[Endocrine paraneoplastic syndromes]. / Endokrine paraneoplastische Syndrome.

Endocrine paraneoplastic syndromes result from the production of bioactive substances from neoplastic cells, of endocrine or neuroendocrine origin. Typically these are located in the lungs, the gastrointestinal tract, pancreas, thyroid gland, adrenal medulla, skin, prostate or breast. In endocrine paraneoplastic syndromes the secretion of peptides, amines or other bioactive substances is always ectopic and not related to the anatomical source. The clinical presentation, however, is indistinguishable from a suspected eutopic endocrine tumor posing a diagnostic challenge. The most common endocrine paraneoplastic syndromes are based on the secretion of antidiuretic hormone (ADH) resulting in hyponatremia, secretion of adrenocorticotropic hormone (ACTH) or rarely corticotropin-releasing hormone (CRH) resulting in Cushing syndrome as well as secretion of growth hormone-releasing hormone resulting in acromegaly. Paraneoplastic endocrine syndromes mainly occur in highly malignant tumors; however, the development of these tumors does not necessarily correlate with tumor stage, malignant potential or prognosis. As endocrine paraneoplastic syndromes are a rare complication, there are hardly any evidence-based therapeutic recommendations. Treatment of the underlying tumor is the first choice and in a palliative setting symptomatic therapy is possible.

Mice with inactivation of aryl hydrocarbon receptor-interacting protein (Aip) display complete penetrance of pituitary adenomas with aberrant ARNT expression.

Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene have been shown to predispose to pituitary adenoma predisposition, a condition characterized by growth hormone (GH)-secreting pituitary tumors. To study AIP-mediated tumorigenesis, we generated an Aip mouse model. Heterozygous mice developed normally but were prone to pituitary adenomas, in particular to those secreting GH. A complete loss of AIP was detected in these lesions, and full penetrance was reached at the age of 15 months. No excess of any other tumor type was found. Ki-67 analysis indicated that Aip-deficient tumors have higher proliferation rates compared with Aip-proficient tumors, suggesting a more aggressive disease. Similar to human AIP-deficient pituitary adenomas, immunohistochemical studies showed that expression of aryl hydrocarbon receptor nuclear translocator 1 or 2 (ARNT or ARNT2) protein was lost in the mouse tumors, suggesting that mechanisms of AIP-related tumorigenesis involve aberrant ARNT function. The Aip(+/-) mouse appears to be an excellent model for the respective human disease phenotype. This model constitutes a tool to further study AIP-associated pituitary tumorigenesis and may be potentially valuable in efforts to develop therapeutic strategies to treat pituitary adenomas.

Radiation-induced ocular motor cranial nerve palsies in patients with pituitary tumor.

BACKGROUND: Radiation therapy is often used in the treatment of pituitary tumor. Diplopia due to radiation damage to the ocular motor cranial nerves has been infrequently reported as a complication in this clinical setting. METHODS: Retrospective case series of 6 patients (3 men and 3 women) with pituitary adenoma, all of whom developed diplopia following transsphenoidal resection of pituitary adenoma with subsequent radiation therapy. None had evidence of tumor involvement of the cavernous sinus. RESULTS: Five patients developed sixth nerve palsies, 3 unilateral and 2 bilateral, and in 1 patient, a sixth nerve palsy was preceded by a fourth cranial nerve palsy. One patient developed third nerve palsy. Five of the 6 patients had a growth hormone-secreting pituitary tumor with acromegaly. Following transsphenoidal surgery in all 6 patients (2 had 2 surgeries), 4 had 2 radiation treatments consisting of either radiosurgery (2 patients) or external beam radiation followed by radiosurgery (2 patients). CONCLUSIONS: Patients with pituitary tumors treated multiple times with various forms of radiation therapy are at risk to sustain ocular motor cranial nerve injury. The prevalence of acromegalic patients in this study reflects an aggressive attempt to salvage patients with recalcitrant growth hormone elevation and may place the patient at a greater risk for ocular motor cranial nerve damage.

Association between radiological parameters and clinical and molecular characteristics in human somatotropinomas.

Acromegaly is a rare but severe disease, originated in 95% of cases by a growth hormone-secreting adenoma (somatotropinoma) in the pituitary. Magnetic resonance imaging (MRI) is a non-invasive technique used for the diagnosis and prognosis of pituitary tumours. The aim of this study was to determine whether the use of T2-weighted signal intensity at MRI could help to improve the characterisation of somatotropinomas, by analysing its relationship with clinical/molecular features. An observational study was implemented in a cohort of 22 patients (mean age = 42.1 ± 17.2 years; 59% women; 95% size>10 mm). Suprasellar-extended somatotropinomas presented larger diameters vs. non-extended tumours. T2-imaging revealed that 59% of tumours were hyperintense and 41% isointense adenomas, wherein hyperintense were more invasive (according to Knosp-score) than isointense adenomas. A higher proportion of hyperintense somatotropinomas presented extrasellar-growth, suprasellar-growth and invasion of the cavernous sinus compared to isointense adenomas. Interestingly, somatostatin receptor-3 and dopamine receptor-5 (DRD5) expression levels were associated with extrasellar and/or suprasellar extension. Additionally, DRD5 was also higher in hyperintense adenomas and its expression was directly correlated with Knosp-score and with tumour diameter. Hence, T2-weighted MRI on somatotropinomas represents a potential tool to refine their diagnosis and prognosis, and could support the election of preoperative treatment, when required.

A case of coexistence of TSH/GH-secreting pituitary tumor and papillary thyroid carcinoma: Challenges in pathogenesis and management.

Co-existence of thyrotropin/growth hormone-secreting pituitary adenoma with differentiated thyroid carcinoma is exceedingly rare, with less than 15 cases having been reported. Its clinical presentation and treatment strategy are challenging. We report a case of pituitary macroadenoma, with clinical syndromes of acromegaly and hyperthyroidism, and a thyroid nodule, with cytologically confirmed to be a papillary thyroid carcinoma. Clinical implications, focusing on the strategy for proper management, and possible pathogenesis were discussed.

Adenomas hipofisarios en la infancia / Pituitary adenomas in childhood

Los adenomas hipofisarios son raros en la población pediátrica, constituyen menos del 3 por ciento de los tumores supratentoriales en el niño, con una incidencia anual de 0,1 por millón de niños. El objetivo de nuestro trabajo fue caracterizar el comportamiento de esta entidad, así como los resultados del tratamiento quirúrgico. Realizamos un estudio descriptivo retrospectivo en pacientes menores de 16 años, diagnosticados y tratados en nuestro centro, en el período comprendido entre Enero de 1991 y junio del 2010. Nuestra muestra quedó conformada por 6 pacientes, la edad promedio fue de 11 años, predominó el sexo femenino y la raza no tuvo predilección. Las alteraciones endocrinas fueron las formas más frecuentes de presentación. El diagnóstico imagenológico se realizó con la Tomografía Computarizada y la Resonancia Magnética Nuclear, en la valoración oftalmológica, la campimetría alcanzó una alta sensibilidad y desde el punto de vista hormonal, la prolactina y la GH fueron las comprometidas. Predominaron los macroadenomas y las lesiones funcionantes. Estas lesiones en su mayoría fueron intervenidas a través de abordajes frontopterional y transesfenoidales, nuestro grupo presentó dos complicaciones, una fístula de líquido cefalorraquídeo y un aracnoidocele. Predominaron los buenos resultados. No tuvimos fallecidos en relación con la cirugía.