. Este estudo sugere que a cirurgia permanece como o tratamento de primeira escolha para pacientes idosos com macroadenomas não secretores de hipófise e a idade por si só não é contraindicação para cirurgia.

Clinical analyses of 11 cases with pituitary stalk interruption syndrome / 中华全科医师杂志

Eleven male patients with pituitary stalk interruption syndrome (PSIS) at our hospital were retrospectively analyzed with respects to clinical features,endocrine status and imaging characteristics.The clinical manifestations included growth retardation and delayed puberty.All of them were deficient in growth hormone and pituitary gonadotropin secretion.Secondary hypothyroidism and hypocortisolism occurred in 8 patients and one had concurrent central diabetes insipidus.MRI with gadolinium contrast revealed no pituitary stalk or slim and anterior pituitary hypoplasia with ectopic posterior pituitary.The clinical characteristics of PSIS are growth retardation and delayed puberty,partial or complete adenohypophyseal dysfunction.The detection of hypothalamic pituitary region by MRI is an important diagnostic tool.

Adenoma de hipófisis como forma infrecuente de insuficiencia suprarrenal secundaria. Presentación de un caso / Pituitary Adenoma as a Rare Form of Secondary Adrenal Insufficiency. A Case Report

Los adenomas de hipófisis son tumores benignos originados en uno de los cinco tipos celulares de la hipófisis anterior. La insuficiencia suprarrenal secundaria ocurre cuando las glándulas adrenales no producen hormonas por la falta de hormona adenocorticotrópica hipofisaria o del factor liberador de corticotropina hipotalámico. Se presenta el caso de una paciente de 37 años de edad, que un año atrás comenzó con fasciculaciones musculares de piernas y brazos, debilidad muscular, cansancio fácil, dolores musculares, cefalea hemicránea derecha, intensa y pulsátil, entre otros síntomas. Se le realizaron varios estudios (dosificación de cortisol en sangre, hormona adenocorticotrópica, calcio y fósforo en sangre y orina, resonancia magnética de cráneo) que permitieron el diagnóstico de adenoma de hipófisis con déficit aislado de hormona adenocorticotrópica e insuficiencia suprarrenal secundaria. El tratamiento con esteroides y suplementos de calcio garantizaron la evolución favorable.

Pituitary adenomas are benign tumors arising from one of the five cell types in the anterior pituitary. Secondary adrenal insufficiency occurs when the adrenal glands do not produce hormones due to the lack of pituary adrenocorticotropic hormone or hypothalamic corticotropin-releasing factor. The case of a 37-year-old female patient who started developing muscle twitching in legs and arms, muscular weakness, fatigue, muscle aches, severe and throbbing hemicrania on the right side, among other symptoms, a year ago is presented. Several tests were performed (cortisol level, adrenocorticotropic hormone, calcium and phosphorus in blood and urine, magnetic resonance imaging of the skull), leading to the diagnosis of pituitary adenoma with isolated adrenocorticotropic hormone deficiency and secondary adrenal insufficiency. Treatment with steroids and calcium supplements ensured a satisfactory recovery.

Efeitos do cetoconazol e seus mecanismos de ação in vitro sobre linhagens hipofisárias tumorais imortalizadas / Effects of ketoconazole and its mechanisms of action in pituitary tumoral immortalizaded cell lines

O cetoconazol, inicialmente descrito como um agente antifúngico, revelou-se um potente inibidor da esteroidogênese adrenal, podendo, assim, ser utilizado no manejo da doença de Cushing, como terapia primária ou após insucesso cirúrgico, enquanto aguarda o efeito da radioterapia. Durante o tratamento com cetoconazol, uma redução dos níveis de cortisol é observada, usualmente não acompanhada por uma elevação do ACTH plasmático, como poderia ser esperada. Este fenômeno paradoxal, caracterizado pela redução do cortisol com níveis de ACTH inadequadamente normais ou não elevados, pode estar relacionado a uma ação adicional do cetoconazol nas células hipofisárias produtoras de ACTH. Para se testar essa hipótese, alguns estudos in vitro realizados na década de 80, avaliando a secreção de ACTH na vigência do cetoconazol, sugeriram a sua ação em células adenohipofisárias. Em adição, foi evidenciado que o cetoconazol ativou vias de apoptose em linhagens tumorais não hipofisárias. O presente estudo tem como objetivo avaliar o efeito in vitro do cetoconazol na viabilidade celular e na expressão de genes envolvidos na apoptose e replicação do DNA em linhagens tumorais hipofisárias imortalizadas corticotróficas (AtT-20), gonadotróficas (alfaT3.1), mamossomatotróficas (GH3) e mamotróficas (MMQ), utilizando-se a técnica de RT-qPCR. Os resultados mostraram que, na presença do cetoconazol, ocorreu uma redução da viabilidade celular nas linhagens hipofisárias, de forma concentração-dependente, às custas do estímulo da via extrínseca e intrínseca da apoptose, com aumento da expressão dos receptores de morte celular (ex.: Fas, TNFR) e/ou caspases (ex.: -2, -3, -6 ,-7 ,-9). Estes resultados foram associados a um aumento da expressão gênica dos inibidores do ciclo celular p21 (nas linhagens GH3 e alfaT3.1) e p27 (nas linhagens GH3 e MMQ), com uma redução acentuada da expressão destes genes após retirada do cetoconazol do meio de cultura...

Ketoconazole, initially described as an antifungal agent, proved to be a potent inhibitor of steroidogenesis, allowing its use in the management of Cushing's disease as primary or after unsuccessfully surgery and waiting the effect of radiotherapy. During treatment with ketoconazole, there a reduction in the cortisol levels is observed, usually not accompanied by an elevation of plasmatic ACTH, as could be expected. This paradoxical phenomenon, characterized by reduced cortisol with ACTH levels inappropriately normal or not elevated, could be related to an additional action of ketoconazole on ACTH-producing pituitary cells. In agreement with this hypothesis, some in vitro studies in the 80's, evaluating ACTH secretion in the presence of ketoconazole, suggested its action in pituitary cells. In addition, ketoconazole activated apoptosis pathways in non-pituitary tumor cell lines. Therefore, the present study aims to revisit this topic and evaluate the in vitro effect of ketoconazole on cell viability and expression of genes involved in apoptosis and DNA replication by RT-qPCR in immortalized pituitary tumoral corticotroph (AtT-20), gonadotroph (alphaT3.1), mammosomatotroph (GH3), mammotroph (MMQ) cell line. As a result, there was a reduction in pituitary cell viability with ketoconazole, in a concentration-dependent manner, due to stimulation of the extrinsic and intrinsic pathway of apoptosis, with increased expression of cell death receptors (eg. Fas, TNFR) and/or caspases (eg. -2, -3, -6, -7, -9). These results were associated with an increased gene expression of the cell cycle inhibitors p21 (in GH3 and alphaT3.1 cell line), and also p27 (in GH3 and MMQ cell line), with a significant reduction in the expression of these genes after removal of ketoconazole in the media. In conclusion, the ketoconazole have the potential of reduce cell viability in pituitary tumoral lineages possibly due to a cytotoxic effect (by increasing...

Oronasal complications in patients after transsphenoidal hypophyseal surgery / Complicações oronasais em pacientes pós-abordagem hipofisária via transesfenoidal

Transsphenoidal surgery is the most commonly used surgical procedure to handle the hypophyseal region, sometimes associated with oronasal complications. MATERIAL AND METHODS/AIM: To evaluate prospectively (specific questionnaire, clinical evaluation) undiagnosed chronic oronasal complications in patients submitted to conventional transsphenoidal adenomectomy surgery, operated at different neurosurgery services more than 6 months ago. RESULTS: 49 patients were evaluated, 37/45 presented macroadenoma. 28,5 percent were submitted to more than one intervention, 2/5 transsphenoidally. Transsphenoidal approach 92.8 percent through sublabial route. No patient had spontaneous complaint. With the specific questionnaire 63.2 percent presented complaints. One patient presented an oronasal fistula, 1 stenosis of the nasal valve area with external nasal deformity. Rhinoscopy detected alterations in 77.5 percent, nasal endoscopy in 87.7 percent. Septal perforation was present in 10/12 patients with scabs and 2 with purulent secretion. All 4 patients submitted to 2 transsphenoidal approaches presented septal perforation and nasal synechiae. In the endonasal, synechiae (2), alteration in medium meatus (1) and stenosis of the nasal valve area (1) were observed. Only two patients presented normal evaluation. CONCLUSION: A high incidence of nasal complications after conventional transsphenoidal surgery observed through examination and not reported spontaneously point to the need of otorhinolaryngological investigation complemented by nasal endoscopy in patients submitted to procedures through this route.

A cirurgia transesfenoidal é o procedimento cirúrgico mais utilizado para abordagem da região hipofisária, sendo por vezes associada a complicações oronasais. MATERIAL E MÉTODOS/OBJETIVO: Estudo prospectivo, através de questionário específico e avaliação clínica complicações oronasais crônicas não-diagnosticadas, em pacientes submetidos à cirurgia transesfenoidal convencional em diferentes serviços de neurocirurgia há mais de 6 meses. RESULTADOS: 49 pacientes, 37/45 com macroadenoma. 14/49 submetidos a mais de uma intervenção, em 2/5 por via transesfenoidal. Abordagem transesfenoidal 92,8 por cento via sublabial. Nenhum apresentava queixa espontânea. Com o questionário específico, 63,2 por cento apresentaram queixas. Um apresentava fístula oronasal, outro, estenose da área de válvula nasal com deformidade nasal externa. A rinoscopia detectou alterações em 77,5 por cento e a endoscopia nasal em 87,7 por cento. Perfuração septal presente em 10/12 pacientes com crostas e 2 com secreção purulenta. Todos 4 pacientes submetidos a 2 abordagens transesfenoidais apresentaram perfuração do septo e sinéquias nasais. Nos casos com abordagem endonasal observaram-se sinéquias2, alteração em meato médio1 e estenose em área de válvula nasal1. Apenas 2 pacientes apresentaram avaliação normal. CONCLUSÃO: Alta incidência de complicações nasais após abordagem transesfenoidal convencional, observadas (exame) e não referidas espontaneamente indicam a necessidad de investigação otorrinolaringológica complementada com endoscopia nasal sistemática nestes pacientes.

Pituitary abscess:a review of 7 cases and some points about its diagnosis / 中国实用内科杂志

Objective To analyze the clinical features,auxiliary examination,diagnosis and treatment of pituitary abscess.Methods A retrospective analysis was done in 7 cases of pituitary abscess.All cases’ final diagnose were confirmed by histopathological results.Results 1.Four cases were diagnosed as primary pituitary abscess,the others 3 cases as secondary pituitary abscess which was associated with pituitary adenoma,pituitary cyst,craniopharyngeal duct tumor respectively.2.Clinical features:Of 7 cases,fever was determined in 6 cases,visual disturbance or temporal hemianopia in 5 cases,headache associated with anorexia and nausea and vomitting in 4 cases.High white blood cell counts was present in 3 cases,high PRL levels in 4 cases.Three cases were associated with hypothyroidism,2 cases with hypoadrenocorticism.MR image showed isointense or hypointense signal on T1WI and isointense or hyperintense signal on T2WI in pituitary abscess.Postcontrast T1WI showed a ring-shaped enhancement.Two cases were diagnosed by MR images and clinical features before surgery,the others by surgical histopathology.3.Treatment:All cases were treated with surgery,followed by antibiotics therapy.After operation all symptoms were improved except for optic nerve function.Conclusion It is suggestive of pituitary abscess when any patient present firstly with fever,headache,visual or eyeshot disturbance,partial or whole hypopituitarism associated with saddle area mass.Earlier diagnosis,timely surgery and postoperative proper antibiotics therapy are the keys to the treatment of pituitary abscess.

First Male Case of Lymphocytic Hypophysitis in Korea

Lymphocytic hypophysitis is a rare inflammatory disorder which is caused by autoimmune destruction of the pituitary gland. Almost all reported cases have been in women and the disease is often associated with pregnancy. We describe here the first male case of lymphocytic hypophysitis in Korea. The patient presented with headache, impotence, decreased libido, and deteriorated vision. Endocrinologic studies showed panhypopituitarism, and pituitary MRI imaging revealed a homogeneously enhanced pituitary mass with a thickened stalk. Treatment with prednisolone and thyroid hormone for five months was ineffective. Transsphenoidal resection of the pituitary mass was performed successfully with normalization of the visual field defect. Histologic examination revealed diffuse lymphocytic infiltration with dense collagenous fibrosis, consistent with lymphocytic hypophysitis. Lymphocytic hypophysitis should be considered in differential diagnosis even in men with hypopituitarism and an enlarged pituitary gland.