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G Kontogeorgos

Publications and source records attributed to G Kontogeorgos.

At least 19 recordsLinked to original sources
PubMed2006

Mapping of somatostatin receptor types in GH or/and PRL producing pituitary adenomas.

BACKGROUND: Somatostatin is a tetradecapeptide exerting inhibitory action on endocrine and exocrine cell secretion and proliferation. Somatostatin receptors (SST) are widely expressed in various neoplasms including endocrine tumours. Using immunohistochemistry, the expression of SST(1), SST(2A), SST(2B), SST(3), SST(4), and SST(5) was studied in tissue microarrays (TMAs), using a series of 90 human pituitary adenomas producing growth hormone and/or prolactin, including 30 of each somatotroph, lactotroph, and mixed somatotroph/lactotroph adenoma type. METHODS: For immunohistochemistry, the standard avidin biotin complex method enhanced by tyramide was used, using polyclonal antisera for all SST types. A four point scoring system was used to assess the membranous immunopositivity. RESULTS: All SST types were positive in all tumour types, showing varying immunoreactivity scores. SST(5) and SST(2A) were the predominant receptors, showing strong expression in high frequency in all three adenoma types. Strong expression of SST(1) was higher in lactotroph adenomas than in other tumour types. CONCLUSIONS: The immunohistochemical results of SST expression are in agreement with most findings of previous molecular studies. The fact that SST(2A) expression is predominant suggests that pharmaceutical octapeptide somatostatin analogues may act through this receptor, while the role of SST(2B) may be merely synergistic.

Adenoma↗
PubMed2005

Evolving radiological features of hypothalamo-pituitary lesions in adult patients with Langerhans cell histiocytosis (LCH).

Langerhans cell histiocytosis (LCH) is a rare, systemic disease caused by monoclonal expansion of dendritic cells that shows a particular predilection for the hypothalamic-pituitary system (HPS). We studied the function (anterior and posterior pituitary hormonal secretion) and morphology using magnetic resonance imaging (MRI) of the HPS in 17 adult patients (seven males, median age 35 years, range 18-59 years) with multisystem LCH. We also evaluated the evolution of structural HPS abnormalities in relation to pituitary function and response to treatment in 12 of these patients during a median follow-up period of 3.75 years (range 1.5-10 years). Of the 17 patients, 14 (82%) had abnormal HPS imaging, and 12 (70%) had more than one area involved. Lack of the bright spot of the posterior pituitary lobe was typically found in all patients with the diagnosis of diabetes insipidus (DI). Eight patients (47%) had infundibular enlargement, six (35%) pituitary infiltration, four (24%) partially or completely empty sella, three (18%) hypothalamic involvement, and two (12%) infundibular atrophy. DI was found in 16 patients (94%) and anterior pituitary hormonal deficiency (APHD) in 10 patients (59%); two patients had single (12%) and 8 (47%) multiple APHD. During the follow-up period there was improvement of the initially demonstrated HPS pathology in seven (47%) patients, and five (33%) of them had received at least one form of treatment. APHD and DI persisted in all patients except in one in whom established gonadotrophin deficiency recovered. In summary, DI and APHD are very common in patients with multisystem LCH and are almost always associated with abnormal HPS imaging.

Adolescent↗
PubMed2005

Ectopic bioactive luteinizing hormone secretion by a pancreatic endocrine tumor, manifested as luteinized granulosa-thecal cell tumor of the ovaries.

Endocrine pancreatic tumors are rare neoplasms consisting of multipotent cells capable of secreting various bioactive substances causing characteristic clinical syndromes. Ovarian stromal hyperthecosis is characterized by varying degrees of luteinized stromal cell proliferation after sustained LH and/or human chorionic gonadotropin stimulation, clinically manifested by symptoms/signs of virilization resembling the polycystic ovary syndrome (PCOS). We report a case of ectopic bioactive LH production from a pancreatic endocrine tumor in a 33-yr-old woman with rapidly developing symptoms/signs of hyperandrogenism and markedly elevated serum androgen and LH levels leading to hyperthecosis and bilateral luteinized granulosa-thecal cell tumors of the ovaries. Although the patient was initially thought to have either severe PCOS or an LH-secreting pituitary tumor, an LH-producing pancreatic endocrine tumor bearing somatostatin receptors was demonstrated on scintigraphy with [111In]octreotide and abdominal imaging. Symptoms and signs of hyperandrogenism resolved after the resection of the tumor. Immunohistochemistry, in situ hybridization, and electron microscopy studies confirmed LH synthesis by the tumor cell. Although extremely rare, ectopic LH production from nonpituitary endocrine tumors should be considered in the differential diagnosis of hyperandrogenism, particularly when associated with highly elevated serum LH levels.

Adult↗
PubMed2005

Treatment with oral biphosphonates can increase the sensitivity of sestamibi radionuclide imaging in patients with primary hyperparathyroidism.

The sensitivity of 99mTc-sestamibi scan in detecting parathyroid disease in primary hyperparathyroidism (PHP) is almost 90%, and therefore facilitates successful parathyroidectomy. To enhance the diagnostic accuracy of the procedure, we repeated imaging with 99mTc-sestamibi in 15 patients with PHP and an initially negative (11 patients) or weakly positive (four patients) 99mTc-sestamibi scan after the administration of 10 mg of oral alendronate for 2 months. Serum calcium, phosphate and parathormone (PTH) measurements were obtained at presentation and after 1 and 2 months' treatment with alendronate. Eight patients with an initially negative 99mTc-sestamibi scan demonstrated at least one area of uptake in the repeated scan. Six of these patients underwent surgery and obtained a biochemical cure; a single adenoma was found in four and hyperplasia in the remaining two. In all four patients with an initially weakly positive 99mTc-sestamibi scan, the repeated scan demonstrated enhanced uptake and also revealed further areas of uptake. Two of these patients underwent surgery with a biochemical cure; an adenoma was found in one and hyperplasia in another. Compared with baseline there was a significant increase in PTH but not in calcium or phosphate levels during treatment with alendronate. We suggest that, in patients with PHP and a negative or weakly positive initial 99mTc-sestamibi scan, administration of oral alendronate may be associated with a positive repeated 99mTc-sestamibi scan and can thus enhance the sensitivity of the procedure.

Adenoma↗
PubMed2001

Composite somatotroph--ACTH-immunoreactive pituitary adenoma with transformation of hyperplasia to adenoma.

The majority of pituitary adenomas are solitary and monohormonal, producing only one hormone. Double or multiple adenomas are rare. Plurihormonal adenomas may be monomorphous consisting of one cell type producing more than one hormones or plurimorphous composed of two or more distinct cell populations each producing different hormones. Primary pituitary hyperplasia is uncommon and transformation to adenoma has rarely been documented. We describe a unique case of somatotroph adenoma combined with ACTH-immunoreactive cell hyperplasia and focal transformation to adenoma. The 53-yr-old man was presented with a 2-yr history of headaches, enlargement of the hands and feet and coarsening of facial features. His blood GH was 17.5 ng/ml and he had absence of GH suppressional oral glucose tolerance testing. MRI demonstrated a mass with maximum diameter of 1.5 cm, on the left side of the pituitary, without invasion of surrounding tissues. Transsphenoidal surgery was performed. Morphology disclosed a mostly chromophobic tumor, immunoreactive for GH with ultrastructural characteristics of sparsely granulated somatotroph adenoma. The adenoma cell population was focally admixed with hyperplastic PAS positive and ACTH immunoreactive cells showing the electron microscopic features characteristic of corticotrophs. In these areas the acini were enlarged with distorted architecture of the reticulin pattern. Dissolution of the reticulin fiber network and transformation of hyperplastic ACTH-immunoreactive cells to adenoma was evident in small areas. The hyperplastic and adenomatous ACTH-immunoreactive cells were admixed with somatotroph adenoma cells. Due to lack of biochemically obvious cortisol hypersecretion, this ACTH-immunoreactive adenoma was classified as silent "corticotroph" subtype 1. This is an unusual case of composite pituitary adenoma consisting of somatotroph cells and hyperplastic ACTH-immunoreactive cells transforming to a frank adenoma.

Adenoma↗
PubMed2001

Monosomy of chromosome 11 in pituitary adenoma in a patient with familial multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN 1) represents an endocrine syndrome characterized by complex pituitary, parathyroid and pancreatic neoplasia. Loss of heterozygosity of the specific region 11q13 has been reported in several tumours from patients with MEN 1 inherited disorder. We present a case of a young patient with familial MEN 1 syndrome with a pituitary adenoma exhibiting monosomy of chromosome 11. The patient presented with a large and rapidly growing pituitary adenoma associated with markedly elevated serum PRL levels, progressive bilateral visual loss and hydrocephalus. The resected adenoma was chromophobic, mainly PRL-producing and to a lesser degree immunoreactive for GH. Fluorescence in situ hybridization (FISH) using an alpha-satellite centromeric probe detected loss of one chromosome 11 copy in almost all pituitary adenoma cells. Clinical and biochemical studies revealed parathyroid hyperplasia and MRI studies detected a pancreatic tumour in addition to the pituitary adenoma. To our knowledge this is the first study reporting monosomy 11 in pituitary adenoma in a patient associated with familial MEN 1 syndrome.

Adenoma↗
PubMed2000

Expression of leukemia inhibitory factor in human pituitary adenomas: a morphologic and immunocytochemical study.

Leukemia inhibitory factor (LIF) is a pleiotropic, neuropoietic cytokine found in bovine, murine, and human fetal and adult pituitary cells, mostly in corticotrophs and somatotrophs. In addition, it has been found in a few GH- and ACTH-producing human pituitary adenomas. The aim of our study was to investigate the presence of LIF in various morphologic types of human pituitary adenomas. Ninety-eight operated pituitary adenomas diagnosed by light microscopy and classified by pituitary hormone immunocytochemistry and electron microscopy were studied. Sixty-eight tumors were functioning and included 15 densely granulated (DG) and 10 sparsely granulated (SG) somatotroph (SM) adenomas, 5 lactotroph (LT), 7 mixed SM-LT and 31 corticotroph (CRT) adenomas. The remaining 30 nonfunctioning tumors included 11 gonadotroph (GON) and 19 null cell (NULL) adenomas. For immunocytochemical demonstration of LIF, a specific polyclonal antiserum was applied on formalin-fixed, paraffin-embedded tissues. The immunohistoscore ranging from 1 to 64 grades was determined by multiplying the immunostaining grade (1-4) by the staining intensity grade (1-4), and by the heterogeneity grade (1-4). Ninety adenomas (92%) were variably immunopositive for LIF. LIF was expressed in 77.5% of CRT, 81.8% of GON, 93.3% of DG-SM, and in all SG-SM, LT, SM-LT and NULL adenomas. LT adenomas showed the highest immunostaining grade, followed by SG-SM, GON, NULL, SM-LT, DG-SM, LT and CRT adenomas. GON adenomas showed the highest immunohistoscore, followed by NULL, DG-SM, SM-LT, SG-SM, LT and CRT adenomas. Nonfunctioning tumors showed a significantly higher immunohistoscore compared to functioning adenomas (p < 0.01). We conclude that LIF expression is frequent in all types of functioning and nonfunctioning pituitary adenomas.

Adenoma↗
PubMed2000

Intrasellar chordomas mimicking pituitary adenoma.

OBJECT: Whereas chordomas involving the sellar region are uncommon, largely or entirely intrasellar examples are rare. The goal in this study was to present examples of these rare tumors as a guide to their proper diagnosis and treatment. METHODS: The authors report three cases in which the chordomas filled the pituitary fossa and presented as nonfunctioning pituitary adenomas. All lesions exhibited the typical histological patterns and immunophenotype of chordoma. One tumor, studied ultrastructurally and subjected to DNA analysis, was shown to have a diploid histogram. The authors present a clinicopathological study of these three cases and review the literature on intrasellar chordomas. CONCLUSIONS: Although these tumors are easily misdiagnosed and therefore may not receive optimal treatment, aggressive surgical resection can yield a favorable prognosis in lesions with a limited extent.

Adenoma↗
PubMed2000

Differential distribution of the neuron-associated class III beta-tubulin in neuroendocrine lung tumors.

OBJECTIVE: To study the immunoreactivity profile of the neuron-associated class III beta-tubulin isotype (beta III) in epithelial lung tumors. DESIGN: One hundred four formalin-fixed, paraffin-embedded primary and metastatic lung cancer specimens were immunostained with an anti-beta III mouse monoclonal antibody (TuJ1) and an anti-beta III affinity-purified rabbit antiserum. Paraffin sections from fetal, infantile, and adult nonneoplastic lung tissues were also examined. RESULTS: In the fetal airway epithelium, beta III staining is detected transiently in rare Kulchitsky-like cells from lung tissues corresponding to the pseudoglandular and canalicular but not the saccular or alveolar stages of development. beta III is absent in healthy, hyperplastic, metaplastic, and dysplastic airway epithelium of the adult lung. In contrast, beta III is highly expressed in small cell lung cancer, large cell neuroendocrine carcinoma, and in some non-small cell lung cancers, particularly adenocarcinomas. There is no correlation between expression of beta III and generic neuroendocrine markers, such as chromogranin A and/or synaptophysin, in pulmonary adenocarcinomas. Also, focal beta III staining is present in primary and metastatic adenocarcinomas (to the lung) originating in the colon, prostate, and ovary. beta III is expressed to a much lesser extent in atypical carcinoids and is rarely detectable in typical carcinoids and squamous cell carcinomas of the lung. The distribution of beta III in small cell lung cancer and adenocarcinoma metastases to regional lymph nodes and brain approaches 100% of tumor cells, which is substantially greater than in the primary tumors. CONCLUSIONS: In the context of neuroendocrine lung tumors, beta III immunoreactivity is a molecular signature of high-grade malignant neoplasms (small cell lung cancer and large cell neuroendocrine carcinoma) although its importance in atypical carcinoids must be evaluated further. In addition, beta III may be a useful diagnostic marker in distinguishing between small cell lung cancers and certain non-small cell lung cancers (poorly differentiated squamous cell carcinomas), especially in small biopsy specimens. To our knowledge, beta III is the only tumor biomarker that exhibits a substantially more widespread distribution in poorly differentiated than in better differentiated pulmonary neuroendocrine tumors. However, the significance of beta III phenotypes in non-small cell lung cancer, particularly adenocarcinoma, with respect to neuroendocrine differentiation and prognostic value, requires further evaluation.

Adult↗
PubMed1999

Mice lacking mature T and B lymphocytes develop arthritic lesions after immunization with type II collagen.

Collagen-induced arthritis in DBA/1 mice is a widely used experimental model of rheumatoid arthritis. The induction phase of the disease is thought to be dependent upon MHC-restricted T and B cell-mediated immune responses to type II collagen, but an influence of additional non-MHC-restricted mechanisms has also been proposed. In this study, we report that type II collagen immunization of DBA/1 mice lacking mature T and B lymphocytes resulted in the development of arthritic lesions, which were characterized by synovial hyperplasia with occasional inflammation as well as cartilage and bone destruction. The specificity of disease induction to type II collagen was confirmed, because arthritis could not be induced when control preparations of OVA or adjuvant alone were administered. A delay in clinical disease onset and a reduction in severity between lymphocyte-positive and -negative DBA/1 mice confirmed that lymphocytes play an important role in disease; however, similar pathologic features and normal incidence suggest that lymphocyte-independent mechanisms of disease induction also operate in the standard collagen-induced arthritis model. We conclude that adaptive immune responses are not the only arthritogenic mechanism and hypothesize that the nonantigenic properties of type II collagen can also lead to arthritis.

Animals↗
PubMed1999

Structure-function correlations of growth hormone or/and prolactin-producing pituitary adenomas: an in vitro study with the reverse hemolytic plaque assay.

The purpose of this study was to detect in vitro growth hormone (GH) and prolactin (PRL) secretion from adenomas clinically associated with GH or PRL hypersecretion. The reverse hemolytic plaque assay (RHPA) was applied in order to reveal possible differences among various morphologic adenoma types, and to examine the inhibitory effects of octreotide on GH release as well. The 20 surgically resected pituitary adenomas studied included 15 from acromegalic patients and 5 from patients with hyperprolactinemia. All adenomas were diagnosed by histology, immunocytochemistry and electron microscopy. Among tumors associated with acromegaly, 5 were densely granulated (DG), 5 were sparsely granulated (SG) somatotroph (SM) adenomas, 2 were mammosomatotroph (MSM) and 3 mixed somatotroph-lactotroph cell (mixed SM-LT) adenomas; tumors causing hyperprolactinemia included 4 lactotroph (LT) adenomas and 1 mixed SM-LT adenoma. GH release assessed by the RHPA corresponded to in vivo hormone secretion and to tissue immunoreactivity. Statistical analysis showed significant differences among all morphologic types of SM adenomas, exclusive of SG-SM adenomas compared to mixed SM-LT adenomas. The mean plaque size in DG-SM and MSM adenomas was significantly greater than that of SG-SM and mixed SM-LT adenomas, indicating higher GH secretion by the former two types during the same incubation time. PRL secretion was documented in 2 mixed SM-LT adenomas. Plaques for PRL, but not for GH were formed in all LT adenomas. In all SM and LT adenomas, cells producing large plaques represented a minority of the plaque-forming cell population, however, they accounted for the largest part of the total plaque area, thus the largest part of hormone secretion. Octreotide effects on GH release were studied in 6 adenomas by the RHPA. Octreotide treatment induced a rapid and significant reduction in GH secretion by SM cells in vitro, with a selective effect on high-secreting cells.

Acromegaly↗
PubMed1999

Ossifying pituitary gonadotroph adenoma: A case report.

BACKGROUND: Bone formation in pituitary adenomas is a rare finding. Only two previous cases were published, occurring in a prolactin- producing and a growth hormone- producing pituitary adenoma respectively, both in pre-menopausal women. CLINICAL MATERIAL: This is the third report of an ossified pituitary adenoma and the first report of a pituitary gonadotroph adenoma with bone formation occurring in an elderly man. MRI imaging revealed an unusual eggshell cap-like calcified structure surrounding the tumor. Histologically, the adenoma contained irregularly anastomosing trabecules with well formed lacunae and osteoblasts along the margins. CONCLUSIONS: Insufficient tumor blood supply may trigger proliferation of connective tissue that subsequently undergoes osteoid metaplasia. Pituitary adenoma with osteoid metaplasia should be included in the differential diagnosis of calcifying tumors in the sella region.

Adenoma↗
PubMed1999

Molecular cytogenetics of chromosome 11 in pituitary adenomas: a comparison of fluorescence in situ hybridization and DNA ploidy study.

Chromosome 11 abnormalities were detected by fluorescence in situ hybridization (FISH) technique and compared with DNA ploidy in 24 surgically removed pituitary adenomas. The tumors were diagnosed and classified by histology, electron microscopy, and pituitary hormone immunocytochemistry. They included 2 densely granulated somatotroph (DG-SM) and 4 sparsely granulated somatotroph (SG-SM) adenomas, 3 SG lactotroph (LT), 2 mixed somatotroph-lactotroph (SM-LT), 4 functioning corticotroph (CRT), 1 silent CRT subtype 1, 1 thyrotroph, 1 mixed thyrotroph-somatotroph, 2 gonadotrophs, and 4 null cell adenomas. FISH analysis with an alpha-satellite DNA probe specific for chromosome 11 showed numerical abnormalities in 16 functioning (94%) and 5 nonfunctioning (71%) adenomas. Ten functioning tumors showed aneuploid histograms, whereas the remaining and all nonfunctioning adenomas were diploid. Aberrant chromosome 11 signals were noted mostly in aneuploid adenomas involving 17% to 100% of their cell population. The severity of chromosome 11 aberrations in adenomas containing extra copies often correlated with a higher DNA index (DI). Monosomy 11 as dominant aberration was noted in a mixed SM-LT and to a lesser degree in 3 CRT adenomas involving 21% to 97% of their cell population. Two of these CRT adenomas were associated with normal DI, whereas the remaining third showed a high DI, indicating increased copy number of chromosomes other than of chromosome 11. In conclusion, chromosome 11 abnormalities are common in all types of pituitary adenomas, occurring more frequently in functioning tumors. Specific numerical abnormalities, such as monosomy and trisomy, tend to be associated with certain adenoma types, whereas tumors with extra chromosome 11 copies often exhibit aneuploid histograms.

Adenoma↗
PubMed1999

Immunocytochemical accumulation of p53 in corticotroph adenomas: relationship with heat shock proteins and apoptosis.

The pathogenesis of corticotroph adenomas is unknown. In a recent study accumulation of p53 protein was detected by immunohistochemistry in a substantial proportion of pituitary corticotroph adenomas, and it has been suggested that it may be causally related to their development. However, other immunohistochemical studies have not confirmed the high incidence of p53 accumulation in this tumor type. Therefore, in the present study, p53 protein accumulation was re-examined in a series of 31 cases of corticotroph adenomas, using different sets of well validated anti-p53 antibodies. Furthermore, in view of the known association of p53 protein with apoptosis, and the known property of p53 to form complexes with heat shock proteins (HSPs), the relationship of p53 accumulation in corticotroph adenomas with apoptosis and HSP-70 was also investigated. Tumor samples from 31 patients with Cushing's disease or Nelson's syndrome were studied. Accumulation of p53 protein was tested by the standard ABC method using two different sets of clone Pab1801 and DO-7 monoclonal antibodies, applied after incubation of sections in a microwave oven. Using the DO-7 antibody, nuclear accumulation of p53 protein was detected in a total of 15 cases, with cytoplasmic staining observed in only 3 tumors. In contrast, using the Pab1801 antibody nuclear staining was observed in only 5 adenomas, with 11 adenomas demonstrating focal cytoplasmic immunoreactivity. Parallel sections of all corticotroph tumors demonstrating cytoplasmic accumulation of p53 protein were tested for the immunohistochemical presence of heat shock protein HSP-70. A striking similar distribution pattern of these two proteins was observed. Apoptosis, identified by the in situ end labeling technique, was detected in a total of 15 out of 28 corticotroph adenomas tested. Calculation of the apoptotic labeling index (ALI) by image analysis showed a significantly lower ALI in those corticotroph adenomas demonstrating nuclear p53 accumulation compared to those with no nuclear p53 immunostaining (p < 0.05). There was no significant difference in the ALI between cytoplasmic p53 positive and negative tumors. It is concluded that depending on the antibody used there is a significant variation of p53 protein detection in corticotroph adenomas. Overall, a significant proportion of corticotroph adenomas studied expressed the p53 protein, which depending on the antibody used, was located either in the nucleus and/or the cytoplasm of tumorous corticotroph cells. Cytoplasmic accumulation of p53, as shown by our colocalization studies with HSP-70, may be due to p53/HSP-70 complex formation. Although such a complex-mediated cytoplasmic exclusion of p53 has no significant effect on apoptosis, nuclear accumulation of p53 protein is associated with a significantly lower apoptotic index indicating a failure of p53 protein to exert its apoptotic action in at least a subset of this tumor type.

Adenoma↗
PubMed1999

Intrasellar paraganglioma presenting as nonfunctioning pituitary adenoma.

Paragangliomas arising in the sellar region are rare. We report a case of intrasellar paraganglioma of a 54-year-old man who presented with gradually decreasing visual acuity. Physical examination revealed bitemporal hemianopsia with no apparent signs of endocrinologic dysfunction. Magnetic resonance imaging revealed a large sellar mass believed to be a nonfunctioning pituitary adenoma. The tumor was removed transsphenoidally and submitted for histologic examination. The morphologic features, based on histologic, immunocytochemical, and electron microscopic analyses, were consistent with the diagnosis of paraganglioma. The diagnostic morphologic features and the immunocytochemical profile of the tumor are reported.

Adenoma↗
PubMed1999

Surgical and non-surgical treatment of pituitary adenomas.

Pituitary adenomas are slow growing, benign lesions originating from various hormone producing cells of the anterior lobe of the pituitary gland. The currently used morphofunctional classification is based on histology, immunocytochemistry and electron microscopy. Pituitary adenomas may present clinically with certain endocrinopathies attributable to pituitary hypersecretion of pituitary hormones, or with neurologic symptoms of tumor mass effect due to compression of the adjacent brain structures, such as optic or other cranial nerves, and may induce increased intracranial pressure.

Journal Article↗
PubMed1998

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.

Adenoma, Basophil↗