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PubMed2003

Development of a meningioma in a patient with acromegaly during octreotide treatment: are there any causal relationships?

Somatostatin receptors are highly expressed in almost all meningiomas but in this setting their functional role is not clear. A 59-yr-old woman had been treated with octreotide after an unsuccessful operation for a GH-secreting pituitary adenoma. After 8 yr of treatment, a nuclear magnetic resonance (NMR) scan disclosed a 3 cm meningioma of the tentorium. Mean GH was 2.2 ng/ml and IGF-I 325 ng/ml. Meningioma was resected and tissue was digested to obtain tumor cell suspension. Aim of the study was to measure epidermal growth factor (EGF)-induced proliferation of cultured meningioma cells in the presence of either somatostatin or octreotide. Cells were grown to semiconfluency in Dolbecco's modified eagle medium (D-MEM) supplemented with 10% fetal calf serum (FCS). After 48 h in D-MEM without serum, the medium was replaced by fresh medium plus recombinant EGF (10 ng/ml) and somatostatin or octreotide were added in the final concentrations of 1, 10 and 100 nM. 20 h later 1 microcgCi of 3H-thymidine was added to each well. After 4 h, incorporated radioactivity was measured. While octreotide did not influence significantly cell growth at the three dose tested, somatostatin increased thymidine incorporation dose-dependently (peak 100 nM: 150% +/- 27% vs medium plus EGF, p<0.05). Octreotide effectively suppressed GH secretion in our acromegalic patient but is unlikely that its long-term use could have stimulated the growth of meningioma since it did not significantly influence the in vitro proliferation of the meningioma cells. These results suggest that somatostatin-mediated proliferative effect on meningioma cells is not mediated by the subtype 2 of the somatostatin receptor.

Acromegaly↗
PubMed1999

Evaluation of disease activity by IGF-I and IGF binding protein-3 (IGFBP3) in acromegaly patients distributed according to a clinical score.

UNLABELLED: To facilitate the estimation of acromegalic activity a prospective study was done comparing, against a clinical score, the effectiveness of serum IGF-I, IGFBP3 and the IGF-I/IGFBP3 molar ratio. Sixty nine observations were distributed in three groups: Group I=patients before surgery; group II=patients improved but still clinically active; group III=patients clinically inactive. Suppression of serum GH levels one hour after an oral glucose load was in agreement with the clinical score in 21/22 observations. Increases in serum IGF-I and IGFBP3 levels were similarly frequent: both 100% in group I, 80% and 95% in group II, 9% and 36% in group III, respectively. The frequency of abnormal molar ratios was 95%, 40% and 0% in the same groups. Log IGF-I, log IGFBP3, and log molar ratio correlated significantly with the clinical scores (r=0.873, r=0.692, and r=0.829, respectively). CONCLUSIONS: The IGF-I/IGFBP3 molar ratio was not better than either IGF-I or IGFBP3 in detecting activity in the three groups of patients studied. Both IGF-I and IGFBP3 appear comparably useful for the diagnosis and follow-up of acromegalic patients. Since IGF-I is a more biologically meaningful parameter it might be preferable.

Acromegaly↗
PubMed1991

Doxorubicin for acromegaly: a case report.

We report the case of an acromegalic woman, aged 35 years, with a huge GH-secreting tumor, repeatedly treated with neurosurgery and radiotherapy, not responsive to bromocriptine (Br) and octreotide (SMS), whose clinical picture evolved to coma due to endocranic hypertension. Since remnant size was too large to be further treated by surgery, chemotherapy with doxorubicin (DOX) (100 mg i.v. every three weeks up to 0.5 mg/m2 over 7 months) was started. Treatment was followed by a rapid improvement of clinical picture with resumption out of coma, progressive decline of GH levels (from 800 ng/ml to 15 ng/ml) and a slight shrinkage of tumor. No side effects were observed during DOX administration. We suggest that in those few acromegalic patients resistant both to SMS and Br, and with poor prognosis, DOX may be effectively used.

Acromegaly↗
PubMed1991

Evaluation of a repeatable depot-bromocriptine preparation(Parlodel LAR) for the treatment of acromegaly.

The effectiveness and side effects of a newly developed, repeatable depot-bromocriptine preparation, (Parlodel LAR, depot-bromocriptine), were studied in 7 acromegalic patients. A dose of 100 mg was injected at intervals of 28 days for 4 months, followed by 200 mg for 2 months. GH profiles (14 h) and an oral glucose load (oGTT) were performed prior to each injection. Depot-bromocriptine suppressed the mean serum profile GH concentration to less than 50% of the pretreatment value in 3 out of 7 patients (responders). Normalization of GH secretion was not achieved. During oGTT the mean serum GH concentration declined to 73%, 19% and 56% of the pretreatment value in the three responders (while on depot-bromocriptine 200 mg). IGF-I was reduced to 84% and 65% with 200 mg depot-bromocriptine in 2 GH responders only. No tumour shrinkage was observed in 3 patients with a visible tumor mass in NMR tomography. Side effects consisted of pronounced orthostatic dysregulation, nausea and vomiting on the day of injection in 3/7 patients. These results are comparable to the reported effectiveness and side effects of oral bromocriptine therapy. Depot-bromocriptine may be useful in selected responsive patients, particularly when compliance during oral therapy is a problem.

Acromegaly↗
PubMedDate not supplied

Effects of bromocriptine on CSF proteins and amines in patients with empty sella syndrome, acromegaly and prolactin producing pituitary adenomas.

The effect of the dopamine agonist bromocriptine (5-40 mg/day) on cerebrospinal fluid proteins and amines was studied in 7 hyperprolactinemic patients, 4 with empty sella syndrome and 3 patients with pituitary adenoma. Small as well as high doses of bromocriptine depressed the endogenously formed dopamine, noradrenalin and adrenalin. Five patients initially exhibited changes consistent with slight to marked blood-cerebrospinal-fluid (CSF) barrier disturbances and 5 abnormal CSF-protein fractions. One CSF-protein fraction (isolelectric points (pI) approximately 5.3 pH-units) became more prominent during bromocriptine treatment. Analyses of his fraction indicated that it represented a transferrin component. It is stated that bromocriptine treatment besides affecting amine and trace metal metabolism also affects protein metabolism.

Acromegaly↗
PubMed1992

A marked molecular heterogeneity of growth hormone (GH) detected in the plasma but not pituitary of a patient with acromegaly: comparison with other acromegalics and an implication for discrepant plasma levels of GH and insulin-like growth factor.

We experienced a 41-year-old acromegalic male (Case 1) in whom the basal plasma GH was extremely high (320-450 ng/mL) but plasma IGF-I was only slightly elevated (2.0-2.8 U/mL). His nutritional condition and associated diabetes mellitus did not appear to be responsible for the relatively low IGF-I level, and a GH-autoantibody in the plasma was absent. We thus performed gel filtration analyses of his plasma and somatotroph adenoma to determine elution patterns of immunoreactive (IR) and receptor active (RA) GH. For comparison, the same studies were carried out on plasmas and somatotroph adenomas obtained from three other acromegalics (Cases 2-4) whose basal plasma GH and IGF-I levels were 22-45 ng/mL and 3.5-6.0 U/mL, respectively. IR GH in Case 1's plasma distributed over an extremely wide range keeping similar titers rather than showing three discernible components (big-big, big, and little GH) as did plasmas and adenomas from Cases 2-4. And, most of the IR GH in Case 1's plasma was eluted in such fractions that contained low levels of RA GH, indicating a minor proportion of biologically active GH. However, interestingly, the chromatographic profile and total GH content of Case 1's adenoma were similar to those of Cases 2-4's adenomas. These results may, at least in part, explain the discrepancy between the plasma GH and IGF-I levels of Case 1. The unexpectedly different GH elution patterns between the plasma and adenoma from this patient, may suggest a contribution of certain plasma factor(s) to the unusual chromatographic profile of plasma GH.

Acromegaly↗
PubMedDate not supplied

Effectiveness of the dopamine agonist lisuride in the treatment of acromegaly and pathological hyperprolactinemic states.

We have studied the effects of the chronic administration of the dopamine agonist lisuride (L) in 21 acromegalics (group 1) and in 25 patients with pathological hyperprolactinemia (group 2). Before starting the treatment levels of PRL and/or GH were determined during acute tests with L (0.3 mg po) or TRH (0.2 mg iv). L was given in doses ranging between 0.4 and 2.4 mg/day. GH and/or PRL were determined at monthly intervals, TRH (6 patients of group 1 and 10 of group 2) was repeated during L therapy. In 10 patients of group 1 GH levels were reduced below 10 ng/ml by L therapy; in the remaining patients GH levels were reduced by 50% of the pretreatment values or they were unchanged. The correlation (p less than 0.01) found between GH levels during acute and chronic L administration indicates that GH changes after acute test are predictive of the outcome of the treatment. In all patients PRL was reduced during the therapy to at least 50% of the basal values and in most patients PRL fell to the normal range. No correlation was found between PRL levels during acute and chronic L administration. During the therapy TRH still increased GH levels in most patients whereas it failed to raise PRL. The withdrawal of L was followed by a rapid return of GH to the pretreatment values whereas PRL showed a slower increase. In acromegalics whose GH was lowered by L there was also a marked amelioration of clinical and metabolic parameters. The lowering of PRL was accompanied by the resumption of ovulatory menses even in patients with tumoral hyperprolactinemia. Males reported improvement in sexual performance. An improvement of visual field occurred in 1 patient. In 1 patient with a large prolactinoma serial computerized tomography scans performed during 2 yr of treatment showed a marked reduction of the tumor size.

Acromegaly↗
PubMed2004

[82-year old patient with hyperostosis frontalis, prognathism, makroglossia and cutis gyrata. Acromegaly].

We present a 82 year old female patient with typical acral enlargement. There were no signs of visceromegaly. Magnetic resonance imaging of the pituitary region showed a macroadenoma. Oral glucose tolerance test revealed missing suppression of the Human Growth Hormone (HGH), which could be achieved with a long acting somatostatin analog. A HGH suppressive therapy with a long acting dopamine agonist (Cabergolin) was induced. The patient died one year later following cardiovascular complications.

Acromegaly↗
PubMed2005

Outcome of surgery for acromegaly performed by different surgeons: importance of surgical experience.

AIM: The aim of this study was to evaluate transsphenoidal surgery results in acromegalic patients which were performed not by a single surgeon but by different surgeons. METHODS: The study included 30 (M/F: 13/17) patients whose follow-up data were available. Basal or nadir postglucose growth hormone levels of less than 2 ng/ml were accepted as cure criteria. Six of them underwent a further operation due to previous surgical failure. RESULTS: Cure was achieved in 33% of patients while hypopituitarism was observed in 10% (3/30) of patients after the first operation. The cure rates were 63% and 15% in patients with microadenomas (n = 11) and macroadenomas (n = 19) respectively (p = 0.042). Only one of the patients (16%) who underwent a second operation achieved remission, while hypopituitarism was observed in five of them (83%). There was no significant difference in the cure rates between the first and second operation, but the risk of hypopituitarism was significantly higher in patients who underwent further surgery (p = 0.008). CONCLUSION: The cure rate following surgery is significantly lower in acromegalic patients with macroadenomas than in patients with microadenomas. Cure probability decreases with a further operation, while complication risk increases significantly. Octreotide therapy, which could be used as an alternative therapy to the surgery, revealed high success rates in both microadenomas and macroadenomas. The low cure rates found in this study compared with published series could be attributed to the fact that operations were performed by inexperienced surgeons.

Acromegaly↗
PubMed2005

Serum IGF-1 in treated acromegaly - how normal is "normal"?

We describe four acromegalic patients with persisting typical symptoms - excessive sweating, lack of suppleness of hands, joint pains - despite the achievement of normal serum IGF-1 levels after pituitary surgery. In three patients there was a clear improvement in symptoms when lower IGF-1 levels within the normal range were achieved with pegvisomant treatment. In the fourth patient IGF-1 levels have fluctuated within the normal range with persistence of abnormal sweating, particularly at night. Two of three patients who had an oral glucose tolerance test when serum IGF-1 was in the normal range failed to suppress GH levels to less than 1 ng/ml. We conclude that, in the treated acromegalic patient, IGF-1 levels within the normal range need to be looked at critically to determine what is truly normal for that individual. Relief of symptoms seems a reasonable yardstick, in addition to population norms, by which to judge whether the prevailing IGF-1 level is appropriate; in some cases the aim should be an IGF-1 level in the lower half of the normal range, or perhaps even the lowest quartile.

Acromegaly↗