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The role of ACTH in the episodic release of aldosterone in patients with idiopathic adrenal hyperplasia, hypertension, and hyperaldosteronism.

The relationship of plasma aldosterone concentration to its identified stimuli was examined in three patients with hypertension, hyperaldosteronism, and idiopathic adrenal hyperplasia. Four patients with hyperaldosteronism due to adrenal adenomas served as controls. Plasma aldosterone, cortisol, sodium, and potassium concentrations and renin activity were measured in blood samples taken at 20 minute intervals from 2 A.M. to 8 A.M. during recumbency and sleep. The tests were performed on all patients following a regular sodium diet both before and after short-term treatment with dexamethasone. Two of the three subjects with adrenal hyperplasia were re-examined after 2 weeks of dexamethasone therapy. All four control patients with adenomas had episodic increases of plasma aldosterone which were significantly correlated with those of plasma cortisol (r = +0.48 to +0.90). This confirms the previously reported relationship between aldosterone and ACTH in such patients. Two patients with idiopathic adrenal hyperplasia had a similar secretion pattern and a highly significant correlation of the two hormones (r = +0.76 and +0.77); one did not (r = 0.13). Short-term dexamethasone pretreatment attenuated the episodic release pattern and partially suppressed the mean plasma concentrations of aldosterone in the four patients with an adenoma and in the two patients with idiopathic hyperplasia whose plasma aldosterone and cortisol concentrations were positively correlated. There was no such effect in the third patient. The first two patients with idiopathic hyperplasia were subsequently retested following 2 weeks of dexamethasone treatment to determine if the episodic secretion pattern of plasma aldosterone would correlated with other stimuli following this period of ACTH suppression. One showed little change from the pattern observed after short-term glucocorticoid treatment. The second had a similarly blunted aldosterone response until ACTH secretion led to a resumption of episodic changes in plasma aldosteerone concentrations. These data indicate that ACTH frequently is the dominant stimulus of the episodic secretion of aldosterone in patients with either adrenal adenomas or hyperplasia. When ACTH is suppressed, the hypersecretion of aldosterone is presumably sustained by an intrinsic adrenal abnormality or by an as yet unidentified stimulus.

Adenoma

[Atypical adenomatous hyperplasia of the endometrium].

By women in climacterium and postmenopause the authors found 30 adenomatous atypical hyperplasias out of a total of 909 active hyperplasias. They also detected 68 endometrial carcinomas and 65 other changes. Out of 30 patients with adenomatous atypical hyperplasia, 23 had been subjected to curettage earlier but at that time had revealed only milder forms of hyperplasia. Surgery was performed in 21 patients: in 15 patients the diagnosis based on the operative preparation agreed with that based on curettage findings, in 2 patients endometrial carcinoma and in 2 patients glandular hyperplasia were detected, while in 2 patients there was no functional endometrium. Out of 9 patients who for various reasons were not surgically treated and represented an unintentional prospective study, 5 subsequently developed endometrial carcinoma, 3 mild forms of hyperplasia, and 1 atrophia cystica. In the authors' opinion, the histogenesis of endometrial carcinoma in late postmenopause is still an open question.

Adult

An outbreak of cecal mucosal hyperplasia in hamsters.

Cecal mucosal hyperplasia associated with diarrhea, runting, and high mortality in suckling and weanling hamsters occurred as a natural disease outbreak in a production colony. Young hamsters were runted, and their perineal hair was stained and matted with liquid feces. Their ceca were thickened, contracted, congested, and had scant luminal content. There were severe hyperplasia of cecal crypts, accompanied by increased mitotic activity, inflammation, and focal mucosal erosion. A variety of bacteria was isolated, but none was considered pathogenic. No relationship of cecal hyperplasia to transmissible ileal hyperplasia of hamsters was found. Hyperimmune serum from hamsters with transmissible ileal hyperplasia did not react by immunofluorescence against hyperplastic cecal mucosa. Electron microscopy did not reveal a caustive agent. Transmission attempts have been unsuccessful. Cecal mucosal hyperplasia is apparently a newly discovered disease entity in hamsters with the clinical sign of diarrhea.

Animals

[Atypical hyperplasia and endometrial carcinoma (author's transl)].

Data on 167 cases of atypical hyperplasia of the endometrium and 292 cases of adenocarcinoma of the endometrium from 1966 to 1977 are presented. In 41 cases of atypical hyperplasia (24.5%) also adenocarcinoma of the endometrium coexisted. The age distribution revealed that atypical hyperplasia was much frequent in the age group from 40--59, and adenocarcinoma of the endometrium from 59--69. Out of 61 cases of theca- and granulosa-cell tumors of the ovary, 13 cases (21.3%) related to atypical hyperplasia or adenocarcinoma of the endometrium. Out of 27 cases of the Stein-Leventhal syndrome, 3 cases were atypical hyperplasia, one case adenocarcinoma of the endometrium. The data presented suggest that atypical hyperplasia might be a stage in the development of endometrial carcinoma.

Adenocarcinoma

The dexamethasone-modified adrenal scintiscan in hyporeninemic aldosteronism (tumor versus hyperplasia). A comparison with adrenal venography and adrenal venous aldosterone.

The dexamethasone-modified adrenal scintiscan, a noninvasive procedure, is described for the preoperative distinction between primary aldosteronism (aldosterone-producing ademona) and idiopathic aldosteronism (bilateral hyperplasia) and for the preoperative localization of aldostersone-producing adenomas. This procedure has been carried out on 17 subsequently proved cases of primary aldosteronism and nine cases (four unexplored) of idiopathic aldosteronism. In the tumor cases, it indicated correctly the side of the tumor in 88 per cent. It was correct in predicting the existence of bilateral hyperplasia in all of the five cases explored. It produced the same response in four more cases believed to have bilateral hyperplasia, in which surgical exploration has not been carried out. Many of the same patients had, in addition, standard adrenal scintiscans (SS), adrenal venography, and determinations of aldosterone in adrenal venous blood. These results are compared with those of the dexamethasone scintiscan (DS). In tumor localization, the 88 per cent figure for the DS was only moderately better than that of the other three (71 per cent, SS; 80 per cent, venography; 80 per cent, adrenal venous aldosterone levels). However, in predicting bilateral hyperplasia, the DS was 100 per cent correct, as were the levels of aldosterone in adrenal venous blood. The SS and adrenal venography failed in bilateral hyperplasia and gave many false-positive results indicating tumor. The DS, a relatively simple outpatient procedure, appears to be at least as effective, both in lateralizing tumors and distinguishing between tumor and bilateral hyperplasia, as the more difficult, expensive, and sometimes hazardous invasive procedure of bilateral adrenal vein catheterization.

Adolescent

Small-bowel resection. Oral intake is the stimulus for hyperplasia.

Small-bowel resection leads to hyperplasia of the residual small intestine, However, the factors initiating small-bowel hyperplasia are not clearly understood, although oral intake either by direct contact with the small bowel or via hormonal or neurovascular factors has been suggested as the major stimulus. In order to determine whether oral intake is an obligatory prerequisite for small-intestinal hyperplasia, we compared rats one week after undergoing a 70-cm proximal intestinal resection with sham-operated animals. Resected, orally fed rats demonstrated small-intestinal hyperplasia, whereas resected and sham-operated intravenously alimented rats did not. There were no differences in gut weight, mucosal weight, mucosal protein, or DNA between resected or sham-operated intravenously alimented rats. These data provide direct experimental proof that oral intake is a necessary stimulus for small-intestinal hyperplasia after resection.

Animals

Medullary thyroid carcinoma and pheochromocytoma accompanied with nodular hyperplasia in multiple endocrine neoplasia type 2.

Three patients with familial multiple endocrine neoplasia type 2 underwent total adrenalectomy and subsequently near-total or total thyroidectomy. The overt pheochromocytomas were present bilaterally in two patients and unilaterally in another patient. In addition, multiple nodules measuring a few mm in diameter were demonstrated in all adrenal medullas examined. All patients exhibited bilateral medullary thyroid carcinomas which varied in size from a few minute nodules accompanied by the microscopic C-cell hyperplasia to distinct large tumors. The thyroid C-cell hyperplasia appeared to be confined to the upper and middle thirds of the lateral lobe, and micronodules of the C-cell hyperplasia enlarged to coalesce, forming one large carcinoma mass. On the other hand, nodular hyperplasia of the chromaffin cells was distributed diffusely throughout the adrenal medulla and each nodule appeared to develop individually into a large pheochromocytoma. These findings suggested that, at least in the family members at a high risk for multiple endocrine neoplasia type 2, the development of both medullary thyroid carcinoma and pheochromocytoma was always preceded by a multicentric nodular hyperplasia. On the basis of the pathogenesis of these tumors, the most rational surgical approach was presented.

Adrenal Gland Neoplasms

Focal nodular hyperplasia of the liver: a clinicopathologic study and review of the literature.

We received the clinical records and pathologic material of 20 patients with biopsy proven hepatic focal nodular hyperplasia. The majority of the patients were females of child bearing age, five of whom had a history of oral use of contraceptives. In every instance focal nodular hyperplasia was an incidental finding; liver function tests were always normal. Focal nodular hyperplasia is a distinct histopathologic entity, distinguishable from liver cell adenoma. Specifically it consists of nodular aggregates of cytologically normal hepatocytes with foci of intranodular bile duct proliferation. Focal nodular hyperplasia appears to be a benign entity, even in patients in whom the lesion was not excised. The association between focal nodular hyperplasia and oral use of contraceptives may be coincidental, although hormonally related vascular changes may be responsible for rupture of the lesion.

Adolescent

Focal nodular hyperplasia of the liver, benign hepatomas, oral contraceptives and other drugs affecting the liver.

Due to the claim of an association between focal nodular hyperplasia of the liver, benign hepatomas and oral contraceptives, the files in the departments of pathology at the university hospitals in Lund and Malmö were examined for these two diagnoses made since 1945 and 1957, respectively. 26 cases of focal nodular hyperplasia of the liver and 7 benign hepatomas were found, 18 and 2, respectively, in women. Since 1963, the year before oral contraceptives were introduced in Sweden, focal nodular hyperplasia has been diagnosed in 8 women in the reproductive period of life; 4 of these had taken oral contraceptives. The 4 diagnoses were established in 1972-1974. At most, 25 per cent of Swedish females between the ages of 15 and 44 years have been on oral contraceptives. The Swedish series of 28 patients with focal nodular hyperplasia comprised 3 epileptics and 3 diabetics. At least two of the epileptics had been treated with barbiturates and/or hydantoins. The prevalence of drug-treated epilepsy in Sweden is 0.4-0.5 per cent, and of diabetes about 2 per cent. The possible aetiological role of drugs provoking an increase of the smooth-surfaced endoplasmic reticulum of the liver and proliferation of vascular fibrous tissue in a part of the liver which preveiously may have been damaged by vascular disturbances or trauma, is considered. No relationship between benign hepatomas and drugs was found. The observations support the notion that oral contraceptives may be of aetiological importance in the development of focal nodular hyperplasia of the liver, although the material is too small for epidemiological and statistical analysis.

Adolescent

[Frequency of Kongenital Adrenal Hyperplasia (author's transl)].

The frequency of homozygous congenital adrenal hyperplasia in Tyrol is found to be 1 : 8991, the gene-frequency for congenital adrenal hyperplasia 1 : 95 and the frequency of heterozygous congenital adrenal hyperplasia 1 : 48. Our data is compared on a numerical and statistical base with that in Zürich and Munich with regard to the frequency of congenital adrenal hyperplasia, to its distribution with and without salt loss and to its sex-distribution. According to our study one may assume a frequency of homozygous congenital adrenal hyperplasia in Tyrol, Zürich and Munich of 1 : 7000--10,000.

Adrenal Hyperplasia, Congenital

[Excessive hyperplasia of the exocrine pancreatic tissue and Wernicke's encephalopathy (author's transl)].

A 52 year old woman with a history of mild pancreatitis had a palpable mass in the upper abdomen. She died in an unexplained coma. The autopsy revealed an excessive hyperplasia of the exocrine pancreatic tissue resulting in the largest pancreas ever reported (254 gramm). This hyperplasia was accompanied by a chronic pancreatitis. In the central nervous system a Wernick's encephalopathy had developed; severe loss of neurons was stated in the thalamus; extensive degeneration was found in the upper vermis of the cerebellum. The discussion of this case includes the relationship between the diseases of the pancreas and neuropsychiatric and neuropathologic findings. It is assumed that the hyperplasia of the exocrine pancreatic tissue could only be an additional factor in the occurence of post alcoholic complications. This hyperplasia of the exocrine pancreatic tissue is considered to be a hamartom-like formation and it should therefore be distinguished from other pancreatic hyperplasia.

Diagnosis, Differential

Reversible papillary hyperplasia of the rat urinary bladder.

A rapid reproducible method for the production of ulcers and reversible regenerative hyperplasia of the urinary bladder of rats is described. This method does not involve administration of a toxic chemical or retention of a foreign body. Ulceration was produced by means of applying a steel rod, 5 mm in diameter, frozen at -78 C, to the serosal surface of the bladder for 2 seconds, twice, with a 5-second interval between each application. Sequential histologic observations showed that ulcers were accompanied by necrosis of the entire thickness of the bladder at the site of freezing with extensive acute inflammation. Regenerative hyperplasia was evident at the edge of the ulcer by the second day, with greatest severity at 5 days when papillary and nodular hyperplasia were present. At 15 days the bladders were normal or had only minimal hyperplasia. The labeling index by autoradiography was highest in the mildly hyperplastic area near the ulcer at 2 days and remained relatively high through 5 days. The hyperplastic epithelium surrounding the ulcer observed by scanning electron microscopy had numerous degenerative cells on the surface, and small epithelial cells with numerous short, uniform microvilli on their luminal surface were also observed. The numerous short, uniform microvilli on their luminal surface were also observed. The microvilli had a symmetric luminal membrane, as observed on trasmission electron microscopy. More peripherally the cells had microridges only or microvilli and microridges on their luminal surface. Neither pleomorphic microvili nor a structured glycocalyx fuzz on microvilli was observed during the process of regenerative hyperplasia, distinguishing it from neoplastic bladder proliferations.

Animals

Nodular regenerative hyperplasia of the liver. Report of six cases and review of the literature.

The authors report the cases of 6 adult patients suffering from nodular regenerative hyperplasia of the liver, an uncommon lesion characterized by small-sized hepatocytic nodules scattered throughout the liver, with no or slight fibrosis. The histological recognition of nodular regenerative hyperplasia of the liver was easy on large specimens taken intraoperatively, but was difficult or impossible on small specimens such as those provided by needle biopsy. In all of the patients of this series, the main consequence of nodular regenerative hyperplasia of the liver was portal hypertension. In this series, nodular regenerative hyperplasia of the liver was not associated with rheumatoid arthritis, whereas such an association has been noted in most of the cases previously reported. The etiology and pathogenesis of nodular regenerative hyperplasia of the liver is unknown.

Adolescent

Atypical hyperplasia of the prostate. A pitfall in the cytologic diagnosis of carcinoma.

The cytomorphologic features of atypical hyperplasia were studied in fine-needle aspiration biopsies of the prostate. Atypical hyperplasia material was found in 31 cases. The most usual and distinctive cytologic features of atypical hyperplasia were clustering of poorly-differentiated epithelial cells with acinic pattern and fairly regular nuclei. Another relevant feature was the lack of cytoplasmic fluorescence after acridine orange staining. These features make possible the diagnosis of atypical hyperplasia and the distinction from poorly-differentiated carcinoma. The recognition of atypical hyperplasia cells in fine-needle aspiration biopsies of the prostate is important in the avoidance of cytodiagnostic errors.

Acridines

Aldosterone regulation in primary aldosteronism: differences between adenoma and bilateral hyperplasia.

1. The diurnal patterns of plasma aldosterone, plasma renin activity (PRA), cortisol and adrenocorticotrophic hormone (ACTH) in the supine and in the upright position have been studied in fourteen patients with primary aldosteronism, five with adenoma and nine with bilateral hyperplasia. Blood samples were drawn at intervals from 6 h to 30 min. 2. Supine patients with an adenoma showed marked diurnal variations of aldosterone, with maximal values at 08.00 hours and minimal values of 18.00 hours and secretory spurts beginning after 02.00 hours. Plasma cortisol paralleled aldosterone, and ACTH seemed to anticipate aldosterone and cortisol variations; PRA remained unchanged. In patients with hyperplasia, aldosterone was significantly lower than in the adenoma group at 08.00 hours, and its decline during the day was less marked; fluctuations rather than secretory episodes were seen. 3. After patients assumed the upright posture, aldosterone remained unchanged or decreased in patients with adenoma, whereas it significantly increased in hyperplasia; PRA remained low, although a slight increment was seen in the latter group. The different response of aldosterone in the two groups was not modified by the administration of propranolol, apparently excluding a renin-dependent mechanism. On the other hand, dexamethasone seemed to affect the response of aldosterone to the upright posture in both groups; in adenoma there was a slight but significant increase, and in hyperplasia the usual rise was partially suppressed. 4. It is concluded that ACTH has a predominant role in regulating aldosterone secretion in primary aldosteronism due to adenoma, whereas its action in bilateral hyperplasia is only permissive.

Adenoma

Ectopic ACTH-MSH producing carcinoid tumor with multiple endocrine hyperplasia in a child.

An autopsy case of a 9-year-old Japanese girl revealed a carcinoid tumor originating in the duodenum and hyperplasia of the multiple endocrine organs as manifested by ectopic ACTH syndrome, carcinoid syndrome and giantism. The tumor cells were positive for histochemical argyrophile reaction and two types of secretory granules were identified by electron microscopy. Biochemical assay revealed the production of ACTH and beta-MSH by the tumor cells. Other changes of multiple endocrine organs included acidophil dominant hyperplasia of the pituitary, diffuse hyperplasia of the thyroid, chief cell hyperplasia of the parathyroid, hyperplasia of the islets of Langerhans and the adrenal cortex. This case was considered to be a type of multiple endocrine adenomatosis including carcinoid tumor. The relationship between the carcinoid tumor and multiple endocrine adenomatosis was discussed.

Adenoma

Primary diffuse microscopical hyperplasia of the parathyroid glands: surgical importance.

In two of 182 patients with verified primary hyperparathyroidism, microscopical hyperplasia was present in all parathyroid glands that were normal in size or only slightly enlarged. All parathyroid glands in another two patients showed microscopical hyperplasia and varied from a normal size of 190 mg. In seven additional patients, microscopical hyperplasia was present in one, several, or all parathyroid glands, which varied in weight from normal to 350 mg. Familial hyperparathyroidism or multiple endocrine neoplasia was evident in five of 11 patients. Contributing to difficulties was the experience in five patients in whom removal of mildly enlarged parathyroid glands corrected hypercalcemia, but definite microscopical abnormalities were not evident by routine histologic study of the glands. Thus, there appears to be a spectrum of abnormalities relative to size and microscopical changes in parathyroid glands of patients with primary hyperparathyroidism. The surgeon should be aware of these patterns of parathyroid hyperplasia that require a search for a fifth parathyroid gland and a subtotal parathyroidectomy.

Adult

Survival with mammary cancer related to the interaction of germinal center hyperplasia and sinus histiocytosis in axillary and internal mammary lymph nodes.

In a review of the histologic sections of axillary and internal mammary lymph nodes removed during surgery for invasive ductal carcinoma of the breast, we found that 16 of 17 patients in whom sinus histiocytosis was the dominant lymphoid proliferative reaction are alive with no evidence of cancer 5 or more years after operation. In contrast, 5 of 6 patients in whom germinal center hyperplasia was the only significant reaction found died of cancer in less than 5 years. Patients with both sinus histiocytosis and germinal center hyperplasia in significant amounts had survival that was intermediate; 17 of 25 of these patients are currently alive and apparently free of cancer. In addition, 5 of 6 patients in whom no evidence was found of any lymphoid proliferative reaction and 3 of 3 patients with diffuse cortical hyperplasia in their axillary lymph nodes died of cancer in less than 5 years. Germinal center hyperplasia was associated with nodal metastases anatomically in individual lymph nodes and statistically in the series of cases. The internal mammary lymph nodes of most cases showed less proliferative reaction to tumor than the axillary lymph nodes. The pattern of proliferative reactions in lymph nodes and its correlation with survival after surgery suggest that different immune reactions may either suppress or enhance the growth of carcinoma of the breast.

Axilla