Strikingly low prevalence of pituitary incidentalomas in a teaching hospital in Uruguay.

Background: Pituitary incidentalomas are an occurrence documented in 10.6% of post-mortem examinations, 4%-20% of computed tomography (CT) scans, and 10%-38% of magnetic resonance imaging (MRI) cases, primarily consisting of microincidentalomas (<1 cm in size). However, the prevalence of pituitary incidentalomas in Uruguay remains unexplored. This study aimed to ascertain the prevalence of pituitary incidentalomas at our hospital. Methods: In this investigation, we retrospectively identified patients who underwent brain CT and MRI at our hospital over a 1-year span due to conditions other than suspected or known pituitary disorders. The time frame covered was from 1 January to 31 December 2017. Our analysis encompassed all scans, and we conducted interviews with patients discovered to have pituitary incidentalomas. Furthermore, we conducted biochemical assessments in accordance with clinical and imaging traits. Results: During the study period, a total of 3,894 patients underwent imaging procedures. Of these, 1,146 patients underwent MRI scans, and 2,748 underwent CT scans. The mean age was 53.1 ± 19 years, with a relatively even distribution between genders (50.6% women). The majority of imaging requisitions originated from the emergency department (43%), followed by outpatient clinics (29%), and inpatient wards (28%). Common reasons for imaging requests included trauma (20.4%), headaches (11.3%), and stroke (10.9%). Among these cases, two pituitary incidentalomas were detected, resulting in a prevalence of 5 cases per 10,000 individuals annually (0.051%). Both of these cases were initially identified through CT scans, with subsequent MRI scans performed for further assessment. The final diagnoses were a vascular aneurysm and a sellar meningioma, with the latter patient also exhibiting secondary hypothyroidism. Notably, no instances of pituitary adenomas were encountered. Conclusions: The prevalence of pituitary incidentalomas within our hospital was notably low. Further research is necessary to more comprehensively investigate the occurrence of pituitary incidentalomas in our country.

Enfermedad de Cushing recurrente con hipercortisolismo catastrófico: reporte de caso y revisión de literatura / Catastrophic hypercortisolism and recurrence in Cushing´s disease: a case report and literature review / Doença de Cushing recorrente com hipercortisolismo catastrófico: relato de caso e revisão da literatura

Resumen: Presentamos un caso de una paciente femenina de 27 años, con síndrome de Cushing ACTH dependiente con hipercortisolismo severo, causado por un macroadenoma hipofisario recurrente y resistente pese a dos cirugías transesfenoidales, radioterapia y terapia médica. Dada la falla en las diferentes terapias se realiza una adrenalectomía bilateral como tratamiento definitivo. La paciente fallece en el posoperatorio por causa no clara. Si bien la adrenalectomía bilateral ha sido reportada como un tratamiento efectivo en pacientes con enfermedad de Cushing, se ha relacionado con una mortalidad significativa vinculada con la severidad del hipercortisolismo y las comorbilidades presentes. En este caso la adrenalectomía izquierda se tuvo que convertir a cielo abierto, asociada con mayor morbimortalidad.

Abstract: The study presents the case of a 27-year-old female patient with adrenocorticotropic hormone (ACTH) dependent Cushing's disease and severe hypercortisolism caused by recurrent pituitary macroadenoma that was resistant to treatment despite two transsphenoidal surgeries, radiotherapy and medical treatment. Upon failure of the different therapies a bilateral adrenalectomy was performed as the final treatment. The patient died in after surgery although the case of death was not clear. Despite bilateral adrenalectomy having been reports as an effective treatment in patients with Cushing's disease, it has been related to significant mortality rates in connection with the severity of hypercortisolism and existing comorbilities. In this case the left adrenalectomy ended up being an open surgery, which is associated to a higher mortality rate.

Resumo: Apresentamos o caso de uma paciente de 27 anos com síndrome de Cushing ACTH-dependente com hipercortisolismo grave causado por macroadenoma hipofisário, recorrente e resistente, apesar de haver sido submetida a duas cirurgias transesfenoidal, radioterapia e terapia medicamentosa. Diante do fracasso das diferentes terapias, foi realizada adrenalectomia bilateral como tratamento definitivo. A paciente faleceu no pós-operatório por causa não esclarecida. Embora a adrenalectomia bilateral tenha sido relatada como tratamento eficaz em pacientes com doença de Cushing, ela tem sido associada a mortalidade significativa relacionada à gravidade do hipercortisolismo e às comorbidades presentes. Neste caso, a adrenalectomia esquerda teve que ser convertida para cirurgia aberta, associada a maior morbimortalidade.

18F-fallypride and 11C-methionine positron emission tomography/computed tomography for the study of prolactinomas and nonfunctioning pituitary adenomas: A case series.

Some studies have assessed the expression of dopaminergic dopamine 2 (D2)/3 receptors in prolactinomas and nonfunctioning pituitary adenomas (NFPA) by positron emission tomography/computed tomography (PET/CT) with 11C-raclopride, proving that this modality can be useful to predict the response to treatment with dopamine agonists. However, the use of 11C-labeled radiotracers is limited, as it requires a cyclotron in the PET center. 18F-fallypride is a radiotracer that has proven useful in assessing the expression of D2/3 receptors. As it is labeled with 18F, it can be produced and transported to distant PET centers. There are no studies on the usefulness of 18F-fallypride for the evaluation of patients with prolactinomas and NFPA. The aim of this study was to describe the first case series of patients with prolactinomas and NFPA studied with 18F-fallypride and 11C-methionine PET/CT to reveal D2/3 expression and amino acid (AA) metabolism. 18F-fallypride and 11C-methionine uptake were assessed in a case series of six patients, five with prolactinomas and one with a NFPA, and compared with clinical presentation and follow-up at 6-18 months. All patients presented with macroadenomas, with a wide range of AA metabolism, as revealed by 11C-methionine PET/CT. 18F-fallypride PET/CT identified low to moderate/high D2/3 expression in the tumors. The patient that presented low expression of D2/3 in the tumor and high AA metabolism showed a poor response to DA therapy. 18F-fallypride was able to reveal D2/3 receptor expression in prolactinomas and NFPA, with the advantage of been a more accessible radiotracer in comparison with previous 11C labeled analogs.

Cateterismo de senos petrosos en el diagnóstico etiológico de síndrome de Cushing: primera experiencia en Uruguay / Petrosal sinus sampling for etiological diagnosis of Cushing's syndrome: first experience in Uruguay / Cateterismo dos seios petrosos no diagnóstico etiológico da síndrome de Cushing: primeira experiência no Uruguai

Resumen: Identificar la causa de un síndrome de Cushing dependiente de adrenocorticotropina (ACTH) es esencial para realizar un tratamiento correcto. La hipersecreción de ACTH es debida en su mayoría a un tumor hipofisario (enfermedad de Cushing) o, en un 10%-20%, a tumores con producción ectópica de esta hormona. Los test no invasivos tienen baja sensibilidad y especificidad para diferenciar estas dos etiologías. El patrón oro lo constituye el cateterismo bilateral de los senos petrosos inferiores (CSP). Mediante el CSP se demuestra la hipersecreción de ACTH a nivel hipofisario al documentar un gradiente de ACTH central a periférico en el drenaje del tumor. Se recomienda realizarlo en todo síndrome de Cushing ACTH dependiente, aunque suele reservarse para pacientes con diagnóstico de hipercortisolismo y hallazgos negativos o equívocos en la resonancia nuclear magnética (RNM) de la región selar. Presentamos el primer caso en Uruguay en que se utilizó el CSP como método diagnóstico, una mujer de 55 años que presentó un hipercortisolismo ACTH-dependiente con una imagen adenohipofisaria <6 mm. El gradiente petroso-periférico confirmó el diagnóstico de enfermedad de Cushing y no hubo complicaciones durante el procedimiento. Posteriormente se realizó la resección del adenoma mediante cirugía transesfenoidal, con buena evolución y confirmación inmunohistoquímica del tumor.

Summary: Identifying the cause of adrenocorticotropin (ACTH)-dependent Cushing's syndrome is key to define the appropriate treatment. Hypersecretion of the adrenocorticotropic hormone (ACTH) is mainly caused by a pituitary tumor (Cushing's syndrome) or, in 10% to 20% of cases, by tumors with ectopic production of this hormone. Differentiation between these two etiologies may not be easy due to the low sensitivity and specificity of non- invasive tests. Bilateral sampling of the lower petrosal sinus is the gold standard to differentiate between a pituitary and an ectopic origin, showing the pituitary ACHT hypersecretion and recording the central-to-peripheral ACTH gradient in the tumor's drainage. Despite it being highly recommended for all cases of ACTH-dependent Cushing's syndrome, it is reserved for patients with a diagnosis of hypercortisolism and negative or misleading findings in the MRI of the sellar region. The study presents the first case of petrosal sinus sampling for diagnostic purposes in Uruguay, in a 55-year-old woman with ACHT-dependent hypercortisolism showing an adenohypophysis image < 6 mm. The petrosal-peripheral gradient confirmed the diagnosis of Cushing's syndrome and no complications arose during the procedure. Afterwards a transsphenoidal surgery was performed for resection of the adenoma. Evolution was good and immunochemistry confirmed the tumor's etiology.

Resumo: Identificar a causa da síndrome de Cushing dependente de adrenocorticotropina (ACTH) é essencial para o tratamento adequado. A hipersecreção de ACTH se deve principalmente a um tumor hipofisário (doença de Cushing) ou, em 10%-20%, a tumores com produção ectópica desse hormônio. Os testes não invasivos apresentam baixa sensibilidade e especificidade para diferenciar essas duas etiologias. O padrão ouro é o cateterismo bilateral dos seios petrosos inferiores (CEP). O CSP demonstra hipersecreção de ACTH no nível da hipófise, documentando um gradiente de ACTH central a periférico na drenagem do tumor. É recomendado nos casos de síndrome de Cushing dependente de ACTH, embora seja geralmente reservado para pacientes com diagnóstico de hipercortisolismo e achados negativos ou duvidosos na ressonância magnética (RNM) da região selar. Apresentamos o primeiro caso no Uruguai em que o CSP foi usado como método diagnóstico, uma mulher de 55 anos que apresentava hipercortisolismo ACTH dependente com imagem da hipófise anterior <6 mm. O gradiente petroso-periférico confirmou o diagnóstico de doença de Cushing e não houve complicações durante o procedimento. A seguir, o adenoma foi ressecado por cirurgia transesfenoidal, com boa evolução e confirmação imunohistoquímica do tumor.

Brain and Optic Chiasm Herniation into Sella after Pituitary Tumor Apoplexy.

Brain and optic chiasm herniation has been rarely reported following dopamine agonist treatment for large prolactinomas. We report a case of brain and optical chiasm herniation, secondary to an empty sella due to apoplexy of a prolactinoma, and we focus on the specific presentation of this case. A 32-year-old female presented to a neurologist complaining of headaches. Her past medical history was significant for acute vision loss in both eyes accompanied by right third nerve palsy when she was 16 years old. She does not recall any endocrine or imaging evaluation at that time and she had spontaneous partial recovery of left eye vision within 3 months, with permanent blindness of right eye. She did not return to any follow-up until her neurologist consultation. Brain magnetic resonance imaging (MRI) revealed herniation of frontal lobe and optic chiasm into the pituitary sella, as well as a pituitary hypointense lesion measuring 5 mm × 5 mm after gadolinium injection. Prolactin levels were 206 ng/ml (4.79-23.3 ng/ml). Repeated prolactin was 258 ng/ml (4.79-23.3 ng/ml). She was started on bromocriptine 2.5 mg/day. Prolactin levels and menstrual cycles normalized. A repeat brain MRI performed 5 months later showed disappearance of pituitary mass, with no changes in brain and chiasmal herniation. To our knowledge, this is the first reported case of brain associated with chiasm herniation secondary to pituitary apoplexy of a prolactinoma. In conclusion, this case highlights that frontal lobe herniation in combination with optic chiasm herniation can be a complication of pituitary tumor apoplexy. Long-term surveillance of patients with pituitary apoplexy is warranted to detect delayed complications.

Spontaneous reossification of the sella in transsphenoidal reoperation associated with strontium ranelate.

Spontaneous reossification of the sellar floor after transsphenoidal surgery has been rarely reported. Strontium ranelate, a divalent strontium salt, has been shown to increase bone formation, increasing osteoblast activity. We describe an unusual case of a young patient with Cushing's disease who was treated with strontium ranelate for low bone mass who experienced spontaneous sellar reossification after transsphenoidal surgery. A 21-year-old male presented with Cushing's features. His past medical history included delayed puberty diagnosed at 16 years, treated with testosterone for 3 years without further work-up. He was diagnosed with Cushing's disease initially treated with transsphenoidal surgery, which was not curative. The patient did not come to follow-up visits for more than 1 year. He was prescribed strontium ranelate 2 g orally once daily for low bone mass by an outside endocrinologist, which he received for more than 1 year. Two years after first surgery he was reevaluated and persisted with active Cushing's disease. Magnetic resonance image revealed a left 4 mm hypointense mass, with sphenoid sinus occupation by a hyperintense material. At repeated transsphenoidal surgery, sellar bone had a very hard consistency; surgery was complicated and the patient died. Sellar reossification negatively impacted surgery outcomes in this patient. While this entity is possible after transsphenoidal surgery, it remains unclear whether strontium ranelate could have affected sellar ossification. LEARNING POINTS: Delayed puberty can be a manifestation of Cushing's syndrome. A complete history, physical examination and appropriate work-up should be performed before initiating any treatment.Sellar reossification should always be taken into account when considering repeated transsphenoidal surgery. Detailed preoperative evaluation of bony structures by computed tomography ought to be performed in all cases of reoperation.We speculate if strontium ranelate may have affected bone mineralization at the sellar floor. We strongly recommend that indications for prescribing this drug should be carefully followed.

First neuronavigation experiences in Uruguay.

Neuronavigation is the application of image guidance to neurosurgery where the position of a surgical tool can be displayed on a preoperative image. Although this technique has been used worldwide in the last ten years, it was never applied in Uruguay due to its cost. In an ongoing project, the Engineering Faculty (Universidad de la República), the Hospital de Clínicas (Medicine Faculty - Universidad de la República) and the Regional Hospital of Tacuarembó are doing the first experimental trials in neuronavigation. In this project, a prototype based on optical tracking equipment and the open source software IGSTK (Image Guided Surgery Toolkit) is under development and testing.