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A M Landolt

Publications and source records attributed to A M Landolt.

At least 55 records · Page 3Linked to original sources

Storage and release of secretory granules in human prolactinomas: modification by bromocriptine.

Electron microscopic morphometric evaluation of the effects of bromocriptine on human prolactinomas during and after short-term parenteral (7 days) and long-term peroral (4-6 weeks) treatment showed that a reduction in size of prolactinoma cells occurs within a few days (half-time to maximum shrinkage, 2.2 days). The number of secretory granules discharged into the intercellular space increased after short-term treatment by a factor of three but the total volume of stored secretory granules did not change significantly. The total volume of cellular lysosomes, both primary and secondary, decreased significantly to about one-half of the pretreatment value. The amount of stored lipoids, end-products of lysosomal activity, decreased in specimens treated for 7 days, but returned to pretreatment levels in specimens treated for 4-6 weeks, suggesting that lysosomal material is discharged from the cells together with the secretory material.

Adult↗

Growth rate of human pituitary adenomas.

The immunohistological detection of a proliferation-associated nuclear antigen by the monoclonal antibody Ki-67 allows the determination of the growth fraction in human cell populations. In this study, biopsy specimens of 31 pituitary adenomas representing all major endocrine types were examined. All adenomas contained proliferating cells and the percentage of nuclei that were immunoreactive to Ki-67 ranged from 0.1% to 3.7%. Low values (0.1% to 1.0%) were present in 11 endocrine-inactive adenomas and higher values (1.1% to 1.5%) were found in six acromegalic patients. The percentages of Ki-67-positive cells in 12 prolactinomas and two adenomas from patients with Cushing's disease covered the entire range (0.1% to 3.7%). Preoperative bromocriptine treatment of prolactinomas did not influence Ki-67 expression. Invasive adenomas, as determined by preoperative computerized tomography, surgical observation, and histological examination of the sella dura demonstrated significantly higher Ki-67 values (average 1.15%) than noninvasive adenomas (average 0.60%). Determination of the incidence of proliferating cells by Ki-67 immunoreactivity represents a new tool for intraoperative quantitative assessment of tumor growth characteristics and may aid in the planning of adjuvant therapy and estimation of prognosis.

Adenoma↗

Amyloid deposits in pituitary adenomas. Differentiation of two types.

Two different types of amyloid deposits in pituitary adenomas are described herein. The deposits of the first type are stellate and perivascular masses, with fibrillary inclusions occurring in the intercellular space. No immunoreactive cytokeratin can be detected in the deposits, and the masses are secreted by the adenoma cells. A second, rarer type is characterized by spheroids (40 to 1500 micron in diameter) in which immunoreactive cytokeratin fibrils are present. The fibrils originate in the adenoma cells adjacent to the deposits. The amyloid nature of both types of deposits can be proved by intense red staining with Congo red, green dichroism, and positive immunostaining with antibodies raised against serum amyloid P component. Adenomas with amyloid spheroids are very rare, and most have been proved or suspected prolactin-producing adenomas.

Adenoma↗

Alpha-subunit-producing pituitary adenomas. Immunocytochemical and ultrastructural studies.

Immunohistological techniques demonstrate the alpha-subunit of glycoprotein hormones in the majority of endocrine-inactive, undifferentiated pituitary adenomas and pituitary oncocytomas. In about one-fifth of endocrine-active adenomas, the alpha-subunit is produced in combination with either adrenocorticotropic hormone or prolactin, and it is found in combination with growth hormone in about half of those adenomas causing acromegaly. Pure alpha-subunit-producing, endocrine-inactive adenomas characteristically have small secretory granules that are destroyed by direct osmium fixation, but are well preserved after prefixation with glutaraldehyde. As only a few atypical prolactinomas show similar secretory granules, and as they display a positive reaction for the alpha-subunit only exceptionally, this ultrastructural feature can serve as a guide to differentiate such adenomas.

Adenoma↗

Corticotrophin-releasing factor-test used with bilateral, simultaneous inferior petrosal sinus blood-sampling for the diagnosis of pituitary-dependent Cushing's disease.

Bilateral, simultaneous inferior petrosal sinus blood-sampling for determinations of ACTH levels has improved the ability to establish a differential diagnosis of Cushing's disease, particularly in patients whose endocrinological studies show equivocal results and whose computed tomography scans yield negative or inconclusive findings. Individual anatomical variations in the configuration of the sinus and insignificant differences between the ACTH levels obtained from its two sides may be a problem. Seven patients with clinically and biochemically typical Cushing's disease and one with atypical Cushing's disease were examined. An alternative approach for catheterization of the inferior petrosal sinus through the deep vertebral venous plexus was used in those patients who did not have direct connections between the sinus and the internal jugular vein. In two of the eight patients, only ACTH secretion stimulated with corticotrophin-releasing factor could unmask a significant difference between the ACTH levels on the two sides which was not obvious from the basal ACTH levels. Beta-lipotrophin values showed a behaviour similar to that of ACTH values, but because of a slower turn-over rate, the CRF-induced peaks were better visible. The aetiology of Cushing's disease was established from the results of this examination and corresponded with the surgical findings in this series, with the exception of one in which the patient had a highly atypical form of the disease. The abnormal ACTH source was found later to be a thymus carcinoid.

Adenoma↗

[Prolactin producing hypophyseal adenoma: diagnosis and therapeutic possibilities].

The introduction of radioimmunoassay for prolactin concentrated interest in infertility research on prolactin-producing pituitary adenomas (prolactinomas). In women in the fertile age group these tumors cause amenorrhea and galactorrhea, and in men loss of libido, impotence and occasionally gynecomastia. Microprolactinomas (diameter 10 mm and less) and macroprolactinomas (diameter more than 10 mm) differ in growth characteristics, symptomatology and prognosis. Different therapeutic approaches may be used. Both bromocriptine treatment and selective microsurgical tumor extirpation are successful. Both have advantages and disadvantages, thus rendering the decision as to appropriate treatment increasingly difficult. Recent findings demonstrate that bromocriptine may cause irreversible tumor fibrosis, which decreases the chances of prolactin normalization by subsequent surgery.

Adenoma↗

Bromocriptine-induced removal of endoplasmic membranes from prolactinoma cells.

Adenomatous prolactin cells lose 39% of their cytoplasm volume within 7 days after the beginning of bromocriptine treatment. A simultaneous reduction of the rough-surfaced endoplasmic reticulum and the Golgi apparatus occurs. Their membranes are removed by rapid transport along the secretory pathway to the cell surface and to lysosomal destruction.

Adenoma↗

Immunohistochemical examination of the paraadenomatous "normal" pituitary. An evaluation of prolactin cell hyperplasia.

Prolactin cell hyperplasia has been described to occur in the paraadenomatous normal pituitary gland surrounding prolactinomas. However, compression of the glandular lobules and secretory cells alters profoundly the histological configuration of this tissue. No changes resembling those that occur during pregnancy are found. Immunohistochemical staining and counting of prolactin-(PRL-)secreting and growth hormone-(GH-)secreting cells in the normal, paraadenomatous pituitary gland obtained during extirpation of 24 prolactinomas and 5 adenomas causing acromegaly demonstrated that GH-secreting cells predominated in all biopsies obtained from acromegalic patients. PRL-secreting cells were more frequent than GH-secreting cells in 14 of 24 biopsies of the normal tissue surrounding prolactinomas. A particular predominance of PRL-secreting cells was found in patients with postoperative residual hyperprolactinemia. Direct comparison of adjacent sections demonstrates three cell types: One reacts with both antibodies and the other two react only with one or the other. We suggest that these groups are not stable but that cells belonging to one group can be transformed into cells belonging to the two other groups. Such a process, induced by extrahypophyseal factors, may explain the shift of relative cell frequency observed in the normal pituitary gland surrounding prolactinomas.

Acromegaly↗

Perivascular fibrosis in prolactinomas: is it increased by bromocriptine?

Prolonged treatment of patients with pituitary prolactinomas with bromocriptine may increase the consistency of the tumor thereby making selective extirpation more difficult. We made quantitative determinations of the amount of perivascular fibrous tissue in prolactinomas on random electron micrographs, comparing a group of 21 patients treated with bromocriptine for periods longer than 3 months and a control group of 21 patients who did not receive bromocriptine. Statistical analysis of the data showed a significant increase of perivascular fibrous tissue in the treated group (P less than 0.002). We suspect that this fibrosis is a consequence of the rapid shrinkage of prolactinoma cells caused by bromocriptine. Presumably, this cell shrinkage causes enlargement of the extracellular and perivascular spaces which are filled by the deposition of collagen, producing a more dense consistency of the adenoma.

Adenoma↗

High density of somatostatin receptors in pituitary tumors from acromegalic patients.

Using a SRIH receptor-binding assay previously developed for rat pituitary tissue, we measured SRIH-binding sites in human pituitary adenomas obtained from five acromegalic patients. Saturable and high affinity-binding sites for SRIH were found, with respective dissociation constants (Kd) of 0.57, 1.48, 1.04, 0.24, and 1.04 nM for the different adenomas, which is comparable with the Kd of 0.95 nM for SRIH in normal rat pituitary. In adenomas of most patients, however, the number of sites was much higher than in rat pituitary (100 fmol/mg protein), being, respectively, 757, 800, 441, 103, and 1058 fmol/mg protein. The pharmacological characteristics of these sites were similar in both species, [Des-Trp8]SRIH being inactive but the stable SRIH analog SMS 201-995 [H-(D)Phe-Cys-Phe-(D)Trp-Lys-Thr-Cys-Thr(ol)] being slightly more potent than SRIH. This is the first description of specific SRIH-binding sites in human pituitary tissue and in particular in human pituitary adenomas. These results suggest that the development of GH-secreting pituitary adenomas is not due to the absence of SRIH receptors or to a decrease in their affinity for SRIH. The large number of sites with high affinity for SMS 201-995 suggests that the use of SRIH analogs could be of potential benefit in reducing GH levels in patients with acromegaly.

Acromegaly↗

[Cushing's disease: do patients remain dependent upon substitution therapy following microsurgical exstirpation of hypophyseal adenomas?].

Data on 4 patients with Cushing's disease (2 microadenomas, 2 macroadenomas with chiasma syndromes) demonstrate that a few months after microsurgical extirpation of the pituitary adenoma (and, in macroadenomas, irradiation) the previously suppressed normal ACTH-producing cells recuperate and react adequately to stimulation. Because of the similar behaviour of the remainder of the gland, none of the 4 patients needed hormonal substitution and all were back at work full time about 1 year after the operation. This is in contrast to the obligatory need for corticoid substitution after bilateral epinephrectomy, and affords ground to consider pituitary microsurgery the treatment of choice in these patients.

Adenoma↗

[Prolactin-producing pituitary adenomas as a cause of primary amenorrhea and their neurosurgical treatment].

Among 86 female patients with prolactin producing pituitary adenomas (prolactinomas) 5 were observed with primary amenorrhoea. These 5 females were aged between 30 and 33 years. Diagnosis leading to specific treatment was thus established only 16 to 19 years after failure of the expected menarche. Surgery revealed three microadenomas (diameter 6-10 mm) and two invasive macroadenomas (diameter 20 and 21 mm). After selective microsurgical removal of the adenomas spontaneous ovulation and menstruation occurred in two patients with microadenomas, in the third female it could be induced by bromocriptine treatment of the residual hyperprolactinaemia. Overall there were four successful pregnancies. In contrast, spontaneous menstruation did not occur in two females with macroadenomas due to persistent residual hyperprolactinaemia postoperatively. This remained true even after additional bromocriptine treatment which normalised the level of prolactin. These observations demonstrate the importance of early diagnosis of primary amenorrhoea caused by prolactinoma as in small adenomas selective surgical removal may result in fertility.

Adenoma↗

[Cushing's syndrome in bronchial carcinoid: suppressible ectopic ACTH selection].

In a 60-year-old woman Cushing's syndrome was induced by an ACTH producing bronchial carcinoid. In spite of the presence of an ectopic ACTH syndrome, the clinical, radiological and biochemical findings and the positive dexamethasone suppression test were compatible with Cushing's disease. Selective enucleation of an adenoma or total hypophysectomy was therefore felt to be indicated. Following total hypophysectomy, however, the Cushing's syndrome persisted and this suggested the possibility of an ectopic ACTH syndrome. As tumor localization was impossible, bilateral adrenalectomy was planned, but before this could be done the patient had to be hospitalized for staphylococcal septicemia and died. Autopsy revealed a subpleurally located bronchial carcinoid as the source of ACTH.

17-Hydroxycorticosteroids↗