Feelings of anxiety and associated variables in a very elderly population

The effect of octreotide on morning hyperglycemia and GH levels was evaluated in eight insulin-dependent diabetic patients. Octreotide (50 mcg) was administered through subcutaneous injections at different hours (20:00, 22:00 and 24:00 h) or through continuous subcutaneous night infusion from midnight to 08:00 at increasing rate between 03:00 and 08:00 h. After octreotide injection at midnight we noticed a sharp decrease of both glycemia (p < 0.005) and GH (p < 0.05) at 04:00 h, but not at 08:00 h. Only the night continuous infusion at increasing rate was able to reduce glycemia and GH at 04:00 and at 08:00 h (p < 0.001 and p < 0.01 respectively). The injections of octreotide at 20:00 and 22:00 h lowered GH values at 24:00 h (p < 0.01 and p < 0.05 vs insulin alone) but did not show any significant effect on blood glucose levels and GH at 04:00 and 08:00 h. In conclusion, only the continuous subcutaneous night infusion of octreotide at increasing rate during the last hours of the night was able to reduce simultaneously morning hyperglycemia and GH levels in insulin-dependent diabetic patients, whereas evening subcutaneous injections at different times did not show any appreciable effect.     

An overview of Spanish studies on appropriateness of hospital use

A long-acting depot formulation of octreotide (Sandostatin LAR, Sandoz LTD) has been recently developed. Preliminary studies indicated that, in acromegalic patients previously controlled by Sandostatin 300-600 micrograms/day in 2-3 sc injections, the intramuscular administration of 20-30 mg of Sandostatin LAR achieved, during one month a similar control of GH hypersecretion. In the present study, the variations of plasma levels of octreotide, GH and IGF1 were followed during 2 months in acromegalic patients receiving a unique injection of 20 mg (n = 4) or 30 mg (n = 4) of Sandostatin LAR. Following Sandostatin LAR 20 mg i.m, the baseline values of GH (8.1 +/- 2.5 micrograms/l) and IGF1 (684 +/- 92 micrograms/l) were normalized after 2 weeks and remained into the normal range during the 28 following days. Similar results were obtained, after a 30 mg i.m administration of Sandostatin LAR. In this later case, the maximal inhibition of GH and IGF1 (1.3 +/- 1.0 micrograms/l and 392 +/- 266 micrograms/l respectively) lasted 2 months. These data showed that a monthly injection of Sandostatin LAR (20-30 mg) allowed a correct control of GH hypersecretion in this series of acromegalic patients.     

Effectiveness and tolerability of slow release lanreotide treatment in active acromegaly: six-month report on an Italian multicenter study. Italian Multicenter Slow Release Lanreotide Study Group

The objective of the study was to determine the tolerability and effectiveness of the slow release (SR) somatostatin analog lanreotide in active acromegaly. Fifty-seven patients, unselected in terms of their previous responsiveness to octreotide therapy, were included in a prospective, open label study carried out at 6 Italian endocrinological centers. The effects of 6 months of SR lanreotide, given at first every 14 days at a dosage of 30 mg, im, were recorded. In some patients (33%), drug dosage was adjusted by increasing the dose (to 60 mg, im) and/or shortening the time interval (every 10 days) of SR lanreotide administration. Fifty patients completed the 6-month period of therapy; 2 subjects dropped out because of adverse events, and 5 dropped out because of ineffectiveness after changes in drug administration. The first SR lanreotide injection produced more than 50% suppression of GH levels from the basal value in 93% of patients. Thirteen days later, baseline GH levels were reduced by over 50% in 25% of patients. Mean GH values were normalized in 85% of patients after 6 months, whereas insulin-like growth factor I (IGF-I) levels were normalized in 38% of patients. No correlation was found between pretreatment GH levels and GH response to SR lanreotide or between changes in GH and IGF-I during therapy. During treatment, there was a significant reduction in the percentage of patients complaining of joint pain, hyperhydrosis, and paresthesias. Changes in soft tissue swelling were documented by significant decreases in finger measurements. Diarrhea and abdominal pain were the most frequent side-effects when therapy was started; these progressively decreased. After the first month of therapy, moderate, mild, and no side-effects were reported by 3%, 40%, and 53% of patients. A nonsignificant increase occurred in asymptomatic gallstones and amylase levels. Minimal changes were noted in carbohydrate tolerance, consisting of a slight increase in glycosylated hemoglobin, a rise in glucose and a decrease in pre- and postprandial insulin levels. No effects on PRL, free cortisol, TSH, or free thyroid hormone levels were noted. No significant change in the percentage of visual field abnormalities was noted. Decreases in pituitary tumor size occurred in 3 of 17 patients reevaluated after 6 months of therapy. The 6-month period of SR lanreotide therapy was compared, on an anamnestic basis, with a 6-month or longer period of sc octreotide therapy (median, 300 micrograms/day) in 34 patients. There were no differences in effectiveness or tolerability between the 2 somatostatin analogs. These data indicate that SR lanreotide at a dose of 30 mg, im, every 14 days is an effective treatment in most unselected acromegalic patients. When administered to a group of poorly responsive patients, an increase in drug dose (60 mg im) and/or a shortening of the drug interval (10 days) seem to improve the GH/IGF-I response. Tolerability to SR lanreotide therapy is high. The use of a new sustained release formulation of somatostatin analog is clearly advantageous in improving patient compliance with medical treatment for acromegaly.     

Long-term preoperative management of thyrotropin-secreting pituitary adenoma with octreotide

Thyrotropin (TSH)-secreting pituitary adenomas are the less frequent form of presentation of pituitary tumors. Selective transsphenoidal surgical resection of the tumor is the treatment of choice. Given that native somatostatin inhibits TSH secretion, treatment with somatostatin analogues has been recently employed in patients with unresectable tumors or after surgery. We report on the case of a 58 year-old man with a TSH-secreting pituitary adenoma who was treated with octreotide for long-term before neurosurgery. The patient was referred to us because of a pituitary mass on CT scanning. Hormonal evaluation resulted in hyperthyroidism with high serum TSH concentrations. Serum alpha subunit concentration was elevated and TSH response to exogenous TRH stimulation was absent. Magnetic resonance imaging of the hypothalamic-pituitary area confirmed the presence of a pituitary mass (2.0 by 1.8 by 1.7 cm). Acutely administered subcutaneous octreotide (100 microg) was followed by a reduction of the serum TSH concentrations. Therefore, the patient received octreotide, 100 microg three times daily for 12 months. At first month after beginning therapy serum TSH, free thyroxine, total triiodothyronine, and alpha subunit concentrations were normalized and persisted into the normal range for the next 11 months. On the other hand, a shrinkage of the tumor mass (1.6 by 1.7 by 1.4 cm) was noted after 6 months of octreotide therapy, however, its volume did not modify in the following next months. Then, the tumor was removed by transsphenoidal surgery and the diagnosis was confirmed by immunohistochemical staining. This case demonstrates that long-term treatment with octreotide gave rise to a normalization of the thyroid function and a reduction of the tumor volume before surgery. This clinical observation suggests that octreotide therapy might be useful in preparation for pituitary surgery in patients with TSH-secreting pituitary adenomas.     

Octreotide in hyperinsulinism

In a limited number of case reports in infants, octreotide raised the blood glucose concentrations and decreased glucose requirements sufficiently to avoid pancreatectomy. This response occurs in the presence of frequent feedings and diazoxide therapy, and lasts from 1 month to greater than 5 years. As expected, octreotide reduces growth indices such as growth factors and growth rate in short-term assessment. However, an insufficient sample size, a lack of follow-up, and poor study design provide inconclusive data. Among the few case reports in adults with benign or malignant insulinoma, octreotide can significantly raise blood glucose concentrations. In long-term follow-up, octreotide has alleviated or reduced the frequency of hypoglycemic episodes for periods of 5 months to 2.5 years. Octreotide was administered subcutaneously in regimens of 100-1500 micrograms in three to four divided doses or as a continuous infusion. Continuous subcutaneous infusion may be attempted in patients intolerant to intermittent administration. Octreotide may worsen existing hypoglycemia as result of suppressing glucagon and growth hormone in the presence of unresponsive pancreatic hyperinsulinism. While the long-term effects of growth remain undetermined, current findings suggest octreotide may provide a reasonable addition or alternative to diazoxide in controlling symptoms of congenital hyperinsulinism. Octreotide may be useful in management of hypoglycemic symptoms in adult patients requiring medical treatment for insulinoma who are refractory or intolerant of diazoxide. Additional long-term studies are needed to address the cost effectiveness of octreotide therapy, identify patients most likely to respond, and determine the impact of octreotide on height.     

Heat loss in humans covered with cotton hospital blankets

We have studied the pharmacokinetics and the effects of BIM 23,014 (BIM), a new, long-acting octapeptide somatostatin analogue, on basal and stimulated GH secretion in normal men. BIM 250 micrograms sc significantly reduced a GHRH-induced increase in plasma GH. The continuous sc administration of BIM for 24 h dramatically blunted spontaneous GH secretion; 2000 and 3000 micrograms daily reduced GH secretion to a greater extent than 1000 micrograms daily. During these experiments a significant negative correlation (r - 0.66) was found between plasma GH and BIM levels. Acute sc administration of 1000 micrograms BIM significantly reduced the rise in plasma GH observed in the second part of the oral glucose tolerance test. Plasma BIM levels peaked around 30 min, and the elimination half life was 90 min. Plasma BIM levels were below 1 ng/ml 6 h after the injection of 1000 micrograms BIM, and at that time GH started to rise again. We conclude that BIM 23,014 250 to 1000 micrograms sc is able to reduce the plasma GH response to GHRH or to the fall in glucose following an oral glucose tolerance test; a constant infusion of BIM, in doses 1000 micrograms daily, dramatically suppresses spontaneous GH secretion; 2000 micrograms/day by chronic subcutaneous infusion was the most effective dose of BIM in the suppression of GH secretion, and was associated only with minor adverse effects.     

Case report: defective beta and alpha cell regulation in patients with hyperinsulinemia and acanthosis nigricans

Beta cell hypersecretion is associated with the syndrome of hyperandrogenism, insulin resistance, and acanthosis nigricans. It is unknown whether concomitant alpha cell secretory dysfunction occurs in patients with this syndrome. The authors evaluated the gastroenteropancreatic hormones in four family members with varying degrees of the hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome. Gastroenteropancreatic hormones were measured during oral glucose tolerance test with and without subcutaneous octreotide injection. The study revealed that the administration of subcutaneous octreotide resulted in suppression of beta cell function (insulin and c-peptide) but had no effect or a delayed effect on alpha cell secretion (glucagon). Furthermore, the severity of glucagon abnormalities paralleled that of beta cell hypersecretion and the clinical and phenotypic manifestations of acanthosis nigricans in our four patients. We speculate that this alpha cell aberration could potentially be involved in the altered glucose homeostasis and perhaps the skin manifestations of this syndrome. Therefore, glucagon levels should be evaluated in the hormonal studies in patients with hyperandrogenism, insulin resistance, and acanthosis nigricans syndrome.     

Accumulation of zinc in rainbow trout (Oncorhynchus mykiss) after waterborne and dietary exposure

An acromegalic patient with nontoxic autonomous goiter was sequentially treated with octreotide and bromocriptine. Before therapy, serum GH, PRL and insulin-like growth factor-I (IGF-I) levels were increased. Free T3 and free T4 were within the normal range with suppressed TSH levels, whereas 123Iodine-uptake of thyroid was 5.6% after 24 h. During treatment with octreotide and bromocriptine, serum GH, PRL, and IGF-I became normal and free T3 and free T4 were slightly but significantly decreased, but TSH levels remained very low. After thyroidectomy, thyroglobulin, free T3 and free T4 were further decreased, and the TSH levels were recovered to normal. These findings suggested that octreotide and bromocriptine inhibit the release of thyroid hormones from the autonomous thyroid gland directly or indirectly through the decline in IGF-I.     

Effect of octreotide on dynamic excretion of bile in Chinese acromegalic patients assessed by [99mTc]EHIDA hepatobiliary scan

We used [99mTc]EHIDA hepatobiliary scintigraphy to determine whether both hepatic bile secretion and gallbladder contractility are suppressed in acromegalic patients receiving long-term treatment with the somatostatin analogue octreotide. We studied three groups of patients: group 1, untreated patients; group 2, average dose of octreotide 500 +/- 100 micrograms/day for 33 +/- 4 months; and group 3, 1000 +/- 200 micrograms/day for 33 +/- 4 months. Images were taken at specified time intervals during the 120-min period following injection of EHIDA. After a single injection of octreotide, group 1 patients demonstrated delayed visualization of the radioisotope in the liver, gallbladder, and duodenum. At the end of long-term treatment, group 2 patients showed a delay in appearance of maximal radioactivity in the gallbladder. Two weeks following discontinuation of octreotide, this parameter had decreased significantly (P < 0.001). In group 3, visualization of the liver, gallbladder, and duodenum were prolonged, with delayed visualization of the gallbladder persisting two weeks after withdrawal (P < 0.005). These results indicate that gallbladder contractility is decreased after a single injection of octreotide and that during chronic octreotide therapy the rate of bile secretion is reduced. Impaired gallbladder contractility normalizes more rapidly after discontinuation of octreotide in patients receiving low doses of the analog.     

Superselective bronchial arterial infusion therapy with cisplatin and epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) for hilar lung adenocarcinoma: preliminary clinical experience

A case of hilar lung adenocarcinoma was treated by superselective bronchial arterial infusion therapy with cisplatin and epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) using Tracker -18 infusion catheter. The tumor size was reduced on follow-up CT scans. However, EMILE was also distributed to nontumorous lung tissues around the tumor, and a shrinkage of the right upper lobe and elevations of the right hilus and diaphragm followed. No major complaints and clinical complications during and after the treatment occurred. This therapy was safe and effective for local tumor reduction in a case of hilar lung adenocarcinoma.     

Effects of arginine, growth hormone-releasing hormone (GHRH) and neostigmine administered singly or in paired combinations on growth hormone (GH) release in pigs

OBJECTIVE: A multicentre study was undertaken to determine the value of somatostatin receptor (sst) scintigraphy in predicting hormonal and visual responses to octreotide treatment in GH-secreting and non-functioning pituitary adenomas. SUBJECTS AND METHODS: Somatostatin receptor scintigraphy was performed in 48 patients (19 acromegaly, 29 non-functioning pituitary adenomas with ophthalmological defects). Results were expressed as an uptake index of the pituitary area. A threshold for positivity was determined in 23 subjects considered as controls. Thirty-five patients were treated for 1 month with octreotide (300 micrograms daily). The therapeutic response was assessed on GH and IGF-I suppression or evolution of the ophthalmological defects. The relationships between the somatostatin receptor scintigraphy result, the therapeutic effect of octreotide and in vitro studies performed in 12 tumours were studied. RESULTS: From the results of control subjects the uptake index threshold for positivity was 2. In patients, somatostatin receptor scintigraphy was positive in 64% and there was no relationship between uptake index and tumour size. In GH tumours, somatostatin receptor scintigraphy was positive in 68%; uptake index was related to octreotide-induced GH and IGF I suppression. The positive predictive value was 100% and the negative predictive value was 50%. In vitro studies showed detectable binding sites for somatostatin with sst2 and sst5 expression in the 4 GH tumours studied although somatostatin receptor scintigraphy was negative in 2 cases. In non-functioning pituitary adenomas somatostatin receptor scintigraphy was positive in 62%. Based on visual effects, the positive predictive value was 61% and the negative predictive value was 100%. A wide distribution of somatostatin binding sites was found in 8 non-functioning pituitary adenomas with expression of sst2 only. CONCLUSION: In the conditions of the study, in patients with acromegaly, positive somatostatin receptor scintigraphy predicts a hormonal response but the value of somatostatin receptor scintigraphy is limited by its low negative predictive value. In patients with non-functioning pituitary adenomas, negative somatostatin receptor scintigraphy predicts that there will be no visual improvement during octreotide treatment.     

Scintigraphic imaging of pituitary adenomas: an in vivo evaluation of somatostatin receptors

We have performed pituitary scintigraphy with the somatostatin (SS) analog pentetreotidean by (111In-P) in patients with GH-secreting adenoma or with "clinically non functioning" adenoma (NFA) to evaluate the presence and the functionality of SS receptors (SS-R). 111In-P pituitary accumulation was expressed as Activity Ratio (AR): the ratio between the uptake of radioactivity by the adenoma and that of the normal brain tissue. In subjects without pituitary disease, AR ranged from 1.6 to 2.2 and a value lower than 2.2 was thus arbitrarily considered as normal. In 15 out of the 17 patients with GH-secreting adenoma, an accumulation of the radioligand was shown. Median AR was 3.8 (range 1-6.9; in 14 AR were greater that 2.2) and ARs were directly correlated (r = 0.54; p < 0.05) with the suppressibility of plasma GH levels by octreotide (OC) acute administration. In two patients who repeated scintigraphy during chronic OC treatment, AR values were reduced. In all the 22 patients with NFA an accumulation of 111In-P at the pituitary level was observed and median AR was 3.0 (range 1.5-20; in 14 greater that 2.2). In vitro autoradiography of surgical specimens in 6 NFA patients revealed SS-R in 4 cases with high scintigraphic AR and negative results in two cases with low AR. Scintiscan was repeated during chronic OC treatment in 5 patients with high score: AR decreased in one patient, increased in three, and did not change in the other patient. No changes in tumor size were shown in any of these patients. A total of 8 patients (3 GH secreting and 5 NFA) had "normal" AR values. CONCLUSIONS: In acromegaly scintigraphy with 111In-P visualizes functioning pituitary SS-R coupled to intracellular events that control hormonal hypersecretion and tumor growth. In contrast, in spite of the positivity of 111In-P imaging in most patients with NFA, their receptors might have a defect in the coupling-transduction process, as they are not inhibited by OC treatment and no tumor shrinkage is observed.     

Effect of genetic differences in omeprazole metabolism on cure rates for Helicobacter pylori infection and peptic ulcer

We report a 65-year-old woman with thyrotropin (TSH) secreting pituitary adenoma, who was diagnosed based on the lack of inhibition of serum TSH despite an increased serum free thyroxine (T4), a low response of serum TSH to thyrotropin releasing hormone, and a pituitary tumor as revealed by magnetic resonance imaging. The pituitary adenoma was, however, inoperable due to chronic respiratory failure. The treatment with octreotide in a dose of 100 microg b.i.d. resulted in inhibition of serum TSH and free T4 to euthyroid levels and considerable shrinkage of the pituitary tumor. These effects were continued over 8 months after the start of octreotide therapy without any adverse effects. These findings add further evidence that octreotide is useful for treating inoperable TSH secreting pituitary adenoma.     

Impetigo in French Guyana. A clinical, bacteriological, toxicological and sensitivity to antibiotics study]

Acromegalic patients present an increase of osteoblastic and osteoclastic activity, showing a different effect on the axial and appendicular skeletal structures. At this regard controversial data about bone mineral density (BMD) have been published in literature. In fact an increase of BMD levels in femoral neck and Ward's triangle without any difference in lumbar spine has been described. On the other hand normal BMD levels at forearm and reduced BMD levels at lumbar spine were found. These patients seem to have a reduction of trabecular BMD similar to postmenopausal osteoporotic patients despite normal or slightly elevated cortical BMD. Recently, it has been described that cytokines, in particular tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), are implicated in the pathogenetic mechanism of postmenopausal osteoporosis. Taking into account that growth hormone (GH) can increase TNF-alpha and IL-1 secretion by mononuclear blood cells, the evaluation of possible relationship between the reduced BMD at lumbar spine and circulating cytokines levels was carried out in acromegalic patients. In addition we evaluated the effect of acute octreotide administration on serum TNF-alpha and IL-I concentrations. Eleven patients with active acromegaly and eleven healthy age-, sex-, weight- and heightmatched subjects were enrolled in this study. BMD was significantly reduced at lumbar spine (0.80 +/- 0.29 g/cm2 vs 1.02 +/- 0.11 g/cm2; p < 0.01), but not at femoral neck level or at Ward's triangle level (0.92 + 0.15 g/cm2 vs 0.97 + 0.11 g/cm2, p = NS; and 0.74 +/- 0.16 g/cm2 vs 0.85 +/- 0.1 g/cm2, p = NS) when compared to controls. Baseline serum levels of TNF-alpha and IL-1 were in the normal range both in patients and controls. After acute octreotide administration, no differences in circulating TNF-alpha and IL-1 levels were found. In conclusion, acromegalic patients present a reduced BMD at lumbar spine but not at femoral neck level and Ward's triangle. Circulating cytokines such as TNF-alpha and IL-1 are in the normal range. These data suggest that cytokines are not involved in the pathogenesis of GH-excess induced osteoporosis. The possibility that the GH excess might affect bone turnover inducing an increase of cytokines acting by a paracrine/autocrine mechanism cannot be ruled out.     

Effect of chronic treatment with octreotide nasal powder on serum levels of growth hormone, insulin-like growth factor I, insulin-like growth factor binding proteins 1 and 3 in acromegalic patients

Octreotide nasal powder is a delivery system of the somatostatin analogue developed to overcome the inconvenience of repeated subcutaneous administrations. Eight patients with clinically active acromegaly were treated for three months with octreotide nasal powder which was administered at the initial dosage of 0.125 mg tid, doubling the dosage up to 2 mg tid in order to obtain a mean GH value below 5 micrograms/l during 8 daytime hours. In 4 of these patients, treatment was prolonged till the sixth month. Blood samples were taken on days 15, 29, 43, 55, 90, 120, 150, 180 for GH, IGF-I, IGFBP-3, IGFBP-1 and insulin measurements. Before treatment, mean daytime GH and morning IGF-I serum levels were both increased but not correlated with each other. Serum IGFBP-3 levels were higher than normal and positively correlated with those of GH, IGF-I and insulin. Insulin levels were elevated and positively correlated with those of GH but not with those of IGF-I and IGFBP-1. Serum IGFBP-1 levels were in the low normal range and not correlated with any of the other parameters. Treatment with octreotide nasal powder induced in all patients a marked decrease of GH which lowered below 5 micrograms/l in 7/8 patients and IGF-I levels, which fell within the normal range in 1 patient. Serum IGFBP-3 and insulin concentrations decreased by 26% and 71%, respectively, and those of IGFBP-1 underwent an only transient increase in 5/8 patients. Opposite changes of insulin and IGFBP-1 levels, with a decrease of the former followed by an increase of the latter were noted during the 8 hours following an octreotide nasal insufflation. During chronic octreotide treatment, positive correlations were found between GH and IGF-I, GH and IGFBP-3, IGF-I and IGFBP-3, insulin and IGFBP-3 and insulin and IGF-I. An improvement of the clinical picture was registered in all patients after a few days of octreotide nasal powder administration. Treatment was well tolerated, with only mild side effects and no significant changes in the nasal mucosa, and the patients' compliance was excellent.     

Hypothalamic dysfunction in "cured" acromegaly is treatment modality dependent

The current definition of cure after treatment for acromegaly stipulates a reduction in GH levels to less than 2 ng/mL (< 5 mU/L), as such GH concentrations are believed to be associated with normalization of long term survival. We sought to further define the nature of the cure in such patients, when cure has been achieved by alternative therapeutic modalities, in the expectation that hypothalamic neuroregulatory control of GH secretion might be affected differently by radiotherapy or surgery. In particular we wished to determine the effect of therapy modality on endogenous somatostatin (SMS) tone, using the GH response to i.v. arginine as a paradigm. We studied 20 patients with cured acromegaly (mean 24-h GH concentration, < 2 ng/mL). Eight patients had been cured by surgery only (S; 4 women and 4 men; mean +/- SEM age, 52 +/- 5 yr), and 12 patients had been cured by radiotherapy (R; 4 women and 8 men; age, 52 +/- 3 yr). Sixteen healthy subjects were studied as a control group (C; 6 women and 10 men; age 53 +/- 3]. The median (range) GH during 24-h profiles was similar in each group: S, 1.3 (0.7-1.8) ng/mL; R, 0.6 (0.4-1.8) ng/mL; and C, 0.7 (0.4-3.2) ng/mL (P = 0.57). The median incremental GH responses to arginine were significantly lower in the R group compared with those in the S and C groups: S, 6.4 (2.1-16.6) ng/mL; R, 0.1 (0-1.7) ng/mL; and C, 9.2 (0-16.1) ng/mL (P = 0.0002; S vs. R, P < 0.01; S vs. C, P > 0.05; R vs. C, P < 0.001). We conclude that in acromegalic patients deemed to be cured (GH, < 2 ng/mL), the mode of therapy has considerable influence on the remaining hypothalamic-somatotroph function. In view of the putative mechanism by which arginine releases GH, we suggest that radiotherapy leads to a reduction or complete loss of endogenous SMS tone. This may have implications for the treatment of those acromegalic patients who are not cured (GH, > 2 ng/mL) and who require SMS analog therapy.     

In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide

The somatostatin analog, octreotide, is an inhibitor of growth hormone (GH) secretion that has been used to treat patients with GH-producing pituitary tumors. In this study we investigated the in vivo responsiveness to treatment with this analog in patients harboring different morphological types of GH-producing pituitary adenomas. Both GH and insulin-like growth factor I (IGF-I) plasma levels in 30 patients treated with octreotide (300 micrograms/day) for 4 months preoperatively were compared with those from 30 patients who did not receive treatment preoperatively. Tissue samples were studied using ultrastructural and immunohistochemical techniques. Amongst patients harboring densely granulated (DG) adenomas, mean GH levels were reduced to 32 +/- 9% by octreotide, to 30 +/- 7% by surgery and to 26 +/- 9% of baseline by both interventions. Surgery was equally as effective in lowering GH levels in patients with sparsely granulated (SG) adenomas as it was in those with DG adenomas; in patients with SG adenomas, GH levels were reduced by surgery alone to 37 +/- 16% and to 24 +/- 15% when performed following octreotide pretreatment. In contrast, treatment with octreotide alone in patients harbouring SG adenomas reduced GH levels to only 70 +/- 13% of baseline (p < 0.02 compared to surgery alone, or surgery and octreotide). We conclude that the GH inhibitory effects of octreotide are significantly better in patients harboring DG somatotroph adenomas compared with those harboring SG adenomas.     

A patient with acromegalic heart disease--a case report

A perioperative anesthetic management of a 69 year old woman with acromegaly whose clinical course was characterized by severe heart failure is described. The patient showed symptoms of massive cardiomegaly. Endocrine studies indicated that her pituitary tumor was active with hyperproduction of growth hormone. There was no demonstrable evidence for other known causes of heart disease. Following hormonal therapy using continuous subcutaneous infusion of somatostatin for about two months, there was improvement in daily activity and reduction in heart size. After the improvement of cardiac function, transsphenoidal hypophysectomy was performed under general anesthesia and its perioperative course was quite uneventful. We conclude that because cardiac involvement such as left ventricular dilatation in acromegaly might be reversible with proper treatment, any surgical procedure, as long as the case is elective, should be considered after hormone therapy.     

Preparation and stereoconfigurations of heterodimers of pyrimidines

Plasma levels of growth hormone (GH) and prolactin (PRL) were measured in twelve acromegalic patients after acute administration of an ergoline derivative (methergoline) which has been proposed as a specific serotoninergic blocking agent. The administration of methergoline (4 mg p.o.) was followed by a significant decrease in plasma GH and PRL concentrations. The administration to the same subjects of CB 154 (2.5 mg p.o.), a known stimulator of dopaminergic receptors, led to results almost superimposable to those obtained with methergoline although the suppressive effect of CB 154 on GH and PRL levels was more sustained. Also on the ground of results obtained in these patients with the use of cyproheptadine, phentolamine, or pimozide, we have concluded that methergoline inhibition of GH and PRL release is, in acromegalic patients, most probably due to a dopaminergic mechanism of action.