Biomedical subjects

E Horvath

Publications and source records attributed to E Horvath.

At least 19 recordsLinked to original sources

PubMed1992

Ultrastructural diagnosis of human pituitary adenomas.

Electron microscopy, which has been instrumental in the characterization of normal pituitary cell types, has also played a crucial role in the morphologic classification of pituitary adenomas arising in the presently known 5 cell types, and in the recognition of 3 adenoma types with yet undisclosed cell derivation. This review deals with the application of electron microscopy for study of pituitary adenomas in order to provide specific pathological diagnosis and aid the clinician in selecting appropriate postoperative treatment. In addition to the ultrastructural appearance and diagnostic features of 15 adenoma types, the morphology of hyperplastic proliferations and that of known normal counterparts of various adenoma types are also discussed. Specific morphologic diagnosis of pituitary lesions is important not only for adequate postoperative management of patient, but is also a prerequisite for study of the natural history and biological behaviour of various adenoma types.

Adenoma↗

PubMed1992

Ultrastructure of the neurohypophysis.

This review summarizes our current knowledge of the ultrastructure of the human neurohypophysis and includes comments on its anatomy, physiology, and embryology. The neurohypophysis represents a unique tissue having neural and endocrine characteristics and possessing ultrastructural features distinct from those of conventional endocrine organs such as the anterior pituitary, thyroid, pancreatic islets, etc. In contrast to these glands, the neurohypophysis is composed of the processes of mature neurons. As such, it is not capable of synthesizing hormones but only of their storage and release. Neurosecretion is one of the most exciting areas of neuroendocrinology and, although spectacular progress has been achieved in elucidating the process, a number of aspects are incompletely understood. Recent evidence indicates that the magnocellular nuclei of the hypothalamus, the anatomic origin and functional basis of the neurohypophysis, produce not only vasopressin and oxytocin, the so-called "neurohypophyseal hormones," but a number of other biologically active peptides as well. The physiologic function of these substances is largely unknown but they may be of profound importance in endocrine homeostasis. Based on these novel findings, the role of the neurohypophysis in endocrine regulation has to be re-evaluated.

Exons↗

PubMed1992

Hyperthyroidism due to inappropriate secretion of thyrotropin in 10 patients.

PURPOSE: The syndrome of inappropriate thyroid-stimulating hormone (TSH) secretion, characterized by elevated serum free thyroxine and triiodothyronine levels in association with measurable serum TSH concentrations, remains an uncommon cause of hyperthyroidism that is being recognized with increasing frequency. The hyperthyroidism may be due to either neoplastic pituitary TSH secretion or selective pituitary resistance to thyroid hormone. In an effort to better understand this rare cause of hyperthyroidism, we undertook a retrospective analysis of our institution's experience with this condition. PATIENTS: We reviewed our cumulative experience (10 patients) with hyperthyroidism due to the syndrome of inappropriate secretion of TSH. RESULTS: Six patients were diagnosed with TSH-secreting pituitary adenomas and four were found to have selective pituitary resistance to thyroid hormone. One patient with tumor had a TSH-secreting pituitary adenoma in the setting of multiple endocrine neoplasia syndrome. In all patients with tumor, hyperthyroidism was successfully treated with transsphenoidal adenomectomy with or without pituitary radiotherapy. All four patients with pituitary resistance had thyroid ablation or resection prior to their correct diagnosis. Therefore, therapy for this group of patients involved thyroid hormone replacement and efforts to suppress TSH hypersecretion. All 10 patients have done well clinically, with follow-up ranging from 2 weeks to 13 years. CONCLUSIONS: Adequate treatment exists for the two primary causes of TSH hypersecretion. TSH-secreting pituitary adenomas are treated with surgery and, if necessary, adjuvant pituitary radiotherapy. The results are generally good if the tumor is diagnosed and treated at an early stage. Primary therapy for hyperthyroidism due to selective pituitary resistance to thyroid hormone is aimed at suppression of pituitary TSH hypersecretion. The evaluation of any patient with hyperthyroidism must be thorough and, in some cases, should include measurement of TSH to determine the presence of inappropriate secretion. Eliminating this diagnosis will help avoid improper and potentially harmful treatment of hyperthyroid patients.

Adenoma↗

PubMed1992

Peroxidative activation of o-phenylhydroquinone leads to the formation of DNA adducts in HL-60 cells.

Using 32P-postlabeling we studied DNA adduct formation in HL-60 cells treated with the o-phenylphenol metabolites o-phenylhydroquinone (o-PHQ) and o-phenylbenzoquinone (o-PBQ). Treatment with 25-500 microM o-PHQ for 8 h produced one principal and three minor adducts with a relative distribution of 80, 10, 6 and 4%. The relative adduct levels from these treatments were 0.26-2.31 adducts/10(7) nucleotides. Treatment with 25-250 microM o-PBQ for 2 h resulted in a similar level of DNA modification and adduct distribution. Reaction of purified calf thymus DNA with o-PBQ produced one DNA adduct, which did not correspond to the major adduct produced in HL-60 cells. These results show that o-PHQ and o-PBQ can form DNA adducts. Peroxidase activation of o-phenylphenol may therefore play a role in the carcinogenic effect of this compound.

Benzoquinones↗

PubMed1992

Cushing's syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma.

We describe a case of Cushing's syndrome caused by a phaeochromocytoma secreting corticotrophin-releasing hormone (CRH) and corticotrophin (ACTH). A 49-year-old white woman presented with a 1-month history of lower limb oedema, polydipsia and polyuria. Physical examination revealed a patient with plethoric facies, lanugo-type facial hair, central obesity, red abdominal striae, lower limb oedema, and blood pressure of 210/115 mmHg. Laboratory studies showed high plasma ACTH and markedly elevated urinary cortisol excretion that suppressed more than 50% with high-dose dexamethasone administration. Computed tomographic scan of the abdomen showed a 4-cm left adrenal tumour. Catecholamines and metabolites were markedly increased in a 24-hour urine collection. Results of venous catheterization studies showed that CRH and ACTH were secreted by the tumour. In addition, with ovine CRH administration, inferior petrosal sinus sampling showed pituitary secretion of ACTH. Left adrenalectomy resulted in complete remission of Cushing's syndrome. Light microscopic and immunohistochemical studies revealed a phaeochromocytoma that produced CRH, ACTH and vasopressin. RNA studies showed that this tumour, in contrast to normal adrenal and other reported phaeochromocytomas, transcribed a lone pituitary-sized (1200 nucleotide) pro-opiomelanocortin mRNA. This is the second reported case of a CRH-secreting phaeochromocytoma.

Adrenal Gland Neoplasms↗

PubMed1992

Morphology of adenohypophysial tumors in mice transgenic for vasopressin-SV40 hybrid oncogene.

Transgenic mice for the promoter sequence of bovine arginine vasopressin (AVP) gene fused to large SV40 T-antigen coding sequence develop pituitary tumors and insulin-producing pancreatic tumors. In order to establish the cellular composition of the pituitary tumors, histological, immunocytochemical, in situ hybridization, and electron microscopic technics were applied. Pituitary anterior lobe tumors were identified in 10 out of 14 glands examined. In 2 of these cases, intermediate lobe tumors were also found. The anterior lobe tumors contained a variable number of GH immunoreactive cells. In situ hybridization performed in 7 cases revealed a diffuse distribution of GH messenger RNA over all tumor cells. Ultrastructurally, the tumors contained undifferentiated cells with very small secretory granules and rare cells showing some resemblance to somatotrophs. The results indicate that these pituitary tumors are composed of undifferentiated somatotrophs. The presence of a few PRL immunoreactive cells in four tumors and scattered TSH immunoreactive cells in two tumors supports the view that somatotrophs have the potential to produce PRL and TSH. The intermediate lobe tumors were immunoreactive for ACTH and intensely positive for POMC mRNA. In the nontumorous adenohypophyses, no hyperplasia of any cell type was noted. Several GH immunoreactive cells exhibited pleomorphic, giant nuclei and mitoses. In conclusion, the majority of transgenic mice for AVP/large T-antigen develop pituitary tumors originating in and composed of somatotrophs. Less frequently, intermediary lobe tumors were present as well. AVP/SV40 transgenic mice provide a unique experimental model for somatotroph tumors that are neither preceded by, nor associated with somatotroph hyperplasia.

Animals↗

PubMed1992

Pituitary adenomas in mice transgenic for growth hormone-releasing hormone.

It has been shown that mice transgenic for human GH-releasing hormone (GRH) develop hyperplasia of pituitary somatotrophs, lactotrophs, and mammosomatotrophs, cells capable of producing both GH and PRL, by 8 months of age. We now report that GRH transgenic mice 10-24 months of age develop pituitary adenomas, which we characterized by histology, immunohistochemistry, in situ hybridization, and electron microscopy. Of 13 animals examined, all developed GH-immunoreactive neoplasms that had diffuse positivity for GH mRNA by in situ hybridization. Eleven also contained PRL immunoreactivity; in situ hybridization demonstrated focal PRL mRNA in 3 of 5 immunohistochemically positive tumors. Alpha-Subunit was positive by immunohistochemistry in 8 adenomas, and TSH beta was localized in tumor cells of 5 adenomas. The adenomas had variable ultrastructural appearances, ranging from cells that resembled somatotrophs or mammosomatotrophs to cells with features of the glycoprotein hormone cell line. These findings provide conclusive evidence that protracted GRH stimulation of secretory activity can result in proliferation, hyperplasia, and adenoma of adenohypophysial cells.

Adenoma↗

PubMed1992

Hormone secretion in vitro by plurihormonal pituitary adenomas of the acidophil cell line.

Pituitary tumors producing GH and PRL are morphologically classified as monomorphous bihormonal acidophil stem cell adenomas (ASCAs) which cause hyperprolactinemia and two tumor types which are usually associated with acromegaly, the monomorphous plurihormonal mammosomatotroph adenomas (MSAs) and bimorphous mixed somatotroph-lactotroph adenomas. We studied 12 MSAs, 2 ASCAs, and 10 mixed adenomas in vitro to assess the secretory behavior of these tumors diagnosed by immunohistochemistry and electron microscopy. GH release by MSAs and all but one mixed tumor was greater than that of PRL; the opposite was true of the ASCAs. One mixed tumor which caused impotence and hyperprolactinemia contained predominantly lactotrophs and released greater amounts of PRL than of GH in vitro. All 12 MSAs and 6 of 10 mixed tumors released alpha-subunit of glycoprotein hormones. Incubation with GHRH increased release of GH and PRL by all tumors and of alpha-subunit when present; the responses of all hormones were parallel among MSAs whereas among mixed adenomas, GH and alpha-subunit had greater responses than PRL. TRH stimulated GH, PRL, and alpha-subunit release by MSAs in parallel; among mixed adenomas, PRL response was generally greater than that of GH or alpha-subunit. SRIH markedly reduced GH release by all MSAs; it inhibited GH and alpha-subunit release by mixed tumors more than it affected PRL. Bromocriptine inhibited GH, PRL, and alpha-subunit release by most MSAs and mixed tumors but did not inhibit GH or PRL release by ASCAs. This study demonstrates release of GH, PRL, and alpha-subunit by these morphologically classified plurihormonal tumors in vitro. Variable quantities of GH and PRL released by the different tumor types correlate with immunohistochemical and clinical data. The dynamic studies indicate that regulation of GH, PRL, and alpha-subunit release can be affected by GHRH, TRH, SRIH, and bromocriptine in these adenomas and suggest differences in receptor status. Our data strengthen the view that these three plurihormonal adenomas of the acidophil cell line are not only morphologically but also functionally different and warrant separation.

Adenoma, Acidophil↗

PubMed1992

Coexisting corticotroph and lactotroph adenomas: case report with reference to the relationship of corticotropin and prolactin excess.

A 57-year-old obese woman with hypertension, diabetes mellitus, osteoporosis, and a 40-year history of secondary amenorrhea was diagnosed with corticotropin-dependent Cushing's syndrome. Dynamic endocrine testing and radiological evaluation did not reveal definitively the source of the excess corticotropin. Bilateral adrenalectomy was performed with resolution of the signs and symptoms of hypercortisolism. Four years later, the patient was noted to have rising serum corticotropin levels and an enlarging pituitary mass; hyperprolactinemia also was documented. A diagnosis of Nelson-Salassa syndrome was made, and she underwent a transsphenoidal adenomectomy. A histological examination of the specimen revealed two distinct, albeit contiguous, adenomas: a corticotroph adenoma and a lactotroph adenoma. Postoperatively, the serum prolactin and corticotropin levels decreased significantly. Although the stalk section effect resulting from compression by a pituitary adenoma can raise serum prolactin levels, a concurrent lactotroph adenoma should be considered in patients with nonfunctional or functional pituitary adenomas of other types associated with significantly elevated prolactin levels. The mechanisms underlying simultaneous adrenocorticotropic hormone and prolactin excess are discussed.

Adrenal Cortex↗

PubMed1992

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.

Acromegaly↗

PubMed1991

Local cerebral glucose utilization in the brain of old, learning impaired rats.

The local cerebral glucose utilization (LCGU) was measured in 63 different cortical areas and nuclei of the telencephalon, diencephalon and rhombencephalon of young adult (3 to 4-month-old) rats and of 27-month-old Wistar rats, in which learning impairments had been proven by a water maze test. The LCGU was determined by [14C]2-deoxyglucose autoradiography. In the old rats the mean LCGU of all brain regions was significantly reduced by about 10% compared with the young control group; the mean LCGU was 74.2 mumol glucose/(100 g x min) in the young and 66.7 in the old rats. Different degrees of LCGU decrease were found in the different regions. Most of the brain regions with significantly reduced LCGU values in the aged, learning impaired rats were associated with auditory and visual functions, the dopaminergic system, and structures known to be involved in learning and memory processes. Therefore, the regional pattern of LCGU reduction found in the aged, learning impaired rats did not resemble any known pattern found after lesions of a single transmitter system or systemic administration of transmitter agonists or antagonists.

Aging↗

PubMed1991

Idiopathic prolactin cell hyperplasia of the pituitary mimicking prolactin cell adenoma: a morphological study including immunocytochemistry, electron microscopy, and in situ hybridization.

Prolactin cell adenoma is the most frequently found lesion in surgically removed pituitaries of patients with hyperprolactinemia. However, in several instances, instead of prolactin cell adenoma, other lesions are encountered by morphological investigation. We report here the morphological findings in a patient with hyperprolactinemia who underwent transsphenoidal pituitary surgery for suspected prolactin cell adenoma. A morphological diagnosis of tumor could not be confirmed and massive diffuse prolactin cell hyperplasia was identified. The aim of this publication is to describe the lesion by histology, immunocytochemistry, electron microscopy, and in situ hybridization and to call attention to primary prolactin cell hyperplasia which can mimic prolactin cell adenoma.

Diagnosis, Differential↗

PubMed1991

In situ hybridization study of pro-opiomelanocortin (POMC) gene expression in human pituitary corticotrophs and their adenomas.

Pro-opiomelanocortin (POMC) mRNA was detected on paraffin sections by in situ hybridization (ISH) in corticotrophs of 12 nontumorous pituitaries, 11 functioning corticotroph, and 11 silent pituitary adenomas. ISH combined with immunocytochemistry for adrenocorticotrophic hormone (ACTH), a POMC-derived peptide, was also performed. ACTH immunoreactive cells of the anterior lobes and those invading the posterior lobe showed a high or moderate level of POMC mRNA that was not correlated with the intensity of ACTH immunoreactivity. Variable levels of POMC gene expression were present in Crooke's cells, corticotrophs suppressed by glucocorticoid excess. Most functioning corticotroph adenomas and silent subtype 1 adenomas had an intense hybridization signal and ACTH immunoreactivity. In silent subtype 2 and 3 adenomas, POMC mRNA had a diffuse low level or was absent; in these adenomas ACTH immunoreactivity was diffuse, restricted to some cells, or negative. The results indicate that POMC gene is expressed in both normal and suppressed nontumorous corticotrophs. Intense signals for POMC mRNA are found in most functioning corticotroph adenomas. The difference between POMC gene expression in silent 1 and silent 2 and 3 adenomas suggests that different mechanisms are responsible for the lack of endocrine activity.

Adenoma↗

PubMed1991

Effect of dopamine agonist medication on prolactin producing pituitary adenomas. A morphological study including immunocytochemistry, electron microscopy and in situ hybridization.

Conventional light microscopy, immunocytochemistry, electron microscopy and in situ hybridization were used to evaluate the effect of dopamine agonists (bromocriptine-LAR and bromocriptine) on the morphology of surgically removed prolactin (PRL)-producing pituitary adenomas. Dopamine agonist therapy resulted in decrease of serum PRL, clinical improvement and tumour shrinkage. Using light and electron microscopy cellular atrophy, interstitial and perivascular fibrosis were noted; in several tumours connective tissue accumulation was pronounced. The cellular response was not uniform. In some adenomas populations of large cells and small cells were distinguished. The large cells contained immunoreactive PRL and expressed the PRL gene indicating resistance to dopamine agonists. It appears that these cells retained the potential to secrete PRL and proliferate despite exposure to dopamine agonists. In the small cells, PRL immunoreactivity and PRL gene expression decreased providing evidence that both PRL release and synthesis were blocked. Small cells can persist in tumours after discontinuation of dopamine agonist medication suggesting these small cells are irreversibly suppressed and are not capable of regaining their endocrine function and proliferative capability. The formation of irreversibly suppressed PRL cells may explain why some PRL-producing adenomas do not recur after withdrawal of dopamine agonists.

Adenoma↗

PubMed1991

A case of sparsely granulated growth hormone cell adenoma associated with lymphocytic hypophysitis.

Lymphocytic hypophysitis is in itself rare and usually occurs in the postpartum period or the last trimester of pregnancy. It has not been described in combination with a pituitary tumor. A twenty-two year old woman, who had never been pregnant, presented with a history of nine months amenorrhea and spontaneous galactorrhea. She was not taking any medication and had never used oral contraceptives. Physical examination was unremarkable except that whitish fluid could be expressed from both breasts. Her visual fields were normal. Her serum PRL levels was high at 105.7 micrograms/l and increased to 138.4 micrograms/l at 60 minutes in a triple bolus test. GH values were normal and there was no evidence of overproduction of other pituitary hormones. CT scan showed an intrasellar mass with suprasellar extension. A tumor was selectively removed transsphenoidally. Morphologic examination revealed a clinically silent sparsely granulated growth hormone cell adenoma with lymphocytic infiltration of the adjacent pituitary tissue. Postoperatively her menstrual periods resumed and she conceived despite a slightly elevated PRL level. Three months after an uneventful pregnancy and full term delivery her PRL level was 69.9 micrograms/l and increased to 102.2 micrograms/l at 60 min. Basal GH and cortisol levels were normal. She remains well without replacement fourteen months after delivery. This case is of interest because it is the first reported simultaneous occurrence of a pituitary adenoma and lymphocytic hypophysitis and also because the hypophysitis preceded her first pregnancy.

Adenoma↗

PubMed1991

Changes in hormone production of a recurrent silent corticotroph adenoma of the pituitary: a histologic, immunohistochemical, ultrastructural, and tissue culture study.

A 19-year-old man with blurred vision, headache, and no signs or symptoms of hormone excess was found to have a pituitary adenoma. The tumor was removed by a transfrontal approach. He had postoperative radiation therapy, but subsequently had three recurrences, all removed surgically. By histology, the tumor was a chromophobic, slightly acidophilic pituitary adenoma. Immunohistochemistry revealed the presence of adrenocorticotropin (ACTH) in all four biopsies, alpha-subunit of glycoprotein hormones, and, to a lesser extent, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in the third and fourth tumor resection specimens. Ultrastructurally, the tumor had typical features of a silent corticotroph adenoma subtype 2. In tissue culture, the second, third, and fourth specimens released ACTH, alpha-subunit, FSH, and LH and responded to corticotropin-releasing hormone with increased release of ACTH, alpha-subunit, FSH, and LH. To our knowledge only one silent corticotroph adenoma has been reported previously which expressed plurihormonality. Change in immunohistochemical profile in malignant tumors is a well-known phenomenon; however, it was not reported previously in benign pituitary adenomas. The factors accounting for changing tumor phenotype are unknown.

Adenoma↗

PubMed1991

Gonadotroph adenoma of the pituitary mimicking a prolactinoma.

In a 41-year-old woman with mild hyperprolactinemia and amenorrhea, preoperative hormonal and neuroradiological findings suggested the diagnosis of a macroprolactinoma. She underwent transsphenoidal surgery since the tumor size had not changed in spite of bromocriptine administration for 5 months. Consequently, this case was diagnosed as a female-type gonadotroph adenoma on the basis of its characteristic ultrastructural features including a honeycomb Golgi complex, even though endocrinological and immunohistochemical findings were not those of a typical gonadotroph adenoma.

Adenoma↗

PubMed1991

Multiple adenomas of the human pituitary. A retrospective autopsy study with clinical implications.

In a review of autopsy material from two centers, 20 pituitary glands were found containing multiple adenomas. In total, 44 adenomas were identified histologically; 16 glands contained double tumors and in four glands triple adenomas were found. Size was measured in 30 tumors, all of which were microadenomas. Thirty-four adenomas were located in the lateral wings and 10 lay in the median wedge. Forty-one tumors were chromophobic and three were basophilic. Immunocytochemical analysis of the 44 tumors demonstrated the presence of prolactin in 11, adrenocorticotropic hormone in three, growth hormone in one, and alpha-subunit as well as follicle-stimulating hormone and luteinizing hormone in one. Of the 20 patients studied, there were 11 men and nine women, with an average age of 69 years. All patients died from various nonendocrine causes. With the exception of one patient who appeared mildly acromegalic, no correlation was observed between pituitary morphology and clinical data. This study found a 10.4% frequency of adenomas in pituitaries studied randomly at autopsy. Multiple tumors were encountered in 0.9% of cases. Despite its low frequency, adenoma multiplicity may underlie surgical failure in cases in which one adenoma is removed and the other is left behind.

Adenoma↗