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.

Acromegaly and diabetes mellitus associated with hyperthyroidism.

A 66-year-old woman with acromegaly and diabetes mellitus as well as primary hyperthyroidism is described. Serum GH Levels were inappprpriately high.MRI revealed an enlarged sella turcica with intrasellar mass. Her HbAlc was 12.2% and fasting blood glucose 8.89 mmol/l. Thyroid hormone levels in serum and thyroidal radioiodine uptake values were elevated, while TSH measurements in serum were low. Anti TPO antibodies were negative, TSH receptor antibodies were normal. Thyrotoxicosis as the first presenting illness in acromegaly was particulary uncommon. An ultrasound thyroid scan showed a multinodular goiter. Histology of the pituitary lesion showed a typical eosinophilic adenoma which only secreted GH when tested with specific immunostain. Post-operatively, the patient's clinical conditions improved, however, secondary hypoadrenalism appeared.

Spontaneous resolution of pituitary apoplexy in a giant boy under 10 years old.

AIM: Pituitary gigantism is a very rare condition; the occurrence of pituitary apoplexy in children younger than 10 years old is even rarer. The aim of our study is to report this exceptional association. OBSERVATION: A boy aged 9 years and 6 months was hospitalized for the first time in November 2011 for symptoms suggesting pituitary apoplexy. The onset of his disease was difficult to determine as his health record has been poorly maintained. On October 10, 2011, he presented to an emergency department with a sudden drop of visual acuity with diplopia and retro-orbital headaches. An ophthalmological exam found very low visual acuity (1/20) with papillary edema. An MRI of the patient's brain revealed a hemorrhagic pituitary process reaching the chiasma, which was compressed, especially on the right side. Thereafter, the patient's vision improved spontaneously. Clinical examination was normal except for gigantism (+5 SD compared to the target stature). Hormonal assessment argued for mixed secretion [growth hormone (GH) = 39 ng/mL, n ≤ 5, prolactin ( PRL) = 470 ng/mL, n < 15]. Other pituitary functions were normal. Visual acuity normalized after 2 months, and an MRI showed a spontaneous reduction of the pituitary tumor. CONCLUSION: This unusual observation is a model of symptomatic pituitary apoplexy with spontaneous resolution in a boy with pituitary gigantism: phenomenon quite exceptional and worth to be reported.

Outcomes of endoscopic papillectomy in elderly patients with ampullary adenoma or early carcinoma.

Outcomes for 14 elderly (age ≥ 70 years) patients (79.4 ± 1.0 years) who underwent endoscopic papillectomy for ampullary tumors were compared with those of 22 younger (age < 70 years) patients (52.5 ± 1.9 years). There were no differences in procedural success (100%), bleeding (5/14 vs. 6/22), adenoma recurrence (0/14 vs. 2/22) and median survival (24.0 vs. 25.5 months) between the elderly and younger patients. In younger patients, although adenoma recurrences (n=2) were managed endoscopically, invasive adenocarcinomas (n=3) were treated by pancreatoduodenectomy. All elderly patients with invasive (T2) tumors (n=5) were not surgically fit and underwent successful palliation with further endoscopic resection and stenting. Whilst all younger patients survived, five elderly patients died but three of these deaths were not cancer-related. Advanced age, therefore, did not adversely influence the outcomes of endoscopic papillectomy, suggesting it may be a treatment of choice for elderly patients with ampullary tumors or early cancer who are deemed unfit for surgery.

Adenoma acidófilo de células madre: reporte de un caso atípico / Stem cells acidopylic adenoma: report of an atypical case

Objective. We developed a bibliographic research of this rarely and highly aggressive entity, showing our experience and taking into account the special case of one patient, who developed an extremely aggressive disease. Description. Patient of 71 years that consults our department for left cavernous syndrome associated with moderate headache and bilateral visual accuracy diminish. Pituitary IRM was performed showing a homogeneous selar tumor that causes slight mass effect towards optic quiasm. Both cavernous sinuses were compromised. Intervention.Trasfenoidal surgery was performed, reaching the diagnosis of acidophil stem cell adenoma. The patient is dismissed. One week later and because of the development of sudden visual loss she was admitted once again. Pituitary IRM was performed showing a massive growth of the known lesion, requiring transcranial approach. Important mass reduction was achieved but our patient evolution was erratic. Three weeks after surgery we decided to repeat the IRM where we discovered the great mass reduction achieved in the second surgery did not reflect the voluminous lesion shown. One week later the patient died. Conclusion. Acidophil stem cell adenomas of the pituitary gland are mixed PRL/GH lesions, but because its immaturity non functional secreting hormones are produced; this is why these patients do not express physiognomic changes. We should think of this pathology in any pituitary tumor with low PRL-GH expression and few physiognomic changes, and aggressive natural evolution.

Adenoma acidófilo de células madre: reporte de un caso atípico / Stem cells acidopylic adenoma: report of an atypical case

Objective. We developed a bibliographic research of this rarely and highly aggressive entity, showing our experience and taking into account the special case of one patient, who developed an extremely aggressive disease. Description. Patient of 71 years that consults our department for left cavernous syndrome associated with moderate headache and bilateral visual accuracy diminish. Pituitary IRM was performed showing a homogeneous selar tumor that causes slight mass effect towards optic quiasm. Both cavernous sinuses were compromised. Intervention.Trasfenoidal surgery was performed, reaching the diagnosis of acidophil stem cell adenoma. The patient is dismissed. One week later and because of the development of sudden visual loss she was admitted once again. Pituitary IRM was performed showing a massive growth of the known lesion, requiring transcranial approach. Important mass reduction was achieved but our patient evolution was erratic. Three weeks after surgery we decided to repeat the IRM where we discovered the great mass reduction achieved in the second surgery did not reflect the voluminous lesion shown. One week later the patient died. Conclusion. Acidophil stem cell adenomas of the pituitary gland are mixed PRL/GH lesions, but because its immaturity non functional secreting hormones are produced; this is why these patients do not express physiognomic changes. We should think of this pathology in any pituitary tumor with low PRL-GH expression and few physiognomic changes, and aggressive natural evolution.(AU)

[Clinical and epidemiological characteristics of blastocystis hominis]. / Caractéristiques epidémiologique et cliniques de Blastocystis hominis.

BACKGROUND: Blastocystis hominis is an intestinal parasite known since long. It is cosmopolitan and lives in the colon. It is still the subject of controversy regarding its pathogenicity and possibly opportunistic character. AIM: We exhibit in this article the results obtained for 4 years on the epidemiological, clinical and biological character and opportunistic Blastocystis hominis, often overlooked in the examination of parasitological laboratories city. METHODS: This is a retrospective study of 3257 stool examination (PSE), performed in the Mycology Laboratory of Parasitology of the Charles Nicolle Hospital in Tunis over a period of 4 years (January 2005-December 2008). Detection of Blastocystis hominis has been made by microscopic examination of samples by direct examination and concentration. RESULTS: Blastocystis was found in 7.27% of cases and 48.5% in men. Endolimax nanus is the parasite most frequently associated with Blastocystis (40.4% of cases). The port was symptomatic in 72.1% of cases, diarrhea is the symptom most often found (27.7%). There is a seasonal distribution; in fact, it is more frequently diagnosed in summer and autumn. CONCLUSION: The absence of gravity and the saprophytic nature of this infection do not lead to an indication for treatment even among profoundly immunosuppressed individuals. Only the persistence of clinical disorders associated with the detection of the parasite and in the absence of other micro-organisms and intestinal parasites justifies the treatement. Metronidazole is the molecule used conventionally.

Pituitary acidophil macroadenoma in a pygmy goat (Capra hircus hircus).

This report describes a pituitary acidophil macroadenoma in a goat. Antemortem clinical findings included hypothermia and rumen stasis. Clinicopathologic findings included refractory hypoglycemia, low total thyroxin and insulin concentrations, elevated bile acid concentration, and hyposthenuria. In addition to the pituitary macroadenoma, bilateral atrophy of the zona reticularis of the adrenal glands was observed histologically.

Non-functioning pituitary adenomas infrequently harbor G-protein gene mutations.

BACKGROUND: Mutations of the genes encoding the alpha subunit of the stimulatory G protein (Gs) and of the inhibiting Gi2 protein (GNAS1 and GNAI2 genes, respectively) have been described in various endocrine neoplasias, including pituitary tumors. AIM: To search for mutations of GNAS1 and GNAI2 in a continuous series of non-functioning pituitary adenoma (NFPA) patients neurosurgically treated. SUBJECTS AND METHODS: The surgical samples of 22 patients who have been defined and characterized on a clinical, biochemical, histological, and immunohistochemical point of view have been processed for investigating the presence of the above mutations by PCR amplification of the hot spots exons 8 and 9 of GNAS1, and exons 5 and 6 of GNAI2, followed by direct sequencing. Moreover, the promoter region of GNAI2, in order to assess the prevalence of single nucleotide polymorphisms (SNP), was investigated in the same series. RESULTS: A CGT>TGT mutation at codon 201 of GNAS1 gene in a single case of NFPA was found, but no mutation of GNAI2A was demonstrated. CONCLUSIONS: This finding suggests and confirms that G-protein mutations are rare and not crucial in NFPA development. Additionally, we found a silent SNP at codon 318 in the promoter of the Gi2alpha gene in one out of the 22 NFPA.

Apoplexy accompanying pituitary adenoma as a complication of preoperative anterior pituitary function tests.

Pituitary apoplexy occurs as a very rare complication of the pituitary function test. We have experienced two cases of pituitary apoplexy following anterior pituitary function tests for preoperative assessment: a triple bolus test and a TRH test. To elucidate such a rare complication, we outline our two cases and review 28 cases from the literature. The clinical characteristics, etiology, pathophysiology, and diagnostic and therapeutic implications are also discussed. The combined data suggest that pituitary function tests have the potential to precipitate pituitary apoplexy, and its manifestations range from a clinically benign event to a catastrophic presentation with permanent neurological deficits or even death, although most patients may fortunately have a good outcome. We suggest that the pituitary function test should not be done as a routine test, and when such a test is planned, the patient should be observed with caution for any symptomatic changes for at least 2 hours following the test for appropriate treatment. Further, MRI, especially enhanced studies, may provide an earlier diagnosis of the pituitary apoplexy since CT scan images often fail to demonstrate either density changes or obvious enlargement of the pituitary adenoma at the acute stage.

Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient.

CONTEXT: Criteria to define the response to somatostatin (SS) analogs (SSA) in acromegaly are based on biochemical control of the disease. However, the mechanisms of action of SSAs in inhibiting tumor growth and hormonal secretion are only partially understood, and the two effects may occur independently. OBJECTIVE: The objective of the study was to investigate the dissociation between antiproliferative and antisecretive effects of SSA in an octreotide-resistant patient displaying dramatic tumor shrinkage during primary therapy with octreotide LAR. DESIGN AND SETTING: We characterized somatostatin and dopamine D(2) receptor expression by immunohistochemistry and real-time RT-PCR. The effects of different receptor-selective, bispecific analogs, and chimeric somatostatin/dopamine compounds on GH secretion and cell proliferation in primary cell cultures of the tumor were assessed. RESULTS: The expression of SS receptor subtypes (sst)(5) and D(2) receptor was higher, compared with the other receptor subtypes. GH inhibition by SS-14 and the two chimeric somatostatin/dopamine compounds was scant but greater than subtype-selective and sst(2)/sst(5) bispecific agonists. Conversely, cell growth was potently inhibited by all test substances. However, SS-14, sst(2)/sst(5) bispecific agonist, and chimeric molecules were more potent than the other compounds. CONCLUSIONS: The significant antiproliferative effect of octreotide seems to be related to the higher expression of sst(5) and the negligible antihormonal effect to the lower expression of sst(2). However, activation of multiple receptors by new analogs may produce better control of tumor cell activities. The dissociation between antisecretive and antiproliferative effects observed in vivo and in vitro confirms that SSAs may induce tumor shrinkage despite the lack of effect on GH secretion.

Characterization of human pituitary adenomas in cell cultures by light and electron microscopic morphology and immunolabeling.

The morphology and hormone production of pituitary adenoma cell cultures were compared in order to highlight their characteristic in vitro features. Cell suspensions were prepared from 494 surgical specimens. The 319 viable monolayer cultures were analyzed in detail by light microscopy and immunocytochemistry within two weeks of cultivation. Some cultures were further characterized by scanning, transmission and immunogold electron microscopy. The viability and detailed in vitro morphology of adenoma cells were found to be characteristic for the various types of pituitary tumors. The sparsely granulated growth hormone, the corticotroph and the acidophil stem cell adenomas provided the highest ratio of viable cultures. Occasionally, prolonged maintenance of cells resulted in long-term cultures. Furthermore, a variety of particular distributions of different hormone-containing granules were found in several cases. Both light microscopic and ultrastructural analyses proved that the primary cultures of adenoma cells retain their physiological features during in vitro cultivations. Our in vitro findings correlated with the routine histopathological examination. These results prove that monolayer cultures of pituitary adenoma cells can contribute to the correct diagnosis and are valid model systems for various oncological and neuroendocrinological studies.

Ectopic growth hormone-releasing adenoma in the cavernous sinus--case report.

A 55-year-old woman presented a rare ectopic pituitary adenoma in the right cavernous sinus manifesting as acromegaly. The tumor was removed via transsphenoidal approach. Intraoperative observation showed the adenoma was located entirely within the right cavernous sinus, and separated from the normal pituitary gland by the medial wall of the cavernous sinus. There was no communication between the tumor and the pituitary. Histological examination showed a growth hormone-releasing adenoma. Including our case, only eight of 86 reported ectopic adenomas have occurred in the cavernous sinus. Such ectopic presentation may be responsible for failed transsphenoidal surgery for endocrinologically active tumors.

Bilateral testicular enlargement and seminoma in a patient with acromegaly.

Growth hormone (GH) excess has been associated with soft tissue changes and an increase in the incidence of colonic polyps and gastrointestinal cancer. We describe a patient with endogenous GH excess caused by a pituitary tumour, resulting in acromegaly. The patient had bilateral testicular enlargement, with tumour of the right testicle. Pituitary MRI revealed a macroadenoma. After resection of the pituitary tumour, GH levels fell below 0.5 ng/ml, with acromegaly resolution. Testicular resection revealed seminoma. Following acromegaly resolution, the enlarged remaining testicle decreased in size. The implications of the testicular enlargement and seminoma in the presence of a GH-secreting tumour are discussed.

Patología de los adenomas hipofisarios / Pathology of pituitary adenomas

Los adenomas hipofisarios son neoplasias benignas originadas en células de la adenohipófisis. Representan el tumor más habitual en la silla turca y constituyen un 10-15 por ciento de las neoplasias intracraneales. Inicialmente fueron clasificados, según sus características tintoriales, en adenomas acidófilos, basófilos y cromófobos. La aplicación de técnicas morfológicas como la microscopía electrónica y la inmunohistoquímica, y la integración de los hallazgos morfológicos con los datos clínicos, de laboratorio y de las técnicas de imagen han permitido el desarrollo de la nueva clasificación de los adenomas hipofisarios. Las técnicas genéticas y moleculares están proporcionando información que ayuda a entender la patogénesis de algunas variedades de adenoma hipofisario. Por otra parte, la aplicación de determinados marcadores puede aportar información pronóstica y ayudar a predecir la respuesta a modalidades terapéuticas específicas (AU)

Unmodified prolactin (PRL) promotes PRL secretion and acidophil hypertrophy and is associated with pituitary hyperplasia in female rats.

In this study, we have tested the hypothesis that unmodified prolactin (U-PRL) and phosphorylated prolactin (P-PRL) have differential roles in the autoregulation of PRL secretion in vivo. Recombinant human U-PRL and a molecular mimic of P-PRL (S179D PRL) were administered to male rats and to female rats in different physiological states and the effect on rat PRL release was measured. Administration of U-PRL elevated rat PRL in all female animals, but was without effect in males. By contrast, S179D PRL was inactive in females, but inhibited PRL release in males. Morphometric and immunohistochemical analyses demonstrated acidophil hypertrophy and evidence of increased PRL secretion in the pituitaries of U-PRL-treated females. Analysis of the two forms of PRL during prolactinoma induction in two differentially susceptible strains of rats found a strong temporal correlation among increased ratios of U-PRL: P-PRL, increased circulating PRL, and increased cell proliferation. We conclude (1). that the autoregulatory mechanism(s) can distinguish between the two major forms of PRL and that higher proportions of U-PRL not only allow for higher circulating levels of PRL, but are also autostimulatory, (2). that the autoregulatory mechanism( s) are set differently in males and females such that females are more sensitive to autostimulation by U-PRL and less sensitive to inhibition by P-PRL, and (3). that U-PRL and P-PRL may also have differential roles in the regulation of pituitary cell proliferation.

A 2-year dose-response study of lesion sequences during hepatocellular carcinogenesis in the male B6C3F(1) mouse given the drinking water chemical dichloroacetic acid.

Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver and the known concentrations of this compound in drinking water, reliable biologically based models to reduce the uncertainty of risk assessment for human exposure to DCA are needed. Development of such models requires identification and quantification of premalignant hepatic lesions, identification of the doses at which these lesions occur, and determination of the likelihood that these lesions will progress to cancer. In this study we determined the dose response of histopathologic changes occurring in the livers of mice exposed to DCA (0.05-3.5 g/L) for 26-100 weeks. Lesions were classified as foci of cellular alteration smaller than one liver lobule (altered hepatic foci; AHF), foci of cellular alteration larger than one liver lobule (large foci of cellular alteration; LFCA), adenomas (ADs), or carcinomas (CAs). Histopathologic analysis of 598 premalignant lesions revealed that (a)) each lesion class had a predominant phenotype; (b)) AHF, LFCA, and AD demonstrated neoplastic progression with time; and (c)) independent of DCA dose and length of exposure effects, some toxic/adaptive changes in non-involved liver were related to this neoplastic progression. A lesion sequence for carcinogenesis in male B6C3F(1) mouse liver has been proposed that will enable development of a biologically based mathematical model for DCA. Because all classes of premalignant lesions and CAs were found at both lower and higher doses, these data are consistent with the conclusion that nongenotoxic mechanisms, such as negative selection, are relevant to DCA carcinogenesis at lower doses where DCA genotoxicity has not been observed.