VEGF, VEGF165b and EG-VEGF expression is specifically related with hormone profile in pituitary adenomas.

Vascular endothelial growth factor (VEGF), its inhibitory splice variant, VEGF165b and Endocrine Gland derived VEGF (EG-VEGF) have a controversial role in pituitary gland. We aim to study VEGF, VEGF165b and EG-VEGF expression in pituitary adenomas. A significant correlation was found between growth hormone (GH) and VEGF secretion (P=0.024). For prolactinomas, VEGF and prolactin expression, had a P-value of 0.02 for Kendall coefficient and a P-value of 0.043 for the Spearman coefficient. VEGF-mRNA amplification was detected in both tumor cells and folliculostellate cells. VEGF165b was positive in 16.66% of pituitary adenomas. EG-VEGF was significantly correlated with prolactin (P=0.025) and luteinizing hormone (P=0.028). Our data strongly support VEGF, VEGF165b and EG-VEGF as important players of pituitary adenomas tumorigenesis. Particular hormonal milieu heterogeneity, special vascular network with an unusual reactivity to tumor growth correlated with variability of VEGF, VEGF165b and EG-VEGF secretion may stratify pituitary adenomas in several molecular groups with a direct impact on therapy and prognosis.

Tratamiento de la enfermedad de Cushing con ketoconazol / Treatment of Cushing's disease with ketoconazole

La enfermedad de Cushing (EC), debida fundamentalmente a un microadenoma hipofisario, es un cuadro clínico poco frecuente en la edad pediátrica y se asocia a una significativa morbilidad. La principal indicación terapéutica es la cirugía transesfenoidal, aunque se reserva el ketoconazol como alternativa terapéutica temporal durante el período de espera previo, a fin de controlar el hipercortisolismo. A continuación se presenta el caso de una niña de 13 años y 8 meses con EC. Sus manifestaciones clínicas eran obesidad, disminución de la velocidad del crecimiento, fenotipo cushingoide, cefaleas e hipertensión arterial. Las determinaciones hormonales pusieron de manifiesto valores elevados de cortisol libre urinario y de corticotropina (ACTH). El ritmo de cortisol y de ACTH así como el test corto y largo de dexametasona confirmaron un hipercortisolismo dependiente de ACTH. La resonancia magnética craneal con gadolinio mostró la presencia de microadenoma en hemiadenohipófisis derecha. El diagnóstico se confirmó tras realizar un cateterismo selectivo de senos petrosos inferiores con estímulo de corticoliberina. En espera de cirugía transesfenoidal, el tratamiento con ketoconazol (200mg/24h) durante 6 meses controló el cuadro de hipercortisolismo. Tras la adenomectomía transesfenoidal, recibió tratamiento sustitutivo con hidrocortisona durante un mes. En la actualidad, la niña lleva 2 años y medio en remisión clínica y hormonal sin cumplir los criterios iniciales posquirúrgicos de curación (AU)

Cushing’s disease (CD), which is caused fundamentally by a pituitary microadenoma, is a rare endocrine disease in the paediatric age and which is associated with significant morbidity. The current treatment of choice for CD is trans-sphenoidal selective adenomectomy resulting in long-term remission rates. Pharmacological management of CD is directed at decreasing adrenal steroid secretion. Ketoconazole inhibits adrenal enzyme activity and decreases cortisol secretion. Our patient is a girl of 13 years and eight months of age with CD. The clinical manifestations were obesity, decrease in growth rate, Cushingoid phenotype, headache and arterial hypertension. The hormone determinations showed elevated values of UFC and ACTH. The circadian rhythm cortisol and ACTH and the short and long dexamethasone tests of provide definitive diagnosis of CD. The cranial MRI with gadolinium suggests the presence of microadenoma in the right pituitary lobe. The diagnosis is confirmed after performing a selective catheterisation of the inferior petrosal sinuses with CRH stimulus. While waiting for trans-sphenoidal surgery, the treatment with ketoconazole (200mg/24h) controlled the hypercortisolism. After the surgical procedure, the patient received replacement therapy with hydrocortisone for 1 month. At the present time, the patient, without fulfilling the post surgery cure criteria, has been 2 and a half years in clinical and hormonal remission (AU)

Cushing's disease in a 5-month infant due to a basophilic microadenoma of the pituitary gland.

We report a female patient who developed severe Cushing's disease during the fifth month of life due to a basophilic pituitary adenoma Histological findings showed a basophilic microadenoma of the pituitary gland, leading to the diagnosis of Cushing's disease. The infant died because of untreatable septic shock. The importance of the present report resides in the age of the child at diagnosis, and that it was the necropsy finding of microadenoma which clarified the cause of the Cushing's syndrome, since it was not diagnosed during life. Cushing's disease is most often diagnosed in children older than 7 years, and our patient was only 5 months old when we detected the pituitary adenoma, the earliest case diagnosed so far. Cushing's syndrome in pediatric patients has been rarely reported and most cases are due to functioning adrenal tumors, usually a malignant carcinoma but occasionally a benign adenoma. The present case shows that the pituitary of these patients should be investigated with important implications in terms of therapeutic approaches, such as pituitary radiotherapy, which can cure the patient when treatment is started very soon.

[Neurosurgery and pituitary tumors: etio-pathogenic considerations]. / La neurochirurgie et les tumeurs hypophysaires. Considérations étio-pathogéniques.

PITUITARY ADENOMA: Based on the experience of nearly 5000 cases of surgically treated pituitary tumors at the neurosurgery department of the Foch Hospital, the pituitary adenoma is the most frequent pituitary tumor. Secreting tumors lead to a clinical syndrome depending on the level of hormone overproduction. Gonadotrop or non-functioning pituitary adenomas are mainly macroadenomas presenting with visual symptoms, hypopituitarism or as an incidentaloma. Anatomical features dictate the surgical approach. OTHER TUMORS: The other types of hypophyseal tumors, such as craniopharyngioma, Rathke's cleft cyst or others are usually surgical tumors because medical treatment is ineffective. Malignant pituitary tumors are unusual.

Triple pituitary adenoma in Cushing's disease: case report.

A case of a triple pituitary adenoma identified in a surgically removed pituitary gland from a 52-year-old woman operated on for Cushing's disease is presented. The histology revealed 3 distinctly separate microadenomas, 1 corticotroph and 2 immunoreactive for prolactin (PRL). The latter were apparently silent, since the serum PRL levels were within normal range. The problems associated with the inability to identify multiple adenomas pre-operatively and the possible failure of selective transsphenoidal adenomectomy in case of multiple adenomas are emphasised.

Coexistence of primary empty sella and silent corticotrophic adenoma.

Primary empty sellae are rarely associated with an intact pituitary adenoma. Most of such cases are documented clinically and radiographically. This paper reports a case of coexistence of primary empty sella and a silent corticotrophic adenoma in a 61-year-old woman. The en bloc preparation of the sella turcica demonstrates the anatomical relationship of the empty sella and the flattened pituitary gland and the adenoma. The immunostain shows the presence of all five cell types of the adenohypophysis.

[The treatment of Cushing's disease]. / Le traitement de la maladie de Cushing.

The differential diagnosis of Cushing's disease remains difficult to establish. The selective transsphenoidal adenomectomy is the initial treatment of choice. In a group of 65 patients, 50 (77%) initially responded to surgery with correction of their hypercortisolism. Forty-three out of 51 (84%) patients with small pituitary tumors responded favourably to surgery, but recurrency occurred in 10% of the cases. Medical treatment with steroids inhibitors or antagonists is only an adjuvant treatment. In case of surgery failure or recurrency, bilateral adrenalectomy is usually performed. Conventional radiotherapy may be used after surgery in presence of macroadenomas or invasive adenomas. Correction of the hypercortisolism, after a second surgery, was achieved in 50% of the cases and was always associated with a panhypopituitarism.

Double adenomas of the pituitary: a clinicopathological study of 11 tumors.

Of more than 3000 cases of surgically removed pituitary adenomas, 11 were defined as "double adenomas," i.e., 2 morphologically or immunocytologically distinct tumors. In 8 cases, the lesions exhibited differing histological features and immunophenotypes; in 2 specimens, distinct ultrastructural features were noted as well. In another instance, despite histological and immunocytological uniformity, the two neoplastic components demonstrated distinct ultrastructure. In yet another case, the two adenomas were consecutively removed; despite similar histological features, they differed in immunocytological and ultrastructural characteristics. Last, in one case, the adenoma was histologically uniform, but a portion of the mass exhibited immunoreactivity by ultrastructural features distinct from those of the remainder of the lesion. Hormonal excess attributed to both tumors could be correlated with endocrine manifestations in two cases. Double adenomas of the pituitary occur infrequently. In routine histological sections of surgical material, they are often difficult if not impossible to identify. Presented herein are clinical and endocrinological data on 10 cases of double pituitary adenomas correlated with morphological and immunocytochemical results. The literature regarding multiple adenomas is reviewed as are the diagnostic and therapeutic difficulties associated with these rare lesions.

[Pituitary hemorrhage extending into the third ventricle. Case report].

A case of pituitary apoplexy causing pituitary hemorrhage with extension into the third ventricle is reported. The patient was a 73-year-old, obese female admitted with sudden onset of vomiting and impaired consciousness. Neurological examination revealed that she was stuporous, with marked neck stiffness and a dilated left pupil. A plain skull X-ray showed sellar enlargement and destruction of the dorsum sellae. Computed tomography demonstrated a high-density area in the third and lateral ventricles and a round, high-density mass in the suprasellar cistern. The patient died the next day. Autopsy revealed a large tumor in the sellar and suprasellar areas. The tumor and the hematoma within it compressed the floor of the third ventricle and passed through the lamina terminalis and the hypothalamic region. Histological examination disclosed a basophilic adenoma. The pituitary hemorrhage appeared to be the result of ischemia and necrosis within the pituitary adenoma caused by its acute expansion. The extension of the hematoma into the third ventricle was attributable to the large size of the tumor and its close adhesion to the floor of third ventricle.

Human corticotroph cell adenomas.

Sixty-one pituitary corticotroph adenomas from 47 patients with Cushing's disease, 10 with Nelson's syndrome, and four eucorticoid patients were studied by light microscopy, immunoperoxidase, and electron microscopy. Seventy nine percent of all tumors and 70% of Nelson's cases were microadenomas, sometimes minute. A contiguity between the posterior lobe and the adenoma was seen in ten cases. Spontaneous infarction of the tumor with remission of Cushing's syndrome occurred in one case. Light microscopy revealed that the adenoma cells were basophilic and contained PAS-positive granules also staining with Herlant tetrachrome and lead-hematoxylin. The granules stained positively with antiserum to adrenocorticotrophic hormone (ACTH), beta-lipotropic hormones (beta-LPH) and beta-endorphin. The most characteristic ultrastructural finding was the presence of perinuclear bundles of microfilaments found in all our cases. Oncocytic changes were seen in three tumors. Four silent corticotroph adenomas, two of them originally microadenomas that had enlarged to enclosed adenomas while being treated with bromocriptine for hyperprolactinemia and one a large diffuse invasive tumor, did not differ in their microscopic, immunocytological, or ultrastructural features.

Gonadotroph adenomas of the human pituitary: sex-related fine-structural dichotomy. A histologic, immunocytochemical, and electron-microscopic study of 30 tumors.

Thirty pituitary tumors, removed from 14 men and 15 women, were diagnosed as gonadotroph adenomas on the basis of their immunocytochemical and/or ultrastructural features. Serum follicle-stimulating hormone (FSH), but not luteinizing hormone (LH), was elevated in 8 men, whereas none of the women had gonadotropin levels, as measured by radioimmunoassay, inappropriately high for their age. Immunoreactive FSH (sometimes also LH) was present in 13 of 15 tumors in men but only 6 of 13 adenomas in women. By electron microscopy, gonadotroph adenomas in men had uncharacteristic features often similar to those of null-cell adenomas with poorly or moderately developed cytoplasmic organelles. In women, all tumors were well differentiated, with a highly distinctive vesicular dilatation of the Golgi complex ("honeycomb Golgi") as a diagnostic marker present in 14 of 15 adenomas. To the author's knowledge, this is the first example of sex-linked dichotomy within a tumor type expressed as the markedly different ultrastructural appearance of cytoplasmic organelles, especially the Golgi apparatus.

Immunohistochemical and immunoelectron-microscopic study of pituitary adenomas associated with Cushing's disease. A report of 13 cases.

Thirteen pituitary adenomas were removed from patients with Cushing's disease by the transphenoidal route. All cases demonstrated a typical histochemical and ultrastructural pattern. Immunocytochemical study by means of the immunoperoxidase technique and light or electron microscopy demonstrated 1-24/1-39 adrenocorticotropic hormone (ACTH) in all cases, lipotropin/melanotropin (beta-LPH/beta-MSH) in 10 cases, beta-endorphin in 8 cases, and an absence of calcitonin in all cases. In addition, in 2 cases tumor tissue contained a few antiprolactin immunoreactive cells. These ACTH, beta-LPH, and beta-endorphin immunoreactivities may reflect either the peptides themselves or their precursors or intermediate products. The authors also suggest a possible intermediate-lobe-like processing of beta-LPH leading to beta-endorphin production, which may act on PRL cells. In addition, no positive arguments for the existence of a common precursor for calcitonin and ACTH could be provided from this study.

Tumours of the salivary glands: a histological and clinical review.

The aim of this paper is to try to identify points of correlation between the histological appearance and the clinical behaviour of minor salivary gland tumours. To this end 62 well-documented minor salivary gland tumours have been followed up for at least five years or until recurrence. The discussion is limited to the adenoidcystic carcinoma, the pleomorphic adenoma and the basal cell adenoma, since only these three tumours were represented in sufficient numbers to be analysed. For each tumour a number of histological pointers to prognosis are reviewed. In the case of the basal cell adenoma, a recently recognised tumour, the possibility of confusion with the adenoidcystic carcinoma is discussed.

Cure of Cushing's disease by transsphenoidal removal of a microadenoma from a pituitary gland despite a radiographically normal sella turcica.

A 37-year-old woman had symptoms of Cushing's disease for two years. Galactorrhea was present. The diagnosis was confirmed by finding intermittently elevated urinary 17-hydroxysteroids, absent circadian rhythm, and elevated plasma ACTH. Plasma prolactin was slightly elevated. Films of the sella turcica were normal. A 9 mm basophilic microadenoma was removed by the transphenoidal approach. Immunocytochemical and electron-microscopic studies showed that the tumor was composed exclusively of ACTH secreting cells. Endocrine re-evaluation one year later revealed normal adrenal function. Serum prolactin had returned to normal. This case provides further evidence that Cushing's disease can be caused by a pituitary microadenoma insufficient in size to deform the sella.