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Biomedical subjects

A M Landolt

Publications and source records attributed to A M Landolt.

At least 73 records · Page 4Linked to original sources

Cerebrospinal fluid rhinorrhea: a complication of therapy for invasive prolactinomas.

The majority of invasive prolactinomas can be predicted with a high probability if the preoperative prolactin level is above 2000 ng/ml. As these tumors cannot be extirpated radically, adjunctive radiation therapy is used to improve the results of treatment. On the basis of reports that bromocriptine induces tumor shrinkage and has an antimitotic effect, we combined adjunctive irradiation with bromocriptine therapy in 14 patients who had particularly extensive invasion. Two of these patients developed cerebrospinal fluid rhinorrhea 3 and 5 months, respectively, after the completion of radiation therapy. In both patients, the fistula was localized in the sellar region and was closed successfully. Rapid tumor shrinkage caused by irradiation combined with bromocriptine therapy may be a factor causing this complication; postoperative rhinorrhea is otherwise extremely rare in our surgical series. We also observed a third patient who did not have an operation, but who developed rhinorrhea after a course of irradiation and bromocriptine treatment. The periods of rhinorrhea coincided with periods of bromocriptine treatment.

Adult↗

ACTH-producing pituitary adenomas in Addison's disease: two cases treated by transsphenoidal microsurgery.

In 2 women with known Addison's disease, progressive hyperpigmentation reappeared years after an initial remission under conventional substitution therapy with cortisone. Excessively elevated plasma ACTH concentrations and radiological evidence of sella turcica deformation led to the diagnosis of ACTH-producing adenomas and prompted their removal by transsphenoidal microsurgery. In one patient, a large Crooke's cell adenoma with extensive extrasellar expansion had caused severe and irreversible bilateral defects of the visual fields and unilateral optic atrophy. Surgical removal of the tumour and radiotherapy brought about a permanent disappearance of the hyperpigmentation, but eventually led to secondary hypothyroidism. In the second patients, the selective removal of a small intrasellar eosinophilic adenoma consisting of ACTH-producing cells did not alleviate the hyperpigmentation and did not lower the plasma ACTH concentration. However, hyperpigmentation regressed markedly within a year of treatment with a higher dose of cortisone. The rarity of similar cases in the literature seems to indicate that insufficient feedback suppression of ACTH-producing cells in treated Addison's disease does not by itself induce the development of a pituitary adenoma, but might promote the growth of an independently and coincidentally occurring microadenoma, which would have caused Cushing's disease in a person with intact adrenal glands.

Addison Disease↗

[Incidence and clinical manifestation of ACTH-producing pituitary adenoma after bilateral adrenalectomy for Cushing's syndrome (Nelson syndrome)].

29 out of 39 patients bilaterally adrenalectomized for pituitary-dependent Cushing's syndrome between 1958 and 1979 have been followed up at regular intervals. ACTH-producing pituitary adenomas were detected and removed in 9 of them up to 1981. In 4 additional patients an enlarged sella turcica was already found at the time they had Cushing's syndrome, and therefore they were first treated by pituitary surgery or radiotherapy. In the adrenalectomized patients hyperpigmentation was the major clinical symptoms of the adenoma. Only in three instances did extrasellar growth of the adenoma cause ophthalmoplegia or narrowing of the visual fields. The existence of intrasellar ACTH-producing microadenomas in 5 additional patients seems highly probable in view of hyperpigmentation, excessively elevated plasma ACTH concentrations and radiological evidence of sella deformations. These observations indicate that in patients adrenalectomized for pituitary-dependent Cushing's syndrome ACTH-producing adenomas are more common than previously assumed. Moreover, according to recent reports, ACTH-producing microadenomas are frequently found in pituitary-dependent Cushing's syndrome and are assumed by many clinical endocrinologists to be the primary cause of this disease. Therefore, bilateral adrenalectomy is no longer the undisputed therapy of first choice and it is necessary in each individual case to consider carefully whether an attempt to remove selectively an ACTH-producing pituitary adenoma by microsurgery might not be preferable.

ACTH Syndrome, Ectopic↗

Subhypothalamic grafts of human pituitary adenomas in total-body irradiated rats.

Human pituitary adenomas proliferate neither in cell culture nor in athymic "nude" mice. We propose that one or several of the humoral factors necessary for the growth of pituitary adenomas is missing in these experimental environments. The purpose of our experiments was to examine the possible influence of the hypothalamus in supporting cellular proliferation, and thus adenoma growth. Fragments from four human pituitary adenomas (three pituitary prolactinomas; one ACTH-secreting adenoma) were transplanted into the pituitary fossa of total-body irradiated, hypophysectomized rats. The rats were killed after two weeks and perfused with a mixture of formalin and India ink. Histologic examination of serial sagittal sections through the pituitary fossa and the adjacent brain showed: vascularization of the grafts from the pituitary stalk and from the scar tissue in the sphenoid bone; survival of some adenomas; and numerous mitoses in an ACTH-secreting specimen obtained from a patient who had Cushing's disease. We conclude from these experiments that as yet unidentified hypothalamus factors are essential for the growth of certain types of pituitary adenomas.

Adenoma↗

Surgical treatment of pituitary prolactinomas: postoperative prolactin and fertility in seventy patients.

The surgical results obtained in 70 patients with pituitary prolactinomas indicate that the success of surgery depends on the preoperative prolactin level and the diameter of the adenoma, and that the former is the more influential factor. Assessment of both of these parameters affords a good prediction of the endocrine result. The cure rates for different patient groups ranged from 4% to 90%. Postoperative results in women (57% with normal prolactin levels) were better than those in men (17% with normal prolactin levels). Of 19 women who desired pregnancy, 11 (58%) achieved successful pregnancies; 1 woman became pregnant twice. In addition, one woman had an extrauterine pregnancy and one suffered a spontaneous abortion. Five required additional bromocriptine therapy. The data were evaluated analytically.

Actuarial Analysis↗

Pituitary adenomas. Clinico-morphologic correlations.

Immunohistochemistry and electron microscopy allow new insights into the biology and natural history of the proliferative processes of the hypophysis. Hyperplasia can be diffuse or focal. Its function and/or growth are controlled by hypothalamic factors. Hyperplasia may precede the formation of an adenoma. Function and/or growth of adenomas is partially or completely independent of hypothalamic regulation. Adenomas are divided according to their functional activity into an endocrine active and inactive group. A further subdivision is made according to the secreted hormone. Inactive adenomas may have lost the ability to produce hormones, may secrete hormones at a very low rate, or may secrete abnormal substances.

Adenoma↗

[Practical value of new knowledge on the structure and function of pituitary adenomas].

The usual classification of pituitary adenomas into eosinophilic, basophilic, and chromophobe types is no longer sufficient to correlate the histologic findings with the increasing number of clinical syndromes described in recent years. Some histologic forms are observed in several clinical syndromes, whereas some clinical entities may be caused by several histologic types. A new classification is mandatory. Recent endocrine, ultrastructural and histo-immunologic research has shown that the endocrine inactive adenoma, which has usually been related to the "chromophobe" adenoma, represents only a small group of the pituitary neoplasms. A more critical evaluation shows that 3 out of 4 patients present clinical or endocrine signs and findings of increased hormone secretion. Several authors have therefore suggested that pituitary adenomas be classified according to their secretory characteristics, which can be determined either by clinical and endocrine examination or by immunohistology and electron microscopy. Abnormally increased hormone secretion allows early detection of the neoplasm when the remaining normal gland is still able to recover its normal function and the endocrine symptoms therefore are fully reversible. The therapy of pituitary adenomas must normalize the hormone hypersecretion without causing new endocrine deficits, and must at the same time reverse neurological compression symptoms. The treatment may be either surgical excision, irradiation, medical inhibition of abnormal secretion, substitution of insufficient hormones or a combination of these methods. The prognosis of the endocrine symptoms is significantly better in small adenomas and full restoration of sexual function is even observed in an increasing number of patients.

Acromegaly↗

Extracellular growth hormone deposits in pituitary adenoma.

Ultrastrucutral examination of 184 pituitary adenomas demonstrated the presence of extracellular accumulations of electron dense material in 3 out of 64 cases with acromegaly. Fibrillary structures were seen in larger deposits of such material. This material was only observed in biopsies fixed directly with osmium tetroxide; initial fixation with glutaraldehyde did not retain the material and left empty spaces. Positive immuno-histochemical reaction with specific antibodies demonstrated that the extracellular material contained growth hormone (GH). The presence of this extracellular material could not be related to the age or sex of the patient nor to the duration of symptoms, size of the tumor, presence of diabetes mellitus, or concomitant secretion of prolactin. The pericapillary fibrous sheath was heavily thickened in the patient with the longest duration of symptoms, intermediate in thickness in the second and normal in the third.

Adenoma↗

The size of growth hormone granules in pituitary adenomas producing acromegaly.

Measurements of the diameters of large numbers of granules in electron micrographs of pituitary adenomas in cases of acromegaly do not show that a typical size exists which allows of the retrospective diagnosis of the hormone secreted by the tumour. The granule diameters found in single cases show a normal distribution. The average values determined in 19 unselected cases of acromegaly range between 160 and 342 nm. They are also normally distributed about the mean for the entire group which is 238 nm. With histo-immunological electron microscopic techniques h GH can be demonstrated in small, medium and large granules. The size of hormone granules is determined by functional factors such as the speed of hormone synthesis and hormone release but not by the type of hormone secreted.

Acromegaly↗

[Functional histopathology of pituitary neoplasms (author's transl)].

The generally accepted classification of pituitary adenomas into eosinophilic, basophilic, mixed, and chromophobe types has not been very useful since no clear correlation exists between the staining character of the tumor cells and the clinical syndrome produced. The ultrastructural examination of different adenoma types with clinically manifest endocrine activity (acromegaly, amenorrhea-galactorrhea-syndrome, Cushing's disease) shows that the type of hormone secreted can only be determined in few cases. The ultrastructure is more representative of the activity of the secretory process than of the type of the product. Histoimmunological methods achieve the specific identification of the various types of adenomas with endocrine symptomatology. The so-called "chromophobe" adenomas, which only manifest signs of a space occupying lesion with pituitary insufficiency of varying degree and compression of the visual pathways, represent a mixed group. The majority of the cases (about 60%) shows increased prolactin secretion with amenorrhea or loss of potency, but without galactorrhea or gynecomastia. A small group of cases may either produce normal hormones (growth hormone or prolactin) at a very low rate, or secrete hormone fragments or abnormal, as yet undeterminable substances. The oncocytomas, which stain with eosin in light microscopy, seem to suffer from a defective metabolism and therefore may have lost the ability of hormone production.

Adenoma↗

Pituitary adenoma calcification.

Calcifications have been found in 9 of 137 different pituitary adenomas (6.6%) that have been examined with skull roentgenograms, light microscopy, and electron microscopy. Electron microscopy was most efficient because seven cases showed positive findings. Skull x-ray films showed calcification in four and light microscopy in only two cases. Six adenomas showed signs of increased prolactin production (either by direct determination or presence of galactorrhea). Two pateitns with calcifications on skull x-ray films and negative microscopic examinations did not show signs of any hormone secretion. The ultrastructural examination showed that the process of calcification started in single necrotic cells undergoing fibrillary transformation. No large areas of necrosis were present as seen in other forms of dystrophic calcification. The deposits consisted of dense accumulation of radially oriented hydroxyapatite crystals. The observations suggest that local factors and the type of hormone secreted may play an important role in the calcification pattern of pituitary adenomas.

Adenoma↗

Ultrastructure of tubular inclusions in endothelial cells of pituitary tumors associated with acromegaly.

Tubular inclusions were present in 13 out of 43 pituitary adenomas of acromegalic patients and in a single chromophobe pituitary adenoma. There were none in 76 other pituitary adenomas with differing endocrinological symptomatology. The arrays were usually located in the perinuclear cistern of capillary endothelial cells. The tubule diameter in osmium fixed material measured 19-26 nm and the light core averaged 6-11 nm. A longitudinal period of about 4.5 nm could be demonstrated with PTA block staining. Fixation with glutaraldehyde and block staining with ethidium bromide as well as permanganate fixation followed by RNAse treatment showed only the core of the tubules consisting of globular subunits. Several histochemical reactions (perchloric acid extraction, methenamine-silver staining, trypsin and DNAse digestion of frozen sections) suggested that the particles consist of a core of DNA coated with protein. No virus multiplication could be detected in cell cultures or in mice innoculated with fresh tumor material. No significant antibody titers against several virus antigens could be demonstrated.

Acromegaly↗