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Biomedical subjects

K Kovacs

Publications and source records attributed to K Kovacs.

At least 19 recordsLinked to original sources
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 corticotroph hyperplasia in rats implanted with a medullary thyroid carcinoma cell line transfected with a corticotropin-releasing hormone complementary deoxyribonucleic acid expression vector.

CRH stimulates both the synthesis and release of ACTH and other derivatives of POMC by the adenohypophysis. It is uncertain, however, whether it also causes proliferation of corticotrophs. Patients with CRH-producing tumors develop Cushing's syndrome, and some have been reported to have pituitary corticotroph hyperplasia. We now report an animal model that accurately reproduces the human disorder of ectopic production of CRH by a neoplasm. Prolonged CRH secretion by a transplanted medullary thyroid carcinoma cell line stably transfected with a CRH cDNA under transcriptional control of a cytomegalovirus promoter resulted in corticotroph hyperplasia and hypertrophy; the percentage of ACTH-containing cells in animals bearing W2CRH tumors was increased at 9.8 +/- 0.5% (controls, 6.2 +/- 0.3%; W2 implanted tumors, 7.7 +/- 0.4%). Occasional mitotic figures were identified, and the cells were larger, with abundant cytoplasm but generally less intense immunohistochemical staining for ACTH due to relative degranulation compared to controls. Melanotrophs of the intermediate lobe were also increased in number and were larger, with abundant cytoplasm. No corticotroph adenomas were found. Our experiment accurately reproduces the gradually increasing CRH levels in the general circulation produced by a growing tumor, as found in the human ectopic CRH syndrome, and confirms that long term exposure to CRH excess, as produced by a tumor, results in an increased number of corticotrophs in the adenohypophysis.

Adrenocorticotropic Hormone↗
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↗
PubMed1979

An immunohistochemical and ultrastructural comparison of the effects of 2-bromo-alpha-ergocryptine on intrasellar and transplanted rat pituitaries.

Following 2 weeks of administration of 2-bromo-alpha-ergocryptine, a marked decrease was observed in prolactin immunoreactivity of the grafted pituitaries, whereas no reduction was noted in the intrasellar pituitaries. No evidence of crinophagy was revealed by electron microscopy in prolactin cells of 2-bromo-alpha-ergocryptine-treated rats.

Animals↗
PubMed1979

Growth hormone-producing pituitary adenoma with giant secretory granules.

Unusually large, oval and pleomorphic secretory granules were noted by electron microscopy in an acidophilic adenoma of the pituitary. The tumor, which was removed by surgery from a 42-year-old woman with elevated blood growth hormone levels and the clinical features of acromegaly, was found to contain growth hormone by the immunoperoxidase technique. This ultrastructural abnormality of secretory granules was not reported so far and was not seen among the 58 cases of growth hormone-producing adenomas investigated in our laboratory. The present case clearly shows that the cytogenesis and cellular composition of pituitary adenomas cannot be determined by solely examining the size and shape of secretory granules.

Acromegaly↗
PubMed1979

Autolytic changes in the rat adenohypophysis. A histologic, immunocytologic and electron microscopic study.

Thirty-nine adult female Long Evans rats were decapitated and the heads stored at room temperature. The pituitaries were removed at intervals from 30 minutes to seven days, fixed, embedded and studied by histology, immunocytology and electron microscopy. Histologically, changes were noticeable after two hours postmortem. Immunoperoxidase staining showed postivity for growth hormone, prolactin, FSH, LH and TSH up to seven days after sacrifice, appearing even stronger in the advanced stages of autolysis. Fine structural alterations were evident at 30 minutes and more conspicuous later. Changes included dilation, partial degranulation and whorl formation of RER, swelling of Golgi complexes and mitochondria, chromatin clumping, lysis, rhexis and pyknosis of nuclei, cytosegresome formation and disruption of cell membranes. Secretory granules remained well preserved throughout, although some exhibited fusion or reduced electron density. Dilation of capillaries with accumulation of erythrocytes, platelets and fibrin fibers were prominent findings. The severity of changes varied considerably from cell to cell indicating that the rate of autolysis is not the same among different cell types and is possibly affected by the actual functional state of the cell. It appears that increased membrane permeability and disruption of plasmalemma represent important steps in the autolytic process.

Animals↗
PubMed1979

Nuclear inclusions in the human adenohypophysis. A fine-structural study of nontumorous and adenomatous pituitaries.

Electron microscopy revealed the presence of nonviral nuclear inclusions in human nontumorous as well as adenomatous adenohypophysiocytes, regardless of cell type. Based on ultrastructural appearances, the inclusions have been classified as simple bodies, complex bodies and filamentous aggregates. Many transitional forms were noted between the simple and complex bodies, however, no relationship between the nuclear bodies and filamentous aggregates was found. It can be concluded that the three types of inclusions are normal nuclear constituents. Since no accumulation of these structures was observed in cells associated with enhanced secretion it appears that they are not related to hormonal hyperactivity in the human adenohypophysis.

Adenoma↗
PubMed1979

Corticotroph cells of the human pituitary in old age.

This study was undertaken, utilizing immunocytologic methods and in particular the immunoperoxidase technique, to evaluate corticotroph cell morphology and distribution in the pituitary glands of aged subjects dying of various diseases. Early histologic studies did not allow for reliable identification of the different adenohypophysial cell types. Corticotroph cell distribution within the gland is described as well as its morphological characteristics. Our findings substantiate conclusions based on biochemical investigations that corticotroph cells remain unchanged and function normally in aged subjects.

Adrenocorticotropic Hormone↗
PubMed1979

Thyrotrophs in old age. An immunocytologic study of human pituitary glands.

In order to reveal whether thyrotroph cells of the human pituitary are affected by aging, a histologic and immunocytologic study was undertaken on the pituitaries of patients over 80 years of age (10 men, 10 women), dying of various acute illnesses and the findings compared with those of a younger age group (10 men, 10 women), dying of various acute illnesses between the age of 20-56 years. The incidence, distribution, granulation, cytoplasmic vacuolization, as well as immunoreactivity of TSH cells, showed no major differences related to age and sex. Lack of involution of thyrotroph cells in old subjects indicates that the pituitary is capable of producing TSH with advancing age.

Adult↗
PubMed1979

Primary empty sella: a histologic and immunocytologic study.

A primary "empty" sella turcica was found incidentally at autopsy, and the anterior lobe of the pituitary gland was studied with the immunoperoxidase technique. All five adenohypophysial cell types, ie, somatotrophs, lactotrophs, corticotrophs, thyrotrophs, and gonadotrophs (containing follicle-stimulating hormone [FSH] and luteinizing hormone [LH], were present in adequate numbers and were well granulated, indicating normal hormone storage.

Empty Sella Syndrome↗
PubMed1978

Sellar enlargement with hyperprolactinemia and a Rathke's pouch cyst.

A woman with secondary amenorrhea was found to have hyperprolactinemia without clinical galactorrhea. Radiological findings of an enlarged sella turcica with displacement of the pituitary stalk were considered consistent with a prolactin macroadenoma. Treatment with bromocriptine corrected the amenorrhea and hyperprolactinemia, and the patient inadvertently became pregnant. However, no complications to the mother or fetus occurred during pregnancy or postpartum. On transsphenoidal surgery three months postpartum, the unexpected presence of a large Rathke's pouch cyst with a microadenomatous or nodular hyperplasia type of prolactin-secreting tumor was observed to account for the preoperative clinical and radiological findings.

Adult↗
PubMed1978

Pyrazole-induced thyroid necrosis: a distinct organ lesion.

One oral dose of pyrazole caused necrosis of rat thyroid follicular epithelial cells but spared the parafollicular (C) cells and the parathyroid glands. Serum thyroxine (T4) and triiodothyronine (T3) were significantly decreased on day 3 after pyrazole administration and were immeasurable on day 5. At day 5 the thyroid was enlarged and the concentration of thyroid-stimulating hormone in the serum was increased, indicating an appropriate pituitary response to a primary lesion in the thyroid. Doses of pyrazole which produced no morphologic change in the thyroids also significantly depressed the concentrations of T4 and T3 in the serum.

Animals↗
PubMed1978

Morphogenesis and significance of fibrous bodies in human pituitary adenomas.

In the course of light and electron microscopic studies of 142 surgically-removed human pituitary adenomas, 28 tumors were found containing fibrous bodies composed of type II microfilaments with an average width of 115A. These spherical structures, measuring up to 4-5 micrometer occur exclusively in sparsely granulated growth hormone cells and acidophil stem cells, but as revealed by the immunoperoxidase technique, contain no growth hormone. Fibrous bodies are located in the Golgi region and are consistently associated with Golgi membranes and smooth-surfaced endoplasmic reticulum. Their association with centrioles is thought to be anatomical rather than functional. Several adenoma cells possess spherical formations composed entirely of smooth-walled membranes or transitional forms between smooth tubules and type II microfilaments, suggesting that smooth membranes may play a key role in the production of fibrillar substance. Fibrous bodies appear to be reliable morphologic markers and are valuable in the differential diagnosis of pituitary adenomas.

Adenoma↗