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PubMed1984

Quantitative differences between immunological and receptor binding activities of hGH in pituitary adenomas from patients with acromegaly.

Human growth hormone (hGH) in the pituitary extracts from patients with acromegaly and normal subjects was measured by radioimmunoassay (RIA) and radioreceptor assay (RRA) using pregnant rabbit liver membrane, and the RRA to RIA ratios of hGH were calculated. The RRA to RIA ratio of hGH for acromegaly was higher than that for normal (0.90 +/- 0.03 vs 0.75 +/- 0.03, p less than 0.01). When the pituitary extracts were gel filtered on Sephadex G-100 column there were three immunoreactive hGH peaks ("pre-big", "big", and "little" hGH); there were no significant differences in gel filtration patterns of hGH between acromegaly and normal. The "little" hGH component (major component) had a higher RRA to RIA ratio than "pre-big" hGH and "big" hGH in both acromegaly and normal. "Little" hGH extracted from acromegaly had a higher RRA to RIA ratio than that from normal (1.14 +/- 0.09 vs 0.93 +/- 0.04, p less than 0.05). These data support the hypothesis that hGH synthesized in acromegaly may be different from normal.

Acromegaly↗
PubMed2000

Current management of acromegaly.

Acromegaly, a chronic disease of growth hormone (GH) hypersecretion, is most typically caused by a pituitary adenoma. Early diagnosis is critical for prompt intervention to prevent deleterious effects of prolonged exposure to elevated GH and insulin-like growth factor Type I (IGF-I) levels. Current therapy for acromegaly includes several options: surgery, radiotherapy and pharmacotherapy. Transsphenoidal adenomectomy remains a mainstay of therapy for acromegaly. Cure rates are high in microadenomas, but < 50% in macroadenomas. Conventional and stereotactic procedures for radiation therapy are also effective in decreasing GH levels in acromegalic patients, but they need years to normalise GH hypersecretion and carry with them the risk of hypopituitarism. The major classes of drugs currently used to treat acromegaly are dopamine agonists and analogues of somatostatin. Dopamine agonists bind to the D2 receptor and suppress GH hypersecretion in some patients with acromegaly. Their clinical effectiveness is modest, although promising results have been obtained with two novel compounds, quinagolide and cabergoline, that possess long duration of action. Somatostatin analogues have been shown to improve clinical symptoms of acromegaly, decrease hypersecretion of GH and IGF-I and reduce tumour volume in a clinically significant number of patients. Octreotide is administered by s.c. route several times a day, but the recently developed sustained release formulations (octreotide LAR and SR lanreotide) are administered only every 7-28 days by i.m. injections. The complications associated with somatostatin analogues are small, relative to the benefits. Lastly, compounds with a novel mechanism of action, the GH receptor antagonists, are presently under investigation.

Acromegaly↗
PubMed2001

Craniofacial abnormalities and their relevance for sleep apnoea syndrome aetiopathogenesis in acromegaly.

OBJECTIVE: To explain the effect of craniofacial relations on the development of the sleep apnoea syndrome (SAS) in acromegaly, and to elucidate how the activity of acromegaly affects the severity of SAS. DESIGN: Prospective observational study. METHODS: Cephalometry and sleep ventilation measurements were performed in 26 acromegalic men and in 96 men with SAS. RESULTS: SAS was found in 20 acromegalic men. Compared with non-acromegalic men with SAS, patients with acromegaly and SAS were found to have: enlargement of almost all linear dimensions; increased angle indicating mandibular protrusion; increased difference between maxillary and mandibular protrusion; articular angle decrease; soft palate lengthening; and pharyngeal airway space (PAS) enlargement in the palatal and uvular-tip planes. A comparison of acromegalic men with and without SAS revealed no significant difference in the craniofacial skeleton, although there was a narrowing of the minimal PAS (MinPAS) and of PAS in the uvular-tip plane in patients with SAS. SAS was more frequent in the patients with active acromegaly. MinPAS in the patients with active acromegaly was narrower than in those without disease activity. CONCLUSION: Skeletal abnormalities in acromegalic men with SAS were different from those in SAS patients without acromegaly. Upper airway narrowing due to changes in pharyngeal soft tissues takes a more relevant share in the development of SAS in acromegalic men than skeletal anomalies.

Acromegaly↗
PubMed2001

Increased glucose-dependent insulinotropic polypeptide (GIP) secretion in acromegaly.

OBJECTIVE: Acromegaly is often associated with fasting and postprandial hyperinsulinemia, and the mechanisms involved are only partly understood. Hypersecretion of incretins such as glucose-dependent insulinotropic polypeptide (GIP) could play a role in determining hyperinsulinemia in acromegaly, but the available data are inconsistent. The aim of this study was to characterize the fasting and postprandial pattern of plasma GIP and insulin in a group of acromegalic patients. DESIGN AND METHODS: Eleven non-diabetic patients with newly diagnosed acromegaly and 11 sex- and age-matched healthy subjects were studied. Blood samples were taken at regular intervals in fasting conditions and for 3 h after a standard solid-liquid meal for growth hormone (GH), GIP and insulin measurements. RESULTS: Not only insulin, but also fasting and postprandial GIP levels were significantly higher in the patients with acromegaly than the healthy subjects (P<0.01). In the former group fasting GIP levels and the integrated GIP response to the meal correlated significantly with GH basal levels (r=0.83, P<0.01 and r=0.65, P<0.05, respectively). Moreover, multivariate linear regression analysis showed that the presence of acromegalic status was associated with higher fasting and postprandial GIP levels independently of sex, age, fasting and postprandial plasma glucose and insulin levels, and the occurrence of normal or impaired glucose tolerance. CONCLUSION: This study provides evidence that in patients with acromegaly fasting and postprandial GIP levels are abnormally high. GIP hypersecretion in turn might play a role in the pathogenesis of hyperinsulinemia that characterizes acromegaly.

Acromegaly↗
PubMed2004

Raloxifene decreases serum IGF-I in male patients with active acromegaly.

OBJECTIVE: Most patients with acromegaly require additional treatments after trans-sphenoidal surgery. Although traditional methods of treatment aim at suppressing GH hypersecretion from the pituitary tumor, recent studies on the use of the GH receptor antagonist have shown that targeting the action of GH on peripheral tissues may be more effective. Estrogens and the selective estrogen receptor modulator tamoxifen have been used previously to suppress circulating IGF-I levels in patients with acromegaly. Positive effects of raloxifene in women with active acromegaly have been reported recently. This study was designed to examine the potential role of raloxifene in the treatment of acromegaly in male patients. DESIGN: We studied eight men with active acromegaly despite the fact that they were receiving traditional treatments. All subjects were treated with raloxifene (60 mg twice a day) for a median of 5 weeks. METHODS: The effects of raloxifene on GH secretion were assessed by obtaining 24-h GH profiles and studying the response of GH to various stimuli before and after treatment with raloxifene. Serum IGF-I was measured before and after raloxifene treatment. RESULTS: Raloxifene did not affect basal GH secretion or response of GH to TRH, GHRH or glucose, but it decreased circulating IGF-I by 16+/-4% (P=0.001), and normalized plasma IGF-I in two patients. No changes in clinical parameters were observed. Prolactin levels, the prolactin response to TRH and free testosterone levels remained unchanged. Raloxifene was well tolerated. CONCLUSION: Raloxifene might be useful in the treatment of male patients with active acromegaly, but longer term studies are clearly needed.

Acromegaly↗
PubMed2005

Long-term maintenance of the anabolic effects of GH on the skeleton in successfully treated patients with acromegaly.

INTRODUCTION: The anabolic actions of growth hormone (GH) are well documented. In acromegaly, the skeletal effects of chronic GH excess have been mainly addressed by evaluating bone mineral density (BMD). Most data were obtained in patients with active acromegaly, and apparently high or normal BMD was observed in the absence of hypogonadism. Data on BMD are not available after successful treatment of acromegaly. Whether the positive effect of GH excess on bone mass is maintained in the long term after clinical and biochemical cure of acromegaly remains to be established. PATIENTS AND METHODS: In a cross-sectional study design, lumbar spine and femoral neck BMD was measured in 79 acromegalic patients cured or well controlled on octreotide treatment (45 male and 34 female patients; mean age 57+/-1 years). Successful treatment (by surgery, radiotherapy and/or use of octreotide) was defined as normal age-adjusted IGF-I. Mean time after biochemical remission was 10.2+/-7 years. RESULTS: Normal or increased BMD was observed at the femoral neck and lumbar spine in both men and women in remission after treatment for acromegaly. Similar results were obtained in patients in remission for 5 years or longer. Osteoporosis was present in 15% of the patients, with similar prevalence in men and women. There was no relationship between BMD and duration or severity of GH excess before treatment, gonadal status and presence of pituitary hormone deficiencies. Pituitary irradiation was a strong negative predictor of bone mass at the femoral neck. Long-term bone loss was observed only at the femoral neck. CONCLUSION: Our data suggest that the anabolic effect of GH on trabecular and cortical bone remains demonstrable after remission of acromegaly, although it may not be maintained at cortical sites in the long term. In the present study, the lack of effect of gonadal status on BMD may be explained by the presence of only mild hypogonadism and by our policy of prompt hormonal replacement therapy for severe hypogonadism. The negative effect of pituitary irradiation on femoral neck BMD remains intriguing, although it is probably related to some degree of the diminished GH secretion frequently observed after this form of treatment.

Absorptiometry, Photon↗
PubMed2006

Validity and clinical applicability of the acromegaly quality of life questionnaire, AcroQoL: a 6-month prospective study.

OBJECTIVE: Validate the acromegaly quality of life (AcroQoL) questionnaire as a disease-generated questionnaire, which analyses physical and psychological domains, the latter subdivided into appearance and personal relationship sub-scales, to evaluate health-related quality of life (HRQoL) in acromegaly. DESIGN: Prospective, observational multicenter study. METHODS: One hundred and six patients with acromegaly, 42 with active disease studied basally and 6 months after treatment ('sensitivity to change' group), and 64 with treated, stable disease, studied twice within 1 month ('reliability' group) were included. As controls, a reference Spanish population (n=12,245 for the EuroQoL questionnaire) and 157 obese patients (body mass index>30 kg/m2) were studied basally. Socio-demographic data, clinical activity, co-morbidity, GH, IGF-I, and HRQoL (overall perception of health state, EuroQoL and AcroQoL in the obese controls and acromegalic patients) were evaluated. RESULTS: Globally, AcroQoL scored worse in the 'sensitivity to change' group than in the 'reliability' group (56+/-20 vs 65+/-18, P<0.05), but did not discriminate between patients and obese controls. The psychological domain was worse in the 'sensitivity to change' group than obese controls (P<0.05). Appearance was the most affected sub-scale in acromegaly and significantly worse than in obese controls. The sub-scale personal relationships of AcroQoL were less affected in the 'reliability' group than in obese controls (P<0.05). Patients with acromegaly and obese controls showed more problems on the EuroQoL than general Spanish population. Significant correlations were observed globally and for each dimension between AcroQoL and the generic questionnaires. On re-testing, no change was observed in the 'reliability' group in any questionnaire, demonstrating good test-re-test reliability. In the 'sensitivity to change' group after 6 months of treatment, there was improvement in the generic questionnaires and in AcroQoL score (P<0.01). Internal consistency of AcroQoL was good (Cronbach's alpha>0.7). No correlation between AcroQoL and GH or IGF-I was observed. CONCLUSION: AcroQoL questionnaire is a valid tool for the assessment of HRQoL in clinical practice in patients with acromegaly.

Acromegaly↗
PubMed2006

Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients.

OBJECTIVE: Acromegaly is characterized by a persistent hypersecretion of GH and provides information on long-term effects of GH on bone metabolism. The aim of this study was to examine the effect of gonadal status and disease activity on bone metabolism in active acromegaly. METHODS: Seventy-three consecutive patients with active acromegaly: 40 women and 33 men (50 +/- 13 (mean +/- s.d.) and 49 +/- 10 years respectively) were evaluated and compared with age-, sex-, and body mass index (BMI)-matched controls by X-ray absorptiometry and biochemical analysis (markers of disease activity and bone turnover). RESULTS: We found that bone turnover, as evaluated by biochemical bone markers, is coupled and markedly increased in relation to disease activity in active acromegaly. Acromegalic women, but not men, were characterized by an increased bone area and slightly decreased bone mineral content resulting in significantly decreased bone mineral density (BMD) in the ultradistal radius, proximal radius, and total body. No differences in bone turnover or BMD were found between eu-and hypogonadal subjects. Multivariate analysis identified age, BMI, and gender as independent predictors of total BMD in acromegaly. CONCLUSION: Our study demonstrates a decreased total body BMD in women, not men, with active acromegaly, regardless of gonadal status or disease activity. Bone turnover is markedly increased in relation to disease activity, possibly counteracting the anabolic effects of excess GH/IGF-I in these subjects. We suggest more focus on biomechanical analyses when investigating endocrine disorders affecting bone size and distribution between compartments.

Acromegaly↗
PubMed2005

Usefulness of the thyrotropin-releasing hormone test in pre-clinical acromegaly.

Acromegaly is caused primarily by pituitary growth hormone (GH)-secreting tumors. It is usually recognized because of characteristic manifestations, and diagnosed clinically. However, there exists a mild stage of acromegaly, which poses a diagnostic problem due to the absence of typical clinical manifestations. Here we present four patients with pre-clinical acromegaly, who showed minimal acromegaloid features with elevated levels of insulin-like growth factor-I. Basal GH levels were within normal levels in 3 of 4 cases, while insulin-like growth factor-I levels were elevated above normal in all cases. Plasma GH levels were elevated in response to thyrotropin-releasing hormone (TRH) in all cases, indicating a diagnostic value of the TRH stimulation test. In contrast, an oral glucose tolerance test was not useful for the diagnosis, because of the low GH levels (less than 1 ng/ml) and/or secondary to diabetes mellitus. In response to a dopamine agonist, GH levels were increased in the two cases, whereas GH levels were decreased or remained unchanged in the other two cases. We therefore suggest that the TRH stimulation test would be helpful to examine the presence of pre-clinical acromegaly. Diagnosis of the early stages of acromegaly is important to prevent progression to overt acromegaly.

Acromegaly↗
PubMed2004

Cardiac abnormalities in acromegaly. Pathophysiology and implications for management.

Cardiovascular disease is claimed to be one of the most severe complications of acromegaly, contributing significantly to mortality in this disease. In fact, an excess of growth hormone (GH) and insulin-like growth factor 1 (IGF-I) causes a specific derangement of cardiomyocytes, leading to abnormalities in cardiac muscle structure and function, inducing a specific cardiomyopathy. In the early phase of acromegaly the excess of GH and IGF-I induces a hyperkinetic syndrome, characterized by increased heart rate and increased systolic output. Concentric hypertrophy is the most common feature of cardiac involvement in acromegaly, found in more than two thirds of patients at diagnosis. This abnormality is commonly associated with diastolic dysfunction and eventually with impaired systolic function ending in heart failure, if the GH/IGF-I excess is left untreated. In addition, abnormalities of cardiac rhythm and of heart valves have also been described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes mellitus, aggravates acromegalic cardiomyopathy. Successful control of acromegaly induces a decrease in left ventricular mass and an improvement in diastolic function, while the effects of GH/IGF-I suppression on systolic function are more variable. However, since cardiovascular alterations in young patients with short disease duration are milder than in those with longer disease duration, it is likely to be easier to reverse and/or arrest acromegalic cardiomyopathy in young patients with early-onset disease. In conclusion, careful assessments of cardiac function, morphology, and activity are required in patients with acromegaly. An early diagnosis and prompt effective treatment are important in order to reverse acromegalic cardiomyopathy.

Acromegaly↗
PubMed2001

Clinical features and therapeutic outcomes of 65 patients with acromegaly at Tokyo Women's Medical University.

OBJECTIVE: The purpose of this study was to survey the clinical characteristics, complications, and therapeutic outcome in patients with acromegaly. PATIENTS AND METHODS: The clinical features of 65 patients with acromegaly (31 males, 34 females; mean age: 50+/-2 yr.) who were admitted to Tokyo Women's Medical University between 1990 and 1999 were analyzed retrospectively from medical records. RESULTS: The retrospective analysis revealed that the diagnosis of acromegaly was preceded by approximately 8.1+/-1.1 years of signs and symptoms of the disease. Forty-six of the 65 patients (71%) had macroadenomas, 16 (25%) had microadenomas, and the remaining three had empty sella. The rate of biochemical cure or remission was 81% for microadenoma (13/16), 64% for macroadenoma without extrasellar extension (9/14), and 13% for macroadenoma with cavernous sinus extension (2/15). Eighteen (28%) patients had impaired glucose tolerance (IGT) and 32 (49%) had diabetes mellitus (DM). After treatment for acromegaly, glucose metabolism was analyzed again in 38 patients, and it improved in 26 patients with IGT or DM. Twenty-five of 65 patients (38%) had hypertension. Of 26 patients who underwent barium enema or colonoscopy, 10 had colonic polyps and 4 had colon cancer. CONCLUSION: This study suggests that long-term excessive growth hormone (GH) secretion causes many complications. Therefore, awareness of the early symptoms and signs of acromegaly and long-term careful management of complications, along with therapy to reduce serum GH/insulin-like growth factor (IGF)-I levels, are important for patients with acromegaly.

Acromegaly↗
PubMed1999

[What is the value of determining immunoreactive GHRH in acromegaly?].

Acromegaly is usually due to autonomous, excessive secretion of growth hormone from a pituitary adenoma. One would expect growth hormone-releasing factor (GHRH) in these patients to be suppressed. In the available literature referring to acromegaly, immunoreactive GHRH levels were determined in 259 acromegalic patients. When growth hormone was measured simultaneously, no correlation was found between serum growth hormone and plasma GHRH concentrations, irrespective of whether the acromegalic patients were treated or not. A possible explanation for this finding might be the lack of a feedback regulation between plasma growth hormone and GHRH. Also, since growth hormone is secreted in a pulsatile fashion the interpretation of single growth hormone values can be difficult. IGF I, which correlates well with mean growth hormone production, may therefore represent a more valuable criterion for the assessment of activity and GHRH plasma levels in acromegalics. However, no study has yet been performed to elucidate the relationship between GHRH and IGF I in acromegaly. To examine this relationship we measured the concentration of plasma GHRH and IGF I in 18 treated patients with acromegaly (age range 32-64 years median 50.5 years; median follow-up 6.5 years, range 3 months to 33 years). All immunoreactive GHRH levels were within the limits described as normal in the literature (mean +/- SD 22.89 +/- 2.72 pg/ml, range 19-28 pg/ml). The IGFI level was 396.78 +/- 224.26 ng/ml (mean +/- SD, range 71-876 ng/ml; reference ranges, age group 25-39 years: 114-492 ng/ml; 40-54 years: 90-360 ng/ml; > 55 years: 71-290 ng/ml). We found no correlation between IGF I and GHRH concentrations (r = 0.17). We therefore conclude that measuring plasma GHRH is not useful in the evaluation of the activity or therapy of acromegaly but may be helpful in its differential diagnosis since a massive elevation of GHRH is typically associated with the ectopic GHRH syndrome, a rare cause of acromegaly.

Acromegaly↗
PubMed1999

Markers of ventricular tachyarrythmias in patients with acromegaly.

INTRODUCTION: Sudden cardiac death is a known complication of acromegaly. Little is known of the exact mechanism leading to sudden cardiac death in these patients. Ventricular tachyarrhythmias may be an important cause. If this is so, clinical markers of ventricular tachyarrhythmias may be more common in this group of patients. The presence of these markers allow better risk stratification among acromegalic patients. METHODS: We performed signal averaged electrocardiography and analysed 12 lead electrocardiography for QT dispersion on 17 acromegaly patients who attended the UKM endocrine clinic within a period of 5 months and compared them with similar age matched controls. Signal averaged electrocardiogram was performed using Marquette Mac 12/15 ECG analyser and QT intervals were measured manually from 12 lead ECG tracings. Late potential positivity was defined by the standard Breithardt criteria. QT dispersion was defined as the longest minus the shortest QT interval from all 12 lead tracings. Echocariography was done to assess left ventricular hypertrophy in patients and controls. RESULTS: Late potential positivity was found to be more common in acromegaly patients compared with controls (chi-square, p < 0.05, n = 34) and QT dispersion was also found to be significantly higher in the acromegaly group compared with control s (mean +/- SE QT dispersion respectively 121.0 +/- 8.6 ms vs 86.2 +/- 7.0 ms, t-test, p < 0.05, n = 34). Left ventricular hypertrophy was present in five acromegaly patients and two in the control group. CONCLUSION: Acromegaly patients have a higher incidence of late potential positivity and higher QT dispersion compared with age matched controls. These findings might explain the increase susceptibility of these patients to sudden cardiac deaths from ventricular tachyarrhythmias.

Acromegaly↗
PubMedDate not supplied

Concurrent diagnosis of acromegaly and diabetic ketoacidosis.

OBJECTIVE: To report the occurrence of diabetic ketoacidosis (DKA) in a patient with acromegaly. METHODS: A case report with clinical and laboratory details is presented, and the few other cases of DKA and acromegaly from the literature are discussed. RESULTS: A 37-year-old man requested a consultation because of nausea, vomiting, polydipsia, polyuria, and weight loss. Physical examination revealed findings suggestive of acromegaly, including coarse facial features and enlargement of his hands and feet. Laboratory studies confirmed the diagnoses of DKA and acromegaly. Magnetic resonance imaging disclosed the presence of a pituitary adenoma, which was subsequently removed surgically. Although the DKA had been managed with insulin therapy, 2 weeks postoperatively the insulin dose was tapered and then discontinued because of hypoglycemia. Follow-up showed normalization of growth hormone levels and plasma glucose levels. Only three other cases of DKA associated with acromegaly were found in the medical literature. CONCLUSION: Although DKA is rarely diagnosed in conjunction with acromegaly, this unusual association was confirmed in the current patient.

Acromegaly↗
PubMed2005

[Serum adiponectin levels in patients with acromegaly].

UNLABELLED: Acromegaly is frequently associated with impaired glucose tolerance or diabetes. Insulin resistance has been reported to be related to low levels of adiponectin, which is exclusively produced by adipose tissue, as well as to decreased concentration of sex hormone binding globuline (SHBG). Growth hormone (GH) excess is associated with increased muscle mass and decreased fat mass. Influence of GH on production and secretion of adiponectin is not completely understood. The aims of this study were to assess serum adiponectin levels in patients with active acromegaly and to compare them with concentrations in the control group and to investigate relationships between adiponectin and indexes: body mass index (BMI) and waist-to-hip ratio (WHR) as well as SHBG levels. MATERIALS AND METHODS: Serum adiponectin and SHBG levels were measured by radioimmunoassay in 30 patients with active acromegaly and in 22 sex-, age-, BMI- and WHR-matched controls. The groups were comparable in prevalence of hypertension and disturbances of glucose metabolism. RESULTS: Serum adiponectin concentrations were higher in acromegalic patients compared with control group (24.03 +/- 9.85 mg/ml vs. 14.46 +/- 3.96 mg/ml, p<0.001). When the subjects were fallen into two groups according to sex, significant differences were also observed. Serum SHBG levels were lower in cases compared with controls (25.36 +/- 22.89 nmol/l vs. 33.54 +/- 15.07 nmol/l, p=0.03). In the control group we found adiponectin positively correlated with SHBG concentrations (r=0.53, p=0.01) and negatively correlated with BMI (r=-0.52, p=0.02) and WHR (r=-0.51, p=0.03). However, these relationships were not observed in patients with acromegaly. No significant associations were found between adiponectin and GH or IGF-I. CONCLUSIONS: Serum concentration of adiponectin is significantly higher in patients with acromegaly when compared with the control group and is independent of BMI, WHR and SHBG. The results suggest that adiponectinemia does not directly affect development of insulin resistance in acromegaly.

Acromegaly↗
PubMedDate not supplied

[Five year remission of GHRH secreting bronchial neuroendocrine tumor with symptoms of acromegaly. Utility of chromogranin A in the monitoring of the disease].

Acromegaly is usually caused by excess GH (growth hormone) secretion by pituitary adenoma. Extremely rare (< 1% of cases) acromegaly can be a result of ectopic GHRH (growth hormone releasing hormone) secretion by bronchial tubes, lung, pancreatic or intestinal tumor. The aim of this description is to present the case of successfully treated acromegaly caused by ectopic GHRH secretion by bronchial neuroendocrine tumor and the usefulness of chromogranin A assay in the disease monitoring. The diagnosis of acromegaly in 61-year old woman was based on typical clinical picture and elevated GH and IGF-1(insulin-like growth factor-1) levels. MRI (magnetic resonance imaging) images revealed no tumor in the pituitary but only the pituitary enlargement. Moreover, the right lung tumor (10 cm size) and elevated GHRH level were documented. The secretion of GH, IGF-1 and GHRH were normalized and progression of acromegaly was stopped after the carcinoid tumor surgery. Currently, 5 year after surgery, acromegaly is still in the remission, as the normal levels of GH, IGF-1, chromogranin A and normal chest and pituitary images confirm. The authors emphasize usefulness of measurement of chromogranin A concentration for the evaluation of the tumor remission in case the routine GHRH assay is not accessible.

Acromegaly↗
PubMedDate not supplied

[Lowered ghrelin levels in acromegaly—normalization after treatment].

UNLABELLED: Ghrelin has been found as a natural ligand of growth hormone secretagouges receptors (GHSR-1a) that exerts a marked stimulatory effect on growth hormone (GH) secretion. It is also thought to be involved of eating behavior and control of energy homeostasis. However, still little is known about the physiology of ghrelin secretion in acromegaly. OBJECTIVE: The objective of the study was to examine effects of surgical and pharmacological treatment in patients with acromegaly on serum ghrelin levels. MATERIAL: 28 patients (17 women and 11 men) aged 47.7+/-11.4 years (mean+/-SD) with body mass index (BMI)=31.6+/-4.9 kg/m2. Diagnosis was based on: 1/peak GH in oral glucose tolerance test>or=1ng/mL, 2/serum IGF-1 levels above normal for gender and age, 3/ pituitary adenoma in magnetic resonance imagining. Patients were divided into two groups: Group I-surgically treated (transsphenoidal surgery): 10 women and 7 men aged 45+/-10.9 years with BMI=31.3+/-4.9 kg/m2. Criteria of cure in acromaegaly were: 1/peak GH<1 ng/ml in OGTT, 2/serum IGHF-1 levels according to gender and age. Group II-pharmacologically treated (Sandostatin LAR, Novartis Pharm. Ltd, 20 mg im, monthly): 7 women and 4 men aged 52+/-11 years, BMI=29.4 kg/m2. Criteria of good control of acromegaly were: 1/peak GH<1 ng/ml in OGTT, 2/serum IGHF-1 levels according to gender and age. Control group-healthy subjects: 10 women and 19 men aged 47.7+/-11.4 years, BMI=25.6 kg/m2. METHODS: In patients before and after treatment and in healthy subjects fasting serum levels of total ghrelin, leptin, growth hormone (GH), insulin-like growth factor I (IGF-1), glucose, insulin, total cholesterol and trigliceryde levels were measured. HOMA index of insulin resistance was calculated. The patients and control subjects underwent assessment of body height, weight and BMI. RESULTS: Body weight and BMI in patients before treatment were higher compared to healthy controls (87.3+/-18 to 74.4+/-16 kg, p<0.02 (body weight) and 31.6+/-4.9 to 25.5+/-4.1 kg/m2, p<0.0002 (BMI). Body weight and BMI after successful surgical treatment were still higher compared to healthy subjects (92.7+/-19 to 74.4+/-16 kg, p=0.02 (body weight) and 31.5+/-5 to 25.5+/-4.1 kg/m2, p<0.0003 (BMI). Body weight decreased during pharmacological treatment although BMI was still higher then in control subjects (30.1+/-6.3 to 25.2+/-4.1 kg/m2; p<0.003). Serum fasting GH and IGF-1 levels decreased after successful surgical treatment, from 26.3+/-29 to 1.6+/-2.5 microg/l (p<0.007) and from 926.1+/-325 to 337+/-213 microg/l (p<0.00003), respectively. Also during pharmacological treatment decrease in serum GH and IGF-1 levels were observed, from 29.4+/-40 to 5.8+/-7.6 microg/l and from 976.3+/-328 to 358.3+/-203 microg/l (p<0.002), respectively. Serum insulin levels decreased after successful surgical treatment, from 29.1+/-9.8 do 15.8+/-7.3 microU/ml (p<0.02). Also during pharmacological treatment serum insulin levels and HOMA index decreased, from 29.8+/-12.9 to 14.6+/-2.1 microU/ml (p<0.03) and from 9.1+/-3.6 to 3.5+/-0.4 (p<0.007), respectively. Serum fasting insulin and glucose levels and HOMA index were higher in patients before treatment compared to healthy subjects and didn't differ significantly after successful surgery and during pharmacotherapy. Serum ghrelin levels in patients with acromegaly were decreased compared to healthy subjects (1055.2+/-325 to 1266.8+/-374 pg/ml, p<0.04) and increased after successful surgical treatment, from 1164.2+/-321 to 1553.6+/-542 pg/ml (p=0.01). During pharmacotherapy decrease in serum ghrelin levels was observed, from 1038.7+/-344 to 568.5 +/-252 pg/ml (p<0.03). There were no significant differences in serum ghrelin level between healthy controls and patients after treatment. Significant negative correlation between serum ghrelin levels and body weight (r=-0.40, p=0.04) in healthy subjects was found. In patients with acromegaly significant negative correlation between serum ghrelin levels and insulin levels and HOMA index were found (r=-0.48; p<0.02 and r=-0.57; p<0.03, respectively. CONCLUSIONS: In patients with acromegaly: 1/serum ghrelin levels are decreased compared to healthy subjects. It can be speculated, that its at least partially caused by negative feedback control of ghrelin production and by GH-induced hyperinsulinaemia. 2/serum ghrelin levels increase after successful transsphenoidal surgery. 3/ treatment with somatostatin analoges causes decrease in serum ghrelin levels, despite of serum GH and IGF-1 normalization.

Acromegaly↗
PubMed1991

Cardiac hypertrophy and function in asymptomatic acromegaly.

Heart disease frequently occurs in advanced acromegaly. In order to investigate cardiac mass and function in acromegaly in the absence of obvious cardiac disease, we performed Doppler echocardiography in 15 asymptomatic acromegalic patients (six of them had systemic hypertension). The data were compared with those of a group of 10 age-matched controls. Left ventricular mass index (LVMI) was increased in acromegaly (110 +/- 32 vs 32 +/- 12 g m-2, P = 0.02), but shortening fraction and systolic time intervals did not differ. Mitral EF slope was decreased (80 +/- 21 vs 101 +/- 30 mms-1, P less than 0.02), while the duration of the isovolumic relaxation period (IRP) was increased (92 +/- 13 vs 69 +/- 16 ms, P less than 0.01). Hypertensive acromegalic patients (n = 6) had a higher LVMI than normotensive acromegalic patients (n = 9) (133 +/- 27 vs 94 +/- 24 g m-2, P = 0.02) and this was confirmed by a meta-analysis of data in the literature: the prevalence of hypertrophy was 76% in the presence of hypertension vs 50% in its absence, P less than 0.002. IRP was prolonged in normotensive acromegalic patients vs normal controls (90 +/- 11 vs 69 +/- 16 ms, P less than 0.01). In conclusion, subclinical cardiac abnormalities occur frequently in acromegaly in the absence of obvious heart disease, and hypertrophy is observed in asymptomatic hypertensive acromegaly. Moreover, diastolic abnormalities are found in asymptomatic acromegaly and could be caused by several heart-related factors.

Acromegaly↗