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PubMed2002

Effect of a six-month treatment with lanreotide on cardiovascular risk factors and arterial intima-media thickness in patients with acromegaly.

OBJECTIVE: To evaluate the effect of a 6-month treatment with slow-release lanreotide (LAN) on cardiovascular risk and atherosclerosis in 24 normotensive patients with active acromegaly (GH=67.4 +/- 12.6 mU/l, IGF--I=866.0 +/- 55.8 microg/l) and 24 healthy subjects sex-, age- and body mass index-matched with the patients (as controls). DESIGN: Open, prospective, multicenter. METHODS: The following were measured before and after 6 months of LAN treatment (dose 60-90 mg/month): fasting GH, IGF-I, LDL, HDL and total cholesterol, triglyceride, glucose, glycosylated hemoglobin, insulin and fibrinogen levels, intima-media thickness (IMT) and blood systolic and diastolic peak velocity (SPV and DPV respectively) in both common carotids. RESULTS: At study entry, insulin, total and LDL cholesterol, triglyceride and fibrinogen levels were higher while HDL cholesterol levels were lower in patients than in controls. At the right (0.88 +/- 0.04 vs 0.77 +/- 0.03 mm, P=0.05) and left (0.93 +/- 0.03 vs 0.78 +/- 0.02 mm, P=0.01) common carotid IMT was significantly higher in patients than in controls; 12 patients and two controls showed an IMT of > or = 1 mm (chi(2)=8.2, P=0.004). After 6 months of LAN treatment, disease control was achieved in 15 patients (62.5%). Insulin, triglyceride and fibrinogen levels were significantly decreased, and a trend toward a decrease of IMT in the right (from 0.90 +/- 0.05 to 0.78 +/- 0.04 mm, P=0.06) and left (from 0.95 +/- 0.04 to 0.84 +/- 0.04 mm, P=0.06) common carotid arteries was observed only in patients with disease control, while SPV and DPV did not change. CONCLUSIONS: LAN treatment for 6 months significantly lowered GH, IGF-I, insulin and fibrinogen levels and reduced IMT of both common carotid arteries in normotensive patients with acromegaly.

Acromegaly↗
PubMed2003

Twelve months of treatment with octreotide-LAR reduces joint thickness in acromegaly.

OBJECTIVE: To evaluate the role of age, gender, duration and control of acromegaly on the reversibility of arthropathy. PATIENTS AND DESIGN: 30 de novo patients with active acromegaly, 30 cured patients and 30 healthy subjects were studied in a tranverse and an open longitudinal study design. METHODS: Shoulder, wrist and knee thickening was measured by ultrasonography at study entry in all 90 subjects and after 12 Months of treatment with octreotide-LAR (OCT-LAR) at a dose of 10-40 mg every 28 days in the 30 de novo patients. RESULTS: Thickness at all joint sites was greater in the active than in the cured patients and controls (P<0.001), and was greater in the cured patients than in the controls (P<0.001). There was no gender difference, but joint thickness was less in the patients with disease duration >10 Years. Age significantly correlated with wrist (r=-0.55; P<0.001), right knee (r=-0.45; P=0.01), and left knee thickness (r=-0.42; P=0.02) in patients with active disease, and with wrist thickness (r=0.88; P<0.0001) in controls. Twelve Months of OCT-LAR treatment led to disease control in 18 patients (60%). There was a decrease in the thickness of the shoulder (15.1+/-3.2%), wrist (20.5+/-3.1%), right knee (22.2+/-3.4%) and left knee (18.2+/-2.8%) in all patients but the reduction in joint thickness at all sites was greater in the patients with controlled disease after OCT-LAR treatment than in the uncontrolled patients (P<0.01). Shoulder and right knee thickening normalized in respectively 11 (61.1%) and 16 (88.9%) well-controlled patients. CONCLUSIONS: Growth hormone and insulin-like growth factor-I (IGF-I) suppression by 12 Months' OCT-LAR treatment is accompanied by a significant decrease in the thickness of both weight-bearing and non-weight-bearing joints (mainly in patients whose disease is controlled) regardless of disease duration. These findings suggest that tIssue hypertrophy in the context of the acromegalic arthropathy can be improved by suppressing IGF-I levels.

Acromegaly↗
PubMed2003

Pegvisomant: an advance in clinical efficacy in acromegaly.

Acromegaly is a chronic disorder invariably caused by a growth hormone (GH)-secreting pituitary tumour and is characterised by disabling symptoms (sweating, arthralgia, headache, paraesthesiae, fatigue), significant comorbidities (diabetes mellitus, hypertension, sleep apnoea), and premature mortality. Symptomatic control can be achieved by lowering insulin-like growth factor-I (IGF-I) concentrations to within the age-adjusted normal range, and survival can be improved to match that of the general population. However, even with optimal surgery and current medical therapies (dopamine agonists, somatostatin analogues), 30% to 50% of patients do not achieve target concentrations of IGF-I and GH. Pegvisomant is a new GH-receptor antagonist that blocks GH activity by inhibiting functional dimerisation of GH-receptors. Given as subcutaneous injections at dosages of 10 mg, 15 mg, or 20 mg/day for 3 Months, pegvisomant normalised serum IGF-I concentrations in, respectively, 54%, 81%, and 89% of acromegalic patients. Moreover, long-term pegvisomant therapy normalised IGF-I concentrations in 97% of patients treated for 12 Months or longer, with no evidence of tachyphylaxis. Pegvisomant is the most effective medical therapy, reported to date, in terms of normalisation of circulating IGF-I concentrations. In addition, pegvisomant appears to be safe and well tolerated. Although additional long-term studies are required to further assess safety, the introduction of this innovative treatment should allow for optimal disease control in patients with acromegaly.

Acromegaly↗
PubMed2004

Ghrelin administration affects circulating pituitary and gastro-entero-pancreatic hormones in acromegaly.

OBJECTIVE: Ghrelin, a gut-brain peptide involved in the control of energy homeostasis, affects antero-pituitary and gastro-entero-pancreatic (GEP) hormone secretion in healthy subjects. We aimed to verify whether such hormonal responses are retained in acromegaly, a disease characterized by high GH, subnormal ghrelin and abnormal GEP hormone levels. DESIGN AND METHODS: The effect of ghrelin (3.3 microg/kg given after overnight fasting as an i.v. bolus) on GH, prolactin (PRL), adrenocorticotropin (ACTH), cortisol, insulin, glucose, total somatostatin (SS) and pancreatic polypeptide (PP) circulating levels were evaluated in seven non-diabetic patients with newly diagnosed acromegaly and in nine healthy controls. RESULTS: Ghrelin elicited a prompt, marked increase of serum GH and PRL levels in all normal (from 1.6+/-0.6 to 52.9+/-7.8 and from 9.7+/-0.8 to 24.2+/-4.8 microg/l (means+/-S.E.M.), respectively) and acromegalic subjects (from 11.2+/-4.9 to 91.6+/-21.0 and from 42.9+/-26.1 to 113.8+/-79.0 microg/l, respectively). Both plasma ACTH and serum cortisol levels rose significantly in the controls, whereas the cortisol response was blunted in the acromegalic patients. Glucose levels rose earlier and insulin levels fell later in all subjects, with a significantly greater net insulin decrease in acromegalic than in healthy subjects (-80+/-21 vs -17+/-4 pmol/l, P<0.01). A prompt PP rise and a biphasic SS response occurred in all controls, whereas in the acromegalic group the PP response (from 26.1+/-5.0 to 92.2+/-39.0 pmol/l) and the SS response (from 11.9+/-3.0 to 19.7+/-4.0 ng/l) were quite variable. CONCLUSIONS: Ghrelin affects both pituitary and GEP hormones in acromegalic patients as in normal subjects. These findings suggest that ghrelin actions on the energy balance are mediated by complex interactive endocrine loops that involve also the gut and pancreas.

Acromegaly↗
PubMed2004

Evaluation of cardiac structure by echoreflectivity analysis in acromegaly: effects of treatment.

OBJECTIVES: Cardiac echoreflectivity is a noninvasive tool for evaluating cardiac fibrosis. The present paper aimed to study the modifications of cardiac echoreflectivity in a group of acromegalic patients before and after therapy, and to assess possible correlations with serum levels of procollagen III (PIIINP), a peripheral index of collagen synthesis. DESIGN AND METHODS: Cardiac echoreflectivity (as assessed by analyzing 2-D echocardiograms digitized off-line onto a personal computer) and PIIINP levels were evaluated in 16 acromegalic patients of new diagnosis not affected by arterial hypertension (10 males, six females, age+/-s.d.: 38+/-10 years), and in a group of 16 sex- and age-matched healthy subjects. All the patients were re-evaluated after surgical and/or medical therapy for acromegaly. The echo patterns were analyzed by software that supplies the derived collagen volume fraction (dCVF), an index of fibrosis. RESULTS: At baseline, acromegalic patients showed significantly higher dCVF values and PIIINP levels than healthy controls (3.1+/-0.5% vs 1.6+/-0.3%, P<0.01 and 8.7+/-2.2 vs 3.1+/-1.1 ng/ml, P<0.05, respectively, by unpaired Student's t-test). After therapy, dCVF and PIIINP levels normalized in the six controlled patients (that is, GH of <2.5 microg/l and IGF-I within normal range) (dCVF from 2.8+/-0.4% to 1.4+/-0.2%, P<0.001; PIIINP from 8+/-2.7 to 3.3+/-1.9 ng/ml, P<0.05), while no significant changes were found in noncontrolled patients (dCVF from 3.3+/-0.6% to 2.9+/-1.2% and PIIINP from 9.1+/-1.9 to 7.9+/-3.5 ng/ml, P=NS). A positive correlation between dCVF and PIIINP (r=0.75, P<0.001) and between IGF-I and both dCVF and PIIINP (r=0.65 and 0.61 respectively, P<0.05) was found in acromegalic patients. CONCLUSIONS: Cardiac echoreflectivity, which may be a reflection of heart collagen content, is increased in patients with active acromegaly and correlates with PIIINP concentrations. After cure or adequate control of the disease, both parameters revert to normal. Echoreflectivity analysis could be a useful adjuvant parameter in the assessment of the activity of acromegalic disease.

Acromegaly↗
PubMed2005

Limited predictive value of an acute test with subcutaneous octreotide for long-term IGF-I normalization with Sandostatin LAR in acromegaly.

OBJECTIVES: To study whether the growth hormone (GH) response after the subcutaneous administration 50 microg of octreotide (acute octreotide test) has any predictive value for long-term IGF-I normalization with Sandostatin LAR. DESIGN: Twenty four therapy-naive patients with active acromegaly were studied. RESULTS: > 75% GH decrease in the acute octreotide test predicted long-term IGF-I normalization with Sandostatin LAR in 8/11 (73%) of patients. 3/13 (23%) patients with < 75% GH decrease in the acute octreotide test were long-term biochemically controlled with Sandostatin LAR. Using the > 75% GH reduction criterion, the sensitivity and specificity of this test for predicting long-term normalization of serum IGF-I with Sandostatin LAR treatment were 73% and 77%, respectively (positive and negative predictive values: 73% and 77%, respectively). 6/8 (75%) patients with GH suppression to levels < 1.1 microg/l and 9/16 (56%) patients with GH suppression to levels < 2 microg/l in the acute octreotide test showed normalization of serum IGF-I with long-term Sandostatin LAR treatment. The sensitivity and specificity of GH suppression < 1.1 microg/l for predicting of the long-term normalization of serum IGF-I with Sandostatin LAR therapy were 55% and 85%, respectively (positive and negative predictive values: 75% and 69%, respectively). The sensitivity and specificity of GH suppression < 2 microg/l for predicting of the long-term normalization of serum IGF-I with Sandostatin LAR therapy were 82% and 46%, respectively (positive and negative predictive values: 56% and 75%, respectively). CONCLUSION: The acute octreotide is not recommended for clinical decision making with regard to long-term treatment using the long-acting somatostatin analog Sandostatin LAR in acromegaly.

Acromegaly↗
PubMed2005

Consensus statement: medical management of acromegaly.

In November 2003, the Pituitary Society and the European Neuroendocrine Association sponsored a consensus workshop in Seville to address challenging issues in the medical management of acromegaly. Participants comprised 70 endocrinologists and neurosurgeons with international expertise in managing patients with acromegaly. All participants participated in the workshop proceedings, and the final document written by the scientific committee reflects the consensus opinion of the interactive deliberations. The meeting was supported by an unrestricted educational grant from Ipsen. No pharmaceutical representatives participated in the program planning or in the scientific deliberations.

Acromegaly↗
PubMed2006

Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience and a report of a patient with histologically proven chronic mild active hepatitis.

OBJECTIVE: The new GH receptor antagonist pegvisomant is the most effective medical therapy to normalize IGF-I levels in patients with acromegaly. Based on currently available data pegvisomant is well tolerated; however, treatment-induced elevation of transaminases has been reported and led to the necessity for drug discontinuation in some patients in the pivotal studies. The aim of this study was to evaluate and characterize the prevalence of elevated transaminases and to describe in detail the findings in a single case who required drug discontinuation because of elevation of transaminases which emerged during treatment and who underwent liver biopsy. DESIGN AND METHODS: Retrospective safety analyses were carried out on 142 patients with acromegaly receiving pegvisomant treatment in Germany between March 2003 and the end of 2004. Of these patients, 123 were documented in a post-marketing surveillance study, one case of elevated transaminases was reported spontaneously and the other patients were treated in a clinical study. RESULTS: Mean treatment duration with pegvisomant in the ongoing observational study at the end of 2004 was 28.3 +/- 19.9 (S.D.) weeks. Twelve out of the 142 patients had elevated transaminases above three times the upper limit of normal, likely caused by biliary obstruction in five of the patients. All patients but one affected by elevated transaminases had been previously treated with somatostatin analogues. In six out of 142 (4%) of patients, pegvisomant was permanently withdrawn because of elevated transaminases. The same number of patients showed a transient increase of transaminases with either spontaneous remission without dose modification (n = 4) or no re-increase of transaminases after temporary discontinuation and re-exposure (n = 2). The liver biopsy of one patient who was permanently withdrawn showed a chronic mild hepatitis with a mixed portal inflammation including eosinophilic granulocytes. CONCLUSIONS: Liver function tests should be regularly followed on pegvisomant treatment. Biliary complications, which may arise from restitution of normal gall bladder motility after cessation of somatostatin analogue treatment, need to be differentiated from pegvisomant-induced abnormalities. The histological pattern of the liver biopsy performed in one of the patients showed a mild chronic active hepatitis. The lack of dose dependency and rather low frequency of elevated transaminases in those cases where a biliary disorder was excluded render this reaction an idiosyncratic drug toxicity.

Acromegaly↗
PubMed2006

Changing paradigms in the surgical and medical management of acromegaly.

Acromegaly is a serious, but rare, form of pituitary tumor. This review will discuss recent progress in surgical and medical care, highlight data on choosing the order for primary and secondary therapy and preview emerging drugs. Several controversial areas will be discussed, including the role of preselecting subjects for drug responsiveness, whether or not a brief course of medical therapy before surgery improves outcomes, and trials of combination drug therapy. It is hoped that earlier diagnosis, referral of patients to dedicated pituitary surgeons or neuroendocrinology teams, development of more effective and affordable drugs, and further advances in surgery and radiotherapy will continue to improve the morbidity and mortality from acromegaly.

Acromegaly↗
PubMed2006

Etiologic aspects and management of acromegaly.

Acromegaly is a systemic disease with various etiologies. It can occur as a sporadic or, more rarely, as a familial disease. Numerous complications such as endocrine, cardiovascular, respiratory, metabolic, osteoarticular and neoplastic disturbances occur and must be taken into account when establishing a therapeutic strategy. For this reason, the decision as to a treatment modality of acromegaly must be followed by a thorough evaluation of the patient and once the diagnosis of complications is settled, adequate treatment should be instituted. Follow up of the patients requires periodical re-assessment of complications status.

Acromegaly↗
PubMed2006

[Outcome of surgical treatment for acromegaly performed by a single neurosurgeon and cumulative meta-analysis].

The aim of this retrospective study was to evaluate the results of transsphenoidal surgery in a group of patients with acromegaly who were operated by the same neurosurgeon. Our results were compared to those from a cumulative meta-analysis of 10 series (1,632 patients) published between 1992 and 2005. We followed 28 patients (17M/11F; 44.1 +/- 12.7 yr; 27 with macroadenomas; 86% being invasive) during 21.4 +/- 17.6 months after treatment. Patients were classified according to disease activity as follows: 1) controlled (CD): basal or mean GH < 2.5 ng/ml or nadir GH (OGTT) < 1 ng/ml and normal IGF-1; 2) uncontrolled (UCD): basal or mean GH > 2.5 ng/ml or nadir GH > 1 ng/ml and elevated IGF-1; 3) inadequately controlled (ICD): normal GH and elevated IGF-1 or elevated GH and normal IGF-1. After surgery, GH levels decreased from 61.7 +/- 101.1 ng/ml to 7.2 +/- 13.7 ng/ml (p< 0.001) and mean IGF-1 from 673.1 +/- 257.7 ng/ml to 471.2 +/- 285 ng/ml (p= 0.01). Biochemical remission rate was 57% [10 (35.5%) patients with CD and 6 (21.5%) with ICD], similar to the mean remission rate observed in the meta-analysis of surgical outcome of macroadenomas. Seven of 28 patients were submitted to surgical re-intervention (4 had been previously operated elsewhere and 3 by our neurosurgeon), with CD observed in 5 (71.5%) on follow-up. Cavernous sinuses invasion was more prevalent in UCD and ICD, whereas infundibular stalk deviation occurred only in patients with UCD. Remission rate was significantly higher in series where all surgical procedures were performed by the same surgeon (66% vs. 49%; p< 0.05). Thus, the surgeon's experience significantly improves the surgical outcome in acromegaly, especially in patients harboring large and invasive tumors, and re-intervention performed by an experienced surgeon should be considered in the algorithms for clinical management of this disease.

Acromegaly↗
PubMed2001

Risk factors for glucose intolerance in active acromegaly.

In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33%) had diabetes mellitus and 2 (5%; 1-16%) impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test). A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection) was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

Acromegaly↗
PubMed1984

Plasma growth hormone responses to sulpiride in patients with acromegaly.

The role of endogenous dopamine (DA) on plasma GH secretion was studied in 12 patients with active acromegaly. After intramuscular administration of 100 mg sulpiride, 3 out of 12 patients showed distinct increases in their plasma GH (cases 1-3: sulpiride-responders). The GH increases far exceeded the ranges of physiological fluctuation in two cases studied (case 1 & 3). After domperidone administration, case 3 showed a quite similar GH increase as after sulpiride. Plasma GH responses to TRH and sulpiride were still observed in case 2 even after the basal GH levels were normalized by the transsphenoidal hypophysectomy. The three sulpiride-responders showed so-called paradoxical GH decreases following the administration of L-dopa (500 mg, p.o.) or DA (5 micrograms/kg/min over 90 min, i.v.). However, the basal plasma PRL levels and the responses to sulpiride in these 3 cases were not homogeneous. These results indicate that endogenous DA has a tonic inhibitory effect on GH secretion in some cases of acromegaly, and that tumorous somatotrophs rather than elevated GH levels are the critical factor for such inhibition. Further, the sensitivities of somatotrophs and lactotrophs to DA appeared to be heterogeneous in acromegalic patients.

Acromegaly↗
PubMed1984

Rapid radioimmunoassay of plasma GH and its application to the judgement of surgical results in patients with acromegaly.

To improve the surgical results in patients with acromegaly, rapid radioimmunoassay (RIA) of plasma GH was developed and this method was applied for quick judgement of whether transsphenoidal hypophysectomy was performed successfully or not. The best reaction temperature and the shortest incubation time were proved to be 40 degrees C and 16 min, respectively. The GH values obtained by this method and the usual RIA method were correlated well (r = 0.9, p less than 0.001). Using the rapid RIA it became possible within 35 min just after the termination of the hypophysectomy to report the data to the neurosurgeons. This RIA method was applied for 5 patients with acromegaly undergoing transsphenoidal hypophysectomy. In two cases plasma GH decreased markedly (62.0-71.4% decreases from preoperative value) at the termination of the hypophysectomy, and later fell to normal ranges. The other three cases showed only slight decreases (7.7-17.3%), and the operation was judged as unsuccessful. Therefore, two of these cases were followed by further removal of residual tumors which resulted in steep declines of GH. In the remaining one the further operation was not performed, because surgical removal of the adenoma was believed by the surgeons to be complete. In conclusion, rapid RIA of plasma GH is possible within 16 min and this method is of significant value to improve the surgical results of acromegalic patients.

Acromegaly↗
PubMed1988

The spectrum of GH responses to GHRH and somatostatin in patients with acromegaly.

Plasma GH responses to GHRH and somatostatin were examined in 43 patients with active acromegaly. Thirty-two of these patients showed GH increases 50% above the basal values in response to at least 1 of 3 stimuli (TRH, LHRH, arginine) (categorized as group I). The remaining 11 patients showed no response to any of the stimuli (categorized as group II). Following somatostatin infusion, group I (n = 31) showed significantly greater GH suppression than group II (n = 11) from 30 to 90 min (p less than 0.05-0.01). In addition, plasma GH responses to GHRH at 15 and 30 min was also greater in group I (n = 12) than in group II (n = 5) (p less than 0.05 & 0.01). There was a positive correlation between the log value of the peak GH after GHRH and the maximal % decrement after somatostatin (r = 0.64, p less than 0.02). However there were no differences in the responses of normal thyrotrophs (TSH) to TRH between the two groups. These results indicate that there are two types of acromegaly, i.e., one is more responsive and another is less responsive to either non-specific (TRH & LHRH) or specific GH stimulations (GHRH & somatostatin).

Acromegaly↗
PubMed2003

Evolving criteria for post-operative biochemical remission of acromegaly: can we achieve a definitive cure? An audit of surgical results on a large series and a review of the literature.

Criteria to define the biochemical remission of acromegaly following surgery have changed over the years, and the current use of stringent criteria needs a critical re-evaluation of the surgical results. On the other hand, few data are currently available concerning the possible impact of pituitary surgery on the quality of life of operated acromegalic patients. In this prospective study, we wished to evaluate the initial outcome and long-term recurrence rate in a large series of acromegalic patients operated on by transsphenoidal surgery (TSS), to carefully analyse predictive factors for surgical outcome and to point out possible additional effects of surgery in these patients. Ninety-two out of 98 operated patients could be considered for follow-up. Biochemical remission was strictly defined as plasma GH levels <1 ng/ml during an oral glucose tolerance test (OGTT) and normalisation of age-related IGF-I levels. Hormonal assessment, including an OGTT, was performed 6 months following surgery and then annually to evaluate pituitary function. Fifty-five per cent of patients achieved a biochemical remission of acromegaly. The remission rate at 6 months was 80% for patients with microadenoma and 50% for macroadenoma. Univariate analysis showed that a large extrasellar extension, preoperative high GH levels and dural invasion were correlated with a poor outcome of surgery while, according to multivariate analysis, only invasion of cavernous sinus and preoperative GH levels > 10 ng/ml were independent negative predictors. Mortality was 0% and the overall complication rate was about 10%. Pituitary function worsened in five patients but improved in 16 out of 30 patients with preoperative pituitary defects. No recurrence was observed during a median follow-up of about 8 years. We conclude that TSS is able to achieve a biochemical remission in more than half of acromegalic patients, and that the current criteria for remission seem to indicate a cure in most cases.

Acromegaly↗
PubMed1997

Octreotide long-acting release (LAR). A review of its pharmacological properties and therapeutic use in the management of acromegaly.

Octreotide is a somatostatin analogue: a long-acting release (LAR) formulation of octreotide is designed for once-monthly intramuscular administration. As with native somatostatin, octreotide LAR exerts potent inhibitory effects on the secretion of growth hormone and on various peptides of the gastroenteropancreatic endocrine system. When patients with acromegaly who show a positive response to treatment with subcutaneous octreotide 300 to 600 micrograms/day are switched to octreotide LAR 20 or 30 mg, the resulting decrease in growth hormone levels is stable and sustained. Reductions in growth hormone levels to < 5 micrograms/L for about 4 weeks are seen in 86 to 100% of patients, to < 2 to 2.5 micrograms/L in 39 to 75% and to < 1 microgram/L in 24 to 40%. Levels of insulin-like growth factor-1 (IGF-1) decrease in parallel and are often normalised with repeated drug treatment. There is no evidence of tachyphylaxis with long term therapy (up to 34 months). Treatment with octreotide LAR improves facial appearance and soft tissue thickening, and eliminates or reduces the incidence of symptoms such as headache, fatigue, arthralgia and excessive perspiration. Tumour shrinkage has been noted in some, but not all, patients receiving octreotide LAR, although this has not been widely evaluated in clinical studies. Overall, octreotide LAR is well tolerated, and the mild to moderate gastrointestinal events experienced by up to 50% of patients are of short duration and often subside with continued drug administration. The incidence of gallbladder abnormalities (sediment, sludge, microlithiasis and gallstones) increases in patients receiving long term therapy with subcutaneous octreotide, although most patients remain asymptomatic. The incidence of gallbladder abnormalities in patients receiving octreotide LAR compares favourably with that during subcutaneous administration. Glycaemic control is not usually altered during octreotide LAR treatment. In summary, octreotide continues to be the principal pharmacological option for most patients with acromegaly. Octreotide LAR offers the convenience of once-monthly administration compared with daily subcutaneous drug administration. In addition, the good efficacy and tolerability profile of octreotide LAR should enhance patient compliance and acceptability of octreotide therapy and contribute to an improvement in patient quality of life.

Acromegaly↗
PubMed2005

Pharmacologic therapies for acromegaly: a review of their effects on glucose metabolism and insulin resistance.

Acromegaly is associated with insulin resistance and an increased incidence of cardiovascular disease. However, it remains unclear to what extent the effects of growth hormone (GH) excess on cardiovascular morbidity and mortality are mediated through insulin resistance versus through other direct or indirect effects of GH. Adequate control of GH excess by surgery or pharmacologic interventions is associated with decreased insulin resistance, reflected in decreased plasma insulin levels and fasting glucose levels or improved glucose tolerance. Despite divergent effects of both somatostatin and somatostatin analogs on GH, insulin and glucagon secretion, and glucose absorption, treatment with the somatostatin analogs octreotide and lanreotide has only limited effects on glucose metabolism. However, glucose sensitivity has only been formally examined using a hyperinsulinemic euglycemic clamp in a minority of these studies. Treatment with the GH-receptor antagonist pegvisomant ameliorates insulin sensitivity, reflected in decreased fasting plasma insulin levels and fasting glucose levels. Nonetheless, the effect of pegvisomant on glucose sensitivity has not been formally tested by hyperinsulinemic clamp conditions. In acromegaly, preliminary observations on new octreotide analogs with greater specificity for somatostatin-receptor subtypes indicate that these compounds achieve better control of GH hypersecretion than octreotide, but may also negatively influence insulin release. Assessment of insulin secretion and glucose levels in acromegalic patients during administration of these compounds is thus mandatory.

Acromegaly↗