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PubMed1979

Selective total removal of a growth-hormone-secreting adenoma: evidence that acromegaly is a primary pituitary disease.

Acromegaly is caused by hypersecretion of growth hormone by the pituitary. There is some debate as to whether the primary etiology of the disease is abnormal hypothalamic stimulation of the pituitary or a primary pituitary tumor. This paper presents a case of acromegaly in which growth hormone dynamics in response to stimulation and suppression tests were abnormal. After transsphenoidal adenomectomy of a small tumor, growth hormone levels returned to normal and suppression and stimulation test results reverted to normal within 1 wk postoperatively and remained normal for 2 yr. The findings suggest that the acromegaly in this case was due to a primary pituitary dysfunction. Microsurgical removal of growth-hormone-secreting tumors provides a unique opportunity to study the etiology of acromegaly.

Acromegaly↗
PubMed1993

Arginine blocks the inhibitory effect of hydrocortisone on circulating growth hormone levels in patients with acromegaly.

In patients with acromegaly, circulating growth hormone (GH) levels and GH responses to GH-releasing hormone (GHRH) are decreased by long-term administration of pharmacological doses of glucocorticoids. The aim of our study was to investigate the acute effects of intravenous (i.v.) infusion of hydrocortisone combined either with saline or arginine infusion on circulating GH levels in acromegaly. We studied five adult patients with acromegaly, two men and three women aged 54.6 +/- 4 years having a body mass index of 25.9 +/- 1.2 kg/m2. On two randomized occasions, patients underwent a bolus i.v. injection of 100 mg hydrocortisone succinate at time 0 followed by a 120-minute i.v. infusion of 250 mg hydrocortisone in 250 mL saline, combined with a 90-minute (from -15 to 75 minutes) i.v. infusion of (1) 60 g arginine hydrochloride in 200 mL saline, or (2) 200 mL saline. In all of the acromegalic patients during the infusion of hydrocortisone alone, serum GH levels clearly decreased (nadir range, 26.4% to 68.1%) with respect to GH levels before hydrocortisone administration (mean of time -15 and 0, basal level), with a nadir between 90 and 180 minutes after the beginning of the infusion. After arginine pretreatment, GH levels were significantly enhanced compared with levels attained with hydrocortisone saline, and they were also significantly increased (peak, 167.5% +/- 27.7%) with respect to basal levels. Our data show that arginine blocks the inhibitory effect of acute and sustained hypercortisolism on circulating GH levels in acromegaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1994

Lack of involvement of the cholinergic mechanism in vasoactive intestinal peptide- and peptide-histidine methionine-induced growth hormone (GH) responses in acromegaly: comparison with the GH responses to thyrotropin-releasing hormone and GH-releasing hormone.

We examined whether the cholinergic mechanism is involved in the paradoxical GH responses to vasoactive intestinal peptide (VIP) and peptide histidine methionine (PHM) in acromegaly. 28 patients with active acromegaly underwent i.v. bolus injections of thyrotropin-releasing hormone (TRH, 500 micrograms), GH-releasing hormone (GHRH, 100 micrograms), VIP (100 micrograms), and PHM (100 micrograms) with or without a prior atropine treatment (1 mg, i.m., 30 min before). Blood samples were collected before and at intervals up to 120 min after the injection, and plasma GH levels were measured. In response to TRH, GHRH, VIP and PHM, 23 (82%), 24 (86%), 13 (46%) and 7 (25%) patients, respectively, responded with a significant GH increase (> 50% and 6 micrograms/l above the basal level). The effect of atropine pretreatment was examined in only these responders to the respective peptides. When the GH responses were estimated by the area under the response curve, the atropine pretreatment was able to significantly suppress the GH response to GHRH, but not to TRH, VIP, or PHM. Although the lack of cholinergic involvement in the TRH-induced GH release in acromegaly is confirmatory to previous reports, the same results with the VIP- and PHM-induced GH release are novel. The present study may suggest that in acromegaly the physiological GH response is mediated by the cholinergic mechanism, but the paradoxical ones are not.

Acetylcholine↗
PubMed2004

High levels of 150-kDa insulin-like growth factor binding protein three ternary complex in patients with acromegaly and the effect of pegvisomant-induced serum IGF-I normalization.

OBJECTIVE: To assess the effect of pegvisomant-induced serum insulin-like growth factor 1 (IGF-1) normalization on IGF binding proteins 1, 2, 3 (IGFBP-1, IGFBP-2 and IGFBP-3), total, non-bound (45 kDa) and 150-kDa ternary complex-associated IGFBP-3, and in vivo IGFBP-3 proteolysis in patients with active acromegaly. DESIGN: The above parameters were measured in 16 patients (median age 57 (range 27-78)) with active acromegaly (serum IGF-I at least 30% above the upper limit of an age-related reference range after washout) in a paired manner on samples obtained after washout and the first occurrence of serum IGF-I normalization during pegvisomant therapy (median dose 15 mg/day (10-40 mg)). RESULTS: Total IGFBP-3 and 150-kDa ternary complex-associated IGFBP-3 were significantly elevated in patients at baseline compared to controls ((mean+/-SEM) 4345+/-194 vs. 3456+/-159 microg/L, P<0.01 and 3908+/-160 va. 3042+/-149 microg/L, P<0.01, respectively), but no significant difference in 45-kDa IGFBP-3 or in vivo IGFBP-3 proteolysis was observed. Serum IGF-I normalization (699+/-76 to 242+/-28 microg/L, P<0.0001) was associated with a fall in total IGFBP-3 (4345+/-194 to 3283+/-160 microg/L, P<0.001) due to a reduction in 150-kDa ternary complex-associated IGFBP-3 (3908+/-160 to 3008+/-140 microg/L, P<0.0001). 45 kDa IGFBP-3 and in vivo IGFBP-3 proteolysis were unaffected by GH receptor blockade (326+/-13 to 330+/-18 microg/L, P=0.86; 30+/-3.5 to 30+/-3.9%, P=0.75, respectively). CONCLUSIONS: GH receptor blockade in patients with acromegaly lowers IGF-I and 150-kDa IGFBP-3 ternary complex formation. 50 kDa ternary complex formation (not in vivo IGFBP-3 proteolysis) is GH dependent and measurement of 150-kDa ternary complex-associated IGFBP-3 may provide useful information regarding treatment efficacy in patients with acromegaly.

Acromegaly↗
PubMed2004

The place of pegvisomant in the acromegaly treatment algorithm.

The disfiguring disease acromegaly results from hypersecretion of growth hormone (GH). The main goals of treatment for acromegaly include normalisation of biochemical markers of disease activity to restore normal life expectancy, amelioration of signs and symptoms of the disease, removal of the pituitary tumour without damaging the optic chiasm and other peripituitary structures, and preservation of pituitary function. Conventional options for treatment of acromegaly include surgery, radiotherapy (RT), and medical therapy with either dopamine agonists or somatostatin (SMS) analogues. The advent of the genetically engineered growth hormone analogue pegvisomant is unlikely to alter significantly the place of surgery and RT in the treatment algorithm for acromegaly biochemical control as determined based on serum IGF-I concentrations is achievable with pegvisomant in virtually all patients, and it will clearly become the drug of choice in patients partially or completely unresponsive to SMS analogues. Preliminary studies suggest improved insulin sensitivity for a given IGF-I with pegvisomant compared with SMS analogues; if these results are confirmed by results of future studies, such a metabolic advantage may encourage the use of pegvisomant.

Acromegaly↗
PubMed2004

GSPalpha mutations in Mexican patients with acromegaly: potential impact on long term prognosis.

OBJECTIVE: The frequency of activating mutations of the GSPalpha gene as the etiology of GH-secreting pituitary adenomas has been the subject of important ethnogenetic variability. Whereas up to 40% of Caucasian patients with acromegaly have tumors which harbor these somatic mutations, their prevalence among Asian populations is much lower. The correlation between the presence of these mutations and the clinical and biological behavior of these tumors has also been a matter of controversy. In the present study, we investigated the prevalence of GSPalpha mutations in GH-secreting tumors obtained from a genetically homogenous population of Mexican patients with acromegaly. We also sought to establish whether or not the presence of these mutations correlates in any way with the clinical or biochemical characteristics of the disease. STUDY DESIGN AND METHODS: Fifty eight GH-secreting pituitary adenomas were examined for the presence of point mutations in either codon 201 or 227 of the GSPalpha gene, using PCR and direct sequencing of DNA extracted from either fresh or paraffin-embedded tissues. Patients were prospectively followed clinically and biochemically for up to nine years after pituitary surgery. RESULTS: Heterozygous point mutations in exon 8 (codon 201) were found in 11 patients (19%), and no molecular alterations were evident in exon 9. The frequency and severity of the different clinical features of acromegaly did not differ between patients with and without GSPalpha mutations. Patients with and without mutations had pre-operative GH and IGF-I elevations of similar magnitude, and although microadenomas appeared to be more frequent among patients with GSPalpha mutations, this did not reach statistical significance. Upon short-term follow-up, biochemical cure (normal age- and gender-adjusted IGF-I and post-glucose GH below 1 ng/mL) was similarly achieved in both groups. After 3-9 years of post-operative follow up however, a significantly greater proportion of patients with the mutation achieved a "safe" basal GH value (100% vs 33%, p=0.001) as well a lower nadir post-glucose GH (0.53+/-0.5 vs 2.9+/-6.2 ng/mL, p=0.04) although the rate of IGF-1 normalization did not differ between the 2 groups. CONCLUSIONS: Our results show that the prevalence of GSPalpha mutations in Mexican patients with acromegaly is intermediate between that found in Asian and Caucasian populations. In this well-defined genetic population the presence of codon 201 mutations appeared to be associated with a greater probability of achieving a "safe" GH value upon long-term follow-up.

Acromegaly↗
PubMed2006

Uncontrolled acromegaly is associated with progressive mitral valvular regurgitation.

INTRODUCTION: Recent cross-sectional studies have documented an association between acromegaly and regurgitant valvular heart disease. The aim of this study was to evaluate the change in prevalence of valvular heart disease in relation to the clinical activity, because the natural history of valvular changes in acromegaly is unknown. PATIENTS AND METHODS: Valvular regurgitation was assessed in 37 acromegalic patients (18 patients with active disease, and 19 with controlled disease) by conventional two-dimensional and Doppler echocardiography before and after an interval of 1.9 years (range 1.5-3.0 years). RESULTS: At baseline, valvular regurgitation (mitral and aortic sites combined) was present in 46% of the patients and increased to 67% at follow-up (P=0.008). Mitral regurgitation increased significantly from 32% to 60% (P=0.002), but no change was noted for the aortic valve (27% vs. 31%, NS). In patients with active disease, valvular regurgitation increased significantly from 56% at baseline to 88% at follow-up (P=0.031) due to a significant increase of mitral regurgitation from 39% to 78% at follow-up (P=0.016). In contrast, no increase in valvular regurgitation was found in patients with controlled disease. CONCLUSION: The prevalence of mitral, but not aortic, valvular regurgitation increased in patients with active acromegaly during follow-up. Patients with acromegaly require adequate cardiac evaluation and follow-up to establish the extent and progression of valvular involvement.

Acromegaly↗
PubMed2006

Active acromegaly enhances spontaneous parathyroid hormone pulsatility.

In healthy subjects, parathyroid hormone (PTH) is secreted in a dual fashion, with low-amplitude and high-frequency pulses superimposed on tonic secretion. These 2 components of PTH secretion seem to have different effects on target organs. The aim of our study was to evaluate whether growth hormone excess in acromegaly may modify the spontaneous pulsatility of PTH. Five male patients with newly diagnosed active acromegaly and 8 healthy subjects were evaluated by 3-minute blood sampling for 6 hours. Plasma PTH concentrations were evaluated by multiparameter deconvolution analysis. Plasma PTH release profiles were also subjected to an approximate entropy (ApEn) estimate, which provides an ensemble measure of the serial regularity or orderliness of the release process. In acromegalic patients, baseline serum PTH values were not significantly different from those measured in the healthy subjects, as well as tonic PTH secretion rate, number of bursts, fractional pulsatile PTH secretion, and ApEn ratio. Conversely, PTH pulse half-duration was significantly longer in acromegalic patients vs healthy subjects (11.8+/-0.95 vs 6.9+/-1.6 minutes; P=.05), whereas PTH pulse mass showed a tendency (P=.06) to be significantly greater in acromegalic patients. These preliminary data suggest that growth hormone excess may affect PTH secretory dynamics in patients with acromegaly. Potentially negative bone effects of the modifications of PTH secretory pattern in acromegaly should be investigated.

Acromegaly↗
PubMed2000

Goldmann perimetry in acromegaly: a survey of 307 cases from 1951 through 1996.

OBJECTIVE: Because visual pathway lesions are a common complication of pituitary tumors, visual field examinations in patients with acromegaly were studied. Proportion and outcome of visual field defects in patients with acromegaly were evaluated. DESIGN: Large, retrospective case series. PARTICIPANTS: We reviewed 307 cases of acromegaly seen from 1951 through 1996 at a single referral center. METHODS: Kinetic visual field testing had been performed with the Goldmann perimeter, and the frequency of visual field defects and their correlation with other clinical manifestations and characteristics of the adenoma were examined. MAIN OUTCOME MEASURES: Repeat visual field examinations. RESULTS: Of the 307 patients included in the analysis, a visual field defect that could be attributed to the pituitary adenoma was observed in 62 (20.2%) during follow-up. Visual field defects were bilateral in 38 (61.3%) of these cases. Patients with visual field abnormalities were significantly younger (P = 0.04), had larger tumors (P < 0.001), had more suprasellar extensions (P < 0.001), and had higher levels of growth hormone in their serum (P = 0.04) than patients free of visual field defects. At the end of the follow-up period, visual field examination remained abnormal in 32 (10.4%). Return to a normal visual field examination after treatment was more frequently observed in patients who were less than 40 years of age at the time of diagnosis (P = 0.004). Secondary empty sella syndrome was the main cause of visual field defects after treatment. Abnormal visual field, either at the time of diagnosis or during follow-up, decreased from 27% of patients between 1951 and 1975 to 15.4% of patients between 1976 and 1996, when modern neuroimaging techniques became available. CONCLUSIONS: Endocrinologic and neuroimaging follow-up of patients with acromegaly should be accompanied by ophthalmic assessment. Factors predictive of visual field defects have been identified.

Acromegaly↗
PubMed2001

Clinical experience with Sandostatin LAR in patients with acromegaly.

Patients with acromegaly, who are not cured after transsphenoidal adenomectomy, may be treated with external irradiation and/or octreotide injections. Recently, a long-acting formulation of octreotide (Sandostatin LAR has become available in clinical practice. We assessed the effects of treatment with this long-acting octreotide in 18 consecutive patients with acromegaly treated in our center, who had persistent signs and symptoms of acromegaly despite transsphenoidal surgery with (n=7) or without irradiation (n=11). Twelve had already been treated with regular Sandostatin for a period of 0.5-8 years in dosages of 3 x 50 to 3 x 300 mcg s.c. (median daily dose 300 mcg). All patients started with i.m. injections of 20 mg Sandostatin LAR every 4 weeks. In the patients who started treatment with octreotide for the first time, mean serum IGF-1 levels (measured by IRMA, Nichols Diagnostics) decreased from 634+/-229 to 255+/-88 ng/ml after 3 months, 271+/-81 ng/ml after 1 year and 263+/-97 ng/ml after 2 years (all P<0.05), while random GH levels (DELFIA, Wallac) decreased from 6.6 (range 3.1-67.0) to 2.1 (0.5-3.1) mU/l after 2 years (P<0.05). In the 12 patients who had already been treated with octreotide, mean IGF-1 also fell, from 367+/-193 to 331+/-195 ng/ml (P=0.023) after 3 months, to 342+/-191 ng/ml after 1 year and 277+/-169 ng/ml (P=0.002) after 2 years, while random GH levels decreased from 4.5 (1.1-46) mU/l at baseline to 2.1 (0.4-23.0) after 2 years (P=0.003). Therefore, the average decrease of IGF-1 was 10% after 3 months and 25% after 2 years. One patient had a decrease of less than 5% (but her IGF-1 was normal, 193 ng/ml), and one patient showed no response to both regular and long-acting Sandostatin (ave. IGF-1, 755 ng/ml). No specific side-effects occurred. One patient chose to return to t.i.d. injection of regular octreotide because of slight worsening of her complaints of headache despite normal IGF-1 levels. All other patients favoured continuation of the monthly injections. In six patients, the dose had to be increased to 30-40 mg monthly because the IGF-1 levels still remained elevated. Sandostatin LAR may be considered a great improvement for the treatment of patients with (symptomatic) acromegaly.

Acromegaly↗
PubMed1999

Acromegaly: report of two patients with an unusual presentation.

The presenting features of functionally active pituitary tumours depend on the specific hormone which is overproduced. Growth hormone (GH) producing tumours usually present with the clinical manifestations of acromegaly due to excessive GH secretion or symptoms resulting from mass effects of the enlarging tumour. The changes in physical features and the increase in tumour size are usually insidiously slow and therefore, recognition of the disease is delayed. In this report two patients with acromegaly are described with an atypical presentation due to acute onset of symptoms. The first patient presented with central diabetes insipidus. The diagnosis acromegaly was made on physical examination. The second patient presented with a generalized seizure during sleep. On CT-scanning a large tumour protruding into the left temporal lobe connected to the pituitary gland was seen. Immunohistochemistry of the tumour after partial transcranial resection confirmed the clinical diagnosis of acromegaly. At a later stage transsphenoidal resection of the pituitary tumour was performed with full recovery and without loss of pituitary function.

Acromegaly↗
PubMed1995

Clinical features and differential diagnosis of pituitary tumours with emphasis on acromegaly.

Pituitary adenomas are frequently encountered, benign intracranial tumours. Clinically classified according to their capacity to produce and secrete hormones, pituitary tumours are diagnosed from the clinical manifestations and biochemical findings of specific pituitary hormone overproduction or of impaired pituitary function due to pressure on normal pituitary cells, the pituitary stalk or the hypothalamus. Additionally, the tumour may result in neurological manifestations due to its effect as an intracranial space-occupying lesion. Pituitary adenomas may present acutely with pituitary apoplexy after intrapituitary haemorrhage or infarction. The subsequent hypofunction of the pituitary with concomitant neurological sequelae of an expanding intracranial mass are often associated with excruciating headache, diplopia and visual field defects. Gradually developing neurological deficits or secondary endocrine failure over several years may precede the recognition of non-secretory tumours (30-40% of pituitary adenomas) as well as some of the hormone-producing adenomas, especially when they expand beyond the confines of the sella turcica. Asymptomatic masses occur in the pituitary in 5-27% of unselected autopsy series. About 10-20% of pituitaries imaged as part of a brain study contain lesions 'consistent with a pituitary adenoma', with about half being pituitary adenomas ('incidentalomas'). Many advocate screening such cases for a wide spectrum of pituitary function abnormalities. Clinical judgement should be utilized to determine the extent of the work-up and the frequency of follow-up. Acromegaly, a clinical syndrome caused by excess growth hormone secretion, accounts for one-sixth of resected pituitary tumours. This disorder leads to chronic progressive disability and a shortened life span, with approximately 50% of untreated acromegalic patients experiencing premature death. The prevalence of acromegaly has been estimated to range from 50 to 70 per million, with the age of diagnosis usually between the third and fifth decades. Conditions associated with acromegaly include glucose intolerance, diabetes mellitus, lipid abnormalities, cholelithiasis, goitre, and hyperthyroidism, respiratory complications, hypertension, cardiovascular disease, and calcium metabolism abnormalities. An association between acromegaly and cancer, especially of the colon, is now recognized. Epidemiological series have indicated that cancer of the colon, breast and other types of malignancy are a cause of death with increased frequency in acromegalics compared with expected rates. Hypopituitary symptoms secondary to the mass effect of macroadenomas in acromegalic patients are common. Among premenopausal women, menstrual irregularities and galactorrhoea have been reported in 40-70%, while more than half of the men complain of impotence and decreased libido.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗
PubMed2006

St-segment elevation acute myocardial infarction in a patient with acromegaly: a case report and literature review.

Acromegaly is a disorder caused by the excess production of pituitary growth hormone and is characterized by the enlargement of the hands, feet and head. Increased morbidity and mortality with acromegaly is associated with cardiovascular complications, hypertension, glucose intolerance, cardiomyopathy and coronary artery disease. We report a case of acromegaly, which presented with ST-segment elevation acute myocardial infarction. The patient received successful primary transluminal coronary angioplasty with stent implantation. Acromegaly was suspected from typical appearance, and confirmed with hormonal examination and imaging of the pituitary mass. We discuss this case in comparison with previous literature.

Acromegaly↗
PubMed2000

Skeletal changes in rats bearing mammosomatotrophic pituitary tumors: a model of acromegaly with gonadal dysfunction.

Growth hormone (GH) exerts potent effects on bone metabolism, resulting in an increased bone formation in animals and humans. Acromegaly has been associated with increased bone turnover, whereas the net effect of the increased bone metabolism has been obscured because patients with acromegaly are often associated with hypogonadism. We investigated changes in cortical and cancellous bone in adult rats implanted mammosomatotrophic pituitary tumor cells (GH3) as a model of acromegaly with gonadal dysfunction. Acromegaly model rats were prepared by implanting GH3 cells into female Wistar-Furth rats at 17 weeks of age. At 28 weeks of age, GH3-bearing rats (GH rats) showed very high serum GH levels and a moderate increase in serum prolactin levels, resulting in low circulating estradiol levels. The GH rats showed significant increases in body weight and in length and volume of both the femur and vertebral body. Bone mineral content values of either the midfemur or the whole lumbar body were significantly greater in the GH rats compared with littermate controls, while the areal bone mineral density values of the respective bones were not different between the two groups. The parameters of mechanical strength of the femur were significantly larger in the GH rats than in controls, whereas those of the lumbar vertebral body cylinder specimen were not different between the two groups. Respective normalized mechanical parameters of the femur and the vertebral body were the same in the GH rats as in controls. In the midfemur, the GH rats showed a significant increase in the total cross-sectional area without influencing the bone marrow area, resulting in an increase in the cortical bone area and the moment of inertia compared with controls. The indices of periosteal bone formation in the midfemur were greater in the GH rats compared with controls, but the endocortical bone formation and resorption were not different between the two groups. In the vertebral body cancellous bone, the GH rats had an increase in bone turnover rate, whereas the structural parameters were not different between the two groups. These results from GH3-bearing rats demonstrate that an excess of GH increases cortical bone mass in rats accompanied with estrogen deficiency, while no large effect on vertebral body cancellous bone mass is seen.

Acromegaly↗
PubMed1990

Respiratory problems in acromegaly.

Death from respiratory causes in acromegaly is three times more common than in the general population and is most often the result of upper airways obstruction, although less commonly pulmonary dysfunction and disturbance of the central nervous system may occur. These factors may be found alone or in combination. Despite several reports of laryngeal involvement, upper airway obstruction in acromegaly is usually regarded as being due to macroglossia and pharyngeal soft tissue hypertrophy. We present four cases of acromegaly in which tracheostomy was required for laryngeal obstruction, with a review of the literature concerning the nature of respiratory problems in acromegaly.

Acromegaly↗
PubMed1999

Growth hormone pulsatility in acromegaly following radiotherapy.

Radiotherapy continues to have an important role in the treatment of acromegaly and is particularly effective at halting tumour growth, causing tumour shrinkage and reducing growth hormone (GH) concentrations in the long term. The major disadvantages of radiotherapy include the slow reduction in GH levels and damage to the other hypothalamic-pituitary axes. The 24 hour GH profile in active acromegaly compared with normals, characteristically shows an increased frequency of GH pulses, increased disorderliness (approximate entropy) of GH release, increased mean GH valley nadir, increased non-pulsatile fraction of GH and either similar or increased GH pulse amplitude. Complete surgical excision of a GH secreting adenoma may reverse these abnormalities and reduce circulating insulin-like growth factor-1 (IGF-1) concentrations to normal. However, very few data are available regarding the effects of radiotherapy on GH pulsatility in patients with acromegaly. Radiotherapy rarely leads to normalisation of the pattern of spontaneous GH release and may therefore be associated with an elevated IGF-1 even when 24 hour GH concentrations are comparable to healthy controls. The impact of such a biochemical state on morbidity and mortality in acromegaly is unknown. The continuing effects of radiotherapy may potentially transform an individual from a state of GH excess, to a state of GH deficiency, with as yet undetermined effects. In addition, radiotherapy leads to significant hypothalamic dysfunction, with the possible loss of endogenous somatostatin (SMS) production. This may potentially alter somatostatin (SMS) receptor expression on somatotroph adenomas and alter their responsiveness to subsequent SMS analogue therapy.

Acromegaly↗
PubMed2000

Long-acting octreotide LAR compared with lanreotide SR in the treatment of acromegaly.

The use of somatostatin analogues for the treatment of acromegaly is now well established. Recently long-acting preparations of octreotide and lanreotide have been introduced. In this study we have assessed the efficacy and tolerability of the long acting somatostatin analogue octreotide LAR in patients with acromegaly, and compared it with lanreotide SR. Five patients with active acromegaly were recruited; they were treated with lanreotide SR for 6 months and then, following a wash-out period, received octreotide LAR for 6 months. They were assessed at baseline, 3- and 6-months, by clinical score, GH and IGF1. Adverse effects were carefully monitored. Both treatments effectively reduced GH and IGF1 levels. Four of five patients achieved a mean GH level of < 2.5 ng/ml with both drugs; with octreotide LAR only, these patients also had GH < 1 ng/ml after oral glucose loading. The clinical symptoms score improved significantly with octreotide LAR, as did the ring size; the clinical score correlated significantly with GH. Blood glucose was not adversely affected. All patients experienced minor GI symptoms with lanreotide SR, but less frequently with octreotide LAR. Both drugs caused biliary stasis and had a tendency to form biliary sludge. Octreotide LAR proved effective for the treatment of acromegaly and was well tolerated. Octreotide LAR had some advantages over lanreotide SR, although the differences were not great.

Acromegaly↗
PubMed2001

Prevalence and pathogenesis of sleep apnea and lung disease in acromegaly.

Respiratory disorders are common and important complications in acromegaly. Patients suffering from acromegaly display a 1.6-3.3 fold increase in mortality rate, which is due to respiratory disorders in 25% of cases. In these patients, mortality for lung disease is 2-3 fold higher than in the general population. Every portion of the respiratory system may be involved. Deformities of facial bones, edema and hypertrophy of the mucosae and pharyngeal and laryngeal cartilages, enlargement of the tongue and inspiratory collapse of the hypopharinx, all may contribute to respiratory alterations. Nasal polyps, "hormonal rhinitis", changes of the voice and snoring are common occurrences. Though rarely, a laryngocele may ensue. Pneumomegaly is frequently observed and, as suggested by functional studies, might be due to an increased number rather than volume of the alveoli. An obstructive respiratory syndrome caused by mucosal thickening of the upper airways and bronchi is observed in 25% of female and 70% of male patients. The sleep apnea syndrome (SAS) affects 60-70% of acromegalic patients. SAS may be of obstructive, central or mixed type. Obstructive SAS is the prevailing form in acromegaly. It is due to intermittent obstruction of upper airways with preserved activity of the respiratory center, as testified by the remarkable thoracic and abdominal respiratory efforts. The pathogenesis of the central type of SAS is more complex. Narrowing of the upper airways may induce reflex inhibition of the respiratory center. Moreover, increased GH levels and, possibly, defects in the somatostatinergic pathways, may increase the ventilatory response of the respiratory center to carbon dioxide, thereby leading to respiratory arrest. In the mixed type of SAS, the phenomena underlying the other two forms coexist. Oxygen desaturation concomitant with the apneic episodes accounts for the frequent nocturnal wakening and diurnal drowsiness. Among the clinical correlates of SAS, arterial hypertension is of particular interest due to the close correlation existing between the two disorders. Sleep deprivation related to SAS seems per se to favor the appearance of hypertension. Moreover, short lasting hypoxemia may induce prolonged elevations of blood pressure, mediated by decreased endothelial generation of nitric oxide. Thus, since cardiovascular events are the main cause of mortality in patients with acromegaly, it is reasonable to hypothesize that SAS is involved in the reduced life span of these patients.

Acromegaly↗