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Biomedical subjects

W Saeger

Publications and source records attributed to W Saeger.

At least 145 records · Page 8Linked to original sources

A pituitary adenoma secreting high molecular weight adrenocorticotropin without evidence of Cushing's disease.

We report a patient with hypersecretion of a high mol wt ACTH from an aggressive corticotropic pituitary tumor who did not have hypercortisolism. Basal plasma ACTH levels were clearly elevated (26-121 pmol/L), whereas basal and stimulated serum cortisol levels were in the normal range. The pituitary source of the ACTH hypersecretion was confirmed by selective venous catheterization. Gel chromatography of the patient's plasma showed two peaks of ACTH immunoreactivity, one major peak eluting near the void volume (high mol wt form of ACTH), accounting for more than 95% of the ACTH detected, and a very small peak at the expected position of ACTH-(1-39). Plasma ACTH levels were not altered by metyrapone or bromocriptine. During high dose dexamethasone administration plasma ACTH decreased, but was not fully suppressed. Immunohistochemical evaluation of tumor tissue demonstrated ACTH immunoreactivity in 40% of the tumor cells. The patient died from postoperative complications after a second operation performed after tumor recurrence. This patient's course confirms the observations of relatively rapid growth and high recurrence rate in clinically silent corticotropic pituitary adenomas.

Adenoma↗

Light microscopical morphometry, immunocytochemistry, and clinical correlations of pituitary adenomas at various stages of oncocytic transformation.

In a series of 124 pituitary adenomas displaying oncocytic alterations, we studied the degree of oncocytic transformation by light microcopical and morphometrical means for semiquantitative analysis. We established three groups with different percentages of oncocytically transformed cells for comparison of clinical and immunocytochemical data. Of the patients, 32.3% exposed adenomas with less than 50% oncocytic alterations (group I), whereas 22.6% showed tumours with oncocytic transformations between 51% and 75% (group II). Oncocytic parts consisting of more than 75% of the tumour cells were found in 41.1% of the patients (group III). All three groups differed in the rate of immunocytochemically positive cases, but not in sex distribution, tumour size, and rate of recurrency. Immunocytochemical analyses for PRL and GH (81 vs 78 adenomas) showed a decline of immunohistochemically positive adenomas with increasing proportions of oncocytic transformation for both hormones. Whereas in group I 38% of the adenomas were PRL-positive and 15% GH-positive, group III displayed only 9% PRL-positive and 3% GH-positive adenomas. The results display the correlation between the increasing volume of oncocytic transformation and its effect on decreasing hormone content in pituitary adenomas.

Adenoma↗

Light microscopical morphometry of prolactin secreting adenomas under treatment with dopamine agonists.

In order to study the light microscopical alterations of pituitary tumours under dopamine agonist treatment, three groups of a total of 18 large or small cell chromophobe adenomas were analysed by light microscopical, immunohistological and morphometrical methods. They were all removed by transsphenoidal surgery. 6 of them were treated preoperatively with dopamine agonists, bromocriptine and/or lisuride, for various periods of time. 8 adenomas remained preoperatively untreated. 4 additional untreated tumors were small cell inactive adenomas for comparison. One case was excluded from the final evaluation of the data because it appeared to be a typical non-responder, clinically as well as histologically. Immunohistological positivity for prolactin was to be found in all cases in various degrees. Clinically active adenomas contained many prolactin positive cells, whereas in inactive adenomas only scattered cells were prolactin positive. The morphometric analysis revealed a reduction of the cytoplasmic area in a statistically significant degree in the group of adenomas under treatment, which explains adequately the shrinkage of the entire adenoma and the reduction of prolactin plasma levels. The morphometric data of treated adenomas resembled those of untreated inactive adenomas.

Adult↗

Morphology of a GHRH producing pancreatic islet cell tumour causing acromegaly.

A 54 year old woman suffered from acromegaly due to a pancreatic islet cell tumour producing GHRH. The tumour was demonstrated on CT scan. The diagnosis was established from elevated plasma levels of GHRH, GH and prolactin, and by the lack of signs of a pituitary adenoma in trans-sphenoidal surgery. Acromegaly was cured by tumour removal. Light microscopically, the tumour showed a medullary and microlobular pattern. The cells were large and often cuspidal. Small granules were found in semi-thin sections. Small aggregations of amyloid fibres were seen, mostly around capillaries. Immunocytochemistry revealed GHRH, NSE, neurotensin, serotonin, VIP and PP. S 100 was positive only in nerve fibres. Staining for GH, ACTH, calcitonin, alpha-HCG, beta-HCG, insulin, glucagon, gastrin, substance P, bombesin and somatostatin was negative. Ultrastructure showed oval partly lobulated nuclei with small nucleoli, moderate amounts of rough endoplasmic reticulum, many free ribosomes, some large Golgi fields and small numbers of secretory granules measuring 150 nm or, in a few cells, 650 nm. Only 4 other cases of pancreatic endocrine tumours causing acromegaly by ectopic GHRH secretion are described in the literature and these were similar to our case in many respects.

Acromegaly↗

Ultrastructural morphometry of prolactin secreting adenomas treated with dopamine agonists.

19 macroprolactinomas and 1 microprolactinoma were analysed by light microscopical, immunohistological and ultrastructural as well as morphometrical methods. 8 adenomas were removed from patients who were treated preoperatively with bromocriptine and/or Lisurid for different periods. 18 of 20 adenomas were positive for PRL on the immunohistological level. One case was negative. This patient showed a good response to the pharmacological treatment. The ultrastructure of this case revealed many secretory granules. A morphometric analysis of the ultrastructure could be performed in 19 cases; 1 case had to be excluded because of large necrotic areas. The following qualitative significant alterations after the treatment could be established: Reduction of the volume density of the rough endoplasmatic reticulum; Reduction of the size of the granula diameter; Increase of the volume density of the more irregular and indented nuclei. Other alterations were as follows: Reduction of the nuclear size; Increase of the number of secretory granules and of the volume density of lysosomes. These changes were to be observed in most of those tumors which responded to the dopamine agonist treatment. The non-responding adenomas and one which was removed 6 days after having discontinued a successful preoperative medical therapy were similar to the untreated adenomas. The results display the influence of dopamine agonist on the hormone synthesis, release and degradation in PRL secreting adenoma cells.

Adenoma↗

Light and electron microscopical morphometry of pituitary adenomas in hyperprolactinemia.

Two highly differentiated acidophil prolactin-cell adenomas with hyperprolactinemia (group I), 8 large cell chromophobe adenomas with hyperprolactinemia (group II), and 2 small cell chromophobe adenomas (group III), one of which was combined with hyperprolactinemia, were studied immunohistologically. Morphometry was performed on the light- and electron microscopical level. The 11 active adenomas were immunohistologically positive for prolactin, the 12th adenoma with normal prolactin plasma level was negative for prolactin. Light microscopical morphometry displayed significantly more cells of smaller size in the "small cell chromophobe" adenomas, whereas the large cell chromophobe adenomas and the highly differentiated prolactin cell adenomas were not different. Ultrastructural morphometry demonstrated significant differences between highly differentiated prolactin cell adenomas (group I), and large cell chromophobe adenomas (group II). The latter contain smaller "relative volumes" of nucleoli and of secretory granules, whereas the rough endoplasmic reticulum, the Golgi fields and the nuclei were not different. Comparison of large cell chromophobe adenomas (group II), and small cell chromophobe adenomas (group III) revealed significantly larger relative volumes of nuclei and of mitochondria but smaller volumes of rough endoplasmic reticulum and of Golgi fields in the small cell chromophobe adenomas. Significant differences between the active and the inactive adenoma of small cell chromophobe type in the group III were not found. In spite of the low quantity of small cell chromophobe adenomas and of acidophil prolactin cell adenomas, our data demonstrate that there exist distinct and significant light microscopical and ultrastructural differences between the three adenoma types.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma, Acidophil↗

Sellar lesions associated with isolated hyperprolactinaemia. Morphological, immunocytochemical, hormonal and clinical results.

In 204 patients with sellar lesions and isolated hyperprolactinaemia we analysed and compared many different morphological, immunocytochemical, hormonal, and clinical data for a differentiation of primary (Prl produced by a tumour) and secondary (Prl elevation by PIF inhibition) hyperprolactinaemia. We found Prl-positive pituitary adenomas with primary hyperprolactinaemia in 62.7% and a secondary Prl elevation with different alterations in 37.3% (Prl-negative adenomas 28.9%, craniopharyngeomas 5%, and non-tumourous conditions 3.4%). In secondary hyperprolactinaemia the Prl values did not exceed 130 micrograms/l, higher levels indicated Prl-producing adenomas with a high probability. In patients with Prl elevation below 130 micrograms/l the clinical and sometimes the morphological analysis were not sufficient for a differentiation. Here immunocytochemical studies are necessary for a clear classification of hyperprolactinaemia.

Adenoma↗

[Histiocytosis X. Follow-up for over 20 years in a patient with Hand-Schüller-Christian disease].

Since 1963 we have observed a patient with Hand-Schüller-Christian disease with involvement of the skeleton, skin and hypophysis/hypothalamus with diabetes insipidus. The diabetes insipidus was successfully treated initially with chlorpropamid and later with carbamazepin. Alterations of the lung parenchyma were seen radiologically in 1966, and two years later the patient complained of exertional dyspnea. The lung disease was progressive with the deterioration of lung function despite corticosteroid and D-penicillamine treatment. The patient now has marked dyspnea even at rest. The osteolytic lesions have not changed in recent years.

Adult↗

Grading of pituitary adenomas in acromegaly. Comparison of light microscopical, immunocytochemical, and clinical data.

In a series of 284 adenomas from cases of acromegaly we studied major morphological variables using light microscopical techniques and compared them with immunocytochemical and clinical results. Using our semiquantitative estimations many inter-relationships were observed. We established the density of secretory granules, nuclear pleomorphism and the rate of occurrence of multinuclear tumour cells, as essential features of tumour differentiation. Mitotic activity and invasive growth patterns did not reveal clear dependences. Immunocytochemical analysis of 105 cases showed growth hormone (GH) in nearly all adenomas (98%), prolactin in 68%, and LH in 40%. The other hormones (ACTH, FSH, and TSH) were present at a much lower rate. Monohormonal GH-adenomas were found in only 29% of our cases. Many different combinations of hormone content could be demonstrated without any relationship to morphological or clinical data. From the linear correlations and advanced method of semiquantitative evaluation, the granular density of the tumour cells is the most useful variable for subclassification and grading of pituitary adenomas in acromegaly.

Acromegaly↗

Tumour ploidy in DNA histograms of pituitary adenomas.

DNA analysis was performed by flow cytometry (FCM) in 59 cases of different types of pituitary adenomas who underwent microsurgery and were actively followed over a period of 3-6 years. Aneuploid DNA patterns were detected in 12 (20%) cases. Frequency of aneuploidy was highest in prolactin-secreting (36%) as compared to 17% in GH- and 7% in non-secreting adenomas. Some adenoma parameters valid for tumour growth, such as rate of recurrences and mitotic index, were correlated with aneuploidy of the tumour. FCM studies are, therefore, recommended to gain further parameters for the estimation of proliferative activity of pituitary adenomas.

Adenoma↗

In-vitro effects of bromocriptine on isolated pituitary adenoma cells. Ultrastructural and morphometrical studies.

3 pituitary adenomas in hyperprolactinemia and 3 GH and prolactin producing tumours were analysed. The adenoma cells were prepared and held in suspension so that they could be treated with bromocriptine (10 ng and 100 ng). At different times after treatment (0.5, 60 and 90 minutes), the cells were fixed and prepared for conventional electronmicroscopy. Electron microscopic photographs were quantitatively analysed by the point counting method. The results were compared to those of an untreated control group. After bromocriptine influence, there was a decrease of the hormone secretion into the supernatant (2 of 3 prolactin producing adenomas). The prolactin secretion was unchanged in all 3 adenomas which produced prolactin and GH, but there was a decrease in the GH production in 1 of these cases. Ultrastructural morphometry revealed the following results: In prolactin producing adenomas, there was a decrease in the number of exocytoses, an increase in the volume density of lysosomes (2 cases) and an increase of the rough endoplasmic reticulum (1 case). The decrease of the "unorganized" cytoplasm was observed in all 3 cases, but was significant only in 1 case. There was a significant increase in secretory granules (1 case). In adenomas which produced prolactin and GH displayed a significant increase of the rough endoplasmic reticulum and of the granules. The outlines of the cellular membranes seemed smoother (1 case). The heterogeneous results may be interpreted as an expression of the reduced hormone secretion (secretory granules, lysosomes), some data are in accordance with the beginning of necrobiotic phenomena (rough endoplasmic reticulum). The decrease of the "unorganized" cytoplasm may be due to a shrinking process.

Adenoma↗

Immunohistochemical examination of pituitary adenomas. Comparison to clinical and endocrinological findings.

A comparison was made with the data of 62 cases of pituitary adenoma, evaluated pre- and postoperatively, including as well the results of immunohistochemical hormone examination (also for calcitonin). Prolactin was found in 18 of the 21 adenomas carrying the preoperative diagnosis of prolactinoma, whereas cells containing other hormones (growth hormone, LH, FSH, TSH, ACTH, beta-endorphin), were only occasionally present. The growth hormone was strongly positive in the adenoma tissue in 16 of the 17 cases of acromegaly. 5 of these adenomas were accompanied by a marked hyperprolactinemia and also contained many prolactin cells. 6 of the 19 adenomas diagnosed as being 'inactive' contained hormone-positive cells, but only a very small number of cells. ACTH was found in 3 of the 4 pituitary adenomas of patients with Cushing's disease. 2 of these were also positive for beta-endorphin. The tissue of 1 gonadotrophic adenoma (with elevated FSH in serum) gave positive results with an anti-LH antiserum. Calcitonin was not found in any adenoma. The preoperative serum prolactin levels did not quantitatively correlate with the percentage of prolactin-positive cells.

Acromegaly↗

Examining Sedlacek's nontraditional variables of minority student success in a summer enrichment program for health careers.

Nontraditional variables associated with minority student success in the health sciences have been identified by Sedlacek and his associates. These eight variables-positive self-concept, realistic self-appraisal, understanding and dealing with racism, long-range goals, availability of a strong support person, leadership, community service and medical interests-are examined with respect to their incorporation into the summer enrichment programs for talented minority students conducted at the University of Tennessee Center for the Health Sciences (UTCHS) during the years 1982-1984. Student comments and illustrations from the summer program's curriculum are provided for five of Sedlacek's variables to demonstrate how the UTCHS program is able to further the development of these nontraditional variables as well as to strengthen the cognitive abilities of students in basic science, mathematics, and communication. Evaluations of the summer program have revealed that the students have an increased academic self-concept, a more realistic view of the requirements to become a health professional, and an enhanced awareness of the health care environment.

Adolescent↗