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Biomedical subjects

A M Landolt

Publications and source records attributed to A M Landolt.

At least 37 records · Page 2Linked to original sources
PubMed1993

Basic fibroblastic growth factor stimulates prolactin secretion from human anterior pituitary adenomas without affecting adenoma cell proliferation.

The effects of human recombinant basic fibroblastic growth factor (bFGF) on the secretion and/or proliferation of 26 human anterior pituitary adenomas secreting PRL alone (6 tumors), PRL and GH (18 tumors), or GH alone (2 tumors) were examined. Secretory studies were performed over 4 h, 4 days, and 21 days, and proliferation studies over 4 days. The acute effect of bFGF on secretion over 4 h was examined in 10 tumors. bFGF (10 nmol/L) increased PRL compared to that in controls (100%) in 2 tumors (126% and 290%; P < 0.05) and PRL and GH in a third tumor (183% and 133%, respectively; P < 0.05), whereas 7 tumors remained unaffected. Fourteen tumors were studied over 4 days. bFGF (10 nmol/L) increased PRL secretion in 9 of 11 tumors (117-525%; P < 0.05) cosecreting PRL and GH and in all 3 tumors secreting PRL alone (156%, 183%, and 691%; P < 0.01). Dose-response curves with 0.1, 1, and 10 nmol/L bFGF in 2 of these tumors cosecreting GH and PRL showed that stimulation was achieved with all 3 concentrations. bFGF (10 nmol/L) stimulated GH secretion in 2 of 11 mixed tumors (159% and 196%, respectively; P < 0.05). In 2 tumors studied over 3 weeks, 5 nmol/L bFGF stimulated PRL secretion progressively without affecting GH secretion (106% and 207%; P < 0.05). Tissue proliferation was determined by double immunostaining after bromodeoxyuridine incorporation for 1 h in 7 tumors after 4 days. The labeling index did not exceed 1.2% in any tumor, and there was no effect of 10 nmol/L bFGF on the proliferation of adenoma cells. These results suggest that bFGF may have a paracrine role in the stimulatory regulation of PRL secretion in human pituitary adenomas, and these effects are most likely due to increased hormonal synthesis. An in vitro cell culture system can be used to study proliferative potential. However, bFGF is not mitogenic for human anterior pituitary adenomas secreting PRL and PRL plus GH in vitro.

Adenoma↗
PubMed1993

Differential effects of insulin-like growth factor 1 on the hormonal product and proliferation of glycoprotein-secreting human pituitary adenomas.

The effects of human recombinant insulin-like growth factor 1 (IGF-1) on the secretion, viability, and proliferation of dispersed human anterior pituitary adenomas secreting FSH, LH, and alpha-subunit (alpha-su) were examined in vitro over 4 h and 4 days. The acute effect of IGF-1 on secretion over 4 h was examined in four tumors secreting FSH, LH, and alpha-su. IGF-1 (100 nmol/L) reduced LH compared to control (100%) in one tumor (61%, P < 0.01), and three tumors remained unaffected. FSH and alpha-su secretion were insufficient to measure over 4 h. Nine tumors were studied over 4 days; relative to control, IGF-1 (100 nmol/L) increased FSH secretion in all seven tumors secreting FSH (28-266%, P < 0.05) and increased alpha-su secretion in all four tumors studied (36%, 63%, 91%, and 121%, P < 0.05). IGF-1 reduced LH secretion in four/nine tumors (13%, 23%, 32%, and 50%, P < 0.05). Dose response curves (1-100 nmol/L IGF-1) were performed on three tumors cosecreting FSH and LH. Stimulation of FSH was achieved with either 1 or 10 nmol/L IGF-1, a single tumor in which alpha-su was measured showed maximal stimulation at 10 nmol/L IGF-1, and one of three tumors showed LH inhibition with 100 nmol/L IGF-1. In situ viability of attached cells was assessed with fluorescein and propidium iodide in seven tumors. After 4 days' exposure to 100 nmol/L IGF-1, in situ viability was increased in five tumors (range 12-19%, 15 +/- 1.3% SEM, P < 0.05). The effects of IGF-1 on the adenoma cell proliferative S-phase fraction was determined in six tumors after 4 days of treatment using double immunostaining with bromodeoxyuridine incorporation for 1 h. In four/six adenomas that stained positive for bromodeoxyuridine in the controls (1-5.6%), the S-phase fraction was increased by 100 nmol/L IGF-1 [(range 2.1-10.6%, increase 90-220%) (P < 0.05)]. These results show that IGF-1 has differential effects on gonadotropins from human pituitary adenomas, stimulating intact FSH and alpha-su, inhibiting or being without effect on intact LH in vitro, and increasing both viability and number of tumorous glycoprotein-secreting cells entering into the S-phase of proliferation.

Adenoma↗
PubMed1991

Results of transsphenoidal extirpation of craniopharyngiomas and Rathke's cysts.

Fourteen patients undergoing transsphenoidal extirpation of craniopharyngiomas or Rathke's cysts underwent endocrinological evaluation before and after surgery. One patient died during the procedure because of uncontrollable arterial bleeding. The other patients were followed for up to 16 years (average, 8.5 years). One patient had recurrence of tumor 12 years after surgery. Another patient, the only one operated on because of a recurrent craniopharyngioma after previous radiation therapy, died 2 years after the transsphenoidal operation. No patient recovered pituitary functions that had been lost before surgery. One patient, who had an isolated growth hormone deficiency, and another, who had panhypopituitarism with sustained antidiuretic hormone secretion, had no change postoperatively from their preoperative endocrine status. The other 11 patients lost pituitary function and required pharmacological replacement of one to four pituitary hormones.

Adolescent↗
PubMed1989

[TSH-producing hypophysis adenoma and secondary hyperthyroidism. Case presentation and literature review].

Hyperthyroidism was diagnosed in a 26-year-old woman with a several years' history of oligo-amenorrhea. Since TSH was found to be elevated, the pituitary was radiologically explored and a TSH-producing macroadenoma was diagnosed and removed by the transnasal, transsphenoidal approach. Postoperatively, TSH and peripheral hormone levels decreased but not to normal, and therefore pituitary irradiation was carried out, the success of which cannot yet be evaluated. In a survey of 68 such cases in the literature and our own case, the findings and the diagnostic and therapeutic problems of this rare cause of hyperthyroidism are discussed.

Adenoma↗
PubMed1989

The growth hormone responses to octreotide in acromegaly correlate with adenoma somatostatin receptor status.

We studied the correlation between the presence of somatostatin (SRIH) receptors in GH secreting tumors and the in vivo GH responsiveness to the SRIH analog octreotide in 11 acromegalic patients. To test in vivo octreotide (SMS 201-995) responsiveness, the patients were given a single dose (100 micrograms, sc) and their plasma GH levels were measured for several hours. Somatostatin receptor content was measured by receptor autoradiography on frozen tumor tissue sections using either a somatostatin-28 analog or a SRIH octapeptide analog (Tyr3-octreotide) as iodinated radioligands. In eight acromegalic patients, who had complete and long lasting GH inhibition after octreotide administration, SRIH receptors with high affinity for octreotide were distributed homogeneously in the tumor tissue. Two patients had moderate, short duration, and incomplete inhibition of GH secretion after octreotide administration, and their tumors had very low capacity and/or affinity SRIH receptors. A further patient who had a moderate response to octreotide had SRIH receptors that were nonhomogeneously distributed throughout the tumor. These data suggest that the therapeutic efficacy of octreotide may be related to tumor SRIH receptor levels; the best in vivo responses to octreotide occurred in patients whose tumors contained a high density of homogeneously distributed receptors which had a high affinity for octreotide.

Acromegaly↗
PubMed1988

[A fatal course of Nelson syndrome].

An unusually therapy-resistant form of Nelson's syndrome developed in a 23-year-old woman two years after treatment of a pituitary-dependent Cushing's syndrome by bilateral adrenalectomy (1977). Removal of a corticotrophic adenoma by a first transsphenoidal pituitary operation (1979) brought only temporary relief. Two years later, regrowth and apoplexy of the pituitary adenoma led to oculomotor paralysis and had to be treated by a second transsphenoidal operation (1981). A second relapse became manifest two years later. Treatment with bromocriptine relieved the headaches but did not diminish the tumor size. A third pituitary operation (1984) became necessary when neurological signs revealed penetration of the cavernous sinus. The tumor was only partly removed by transsphenoidal surgery. Postoperative deterioration of the patient required emergency craniotomy to check a subarachnoidal hemorrhage and for removal of the remaining tumor. The patient died three days later of pneumococcal meningitis which had developed after the third pituitary operation.

Adrenalectomy↗
PubMed1988

Differentiation of two types of amyloid occurring in pituitary adenomas.

Two types of amyloid can be differentiated by light microscopy, immunocytochemistry, and electron microscopy. The more frequent type (stellate/perivascular amyloid) is a secretory product of the adenoma cells whereas the second, rare type (spheroid amyloid) is formed by remnants of the cytoskeleton of necrotic adenoma cells.

Adenoma↗
PubMed1988

Production of the alpha-subunit of glycoprotein hormones by pituitary adenomas.

Positive immunoreactions with alpha-subunit antibodies were present in 43% of biopsy samples obtained from 147 subsequently operated pituitary adenomas representing all major endocrine types (57 endocrine inactive adenomas, 43 prolactinomas, 30 adenomas causing acromegaly, and 17 adenomas causing Cushing's disease or Nelson's syndrome). Marked variations of the incidence, however, were found among the individual endocrine groups. Positive reactions were present in 63% of endocrine inactive adenomas, 57% of adenomas causing acromegaly, 35% of ACTH-secreting adenomas, and 9% of prolactinomas. A positive alpha-subunit reaction was accompanied in a minority of cases only with positive glycoprotein hormone-beta-subunit reactions. There were 21 pure alpha-subunit adenomas in the group of endocrine inactive adenomas.

Acromegaly↗
PubMed1988

Spontaneous postoperative normalization of growth hormone levels in two patients with acromegaly not cured by transsphenoidal surgery.

Postoperative persistence of elevated growth hormone (GH) levels in patients with acromegaly usually suggests residual adenoma tissue secreting GH and is an indication for further treatment. In rare cases, spontaneous normalization of serum GH levels in patients with acromegaly has been reported to occur as a consequence of intratumoral hemorrhage (pituitary apoplexy). We report two patients in whom persisting acromegaly was documented 1 and 2 weeks, respectively, after transsphenoidal operation and who experienced spontaneous normalization of GH levels. In one patient, this favorable outcome was found 1.5 years after the operation and followed a pregnancy. The other patient, whose GH values normalized 3 months after operation, had received preoperative treatment with a new, long-acting somatostatin analog.

Acromegaly↗
PubMed1987

Distribution of growth hormone and prolactin in secretory granules of the normal and neoplastic human adenohypophysis.

Growth hormone [GH] and prolactin [PRL] can be demonstrated simultaneously in electron micrographs by means of the double immunocytochemical labeling technique using colloidal gold particles of two different sizes. This method was used to study biopsy specimens obtained from 15 patients suffering from acromegaly, 11 patients suffering from prolactinomas, and eight biopsy specimens obtained during adenomectomy from the normal, paraadenomatous pituitary tissue. Four granule populations with different immunoreactions were found: (1) granules containing GH only, (2) granules containing PRL only, (3) mixed granules containing GH and PRL, and (4) granules displaying no immunoreactivity. The existence of mixed granules indicated that the two hormones are synthesized by the same cell and in communicating compartments of the cells; i.e., the rough-surfaced endoplasmic reticulum. The number of GH-containing granules (pure GH granules and mixed GH-PRL granules) was greater than that of PRL-containing granules (pure PRL granules and mixed PRL-GH granules) in adenomas causing acromegaly and in the normal pituitary tissue, whereas the opposite was true for prolactinomas. The number of PRL-containing granules was larger in biopsy specimens from patients who had acromegaly and hyperprolactinemia than in patients with acromegaly and normal serum PRL levels.

Acromegaly↗
PubMed1987

A new method for the correction of hypertelorism with preservation of the olfactory nerve filaments.

A method for the preservation of the olfactory nerve filaments in cases of hypertelorism correction is described. The cribriform plate is completely resected and the nerve filaments gathered in the midline after medial rotation of the orbits. In contrast to Converse's (1970) procedure of paramedian osteotomies the method allows full correction of all degrees of hypertelorism, even in the most extreme cases, without olfactory nerve impairment.

Bone Diseases, Developmental↗
PubMed1987

Immunocytochemistry of pituitary tumors.

Pituitary tumors from 376 patients were investigated, using immunocytochemical techniques at the light and electron microscopic level, and autoradiography combined with immunocytochemistry for localizing somatostatin (SRIH) receptors. Prolactinomas, growth hormone-secreting adenomas causing acromegaly, and hormonally inactive adenomas were most frequently observed (153, 86, and 90 tumors, respectively). Among the latter, we could distinguish "alpha-only adenomas," many of which were oncocytomas. At the light and electron microscopic levels, cells containing (and presumably producing) simultaneously both prolactin and growth hormone, and cells containing exclusively either prolactin or growth hormone, could be demonstrated. In addition, a highly variable number and distribution of SRIH receptors could be shown in tumors secreting prolactin, growth hormone, and in tumors not associated with symptoms caused by inappropriate hormone secretion. The systematic combination of clinical, radiological, and biological techniques has currently brought great progress in the behavior and therapeutic concepts of pituitary lesions, and promises new achievements in the near future.

Adenoma↗
PubMed1987

Visualization of somatostatin receptors and correlation with immunoreactive growth hormone and prolactin in human pituitary adenomas: evidence for different tumor subclasses.

Using combined autoradiographic and immunohistochemical techniques, specific somatostatin (SRIH) receptors were measured in 31 human pituitary tumors. SRIH receptor distribution was compared with that of immunoreactive GH and PRL in the same tissue sections. Among the 10 tumors from acromegalic patients, 7 contained a high or medium density of SRIH receptors, whereas only a low density of such receptors was present in the remaining 3 tumors despite a comparably high concentration of immunoreactive GH in all 10 tumors. No correlation between plasma GH levels and SRIH receptors was found. One corticotroph tumor was SRIH receptor negative. Among the 5 prolactinomas tested, only 1 contained a significant density of SRIH receptors, the distribution of which did not correlate with that of immunoreactive PRL cells. Interestingly, among the 15 endocrine-inactive adenomas investigated, 6 had a measurable, sometimes high, density of SRIH receptors despite undetectable GH, PRL, or TSH immunoreactivity. These results suggest that based on their SRIH receptor content, there may be subclasses of GH-producing pituitary adenomas. The difference in SRIH receptor density may be an explanation for the clinically described differential responsiveness of acromegalic patients to SRIH. The results also suggest that subclasses of endocrine-inactive pituitary adenomas may exist; some of them contain significant amounts of SRIH receptors, which may be responsive to SRIH treatment.

Adenoma↗
PubMed1987

Pre-operative treatment of 5 acromegalics with a somatostatin analogue: endocrine and clinical observations.

Five acromegalic patients were treated preoperatively over a period of 1-4 weeks with the somatostatin analogue SMS 201-995. The patients received daily 3 X 100 micrograms of SMS 201-995 subcutaneously. This schedule resulted in a rapid improvement of the clinical symptoms in 4 out of 5 patients. In these same patients plasma growth hormone concentrations decreased markedly. However, only in one patient were growth hormone concentrations normalized. Plasma IGF I, which was elevated in all patients, was normalized only in this same patient. Tumour volume as determined by thin section CT-scans decreased only in one case by 17%. All tumours appeared extraordinarily soft upon operation. Conventional light microscopy showed no difference between tumours of SMS-pre-treated and untreated patients. Ultrastructural investigation showed the usual heterogeneity.

Acromegaly↗